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Cheong C, Kim NW, Shim SR, Kang J. Evaluating the Impact of Induction and Consolidation Total Neoadjuvant Therapies Compared to Conventional Chemoradiotherapy for Locally Advanced Rectal Cancer: A Systematic Review and Network Meta-analysis. Dis Colon Rectum 2025; 68:687-701. [PMID: 40063683 DOI: 10.1097/dcr.0000000000003687] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/27/2025]
Abstract
BACKGROUND Total neoadjuvant therapy has been introduced to enhance oncological outcomes and minimize toxicity in locally advanced rectal cancer, but the superiority between the induction and consolidation of therapy remain unclear. OBJECTIVE To evaluate oncological and postoperative outcomes by comparing induction chemotherapy and consolidation chemotherapy with conventional chemoradiotherapy in patients with locally advanced rectal cancer. DATA SOURCES Systematic searches of PubMed, Embase, and Cochrane databases wereperformed for studies published from the database's inception until June 2023. STUDY SELECTION The inclusion criteria were patients diagnosed with rectal cancer. Interventions included induction chemotherapy and consolidation chemotherapy, and comparisons were specified as conventional neoadjuvant chemoradiotherapy. MAIN OUTCOME MEASURES Primary outcomes were the rates of pathologic or clinical complete response, postoperative results, chemoradiotherapy-related toxicity, and survival outcomes. RESULTS Thirty-three studies, encompassing patients from 1991 to 2021, were eligible for analysis. In network meta-analysis, a significantly increased OR for a pathologic complete response was observed in both the induction therapy group at 1.65 (95% credible interval, 1.18-2.30) and the consolidation therapy group at 1.87 (95% credible interval, 1.40-2.47) compared to conventional chemoradiotherapy. However, no difference was observed in complete response rates, postoperative results, or chemoradiotherapy-related toxicity grade 3 or higher between the groups. There were no differences among the groups in local recurrence, distant metastasis, or disease-free survival, whereas the induction group showed a nonsignificant improvement in overall survival. LIMITATIONS There was significant heterogeneity among the studies, and the short follow-up period in most studies limited the assessment of long-term survival outcomes. CONCLUSIONS Both induction and consolidation total neoadjuvant therapy increase the pathologic complete response rate in locally advanced rectal cancer without compromising safety or postoperative outcomes. However, total neoadjuvant therapy was not associated with a significant improvement in survival outcomes. Although total neoadjuvant therapy strategies for locally advanced rectal cancer are considered safe, additional long-term studies are needed. TRIAL REGISTRATION NO CRD42023445348.
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Affiliation(s)
- Chinock Cheong
- Department of Surgery, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Republic of Korea
| | - Na Won Kim
- Yonsei University Medical Library, Seoul, Republic of Korea
| | - Sung Ryul Shim
- Department of Biomedical Informatics, Konyang University College of Medicine, Daejeon, Republic of Korea
| | - Jeonghyun Kang
- Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
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Liu J, Xu X, Zhong H, Yu M, Abuduaini N, Fingerhut A, Cai Z, Feng B. Optimizing total neoadjuvant therapy in locally advanced rectal cancer: risk stratification should not be overlooked. Future Oncol 2025:1-10. [PMID: 40401643 DOI: 10.1080/14796694.2025.2507560] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2024] [Accepted: 05/14/2025] [Indexed: 05/23/2025] Open
Abstract
Chemoradiotherapy plus total mesorectal excision has been established as the standard treatment for locally advanced rectal cancer (LARC) and can achieve satisfactory local control. However, systemic control of LARC, especially in patients with risk factors for poor prognosis, is still of concern. As application of total neoadjuvant therapy (TNT) has been proposed as a potential solution, a clearer risk stratification of LARC to guide individual treatment is needed. Combination therapy such as targeted therapy or immunotherapy can be used to increase treatment intensity for high-risk LARC. In this review, we evaluate recent trials of several treatment modalities, specifically focusing on intensified TNT regimens for high-risk LARC with the goal of summarizing optimal clinical strategies and future study designs.
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Affiliation(s)
- Jingyi Liu
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Ximo Xu
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Hao Zhong
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Mengqin Yu
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Naijipu Abuduaini
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Abe Fingerhut
- Section for Surgical Research, Department of Surgery, Medical University of Graz, Graz, Austria
| | - Zhenghao Cai
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Bo Feng
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Horesh N, Emile SH, Garoufalia Z, Gefen R, Rogers P, Aeschbacher P, Salama E, Wexner SD. Network meta-analysis of RTCs for efficacy of neoadjuvant treatment in rectal cancer. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2025; 51:110019. [PMID: 40233522 DOI: 10.1016/j.ejso.2025.110019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2025] [Revised: 02/27/2025] [Accepted: 04/04/2025] [Indexed: 04/17/2025]
Abstract
BACKGROUND This network meta-analysis examined the efficacy of different types of neoadjuvant therapy (NAT) for rectal cancer in improving clinical and pathologic outcomes. METHODS PRISMA-compliant systematic review of PubMed and Scopus including only randomized clinical trials comparing two or more NAT regimens for rectal cancer. A network meta-analysis was undertaken for the main outcomes, including pathological complete response (pCR), disease downstaging, R0 resection, permanent stoma, and major adverse effects. Risk of bias was assessed using the ROB-2 tool. RESULTS 19 randomized controlled trials incorporating 7037 patients (62 % males) were included in the analysis. Compared to standard neoadjuvant chemoradiation (NCRT), consolidation total neoadjuvant therapy (TNT) (OR: 1.82, 95 % CI: 1.46-2.27; p < 0.001) and induction TNT (OR: 1.72, 95 % CI: 1.31-2.26; p < 0.001) had higher odds of achieving pCR. Induction TNT was also significantly associated with higher odds of major adverse effects than was NCRT (OR: 3.14, 95 % CI: 2.50-3.94; p < 0.0001). Compared to NCRT, long course chemotherapy significantly increased the odds of R0 resection (OR: 1.42, 95 % CI: 1.13-1.78; p = 0.002), while consolidation TNT significantly increased organ preservation rates (OR: 2.82, 95 % CI: 1.58-5.05; p < 0.001). Short course radiotherapy doubled the odds of positive circumferential resection margins (CRM) compared to NCRT (OR: 1.99, 95 % CI: 1.11-3.55; p = 0.02). CONCLUSIONS Consolidation and induction TNT were superior in achieving better pathological outcomes in rectal cancer, offering significant benefits over standard NCRT. However, they were associated with a higher risk of adverse effects. Conversely, short course radiotherapy was linked to higher rates of positive CRM.
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Affiliation(s)
- Nir Horesh
- Ellen Leifer Shulman and Steven Shulman Digestive Disease Center, Cleveland Clinic Florida, Weston, FL, USA; Department of Surgery and Transplantations, Sheba Medical Center, Ramat Gan, Affiliated with the Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Sameh Hany Emile
- Ellen Leifer Shulman and Steven Shulman Digestive Disease Center, Cleveland Clinic Florida, Weston, FL, USA; Colorectal Surgery Unit, General Surgery Department, Mansoura University Hospitals, Mansoura, Egypt
| | - Zoe Garoufalia
- Ellen Leifer Shulman and Steven Shulman Digestive Disease Center, Cleveland Clinic Florida, Weston, FL, USA
| | - Rachel Gefen
- Ellen Leifer Shulman and Steven Shulman Digestive Disease Center, Cleveland Clinic Florida, Weston, FL, USA; Department of General Surgery, Hadassah Medical Organization and Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
| | - Peter Rogers
- Ellen Leifer Shulman and Steven Shulman Digestive Disease Center, Cleveland Clinic Florida, Weston, FL, USA
| | - Pauline Aeschbacher
- Ellen Leifer Shulman and Steven Shulman Digestive Disease Center, Cleveland Clinic Florida, Weston, FL, USA; Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Switzerland
| | - Ebram Salama
- Ellen Leifer Shulman and Steven Shulman Digestive Disease Center, Cleveland Clinic Florida, Weston, FL, USA
| | - Steven D Wexner
- Ellen Leifer Shulman and Steven Shulman Digestive Disease Center, Cleveland Clinic Florida, Weston, FL, USA.
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Bauer PS, Gamboa AC, Otegbeye EE, Chapman WC, Rivard S, Regenbogen S, Hrebinko KA, Holder-Murray J, Wiseman JT, Ejaz A, Edwards-Hollingsworth K, Hawkins AT, Hunt SR, Balch GC, Wise PE. Short-Course TNT Improves Rectal Tumor Downstaging in a Retrospective Study of the US Rectal Cancer Consortium. J Surg Oncol 2025; 131:498-506. [PMID: 39400312 DOI: 10.1002/jso.27908] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2024] [Accepted: 08/31/2024] [Indexed: 10/15/2024]
Abstract
BACKGROUND AND OBJECTIVES The RAPIDO trial showed promising rates of pathologic complete response (pCR) after neoadjuvant short-course radiation with consolidation chemotherapy (total neoadjuvant therapy [SC TNT]) for rectal cancer. Only single-center reviews comparing tumor downstaging between SC TNT and long-course chemoradiation (LCRT) have been published in the United States. We reviewed our multi-institutional experience with both. METHODS The US Rectal Cancer Consortium database (2007-2018) including data from six high-volume rectal cancer care centers was reviewed. Patients with nonmetastatic, rectal adenocarcinoma who had neoadjuvant LCRT alone or SC TNT before excision or definitive nonoperative management were included. The primary outcome was the rate of complete response (CR), including pCR or durable (12 month) clinical complete response. RESULTS Of 857 included patients, 175 (20%) received SC TNT and 682 (80%) received LCRT. The LCRT group had more low tumors (51.8% vs. 37.1%, p < 0.0001) and more clinically node-negative disease (31.8% vs. 22.3%, p < 0.0001). The CR rate was higher after SC TNT (34.1% vs. 20.3%, p = 0.0001). SC TNT was a predictor of CR (OR: 2.52, CI: 1.68-3.78). SC TNT patients completing 5-6 months of consolidation chemotherapy had a CR rate of 42.9%. There was no difference in 3-year PFS. CONCLUSIONS SC TNT increases CR rate when compared to LCRT. For patients seeking nonoperative options or fewer radiation treatments, SC TRT should be preferred over LCRT alone.
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Affiliation(s)
- Philip S Bauer
- Section of Colon & Rectal Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Adriana C Gamboa
- Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia, USA
| | - Ebunoluwa E Otegbeye
- Section of Colon & Rectal Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, Missouri, USA
| | - William C Chapman
- Section of Colon & Rectal Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Samantha Rivard
- Division of Colorectal Surgery, Department of Surgery, University of Michigan, Ann Arbor, Michigan, USA
| | - Scott Regenbogen
- Division of Colorectal Surgery, Department of Surgery, University of Michigan, Ann Arbor, Michigan, USA
| | - Katherine A Hrebinko
- Division of Colon and Rectal Surgery, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Jennifer Holder-Murray
- Division of Colon and Rectal Surgery, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Jason T Wiseman
- Division of Surgical Oncology, Department of Surgery, The Ohio State University, Columbus, Ohio, USA
| | - Aslam Ejaz
- Division of Surgical Oncology, Department of Surgery, The Ohio State University, Columbus, Ohio, USA
| | - Kamren Edwards-Hollingsworth
- Section of Colon & Rectal Surgery, Division of General Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Alexander T Hawkins
- Section of Colon & Rectal Surgery, Division of General Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Steven R Hunt
- Section of Colon & Rectal Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Glen C Balch
- Division of Colon & Rectal Surgery, Department of Surgery, Emory University, Atlanta, Georgia, USA
| | - Paul E Wise
- Section of Colon & Rectal Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, Missouri, USA
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Giuliani J, Tebano U, Mandarà M, Franceschetto A, Giorgi C, Missiroli S, Gabbani M, Napoli G, Luca N, Mangiola D, Muraro M, Perrone M, Pinton P, Fiorica F. "Add More Arrows to Your Quiver": The Role of Adding Another Chemotherapy Drug to Fluoropyrimidine and Long Term Radiotherapy in Locally Advanced Rectal Cancer: A Systematic Review and Meta-Analysis. J Clin Med 2025; 14:345. [PMID: 39860350 PMCID: PMC11765640 DOI: 10.3390/jcm14020345] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2024] [Revised: 12/23/2024] [Accepted: 01/04/2025] [Indexed: 01/27/2025] Open
Abstract
Objectives: Despite optimal local control obtained with neoadjuvant chemoradiotherapy (CRT), data on overall survival (OS) and disease-free survival (DFS) of local advanced rectal cancer patients are still equivocal. This meta-analysis aimed to estimate the pathological complete response (pCR), regression rate, DFS, and OS probabilities of rectal cancer patients treated with a second chemotherapy drug added to fluoropyrimidine and long-term radiotherapy. Methods: Computerized bibliographic searches of MEDLINE, PUBMED, Web of Science and the Cochrane Central Register of Controlled Trials databases (1970-2023) were supplemented with hand searches of reference lists. Studies were included if they were randomised controlled trials (RCTs) comparing intensified chemotherapy with CRT to preoperative CRT and if they had patients with resectable, histologically proven rectal adenocarcinoma without metastases. Results: Eighteen RCTs (7695 patients) were analysed. Data on population, intervention, and outcomes were extracted from each RCT, following the intention-to-treat method, by three independent observers and combined using the DerSimonian and Laird methods. A chemotherapy with two drug and long-term radiotherapy CRT, compared to preoperative CRT (fluoropyrimidine and long-term radiotherapy), significantly increases the rate of pathological complete response (OR 1.37 (95% CI, 1.16-1.63) p = 0.0003) and the regression rate (OR 1.57 (95% CI, 1.16-2.14) p < 0.00001). Furthermore, it increases DFS (HR 0.87 (95% CI, 0.79 to 0.95) p = 0.002 and OS HR 0.84 (95% CI, 0.74 to 0.95) p = 0.007). The risk of severe adverse events (≥G3) is increased OR 1.96 (95% CI 1.35-2.85), p = 0.0005. Conclusions: In patients with resectable rectal cancer, intensified chemotherapy can reduce by 13% the risk of disease progression and by 16% the risk of death.
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Affiliation(s)
- Jacopo Giuliani
- Department of Clinical Oncology, Section of Medical Oncology, AULSS 9 Scaligera, 37045 Legnago, Italy; (J.G.); (M.M.); (D.M.)
| | - Umberto Tebano
- Department of Clinical Oncology, Section of Radiation Oncology and Nuclear Medicine, AULSS 9 Scaligera, 37045 Legnago, Italy; (U.T.); (A.F.); (M.G.); (G.N.); (N.L.); (M.M.)
| | - Marta Mandarà
- Department of Clinical Oncology, Section of Medical Oncology, AULSS 9 Scaligera, 37045 Legnago, Italy; (J.G.); (M.M.); (D.M.)
| | - Antonella Franceschetto
- Department of Clinical Oncology, Section of Radiation Oncology and Nuclear Medicine, AULSS 9 Scaligera, 37045 Legnago, Italy; (U.T.); (A.F.); (M.G.); (G.N.); (N.L.); (M.M.)
| | - Carlotta Giorgi
- Department of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology, Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, 48033 Ferrara, Italy; (C.G.); (S.M.); (M.P.); (P.P.)
| | - Sonia Missiroli
- Department of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology, Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, 48033 Ferrara, Italy; (C.G.); (S.M.); (M.P.); (P.P.)
| | - Milena Gabbani
- Department of Clinical Oncology, Section of Radiation Oncology and Nuclear Medicine, AULSS 9 Scaligera, 37045 Legnago, Italy; (U.T.); (A.F.); (M.G.); (G.N.); (N.L.); (M.M.)
| | - Giuseppe Napoli
- Department of Clinical Oncology, Section of Radiation Oncology and Nuclear Medicine, AULSS 9 Scaligera, 37045 Legnago, Italy; (U.T.); (A.F.); (M.G.); (G.N.); (N.L.); (M.M.)
| | - Nicoletta Luca
- Department of Clinical Oncology, Section of Radiation Oncology and Nuclear Medicine, AULSS 9 Scaligera, 37045 Legnago, Italy; (U.T.); (A.F.); (M.G.); (G.N.); (N.L.); (M.M.)
| | - Daniela Mangiola
- Department of Clinical Oncology, Section of Medical Oncology, AULSS 9 Scaligera, 37045 Legnago, Italy; (J.G.); (M.M.); (D.M.)
| | - Marco Muraro
- Department of Clinical Oncology, Section of Radiation Oncology and Nuclear Medicine, AULSS 9 Scaligera, 37045 Legnago, Italy; (U.T.); (A.F.); (M.G.); (G.N.); (N.L.); (M.M.)
| | - Mariasole Perrone
- Department of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology, Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, 48033 Ferrara, Italy; (C.G.); (S.M.); (M.P.); (P.P.)
| | - Paolo Pinton
- Department of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology, Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, 48033 Ferrara, Italy; (C.G.); (S.M.); (M.P.); (P.P.)
| | - Francesco Fiorica
- Department of Clinical Oncology, Section of Medical Oncology, AULSS 9 Scaligera, 37045 Legnago, Italy; (J.G.); (M.M.); (D.M.)
- Department of Clinical Oncology, Section of Radiation Oncology and Nuclear Medicine, AULSS 9 Scaligera, 37045 Legnago, Italy; (U.T.); (A.F.); (M.G.); (G.N.); (N.L.); (M.M.)
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Lavingia V, Sardana S, Khanderia M, Bisht N, Patel A, Koyyala VPB, Sheth H, Ramaswamy A, Singh A, deSouza A, Jain SB, Mahajan M, Gohel S, Parikh A, Brown G, Sirohi B. Localized Rectal Cancer: Indian Consensus and Guidelines. Indian J Med Paediatr Oncol 2024; 45:461-480. [DOI: 10.1055/s-0043-1777865] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2025] Open
Abstract
AbstractThe rising incidence of colorectal cancer (CRC) in India, particularly the prevalence of rectal cancer over colon cancer (0.7:1), has been a growing concern in recent decades; especially notable is the trend of increasing cases among young CRC patients. Given the diverse treatment approaches for rectal cancer globally and the varying economic capacities of patients in low to middle-income countries (LMICs) like India, it is essential to establish consensus guidelines that are specifically tailored to meet the needs of these patients. To achieve this, a panel comprising 30 eminent rectal cancer experts convened to conduct a comprehensive and impartial evaluation of existing practices and recent advancements in the field. Through meticulous scrutiny of published literature and a consensus-building process that involved voting on pertinent questions, the panel formulated management strategies. These recommendations are the result of a rigorous, evidence-based process and encapsulate the collective wisdom and judgment of leading authorities in the field.
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Affiliation(s)
- Viraj Lavingia
- Department of Medical Oncology, HCG Cancer Center, Ahmedabad, Gujarat, India
| | - Shefali Sardana
- Department of Medical Oncology, Max Institute of Cancer Care, Max Superspeciality Hospital, New Delhi, India
| | - Mansi Khanderia
- Department of Medical Oncology, SPARSH Hospitals, Bangalore, Karnataka, India
| | - Niharika Bisht
- Department of Radiation Oncology, Army Hospital Research and Referral, New Delhi, India
| | - Amol Patel
- Department of Medical Oncology, Indian Naval Hospital Ship Asvini, Mumbai, Maharashtra, India
| | | | - Harsh Sheth
- Department of Advanced Genomic Technologies Division, FRIGE Institute of Human Genetics, Ahmedabad, Gujarat, India
| | - Anant Ramaswamy
- Department of Medical Oncology, Tata Memorial Centre (HBNI), Mumbai, Maharashtra, India
| | - Ashish Singh
- Department of Medical Oncology, Christian Medical College, Vellore, Tamil Nadu, India
| | - Ashwin deSouza
- Department of Surgical Oncology, Tata Memorial Centre and Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Sneha Bothra Jain
- Department of Medical Oncology, Mittal Institute of Medical Sciences, Bhilai, Chhattisgarh, India
| | - Mukta Mahajan
- Department of Radiodiagnosis, Apollo Proton Cancer Centre, Chennai, Tamil Nadu, India
| | - Shruti Gohel
- Department of Medical Oncology, HCG Cancer Centre, Ahmedabad, Gujarat, India
| | - Aparna Parikh
- Department of Medical Oncology, Mass General Cancer Centre, Boston, United States
| | - Gina Brown
- Department of Gastrointestinal Cancer Imaging, Imperial College, London, United Kingdom
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Ghalehtaki R, Nourbakhsh F, Abyaneh R, Sharifian A, Pashapour‐Khoyi S, Aghili M, Gambacorta M, Couñago F. Optimal Sequence for Total Neoadjuvant Therapy in Locally Advanced Rectal Cancer: An Evidence-Based Review. Cancer Med 2024; 13:e70291. [PMID: 39387519 PMCID: PMC11465286 DOI: 10.1002/cam4.70291] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2024] [Revised: 08/29/2024] [Accepted: 09/22/2024] [Indexed: 10/15/2024] Open
Abstract
INTRODUCTION Historically, multimodal therapeutic strategies involving preoperative chemoradiotherapy (CRT), surgery, and adjuvant chemotherapy (CT) have been employed to treat locally advanced rectal cancer (LARC). Total Neoadjuvant Therapy (TNT) is showing promise in improving outcomes. Despite its benefits, the optimal sequencing within TNT-whether induction chemotherapy should precede or follow chemoradiotherapy-remains a critical question. This study endeavors to explore the effects of different TNT sequencing strategies on patient outcomes, including tumor downstaging, pathological response, organ preservation, and the balance between efficacy and tolerability. METHODS Our methodology entailed a comprehensive literature review conducted on Medline, focusing on recent research, including retrospective studies, systematic reviews, and clinical trials. The review emphasized the comparison of induction chemotherapy versus consolidation chemotherapy within TNT regimens, assessing outcomes such as pathological response, organ preservation rates, and adverse effects. To ensure the selection of appropriate and high-quality studies, specific inclusion and exclusion criteria were applied. RESULTS The analysis revealed that induction chemotherapy might lead to decreased adherence to subsequent chemoradiotherapy while offering an early intervention against micrometastasis and potentially improving overall chemotherapy compliance. Conversely, consolidation chemotherapy has been associated with higher pathological complete response (pCR) rates and improved tolerability, indicating its potential for patients requiring local symptom relief or those eligible for a nonoperative management approach. Comparative studies like CAO/ARO/AIO-12 and the OPRA trials have significantly contributed to our understanding, suggesting that while both strategies have distinct advantages, the choice between induction and consolidation chemotherapy should be tailored based on individual patient profiles and tumor characteristics. CONCLUSION This narrative review underscores the importance of a nuanced approach to TNT sequencing in locally advanced rectal cancer, highlighting the need for further research to refine treatment strategies.
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Affiliation(s)
- Reza Ghalehtaki
- Department of Radiation OncologyCancer Institute, IKHC, School of Medicine, Tehran University of Medical SciencesTehranIran
- Radiation Oncology Research CenterCancer Research Institute, IKHC, Tehran University of Medical SciencesTehranIran
| | - Forouzan Nourbakhsh
- Department of Radiation OncologyCancer Institute, IKHC, School of Medicine, Tehran University of Medical SciencesTehranIran
| | - Romina Abyaneh
- Radiation Oncology Research CenterCancer Research Institute, IKHC, Tehran University of Medical SciencesTehranIran
| | - Azadeh Sharifian
- Department of Radiation OncologyCancer Institute, IKHC, School of Medicine, Tehran University of Medical SciencesTehranIran
| | - Sheyda Pashapour‐Khoyi
- Department of Radiation OncologyCancer Institute, IKHC, School of Medicine, Tehran University of Medical SciencesTehranIran
| | - Mahdi Aghili
- Radiation Oncology Research CenterCancer Research Institute, IKHC, Tehran University of Medical SciencesTehranIran
| | - Maria Antonietta Gambacorta
- UOC di Radioterapia Oncologica, Dipartimento di Diagnostica per ImmaginiRadioterapia Oncologica Ed Ematologia, Fondazione Policlinico Universitario A. Gemelli IRCCSRomeItaly
| | - Felipe Couñago
- Department of Radiation OncologyGenesisCare, Hospital Universitario Vithas Madrid La MilagrosaMadridSpain
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Gaetani RS, Ladin K, Abelson JS. Journey through the Decades: The Evolution in Treatment and Shared Decision Making for Locally Advanced Rectal Cancer. Cancers (Basel) 2024; 16:2807. [PMID: 39199579 PMCID: PMC11353159 DOI: 10.3390/cancers16162807] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2024] [Revised: 08/03/2024] [Accepted: 08/06/2024] [Indexed: 09/01/2024] Open
Abstract
The management of locally advanced rectal cancer has undergone significant transformations over the decades and optimal treatment approaches continue to evolve. There have been numerous advances in surgery, chemotherapy, and radiation therapy from the first description of the abdominoperineal resection in 1908, timing of chemotherapy and radiation therapy in the late 20th and early 21st century, and most recently, the introduction of organ preservation or nonoperative management in 2004. Alongside these advancements, the concept of shared decision making in medicine has evolved, prompting a focus on patient-centered care. This evolution in practice has been fueled by a growing recognition of the importance of patient autonomy and the alignment of treatment options with patients' values and preferences. With the growing number of possible treatment options, variability in patient counseling exists, highlighting the need for a standardized approach to shared decision making in locally advanced rectal cancer. This narrative review will describe the evolution of treatment options of locally advanced rectal cancer as well as the concept of shared decision making and decision aids, and will introduce a decision aid for patients with locally advanced rectal cancer who have achieved a complete clinical response and are eligible for watch and wait.
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Affiliation(s)
- Racquel S. Gaetani
- Department of Colon and Rectal Surgery, Lahey Hospital and Medical Center, Burlington, MA 01805, USA;
| | - Keren Ladin
- Department of Community Health, Tufts University, Medford, MA 02155, USA
| | - Jonathan S. Abelson
- Department of Colon and Rectal Surgery, Lahey Hospital and Medical Center, Burlington, MA 01805, USA;
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9
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Rizzo G, Amodio LE, D'Annibale G, Marzi F, Quero G, Menghi R, Tondolo V. Nonoperative management and local excision after neoadjuvant chemoradiation therapy for rectal cancer. Minerva Surg 2024; 79:470-480. [PMID: 38953759 DOI: 10.23736/s2724-5691.24.10445-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/04/2024]
Abstract
Locally advanced extraperitoneal rectal cancer represents a significant clinical challenge, and currently, the standard treatment is based on neoadjuvant chemoradiation therapy (CRT) followed by radical surgical resection with total mesorectal excision (TME). In the last 30 years, its management has undergone significant changes due to the improvement of complementary radio- and chemotherapy treatments, the improvement of minimally invasive surgical approaches and the diffusion of organ-sparing approaches, such as nonoperative management, commonly called "watch and wait" (NOM) and local excision (LE), in highly selected patients who achieve a major or complete response to neoadjuvant CRT. This review aimed to critically examine the efficacy and oncological safety of NOM and LE compared to those of standard TME in rectal cancer patients after neoadjuvant CRT. Both the pros and cons of these approaches were strictly analyzed, providing a comprehensive and critical overview of these novel management strategies for rectal cancer.
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Affiliation(s)
- Gianluca Rizzo
- Unit of Digestive and Colorectal Surgery, Ospedale Isola Tiberina Gemelli Isola, Università Cattolica del Sacro Cuore, Rome, Italy -
| | - Luca E Amodio
- Unit of Digestive and Colorectal Surgery, Ospedale Isola Tiberina Gemelli Isola, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Giorgio D'Annibale
- Unit of Digestive and Colorectal Surgery, Ospedale Isola Tiberina Gemelli Isola, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Federica Marzi
- Unit of Digestive and Colorectal Surgery, Ospedale Isola Tiberina Gemelli Isola, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Giuseppe Quero
- Unit of Digestive Surgery, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Roberta Menghi
- Unit of Digestive Surgery, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Vincenzo Tondolo
- Unit of Digestive and Colorectal Surgery, Ospedale Isola Tiberina Gemelli Isola, Università Cattolica del Sacro Cuore, Rome, Italy
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10
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Wang Y, Yang Y, Liu QQ, Wang SZ. Compare clinical efficacy and safety of neoadjuvant therapy and neoadjuvant chemoradiotherapy for locally advanced rectal cancer: Meta-analysis. World J Gastrointest Surg 2024; 16:1845-1856. [PMID: 38983334 PMCID: PMC11230002 DOI: 10.4240/wjgs.v16.i6.1845] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2024] [Revised: 04/01/2024] [Accepted: 04/28/2024] [Indexed: 06/27/2024] Open
Abstract
BACKGROUND To compare the efficacy and safety of total neoadjuvant therapy (TNT) and neoadjuvant chemoradiotherapy (nCRT) in the treatment of middle and low locally advanced rectal cancer. Our study will systematically collect and integrate studies to evaluate the ability of these two treatments to improve tumor shrinkage rates, surgical resection rates, tumor-free survival, and severe adverse events. AIM To provide clinicians and patients with more reliable treatment options to optimize treatment outcomes and quality of life for patients with locally advanced rectal cancer by comparing the advantages and disadvantages of the two treatment options. METHODS A full search of all clinical studies on the effectiveness and safety of TNT and nCRT for treating locally advanced rectal cancer identified in Chinese (CNKI, Wanfang, China Biomedical Literature Database) and English (PubMed, Embase) databases was performed. Two system assessors independently screened the studies according to the inclusion and exclusion criteria. Quality evaluation and data extraction were performed for the included literature. We used RevMan 5.3 software to perform a meta-analysis of the pathologic complete response (pCR) rate, T stage degradation rate, resection 0 (R0) rate, anal grade 3/4 acute toxicity rate, perioperative complications, overall survival (OS), and disease-free survival (DFS) in the TNT and nCRT groups. RESULTS Finally, 14 studies were included, six of which were randomized controlled studies. A total of 3797 patients were included, including 1865 in the TNT group and 1932 in the nCRT group. The two sets of baseline data were comparable. The results of the meta-analysis showed that the pCR rate [odds ratio (OR) = 1.57, 95% confidence interval (CI): 1.30-1.90, P < 0.00001], T stage degradation rate (OR = 2.16, 95%CI: 1.63-2.57, P < 0.00001), and R0 resection rate (OR = 1.42, 95%CI: 1.09-1.85, P = 0.009) were significantly greater in the nCRT group than in the nCRT group. There was no significant difference in the incidence of grade 3/4 acute toxicity or perioperative complications between the two groups. The 5-year OS [hazard ratio (HR) = 0.84, 95%CI: 0.69-1.02, P = 0.08] and DFS (HR = 0.94, 95%CI: 0.03-1.39, P = 0.74) of the TNT group were similar to those of the nCRT group. CONCLUSION TNT has greater clinical efficacy and safety than nCRT in the treatment of locally advanced rectal cancer.
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Affiliation(s)
- Ying Wang
- Department of Anus Intestinal Surgery, Feicheng People’s Hospital, Feicheng 271600, Shandong Province, China
| | - Yan Yang
- Department of Gastroenterology, Qingdao Hospital of University of Health and Rehabilitation Sciences (Qingdao Municipal Hospital), Qingdao 266011, Shandong Province, China
| | - Qi-Qi Liu
- Department of Gastrointestinal Surgery, Peking University Shenzhen Hospital, Shenzhen 518036, Guangdong Province, China
| | - Shao-Zhao Wang
- Department of Anorectal Words, Central Hospital Affiliated Shandong First Medical University, Jinan 250013, Shandong Province, China
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11
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Turri G, Ostuzzi G, Vita G, Barresi V, Scarpa A, Milella M, Mazzarotto R, Ruzzenente A, Barbui C, Pedrazzani C. Treatment of Locally Advanced Rectal Cancer in the Era of Total Neoadjuvant Therapy: A Systematic Review and Network Meta-Analysis. JAMA Netw Open 2024; 7:e2414702. [PMID: 38833249 PMCID: PMC11151159 DOI: 10.1001/jamanetworkopen.2024.14702] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2023] [Accepted: 03/30/2024] [Indexed: 06/06/2024] Open
Abstract
Importance Treatment of locally advanced rectal cancer (LARC) involves neoadjuvant chemoradiotherapy plus total mesorectal excision and adjuvant chemotherapy. However, total neoadjuvant therapy (TNT) protocols (ie, preoperative chemotherapy in addition to radiotherapy) may allow better adherence and early treatment of distant micrometastases and may increase pathological complete response (pCR) rates. Objective To assess the efficacy and tolerability of TNT protocols for LARC. Data Sources MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science Core Collection electronic databases and ClinicalTrials.gov for unpublished studies were searched from inception to March 2, 2024. Study Selection Randomized clinical trials including adults with LARC who underwent rectal resection as a final treatment were included. Studies including nonoperative treatment (watch-and-wait strategy), treatments other than rectal resection, immunotherapy, or antiangiogenic agents were excluded. Among the initially identified studies, 2.9% met the selection criteria. Data Extraction and Synthesis Two authors independently screened the records and extracted data. Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA)-compliant pairwise and network meta-analyses with a random-effects model were performed in a frequentist framework, and the certainty of evidence was assessed according to the confidence in network meta-analysis approach. Main Outcomes and Measures The primary outcome was pCR, defined as the absence of residual tumor at pathological assessment after surgery. Secondary outcomes included tolerability, toxic effects, perioperative outcomes, and long-term survival. Results Of 925 records identified, 27 randomized clinical trials, including 13 413 adults aged 18 years or older (median age, 60.0 years [range, 42.0-63.5 years]; 67.2% male) contributed to the primary network meta-analysis. With regard to pCR, long-course chemoradiotherapy (L-CRT) plus consolidation chemotherapy (relative risk [RR], 1.96; 95% CI, 1.25-3.06), short-course radiotherapy (S-RT) plus consolidation chemotherapy (RR, 1.76; 95% CI, 1.34-2.30), and induction chemotherapy plus L-CRT (RR, 1.57; 95% CI, 1.09-2.25) outperformed standard L-CRT with single-agent fluoropyrimidine-based chemotherapy. Considering 3-year disease-free survival, S-RT plus consolidation chemotherapy (RR, 1.08; 95% CI, 1.01-1.14) and induction chemotherapy plus L-CRT (RR, 1.12; 95% CI, 1.01-1.24) outperformed L-CRT, in spite of an increased 5-year locoregional recurrence rate of S-RT plus consolidation chemotherapy (RR, 1.65; 95% CI, 1.03-2.63). Conclusions and Relevance In this systematic review and network meta-analysis, 3 TNT protocols were identified to outperform the current standard of care in terms of pCR rates, with good tolerability and optimal postoperative outcomes, suggesting they should be recognized as first-line treatments.
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Affiliation(s)
- Giulia Turri
- Division of General and Hepatobiliary Surgery, Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, University of Verona, Verona, Italy
| | - Giovanni Ostuzzi
- World Health Organization Collaborating Centre for Research and Training in Mental Health and Service Evaluation, Department of Neuroscience, Biomedicine and Movement Sciences, Section of Psychiatry, University of Verona, Verona, Italy
| | - Giovanni Vita
- World Health Organization Collaborating Centre for Research and Training in Mental Health and Service Evaluation, Department of Neuroscience, Biomedicine and Movement Sciences, Section of Psychiatry, University of Verona, Verona, Italy
| | - Valeria Barresi
- Department of Diagnostics and Public Health, Section of Pathology, University of Verona, Italy
| | - Aldo Scarpa
- Department of Diagnostics and Public Health, Section of Pathology, University of Verona, Italy
| | - Michele Milella
- Section of Oncology, Department of Engineering for Innovation Medicine, University of Verona Hospital Trust, Verona, Italy
| | - Renzo Mazzarotto
- Section of Radiotherapy, Department of Medicine, University of Verona Hospital Trust, Verona, Italy
| | - Andrea Ruzzenente
- Division of General and Hepatobiliary Surgery, Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, University of Verona, Verona, Italy
| | - Corrado Barbui
- World Health Organization Collaborating Centre for Research and Training in Mental Health and Service Evaluation, Department of Neuroscience, Biomedicine and Movement Sciences, Section of Psychiatry, University of Verona, Verona, Italy
| | - Corrado Pedrazzani
- Division of General and Hepatobiliary Surgery, Department of Engineering for Innovation Medicine, University of Verona, Verona, Italy
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12
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Lin W, Li C, Clement EA, Brown CJ, Raval MJ, Karimuddin AA, Ghuman A, Phang PT. Surgical Outcomes in Total Neoadjuvant Therapy for Rectal Cancer Versus Standard Long-course Chemoradiation: A Systematic Review and Meta-analysis of Randomized Controlled Trials. Ann Surg 2024; 279:620-630. [PMID: 38009646 DOI: 10.1097/sla.0000000000006161] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2023]
Abstract
OBJECTIVE This systematic review and meta-analysis seeks to evaluate the impact of total neoadjuvant therapy (TNT) for rectal cancers on surgical complications and surgical pathology when compared with standard long-course chemoradiotherapy (LCRT). BACKGROUND The oncological benefits of TNT are well published in previous meta-analyses, but there is little synthesized information on how it affects surgical outcomes. A recent study has suggested an increase in local recurrence and higher rates of breached total mesorectal excision (TME) plane in TNT patients. METHODS This study conformed to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A search was performed in Medline (via PubMed), Cochrane databases, EMBASE and CINAHL to identify relevant randomized controlled trials (RCTs) comparing outcomes between TNT and LCRT. Meta-analyses of pooled proportions between TNT and LCRT were performed, comparing primary outcomes of surgical mortality, morbidity and all reported complications; surgical-pathology differences, namely mesorectal quality, R0 resection rates, circumferential resection margin positive rates, and sphincter preservation rates. Death and progression of disease during neoadjuvant treatment period was also compared. Risk of bias of RCTs was performed using the Cochrane risk-of-bias tool by 2 independent reviewers. RESULTS A total of 3185 patients with rectal cancer from 11 RCTs were included in the analysis: 1607 received TNT and 1578 received LCRT, of which 1422 (TNT arm) and 1391 (LCRT arm) underwent surgical resection with curative intent. There was no significant difference in mortality [risk ratio (RR)=0.86, 95% CI: 0.13-5.52, P =0.88, I2 =52%] or major complications (RR=1.04, 95% CI: 0.86-1.26, P =0.70, I2 =0%) between TNT and LCRT. There was a significantly higher risk of breached TME in TNT group on pooled analysis (RR=1.49, 95% CI: 1.03-12.16, P =0.03, I2 =0%), and on subgroup analysis there is higher risk of breached TME in those receiving extended duration of neoadjuvant treatment (>17 weeks from start of treatment to surgery) when compared with LCRT (RR=1.61, 95% CI: 1.06-2.44, P =0.03). No difference in R0 resection rates (RR=0.85, 95% CI: 0.66-1.10, P =0.21, I2 =15%), circumferential resection margin positive rates (RR=0.87, 95% CI: 0.65-1.16, P =0.35, I2 =10%) or sphincter preservation rates (RR=1.02, 95% CI: 0.83-1.25, P =0.88, I2 =57%) were observed. There was a significantly lower risk of progression of disease to an unresectable stage during the neoadjuvant treatment period in TNT patients (RR=0.60, 95% CI: 0.39-0.92, P =0.03, I2 =18%). On subgroup analysis, it appears to favor those receiving extended duration of neoadjuvant treatment (RR=0.44, 95% CI: 0.26-0.80, P =0.002), and those receiving induction-type chemotherapy in TNT (RR=0.25, 95% CI: 0.07-0.88, P =0.03). CONCLUSIONS TNT increases rates of breached TME which can contribute to higher local recurrence rates. TNT, however, improves systemic control by reducing early progression of disease during neoadjuvant treatment period. Further research is warranted to identify patients that will benefit from this strategy.
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Affiliation(s)
- Wenjie Lin
- Department of Surgery, Colorectal Surgery Division, St. Paul's Hospital, Vancouver, BC, Canada
- Department of Colorectal Surgery, Singapore General Hospital, Singapore
| | - Christine Li
- Department of Surgery, Colorectal Surgery Division, St. Paul's Hospital, Vancouver, BC, Canada
| | - Elizabeth A Clement
- Department of Surgery, Colorectal Surgery Division, St. Paul's Hospital, Vancouver, BC, Canada
| | - Carl J Brown
- Department of Surgery, Colorectal Surgery Division, St. Paul's Hospital, Vancouver, BC, Canada
| | - Manoj J Raval
- Department of Surgery, Colorectal Surgery Division, St. Paul's Hospital, Vancouver, BC, Canada
| | - Ahmer A Karimuddin
- Department of Surgery, Colorectal Surgery Division, St. Paul's Hospital, Vancouver, BC, Canada
| | - Amandeep Ghuman
- Department of Surgery, Colorectal Surgery Division, St. Paul's Hospital, Vancouver, BC, Canada
| | - Paul T Phang
- Department of Surgery, Colorectal Surgery Division, St. Paul's Hospital, Vancouver, BC, Canada
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Bauer PS, Gamboa AC, Otegbeye EE, Chapman WC, Rivard S, Regenbogen S, Mohammed M, Holder-Murray J, Wiseman JT, Ejaz A, Edwards-Hollingsworth K, Hawkins AT, Hunt SR, Balch G, Silviera ML. Short-course radiation with consolidation chemotherapy does not increase operative morbidity compared to long-course chemoradiation: A retrospective study of the US rectal cancer consortium. J Surg Oncol 2024; 129:254-263. [PMID: 37792637 PMCID: PMC10872853 DOI: 10.1002/jso.27468] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2023] [Accepted: 09/19/2023] [Indexed: 10/06/2023]
Abstract
BACKGROUND AND OBJECTIVES Neoadjuvant short-course radiation and consolidation chemotherapy (SC TNT) remains less widely used for rectal cancer in the United States than long-course chemoradiation (LCRT). SC TNT may improve compliance and downstaging; however, a longer radiation-to-surgery interval may worsen pelvic fibrosis and morbidity with total mesorectal excision (TME). A single, US-center retrospective analysis has shown comparable risk of morbidity after neoadjuvant short-course radiation with consolidation chemotherapy (SC TNT) and long-course chemoradiation (LCRT). Validation by a multi-institutional study is needed. METHODS The US Rectal Cancer Consortium database (2010-2018) was retrospectively reviewed for patients with nonmetastatic, rectal adenocarcinoma treated with neoadjuvant LCRT or SC TNT before TME. The primary endpoint was severe postoperative morbidity. Cohorts were compared by univariate analysis. Multivariable logistic regression modeled the odds of severe complication. RESULTS Of 788 included patients, 151 (19%) received SC TNT and 637 (81%) LCRT. The SC TNT group had fewer distal tumors (33.8% vs. 50.2%, p < 0.0001) and more clinical node-positive disease (74.2% vs. 47.6%, p < 0.0001). The intraoperative complication rate was similar (SC TNT 5.3% vs. 4.4%, p = 0.65). There was no difference in overall postoperative morbidity (38.4% vs. 46.3%, p = 0.08). Severe morbidity was similar with low anterior resection (9.1% vs. 15.3%, p = 0.10) and abdominoperineal resection (24.4% vs. 29.7%, p = 0.49). SC TNT did not increase the odds of severe morbidity relative to LCRT on multivariable analysis (OR 0.64, 95% CI 0.37-1.10). CONCLUSIONS SC TNT does not increase morbidity after TME for rectal cancer relative to LCRT. Concern for surgical complications should not discourage the use of SC TNT when aiming to increase the likelihood of complete clinical response.
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Affiliation(s)
- Philip S. Bauer
- Section of Colon & Rectal Surgery, Department of Surgery, Washington University School of Medicine
| | - Adriana C. Gamboa
- Division of Surgical Oncology, Winship Cancer Institute, Emory University
| | - Ebunoluwa E. Otegbeye
- Section of Colon & Rectal Surgery, Department of Surgery, Washington University School of Medicine
| | - William C. Chapman
- Section of Colon & Rectal Surgery, Department of Surgery, Washington University School of Medicine
| | - Samantha Rivard
- Division of Colorectal Surgery, Department of Surgery, University of Michigan
| | - Scott Regenbogen
- Division of Colorectal Surgery, Department of Surgery, University of Michigan
| | - Maryam Mohammed
- Division of Colon and Rectal Surgery, Department of Surgery, University of Pittsburgh Medical Center
| | - Jennifer Holder-Murray
- Division of Colon and Rectal Surgery, Department of Surgery, University of Pittsburgh Medical Center
| | - Jason T. Wiseman
- Division of Surgical Oncology, Department of Surgery, The Ohio State University
| | - Aslam Ejaz
- Division of Surgical Oncology, Department of Surgery, The Ohio State University
| | | | - Alexander T. Hawkins
- Section of Colon & Rectal Surgery, Division of General Surgery, Vanderbilt University Medical Center
| | - Steven R. Hunt
- Section of Colon & Rectal Surgery, Department of Surgery, Washington University School of Medicine
| | - Glen Balch
- Division of Colon & Rectal Surgery, Department of Surgery, Emory University
| | - Matthew L. Silviera
- Section of Colon & Rectal Surgery, Department of Surgery, Washington University School of Medicine
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Lee SF, Yip PL, Wo B, Wong NSM, Vellayappan BA, Mamon HJ, Lee FAS. Neoadjuvant short-course radiotherapy or chemoradiation plus consolidative chemotherapy followed by radical operation for locally advanced rectal cancer. Front Oncol 2024; 13:1284569. [PMID: 38322287 PMCID: PMC10844885 DOI: 10.3389/fonc.2023.1284569] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2023] [Accepted: 12/21/2023] [Indexed: 02/08/2024] Open
Abstract
Introduction Limited evidence compares short-course radiotherapy (SCRT) and long-course chemoradiotherapy (LCCRT), both of which are followed by consolidative chemotherapy before radical rectal surgery. We conducted a retrospective cohort study to assess treatment response, survival outcomes, and toxicity in patients with locally advanced rectal cancer. Materials and methods Patients (cT3-4 and/or N+) treated with SCRT or LCCRT, consolidative chemotherapy, or total mesorectal excision between 2013 and 2021 were identified. the cause-specific cumulative incidence of disease-related treatment failure, locoregional recurrence, distant metastases, and overall survival were evaluated using flexible parametric competing risk analysis and Kaplan-Meier methods, adjusted for treatment regimens and clinicopathological factors. A pathological complete response (pCR), tumor downstaging, and toxicity have been reported. Results Among the 144 patients, 115 (80%) underwent curative rectal surgery. The LCCRT and SCRT groups achieved pCR in 10 (18%) and seven (12%) patients, respectively (odds ratio, 1.68; 95% confidence interval [CI], 0.59-4.78). The adjusted cause-specific hazard ratio for disease-related treatment failure with LCCRT versus SCRT was 0.26 (95% CI, 0.08-0.87). Three-year cumulative probability of disease-related treatment failure was 10.0% and 25.6% for LCCRT and SCRT, respectively. No significant differences in T-downstaging, N-downstaging, significant pathologic downstaging (ypT0-2N0), locoregional failure, distant metastasis, or overall survival were found. Late rectal toxicity occurred in 10 (15%) LCCRT and two (3%) SCRT patients, respectively. Conclusion LCCRT with consolidative chemotherapy demonstrated improved disease-related treatment failure compared with SCRT, despite higher late rectal toxicity. Further research is needed to assess the long-term oncologic outcomes and toxicity.
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Affiliation(s)
- Shing Fung Lee
- Department of Clinical Oncology, Tuen Mun Hospital, New Territories West Cluster, Hospital Authority, Hong Kong, Hong Kong SAR, China
- Department of Radiation Oncology, National University Cancer Institute, National University Hospital, Singapore, Singapore
| | - Pui Lam Yip
- Department of Clinical Oncology, Tuen Mun Hospital, New Territories West Cluster, Hospital Authority, Hong Kong, Hong Kong SAR, China
- Department of Radiation Oncology, National University Cancer Institute, National University Hospital, Singapore, Singapore
| | - Barry Wo
- Department of Clinical Oncology, Tuen Mun Hospital, New Territories West Cluster, Hospital Authority, Hong Kong, Hong Kong SAR, China
| | - Natalie Sean-Man Wong
- Department of Clinical Oncology, Tuen Mun Hospital, New Territories West Cluster, Hospital Authority, Hong Kong, Hong Kong SAR, China
| | - Balamurugan A. Vellayappan
- Department of Radiation Oncology, National University Cancer Institute, National University Hospital, Singapore, Singapore
| | - Harvey J. Mamon
- Department of Radiation Oncology, Dana-Farber Cancer Institute/Brigham and Women’s Hospital, Boston, MA, United States
| | - Francis Ann Shing Lee
- Department of Clinical Oncology, Tuen Mun Hospital, New Territories West Cluster, Hospital Authority, Hong Kong, Hong Kong SAR, China
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Janczak J, Ukegjini K, Bischofberger S, Turina M, Müller PC, Steffen T. Quality of Surgical Outcome Reporting in Randomised Clinical Trials of Multimodal Rectal Cancer Treatment: A Systematic Review. Cancers (Basel) 2023; 16:26. [PMID: 38201454 PMCID: PMC10778098 DOI: 10.3390/cancers16010026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2023] [Revised: 12/07/2023] [Accepted: 12/18/2023] [Indexed: 01/12/2024] Open
Abstract
INTRODUCTION Randomised controlled trials (RCTs) continue to provide the best evidence for treatment options, but the quality of reporting in RCTs and the completeness rate of reporting of surgical outcomes and complication data vary widely. The aim of this study was to measure the quality of reporting of the surgical outcome and complication data in RCTs of rectal cancer treatment and whether this quality has changed over time. METHODS Eligible articles with the keywords ("rectal cancer" OR "rectal carcinoma") AND ("radiation" OR "radiotherapy") that were RCTs and published in the English, German, Polish, or Italian language were identified by reviewing all abstracts published from 1982 through 2022. Two authors independently screened and analysed all studies. The quality of the surgical outcome and complication data was assessed based on fourteen criteria, and the quality of RCTs was evaluated based on a modified Jadad scale. The primary outcome was the quality of reporting in RCTs and the completeness rate of reporting of surgical results and complication data. RESULTS A total of 340 articles reporting multimodal therapy outcomes for 143,576 rectal cancer patients were analysed. A total of 7 articles (2%) met all 14 reporting criteria, 13 met 13 criteria, 27 met from 11 to 12 criteria, 36 met from 9 to 10 criteria, 76 met from 7 to 8 criteria, and most articles met fewer than 7 criteria (mean 5.5 criteria). Commonly underreported criteria included complication severity (15% of articles), macroscopic integrity of mesorectal excision (17% of articles), length of stay (18% of articles), number of lymph nodes (21% of articles), distance between the tumour and circumferential resection margin (CRM) (26% of articles), surgical radicality according to the site of the primary tumour (R0 vs. R1 + R2) (29% of articles), and CRM status (38% of articles). CONCLUSION Inconsistent surgical outcome and complication data reporting in multimodal rectal cancer treatment RCTs is standard. Standardised reporting of clinical and oncological outcomes should be established to facilitate comparing studies and results of related research topics.
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Affiliation(s)
- Joanna Janczak
- Clinic for General and Visceral Surgery, Hospital for the Region Fürstenland Toggenburg, CH-9500 Wil, Switzerland;
| | - Kristjan Ukegjini
- Department of Surgery, Hospital of the Canton of St. Gallen, CH-9007 St. Gallen, Switzerland; (K.U.); (S.B.)
| | - Stephan Bischofberger
- Department of Surgery, Hospital of the Canton of St. Gallen, CH-9007 St. Gallen, Switzerland; (K.U.); (S.B.)
| | - Matthias Turina
- Department of Surgery and Transplantation, University Hospital Zurich, CH-8091 Zurich, Switzerland;
| | - Philip C. Müller
- Department of Surgery, Clarunis—University Centre for Gastrointestinal and Hepatopancreatobiliary Diseases, CH-4002 Basel, Switzerland;
| | - Thomas Steffen
- Department of Surgery, Hospital of the Canton of St. Gallen, CH-9007 St. Gallen, Switzerland; (K.U.); (S.B.)
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Yu Z, Hao Y, Huang Y, Ling L, Hu X, Qiao S. Radiotherapy in the preoperative neoadjuvant treatment of locally advanced rectal cancer. Front Oncol 2023; 13:1300535. [PMID: 38074690 PMCID: PMC10704030 DOI: 10.3389/fonc.2023.1300535] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2023] [Accepted: 10/30/2023] [Indexed: 04/04/2024] Open
Abstract
Radiotherapy and chemotherapy are effective treatments for patients with locally advanced rectal cancer (LARC) and can significantly improve the likelihood of R0 resection. Radiotherapy can be used as a local treatment to reduce the size of the tumor, improve the success rate of surgery and reduce the residual cancer cells after surgery. Early chemotherapy can also downgrade the tumor and eliminate micrometastases throughout the body, reducing the risk of recurrence and metastasis. The advent of neoadjuvant concurrent radiotherapy (nCRT) and total neoadjuvant treatment (TNT) has brought substantial clinical benefits to patients with LARC. Even so, given increasing demand for organ preservation and quality of life and the disease becoming increasingly younger in its incidence profile, there is a need to further explore new neoadjuvant treatment options to further improve tumor remission rates and provide other opportunities for patients to choose watch-and-wait (W&W) strategies that avoid surgery. Targeted drugs and immunologic agents (ICIs) have shown good efficacy in patients with advanced rectal cancer but have not been commonly used in neoadjuvant therapy for patients with LARC. In this paper, we review several aspects of neoadjuvant therapy, including radiation therapy and chemotherapy drugs, immune drugs and targeted drugs used in combination with neoadjuvant therapy, with the aim of providing direction and thoughtful perspectives for LARC clinical treatment and research trials.
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Affiliation(s)
| | | | | | | | - Xigang Hu
- Department of Radiation Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou, China
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Donnelly M, Ryan OK, Ryan ÉJ, Creavin B, O'Reilly M, McDermott R, Kennelly R, Hanly A, Martin ST, Winter DC. Total neoadjuvant therapy versus standard neoadjuvant treatment strategies for the management of locally advanced rectal cancer: network meta-analysis of randomized clinical trials. Br J Surg 2023; 110:1316-1330. [PMID: 37330950 DOI: 10.1093/bjs/znad177] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2023] [Revised: 05/10/2023] [Accepted: 05/20/2023] [Indexed: 06/20/2023]
Abstract
BACKGROUND This study compared the advantages and disadvantages of total neoadjuvant therapy (TNT) strategies for patients with locally advanced rectal cancer, compared with the more traditional multimodal neoadjuvant management strategies of long-course chemoradiotherapy (LCRT) or short-course radiotherapy (SCRT). METHODS A systematic review and network meta-analysis of exclusively RCTs was undertaken, comparing survival, recurrence, pathological, radiological, and oncological outcomes. The last date of the search was 14 December 2022. RESULTS In total, 15 RCTs involving 4602 patients with locally advanced rectal cancer, conducted between 2004 and 2022, were included. TNT improved overall survival compared with LCRT (HR 0.73, 95 per cent credible interval 0.60 to 0.92) and SCRT (HR 0.67, 0.47 to 0.95). TNT also improved rates of distant metastasis compared with LCRT (HR 0.81, 0.69 to 0.97). Reduced overall recurrence was observed for TNT compared with LCRT (HR 0.87, 0.76 to 0.99). TNT showed an improved pCR compared with both LCRT (risk ratio (RR) 1.60, 1.36 to 1.90) and SCRT (RR 11.32, 5.00 to 30.73). TNT also showed an improvement in cCR compared with LCRT (RR 1.68, 1.08 to 2.64). There was no difference between treatments in disease-free survival, local recurrence, R0 resection, treatment toxicity or treatment compliance. CONCLUSION This study provides further evidence that TNT has improved survival and recurrence benefits compared with current standards of care, and may increase the number of patients suitable for organ preservation, without negatively influencing treatment toxicity or compliance.
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Affiliation(s)
- Mark Donnelly
- Department of Surgery, St Vincent's University Hospital, Dublin, Ireland
- School of Medicine, University College, Dublin, Ireland
| | - Odhrán K Ryan
- Department of Surgery, St Vincent's University Hospital, Dublin, Ireland
- School of Medicine, University College, Dublin, Ireland
| | - Éanna J Ryan
- Department of Surgery, St Vincent's University Hospital, Dublin, Ireland
| | - Ben Creavin
- Department of Surgery, St Vincent's University Hospital, Dublin, Ireland
| | - Mary O'Reilly
- Department of Oncology, St Vincent's University Hospital, Dublin, Ireland
| | - Ray McDermott
- School of Medicine, University College, Dublin, Ireland
- Department of Oncology, St Vincent's University Hospital, Dublin, Ireland
| | - Rory Kennelly
- Department of Surgery, St Vincent's University Hospital, Dublin, Ireland
- Centre for Colorectal Disease, St Vincent's University Hospital, Dublin, Ireland
| | - Ann Hanly
- Department of Surgery, St Vincent's University Hospital, Dublin, Ireland
- Centre for Colorectal Disease, St Vincent's University Hospital, Dublin, Ireland
| | - Seán T Martin
- Department of Surgery, St Vincent's University Hospital, Dublin, Ireland
- Centre for Colorectal Disease, St Vincent's University Hospital, Dublin, Ireland
| | - Des C Winter
- Department of Surgery, St Vincent's University Hospital, Dublin, Ireland
- School of Medicine, University College, Dublin, Ireland
- Centre for Colorectal Disease, St Vincent's University Hospital, Dublin, Ireland
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Nov P, Du K, Huang Z, Li Y, Gong M, Liu X, Li C, Li L, Wang D, Zhang Y, Wang C, Li J. A Meta-analysis of Total Neoadjuvant Therapies Combining Chemoradiotherapy with Induction or Consolidated Chemotherapy for Locally Advanced Rectal Cancer. J Gastrointest Cancer 2023; 54:693-702. [PMID: 36243897 DOI: 10.1007/s12029-022-00864-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/09/2022] [Indexed: 11/25/2022]
Abstract
OBJECTIVE Total neoadjuvant therapy (TNT) combining chemoradiotherapy (CRT) with chemotherapy (CT) was a novel pre-surgical approach to cancer treatment. This meta-analysis aimed to compare the clinical outcomes between neoadjuvant CRT (nCRT) with induction CT and nCRT with consolidated CT in locally advanced rectal cancer (LARC) patients. METHOD In July 2022, a literature search was conducted using the following public databases: PubMed, MEDLINE, Embase, the Cochrane Library, and Web of Science, retrieved all relevant articles comparing nCRT-combining induction CT with nCRT-combining-consolidated CT treatments for LARC patients. RESULTS Four eligible studies were identified, including a total of 995 LARC patients: 473 in the nCRT with consolidated CT group and 522 in the nCRT with induction CT group. The organ preservation (OP) rate of the nCRT with consolidated CT group was higher than that of the nCRT with induction CT group (RR [relative risk]: 1.53; 95% CI (confidence interval): 1.09-2.14). The pathological complete response (PCR, RR: 1.22; 95% CI 0.37-2.17), the 3-year disease-free survival (DFS, RR 1.02; 95% CI 0.71-1.46), the local recurrence (LR, RR 0.98; 95% CI 0.52-1.85), rates of R0 resection (RR 0.74; 95% CI 0.55-1.10), compliance (RR 0.52; 95% CI 0.12-2.26), and grade 3--4 toxicities (RR 0.78; 95% CI 0.57-1.06) were all similar between the two groups. CONCLUSION In this meta-analysis of TNT regimens for rectal cancer, consolidative CT following nCRT was associated with similar PCR, 3-year DFS, LR, R0 resection, compliance, and grade 3-4 toxicities compared to induction CT prior to nCRT but a higher rate of organ preservation.
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Affiliation(s)
- Pengkhun Nov
- Department of Radiation Oncology, Oncology Center, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong Province, 510282, China
| | - Kunpeng Du
- Department of Radiation Oncology, Oncology Center, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong Province, 510282, China
| | - Zijian Huang
- Department of Radiation Oncology, Oncology Center, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong Province, 510282, China
| | - Yanyang Li
- Department of Radiation Oncology, Oncology Center, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong Province, 510282, China
| | - Min Gong
- Department of Radiation Oncology, Oncology Center, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong Province, 510282, China
| | - Xiang Liu
- Department of Radiation Oncology, Oncology Center, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong Province, 510282, China
| | - Chunhui Li
- Department of Radiation Oncology, Oncology Center, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong Province, 510282, China
| | - Lilin Li
- Department of Radiation Oncology, Oncology Center, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong Province, 510282, China
| | - Duanyu Wang
- Department of Radiation Oncology, Oncology Center, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong Province, 510282, China
| | - Yangfeng Zhang
- Department of Radiation Oncology, Oncology Center, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong Province, 510282, China
| | - Changqian Wang
- Department of Radiation Oncology, Oncology Center, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong Province, 510282, China
| | - Jiqiang Li
- Department of Radiation Oncology, Oncology Center, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong Province, 510282, China.
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Sychev S, Ponomarenko A, Chernyshov S, Alekseev M, Mamedli Z, Kuzmichev D, Polynovskiy A, Rybakov E. Total neoadjuvant therapy in rectal cancer: a network meta-analysis of randomized trials. Ann Coloproctol 2023; 39:289-300. [PMID: 37038270 PMCID: PMC10475801 DOI: 10.3393/ac.2022.00920.0131] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2022] [Revised: 12/22/2022] [Accepted: 01/09/2023] [Indexed: 04/12/2023] Open
Abstract
PURPOSE To assess the efficacy of total neoadjuvant therapy (TNT) for rectal carcinoma in comparison with conventional chemoradiotherapy (CRT). METHODS A systematic review was performed according to the PRISMA guidelines. A Bayesian network meta-analysis was done using NetMetaXL and WinBUGS. This study was registered in PROSPERO on March 3, 2022 (No. CRD-42022307867). RESULTS Outcomes of 2,719 patients from 10 randomized trials between 2010 and 2022 were selected. Of these 1,191 (44%) had conventional long-course CRT (50-54 Gy) and capecitabine, 506 (18%) had induction chemotherapy followed by CRT (50-54 Gy) and capecitabine (iTNT), 230 (9%) had long-course CRT (50-54 Gy) followed by consolidation chemotherapy (cTNT), and 792 (29%) undergone modified short-course radiotherapy (25 Gy) with subsequent chemotherapy (mTNT). Total pathologic complete response (pCR) was 20% in the iTNT group, 21% in the mTNT group, 22% in the cTNT group, and 12% in the CRT group. Statistically significant difference in pCR rates was detected when comparing iTNT with CRT (odds ratio [OR], 1.76; 95% credible interval [CrI], 1.06-2.8), mTNT with CRT (OR, 1.90; 95% CrI, 1.25-2.74), and cTNT with CRT groups (OR, 2.54; 95% CrI, 1.26-5.08). No differences were found in R0 resection rates. No significant difference was found in long-term outcomes. CONCLUSION The early administration of systemic chemotherapy in the TNT regimen has improved short-term outcomes, though long-term results are underreported. Randomized trials with survival as the endpoint are necessary to evaluate the possible advantages of TNT modes.
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Affiliation(s)
- Sergey Sychev
- Ryzhikh National Medical Research Center of Coloproctology, Moscow, Russia
| | | | | | - Mikhail Alekseev
- Ryzhikh National Medical Research Center of Coloproctology, Moscow, Russia
| | - Zaman Mamedli
- N.N. Blokhin National Medical Research Center of Oncology, Moscow, Russia
| | - Dmitriy Kuzmichev
- N.N. Blokhin National Medical Research Center of Oncology, Moscow, Russia
| | - Andrey Polynovskiy
- N.N. Blokhin National Medical Research Center of Oncology, Moscow, Russia
| | - Evgeny Rybakov
- Ryzhikh National Medical Research Center of Coloproctology, Moscow, Russia
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20
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Wu Q, Zhou J, Huang J, Deng X, Li C, Meng W, He Y, Wang Z. Total neoadjuvant therapy versus chemoradiotherapy for locally advanced rectal cancer: Bayesian network meta-analysis. Br J Surg 2023; 110:784-796. [PMID: 37191308 DOI: 10.1093/bjs/znad120] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2022] [Revised: 03/08/2023] [Accepted: 03/23/2023] [Indexed: 05/17/2023]
Abstract
BACKGROUND Total neoadjuvant therapy is a promising treatment for locally advanced rectal cancer, utilizing either short-course radiotherapy or long-course chemoradiotherapy, but their relative efficacy remains unclear. The aim of this Bayesian network meta-analysis was to investigate clinical outcomes amongst patients receiving total neoadjuvant therapy with short-course radiotherapy or long-course chemoradiotherapy, and those receiving long-course chemoradiotherapy alone. METHODS A systematic literature search was performed. All studies that compared at least two of these three treatments for locally advanced rectal cancer were included. The primary endpoint was the pathological complete response rate, and survival outcomes were adopted as secondary outcomes. RESULTS Thirty cohorts were included. Compared with long-course chemoradiotherapy, both total neoadjuvant therapy with long-course chemoradiotherapy (OR 1.78, 95 per cent c.i. 1.43 to 2.26) and total neoadjuvant therapy with short-course radiotherapy (OR 1.75, 95 per cent c.i. 1.23 to 2.50) improved the pathological complete response rate. Similar benefits were observed in the sensitivity and subgroup analyses, except for short-course radiotherapy with one to two cycles of chemotherapy. No significant differences in survival outcomes were found amongst the three treatments. Long-course chemoradiotherapy with consolidation chemotherapy (HR 0.44, 95 per cent c.i. 0.20 to 0.99) exhibited higher disease-free survival than long-course chemoradiotherapy alone. CONCLUSION Compared with long-course chemoradiotherapy, both short-course radiotherapy with greater than or equal to three cycles of chemotherapy and total neoadjuvant therapy with long-course chemoradiotherapy can improve the pathological complete response rate, and long-course chemoradiotherapy with consolidation chemotherapy may lead to a marginal benefit in disease-free survival. The pathological complete response rate and survival outcomes are similar for total neoadjuvant therapy with short-course radiotherapy or long-course chemoradiotherapy.
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Affiliation(s)
- Qingbin Wu
- Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
- Colorectal Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Jiahao Zhou
- Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
- Colorectal Cancer Center, West China Hospital, Sichuan University, Chengdu, China
- West China School of Medicine, Sichuan University, Chengdu, China
| | - Jun Huang
- Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
- Colorectal Cancer Center, West China Hospital, Sichuan University, Chengdu, China
- West China School of Medicine, Sichuan University, Chengdu, China
| | - Xiangbing Deng
- Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
- Colorectal Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Changtao Li
- Department of Epidemiology and Medical Statistics, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China
| | - Wenjian Meng
- Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
- Colorectal Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Yazhou He
- Department of Oncology, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China
| | - Ziqiang Wang
- Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
- Colorectal Cancer Center, West China Hospital, Sichuan University, Chengdu, China
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21
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Borelli B, Germani MM, Carullo M, Mattioni R, Manfredi B, Sainato A, Rossi P, Vagli P, Balestri R, Buccianti P, Morelli L, Antoniotti C, Cremolini C, Masi G, Moretto R. Total neoadjuvant treatment and organ preservation strategies in the management of localized rectal cancer: A narrative review and evidence-based algorithm. Crit Rev Oncol Hematol 2023; 186:103985. [PMID: 37059274 DOI: 10.1016/j.critrevonc.2023.103985] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2023] [Revised: 03/26/2023] [Accepted: 04/11/2023] [Indexed: 04/16/2023] Open
Abstract
The multimodal approach with total mesorectal excision preceded by neoadjuvant (chemo)radiotherapy represented the mainstay treatment for locally advanced rectal cancer (LARC) for a long time. However, the benefit of adjuvant chemotherapy in terms of distant relapse reduction is limited. Recently, chemotherapy regimens administered before surgery and incorporated with (chemo)radiotherapy in total neoadjuvant treatment protocols have been established as new options in the management of LARC. Meanwhile, patients with clinical complete response to neoadjuvant treatment can benefit from organ preservation strategies, aimed at sparing surgery and long-term post-operative morbidities, while preserving an adequate disease control. However, the introduction of a non-operative management in clinical practice is a matter of debate with some concerns regarding the risk of local recurrence and long-term outcomes. In this review, we discuss how these recent advances are reshaping the multimodal management of localized rectal cancer and propose an algorithm to place them in the clinical practice.
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Affiliation(s)
- Beatrice Borelli
- Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy; Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Marco Maria Germani
- Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy; Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Martina Carullo
- Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy; Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Roberto Mattioni
- Radiation Oncology Unit, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy
| | - Bruno Manfredi
- Radiation Oncology Unit, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy
| | - Aldo Sainato
- Radiation Oncology Unit, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy
| | - Piercarlo Rossi
- Diagnostic and Interventional Radiology Unit, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy
| | - Paola Vagli
- Diagnostic and Interventional Radiology Unit, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy
| | - Riccardo Balestri
- General Surgery, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy
| | - Piero Buccianti
- General Surgery, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy
| | - Luca Morelli
- General Surgery, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Carlotta Antoniotti
- Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy; Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Chiara Cremolini
- Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy; Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Gianluca Masi
- Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy; Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Roberto Moretto
- Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.
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22
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Aschele C, Glynne-Jones R. Selecting a TNT Schedule in Locally Advanced Rectal Cancer: Can We Predict Who Actually Benefits? Cancers (Basel) 2023; 15:cancers15092567. [PMID: 37174033 PMCID: PMC10177050 DOI: 10.3390/cancers15092567] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2023] [Revised: 04/24/2023] [Accepted: 04/25/2023] [Indexed: 05/15/2023] Open
Abstract
Many consider the standard of care for locally advanced rectal cancer (LARC) to be preoperative chemoradiotherapy, radical surgery involving a total mesorectal excision, and post-operative adjuvant chemotherapy based on the pathology of the specimen. The poor impact on distant control is a major limitation of this strategy, with metastasis rates remaining in the 25-35% range and recovery after radical surgery leading to reluctance with prescription and inconsistent patient compliance with adjuvant chemotherapy. A second limitation is the low rate of pathologic complete response (pCR) (around 10-15%) despite multiple efforts to potentiate preoperative chemoradiation regimens, which in turn means it is less effective at achieving non-operative management (NOM). Total neoadjuvant treatment (TNT) is a pragmatic approach to solving these problems by introducing systemic chemotherapy at an early timepoint. Enthusiasm for delivering TNT for patients with LARC is increasing in light of the results of published randomized phase III trials, which show a doubling of the pCR rate and a significant reduction in the risk of subsequent metastases. However, there has been no demonstrated improvement in quality of life or overall survival. A plethora of potential chemotherapy schedules are available around the radiotherapy component, which include preoperative induction or consolidation with a range of options (FOLFOXIRI, FOLFOX, or CAPEOX,) and a varying duration of 6-18 weeks, prior to long course chemoradiation (LCCRT) or consolidation NACT following short-course preoperative radiation therapy (SCPRT) using 5 × 5 Gy or LCCRT using 45-60 Gy, respectively. The need to maintain optimal local control is a further important factor, and preliminary data appear to indicate that the RT schedule remains a crucial issue, especially in more advanced tumors, i.e., mesorectal fascia (MRF) invasion. Thus, there is no consensus as to the optimum combination, sequence, or duration of TNT. The selection of patients most likely to benefit is challenging, as clear-cut criteria to individuate patients benefiting from TNT are lacking. In this narrative review, we examine if there are any necessary or sufficient criteria for the use of TNT. We explore potential selection for the individual and their concerns with a generalized use of this strategy.
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Affiliation(s)
- Carlo Aschele
- Medical Oncology Unit, Department of Oncology, Ospedale Sant'Andrea, Via Vittorio Veneto 197, 19121 La Spezia, Italy
| | - Robert Glynne-Jones
- Radiotherapy Department, Mount Vernon Centre for Cancer Treatment, Mount Vernon Hospital, Rickmansworth Rd., Northwood, London HA6 2RN, UK
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23
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Xiong K, Bao T, Cao Y, Hu W, Deng J, Chen J, Xiao T. Efficacy and safety of total neoadjuvant therapy in locally advanced rectal cancer: a meta-analysis. Int J Colorectal Dis 2023; 38:89. [PMID: 37004572 DOI: 10.1007/s00384-023-04376-y] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/17/2023] [Indexed: 04/04/2023]
Abstract
PURPOSE The standard of care for locally advanced rectal cancer (LARC) has changed from a single radical surgical treatment to the current multimodality treatment (standard chemoradiotherapy (CRT) and total neoadjuvant therapy (TNT)). The efficacy and safety of both TNT and standard CRT are evaluated in randomized controlled trials (RCTs). METHODS RCTs were comprehensively searched in Chinese and English electronic databases. The experimental and control groups were TNT and the standard CRT, respectively, included in this meta-analysis. The outcomes were assessed through a fixed-effect or random-effect model of pooled odds (OR) or hazard ratios (HR). RESULTS Eleven RCTs, involving 3,101 patients were included in the final analysis. TNT showed increase in the pathological complete response (pCR) (OR = 1.95, 95% confidence interval (CI): 1.57-2.41; P < 0.05) and the R0 resection (OR = 1.19, 95% CI: 0.99-1.43; P = 0.062). There was no significant difference in local recurrence-free survival (LRFS) (HR = 0.97, P = 0.803), but TNT had better 3-year disease-free survival (DFS) (HR = 0.82, 95% CI: 0.72-0.93, P < 0.05), overall survival (OS) (HR = 0.87, 95% CI: 0.74-1.02, P = 0.08) and distant metastasis-free survival (DMFS) (HR = 0.79, 95% CI: 0.67-0.93, P < 0.05) than standard CRT. CONCLUSIONS TNT was safe and feasible as it improved pCR and survival outcomes, and reduced the risk of distant metastasis compared with standard CRT. TNT may be a superior strategy for LARC, but more RCTs are needed to prove it. REGISTRATION AND PROTOCOL PROSPERO CRD42022327697. We added the Chinese database after registration because of the inclusion of fewer RCTs www.crd.york.ac.uk/PROSPERO/ .
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Affiliation(s)
- Kai Xiong
- College of Clinical Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang, China
| | - Tiantian Bao
- Colorectal and Anal Surgery, the First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, No 71 Baoshan North Road, 550001, Guiyang, China
| | - Yibo Cao
- Colorectal and Anal Surgery, the First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, No 71 Baoshan North Road, 550001, Guiyang, China
| | - Wenting Hu
- College of Clinical Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang, China
| | - Jia Deng
- College of Clinical Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang, China
| | - Jiang Chen
- Colorectal and Anal Surgery, the First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, No 71 Baoshan North Road, 550001, Guiyang, China.
| | - Tianbao Xiao
- Colorectal and Anal Surgery, the First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, No 71 Baoshan North Road, 550001, Guiyang, China.
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24
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Simillis C, Khatri A, Dai N, Afxentiou T, Jephcott C, Smith S, Jadon R, Papamichael D, Khan J, Powar MP, Fearnhead NS, Wheeler J, Davies J. A systematic review and network meta-analysis of randomised controlled trials comparing neoadjuvant treatment strategies for stage II and III rectal cancer. Crit Rev Oncol Hematol 2023; 183:103927. [PMID: 36706968 DOI: 10.1016/j.critrevonc.2023.103927] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2022] [Revised: 01/08/2023] [Accepted: 01/23/2023] [Indexed: 01/27/2023] Open
Abstract
AIM Multiple neoadjuvant therapy strategies have been used and compared for rectal cancer and there has been no true consensus as to the optimal neoadjuvant therapy regimen. The aim is to identify and compare the neoadjuvant therapies available for stage II and III rectal cancer. DESIGN A systematic literature review was performed, from inception to August 2022, of the following databases: MEDLINE, EMBASE, Science Citation Index Expanded, Cochrane Library. Only randomized controlled trials comparing neoadjuvant therapies for stage II and III rectal cancer were considered. Stata was used to draw network plots, and a Bayesian network meta-analysis was conducted through models utilizing the Markov Chain Monte Carlo method in WinBUGS. RESULTS A total of 58 articles were included based on 41 randomised controlled trials, reporting on 12,404 participants that underwent 15 neoadjuvant treatment regimens. No significant difference was identified between treatments for major or total postoperative complications, anastomotic leak rates, or sphincter-saving surgery. Straight to surgery (STS) ranked as best treatment for preoperative toxicity but ranked worst treatment for positive resection margins and complete response. STS had significantly increased positive resection margins compared to long-course chemoradiotherapy with short-wait (LCCRT-SW) or long-wait (LCCRT-LW) to surgery, or short-course radiotherapy with short-wait (SCRT-SW) or immediate surgery (SCRT-IS). LCCRT-SW or LCCRT-LW resulted in significantly increased complete response rates compared to STS. LCCRT-LW significantly improved 2-year overall survival compared to STS, SCRT-IS, SCRT-SW. Total neoadjuvant therapy regimes with short-course radiotherapy followed by consolidation chemotherapy (SCRT-CT-SW), induction chemotherapy followed by long-course chemoradiotherapy (CT-LCCRT-S), long-course chemoradiotherapy followed by consolidation chemotherapy (LCCRT-CT-S), significantly improved positive resection margins, complete response, and disease-free survival compared to STS. Chemotherapy with monoclonal antibodies followed by long-course chemoradiotherapy (CT+MAB-LCCRT+MAB-S) significantly improved complete response and positive resection margins compared to STS, and 2-year disease-free survival compared to STS, SCRT-IS, SCRT-SW, SCRT-CT-SW, LCCRT-SW, LCCRT-LW. CT+MAB-LCCRT+MAB-S ranked as best treatment for disease-free survival and overall survival. CONCLUSIONS Conventional neoadjuvant therapies with short-course radiation or long-course chemoradiotherapy have oncological benefits compared to no neoadjuvant therapy without increasing perioperative complication rates. Prolonged wait to surgery may improve oncological outcomes. Total neoadjuvant therapies provide additional benefits in terms of complete response, positive resection margins, and disease-free survival. Monoclonal antibody therapy may further improve oncological outcomes but currently is only applicable to a small subgroup of patients and requires further validation.
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Affiliation(s)
- Constantinos Simillis
- Cambridge Colorectal Unit, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK; Department of Surgery, University of Cambridge, Cambridge, UK.
| | - Amulya Khatri
- Cambridge Colorectal Unit, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Nick Dai
- Cambridge Colorectal Unit, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Thalia Afxentiou
- Department of Oncology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Catherine Jephcott
- Department of Oncology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Sarah Smith
- Department of Oncology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Rashmi Jadon
- Department of Oncology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | | | - Jim Khan
- Department of Colorectal Surgery, Portsmouth Hospitals University NHS Trust, Portsmouth, UK
| | - Michael P Powar
- Cambridge Colorectal Unit, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Nicola S Fearnhead
- Cambridge Colorectal Unit, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - James Wheeler
- Cambridge Colorectal Unit, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Justin Davies
- Cambridge Colorectal Unit, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK; Department of Surgery, University of Cambridge, Cambridge, UK
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25
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Xiao W, Luo H, Yao Y, Wang Y, Liu S, Sun R, Chen G. Total neoadjuvant treatment and PD-1/PD-L1 checkpoint inhibitor in locally advanced rectal cancer. Front Immunol 2023; 14:1149122. [PMID: 37033988 PMCID: PMC10079866 DOI: 10.3389/fimmu.2023.1149122] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2023] [Accepted: 03/15/2023] [Indexed: 04/11/2023] Open
Abstract
For local advanced rectal cancer (LARC), total neoadjuvant treatment (TNT) has shown more complete response (CR), reduced risk of distant metastasis (DM) and increase of the sphincter preservation rate. Now it is the one and only recommendation for high-risk group of LARC according to National Comprehensive Cancer Network (NCCN) rectal cancer guideline, while it is also preferentially recommended for low-risk group of LARC. TNT is also beneficial for distant rectal cancer patients who have need for organ preservation. Even though the prognostic value of programmed cell death-ligand 1 (PD-L1) in the neoadjuvant chemoradiotherapy (NACRT) of LARC patients is undetermined yet, the combination of NACRT and programmed cell death-1 (PD-1)/PD-L1 antibodies seem bring new hope for mismatch repair proficient (pMMR)/microsatellite stable (MSS) LARC patients. Accumulating small sample sized studies have shown that combining NACRT with PD-1/PD-L1 antibody yield better short-term outcomes for pMMR/MSS LARC patients than historic data. However, ideal total dose and fractionation of radiotherapy remains one of unresolved issues in this combination setting. Thorough understanding the impact of radiotherapy on the tumor microenvironment and their interaction is needed for in-depth understanding and exquisite design of treatments combination model.
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Affiliation(s)
- Weiwei Xiao
- Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China
- *Correspondence: Gong Chen, ; Weiwei Xiao,
| | - Huilong Luo
- Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Ye Yao
- Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Yaqin Wang
- Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Shuang Liu
- Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Rui Sun
- Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Gong Chen
- Department of Colorectal Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China
- *Correspondence: Gong Chen, ; Weiwei Xiao,
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Paszt A, Ottlakan A, Abraham S, Simonka Z, Vas M, Maraz A, Szepes Z, Tiszlavicz L, Nyari T, Olah J, Lazar G. Clinical benefits of oral capecitabine over intravenous 5-fluorouracyl regimen in case of neoadjuvant chemoradiotherapy followed by surgery for locally advanced rectal cancer. Pathol Oncol Res 2022; 28:1610722. [PMID: 36567978 PMCID: PMC9773127 DOI: 10.3389/pore.2022.1610722] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2022] [Accepted: 11/23/2022] [Indexed: 12/13/2022]
Abstract
Background: During the last decade, one of the most important treatment options for locally advanced, potencially resectable rectal tumours was neoadjuvant chemoradiotherapy (CRT) followed by surgery. Methods: Effects of the neoadjuvant treatment on surgical outcomes were retrospectively analysed in 185 patients with stage T2-T4 and N0-2, resectable rectal tumour among two patient groups defined by radiosensitizer agents. Group 1 (n = 94) involved radiotherapy (RT) with 50.4 Gy total dose (25 × 1.8 Gy + 3 × 1.8 Gy tumour bed boost), and intravenous 5-fluorouracil (5-FU) (350 mg/m2) with leucovorin (20 mg/m2) on the 1-5 and 21-25 days, while Group 2 (n = 91) RT and orally administrated capecitabine (daily 2 × 825 mg/m2) on RT days. Surgery was carried out after 8-10 weeks. Side effects, perioperative complications, type of surgery, number of removed regional lymph nodes, resection margins and tumour regression grade (TRG) were analysed. Results: More favourable side effects were observed in Group 2. Despite the same rate of diarrhoea (Group 1 vs. Group 2: 54.3% vs. 56.0%), Grade 2-3 diarrhoea ratio was lower (p = 0.0352) after capecitabine (Group 2). Weight loss occurred in 17.0% and 2.2% (p = 0.00067), while nausea and vomiting was described in 38.3% and 15.4% (p = 0.00045) with 5-FU treatment and capecitabine respectively. Anaemia was observed in 33.0% and 22.0% (p = 0.0941). Complete tumour regression occurred in 25.3% after oral- and 13.8% after intravenous treatment (p = 0.049). Ratio of sphincter preservation was higher with laparoscopy than open surgery (72.3% vs. 39.7%) (p = 0.00001). Conclusion: The study confirms advantages of neoadjuvant chemoradiotherapy with oral capecitabine for rectal tumours, such as more favourable side effect profile and overall clinical outcome, with increased rate of complete tumour regression.
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Affiliation(s)
- Attila Paszt
- Department of Surgery, University of Szeged, Szeged, Hungary,*Correspondence: Attila Paszt,
| | - Aurel Ottlakan
- Department of Surgery, University of Szeged, Szeged, Hungary
| | | | - Zsolt Simonka
- Department of Surgery, University of Szeged, Szeged, Hungary
| | - Marton Vas
- Department of Surgery, University of Szeged, Szeged, Hungary
| | - Aniko Maraz
- Department of Oncotherapy, University of Szeged, Szeged, Hungary
| | - Zoltan Szepes
- 1st Department of Internal Medicine, University of Szeged, Szeged, Hungary
| | | | - Tibor Nyari
- Department of Medical Physics and Informatics, University of Szeged, Szeged, Hungary
| | - Judit Olah
- Department of Oncotherapy, University of Szeged, Szeged, Hungary
| | - Gyorgy Lazar
- Department of Surgery, University of Szeged, Szeged, Hungary
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Petrelli F, Trevisan F, Tomasello G, De Stefani A, Viti M, Garrone O, Luciani A, Ghidini M. Different neoadjuvant therapies for locally advanced rectal cancer: A systematic review and network meta-analysis. Crit Rev Oncol Hematol 2022; 180:103853. [DOI: 10.1016/j.critrevonc.2022.103853] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Revised: 09/19/2022] [Accepted: 10/12/2022] [Indexed: 11/07/2022] Open
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Gabbani M, Giorgi C, Napoli G, Tebano U, Perrone MS, Missiroli S, Berretta M, Mandarà M, Zaninelli M, Luca N, Grigolato D, Muraro M, Rinaldi G, Pinton P, Fiorica F. Outcomes of Locally Advanced Rectal Cancer Patients Treated with Total Neoadjuvant Treatment: A Meta-Anaysis of Randomized Controlled Trials. Clin Colorectal Cancer 2022; 21:297-308. [PMID: 36210320 DOI: 10.1016/j.clcc.2022.07.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Revised: 07/21/2022] [Accepted: 07/22/2022] [Indexed: 01/26/2023]
Abstract
BACKGROUND & AIMS Determining outcomes using the total neoadjuvant therapy (TNT) in patients with local advanced rectal cancer is important for stratifying patients according to expected outcomes in future studies in the era of treatment combination. The present meta-analysis estimated the pathological complete response, disease-free survival, and overall survival probabilities of rectal cancer patients and identified predictors of outcomes. METHODS Studies reporting pathological complete response rate and time-dependent outcomes (progression or death) after total neoadjuvant treatment of locally advanced rectal cancer (LARC) were identified in MEDLINE through January 2022. Three independent observers extracted data on patient populations and outcomes and combined the data using a distribution-free summary survival curve. The primary outcomes were actuarial probabilities of recurrence and survival. RESULTS Fourteen RCTs, including 18 TNT arms, met the inclusion criteria. The pooled estimate of pathological complete response (pCR) probability was 23.6%, with moderate heterogeneity between studies. The pooled estimates of actuarial disease-free survival rate were 70.6% at 3 years and 65.4% at 5 years. The pooled estimates of actuarial survival rates were 93% at 3 years and 81.6% at 5 years. In both these outcomes, heterogeneity between studies was highly significant. CONCLUSION This meta-analysis showed that Total Neoadjuvant Therapy is an optimal approach for LARC patients. The results provide a useful benchmark for future comparisons of the benefits of combinations of other drug families as target therapies or immunotherapies.
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Affiliation(s)
- Milena Gabbani
- Department of Radiation Oncology and Nuclear Medicine, Verona, Italy
| | - Carlotta Giorgi
- Dept. of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology, Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, Ferrara, Italy
| | - Giuseppe Napoli
- Department of Radiation Oncology and Nuclear Medicine, Verona, Italy
| | - Umberto Tebano
- Department of Radiation Oncology and Nuclear Medicine, Verona, Italy
| | - Maria Sole Perrone
- Dept. of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology, Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, Ferrara, Italy
| | - Sonia Missiroli
- Dept. of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology, Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, Ferrara, Italy
| | - Massimiliano Berretta
- Department of Clinical and Experimental Medicine, Policlinico "G. Martino" University of Messina, Messina, Italy
| | | | | | - Nicoletta Luca
- Department of Radiation Oncology and Nuclear Medicine, Verona, Italy
| | - Daniela Grigolato
- Department of Radiation Oncology and Nuclear Medicine, Verona, Italy
| | - Marco Muraro
- Department of Radiation Oncology and Nuclear Medicine, Verona, Italy
| | - Giulia Rinaldi
- Department of Radiation Oncology and Nuclear Medicine, Verona, Italy
| | - Paolo Pinton
- Dept. of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology, Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, Ferrara, Italy
| | - Francesco Fiorica
- Department of Radiation Oncology and Nuclear Medicine, Verona, Italy.
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Zhang X, Ma S, Guo Y, Luo Y, Li L. Total neoadjuvant therapy versus standard therapy in locally advanced rectal cancer: A systematic review and meta-analysis of 15 trials. PLoS One 2022; 17:e0276599. [PMID: 36331947 PMCID: PMC9635708 DOI: 10.1371/journal.pone.0276599] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Accepted: 10/11/2022] [Indexed: 11/06/2022] Open
Abstract
Background Neoadjuvant chemoradiotherapy (nCRT) before total mesorectal excision (TME) and followed systemic chemotherapy is widely accepted as the standard therapy for locally advanced rectal cancer (LARC). This meta-analysis was to evaluate the current evidence regarding nCRT in combination with induction or consolidation chemotherapy for rectal cancer in terms of oncological outcomes. Methods A systematic search of medical databases (PubMed, EMBASE and Cochrane Library) was conducted up to the end of July 1, 2021. This meta-analysis was performed to evaluate the efficacy of TNT in terms of pathological complete remission (pCR), nCRT or surgical complications, R0 resection, local recurrence, distant metastasis, disease-free survival (DFS) and overall survival (OS) in LARC. Results Eight nRCTs and 7 RCTs, including 3579 patients were included in the meta-analysis. The rate of pCR was significantly higher in the TNT group than in the nCRT group, (OR 1.85, 95% CI 1.39–2.46, p < 0.0001), DFS (HR 0.80, 95% CI 0.69–0.92, p = 0.001), OS (HR 0.75, 95% CI 0.62–0.89, p = 0.002), nCRT complications (OR 1.05, 95% CI 0.77–1.44, p = 0.75), surgical complications (OR 1.02, 95% CI 0.83–1.26, p = 0.83), local recurrence (OR 1.82, 95% CI 0.95–3.49, p = 0.07), distant metastasis (OR 0.77, 95% CI 0.58–1.03, p = 0.08) did not differ significantly between the TNT and nCRT groups. Conclusion TNT appears to have advantages over standard therapy for LARC in terms of pCR, R0 resection, DFS, and OS, with comparable nCRT and postoperative complications, and no increase in local recurrence and distant metastasis.
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Affiliation(s)
- Xiping Zhang
- Department of General Surgery, Qinan Hospital, Tianshui, China
| | - Shujie Ma
- Department of General Surgery, People’s Hospital of Gannan, Hezuo, China
| | - Yinyin Guo
- Department of Pharmacy, Lanzhou University Second Hospital, Lanzhou, China
| | - Yang Luo
- Department of Neurology, The First Hospital of Lanzhou University, Lanzhou, China
| | - Laiyuan Li
- Department of Anorectal Surgery, Gansu Provincial Hospital, Lanzhou, China
- * E-mail:
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30
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Ma Z, Tan L, Liu ZL, Xiao JW. Total neoadjuvant therapy or standard chemoradiotherapy for locally advanced rectal cancer: A systematic review and meta-analysis. Front Surg 2022; 9:911538. [PMID: 36090336 PMCID: PMC9458916 DOI: 10.3389/fsurg.2022.911538] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2022] [Accepted: 08/10/2022] [Indexed: 11/29/2022] Open
Abstract
Background and Aim The effectiveness of total neoadjuvant therapy (TNT) on patients with locally advanced rectal cancer (LARC) is controversy. This study aims to compare the prognostic value of TNT with standard neoadjuvant chemoradiotherapy (CRT) for LARC. Methods We searched databases (Embase [Ovid], Medline [Ovid], PubMed, Cochrane Library, and Web of Science) for articles published between January 1, 2000, and March 10, 2022. Studies on evaluating the effects of TNT and standard CRT on the prognosis of LARC were included. The primary outcomes were overall survival (OS) and disease-free survival (DFS). Results 19 primary studies, involving 10 randomized controlled trials, 3 prospective studies and 6 retrospective studies, with data on 5,074 patients treated for LARC were included in the meta-analysis. Statistical analyses revealed that, compared with standard CRT, TNT significantly improved OS (hazard ratio [HR]=0.77, 95% confidence interval [CI]=0.65–0.90, I2 = 30%, P = 0.17), DFS (HR = 0.85, 95% CI = 0.74–0.97, I² = 11%, P = 0.35), distant metastases-free survival (DMFS, HR = 0.76, 95% CI = 0.65–0.90, I² = 0%, P = 0.50), pathological complete response rate (pCR, OR = 1.89, 95% CI = 1.61–2.22, I² = 0%, P = 0.47), and R0 resection rate (OR = 1.33, 95% CI = 1.07–1.67, I² = 16%, P = 0.28), but local recurrence-free survival (LRFS, HR = 1.12, 95% CI = 0.90–1.39, I² = 4%, P = 0.37). Conclusions Comprehensive literature research shows that TNT showed excellent short-term efficacy in terms of pCR and R0 resection rate while also improved the long-term outcomes of OS, DFS and DMFS, might become a new standard of treatment in patients with LARC. Even so, more studies and longer follow-up were still warranted.
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Affiliation(s)
- Zhou Ma
- Department of Gastrointestinal Surgery, Clinical Medical College and The First Affiliated Hospital of Chengdu Medical College, Chengdu, China
- Department of Gastrointestinal Surgery, BaZhong Central Hospital, Bazhong, China
| | - Ling Tan
- Department of Urology, People's Hospital Affiliated to Chongqing Three Gorges Medical College, Chongqing, China
| | - Zi-lin Liu
- Department of Gastrointestinal Surgery, Clinical Medical College and The First Affiliated Hospital of Chengdu Medical College, Chengdu, China
| | - Jiang-wei Xiao
- Department of Gastrointestinal Surgery, Clinical Medical College and The First Affiliated Hospital of Chengdu Medical College, Chengdu, China
- Correspondence: Jiang-wei Xiao
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Guida AM, Sensi B, Formica V, D'Angelillo RM, Roselli M, Del Vecchio Blanco G, Rossi P, Capolupo GT, Caricato M, Sica GS. Total neoadjuvant therapy for the treatment of locally advanced rectal cancer: a systematic minireview. Biol Direct 2022; 17:16. [PMID: 35698084 PMCID: PMC9195214 DOI: 10.1186/s13062-022-00329-7] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2022] [Accepted: 05/30/2022] [Indexed: 12/13/2022] Open
Abstract
Colorectal carcinoma is the second leading cause of cancer-related deaths, and indeed, rectal cancer accounting for approximately one third of newly diagnosed patients. Gold standard in the treatment of rectal cancer is a multimodality approach, aiming at a good control of the local disease. Distant recurrences are the major cause of mortality. Currently, Locally Advanced Rectal Cancer (LARC) patients undergo a combined treatment of chemotherapy and radiotherapy, followed by surgery. Eventually, more chemotherapy, namely adjuvant chemotherapy (aCT), may be necessary. Total Neoadjuvant Therapy (TNT) is an emerging approach aimed to reduce distant metastases and improve local control. Several ongoing studies are analyzing whether this new approach could improve oncological outcomes. Published results were encouraging, but the heterogeneity of protocols in use, makes the comparison and interpretation of data rather complex. One of the major concerns regarding TNT administration is related to its effect on larger and more advanced cancers that might not undergo similar down-staging as smaller, early-stage tumors. This minireview, based on a systematic literature search of randomized clinical trials and meta-analysis, summarizes current knowledge on TNT. The aim was to confirm or refute whether or not current practice of TNT is based on relevant evidence, to establish the quality of that evidence, and to address any uncertainty or variation in practice that may be occurring. A tentative grouping of general study characteristics, clinical features and treatments characteristics has been undertaken to evaluate if the reported studies are sufficiently homogeneous in terms of subjects involved, interventions, and outcomes to provide a meaningful idea of which patients are more likely to gain from this treatment.
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Affiliation(s)
- Andrea M Guida
- Department of Surgery, Minimally Invasive Unit, University of Rome Tor Vergata, 00133, Rome, Italy
| | - Bruno Sensi
- Department of Surgery, Minimally Invasive Unit, University of Rome Tor Vergata, 00133, Rome, Italy
| | - Vincenzo Formica
- Department of Systems Medicine, Medical Oncology Unit, Policlinico Tor Vergata, Rome, Italy
| | - Rolando M D'Angelillo
- Department of Biomedicine and Prevention, Radiation Oncology, University of Rome Tor Vergata, 00133, Rome, Italy
| | - Mario Roselli
- Department of Systems Medicine, Medical Oncology Unit, Policlinico Tor Vergata, Rome, Italy
| | | | - Piero Rossi
- Department of Surgery, Minimally Invasive Unit, University of Rome Tor Vergata, 00133, Rome, Italy
| | - Gabriella T Capolupo
- Department of Colorectal Surgery, Colorectal Surgery Unit, Campus Bio-Medico University, 00128, Rome, Italy
| | - Marco Caricato
- Department of Colorectal Surgery, Colorectal Surgery Unit, Campus Bio-Medico University, 00128, Rome, Italy
| | - Giuseppe S Sica
- Department of Surgery, Minimally Invasive Unit, University of Rome Tor Vergata, 00133, Rome, Italy.
- Department of Surgery, Policlinico Tor Vergata, University of Rome, Tor Vergata, Viale Oxford 81, 00133, Rome, Italy.
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Ketelaers SHJ, Jacobs A, Verrijssen ASE, Cnossen JS, van Hellemond IEG, Creemers GJM, Schreuder RM, Scholten HJ, Tolenaar JL, Bloemen JG, Rutten HJT, Burger JWA. A Multidisciplinary Approach for the Personalised Non-Operative Management of Elderly and Frail Rectal Cancer Patients Unable to Undergo TME Surgery. Cancers (Basel) 2022; 14:2368. [PMID: 35625976 PMCID: PMC9139821 DOI: 10.3390/cancers14102368] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2022] [Revised: 05/05/2022] [Accepted: 05/09/2022] [Indexed: 02/07/2023] Open
Abstract
Despite it being the optimal curative approach, elderly and frail rectal cancer patients may not be able to undergo a total mesorectal excision. Frequently, no treatment is offered at all and the natural course of the disease is allowed to unfold. These patients are at risk for developing debilitating symptoms that impair quality of life and require palliative treatment. Recent advancements in non-operative treatment modalities have enhanced the toolbox of alternative treatment strategies in patients unable to undergo surgery. Therefore, a proposed strategy is to aim for the maximal non-operative treatment, in an effort to avoid the onset of debilitating symptoms, improve quality of life, and prolong survival. The complexity of treating elderly and frail patients requires a patient-centred approach to personalise treatment. The main challenge is to optimise the balance between local control of disease, patient preferences, and the burden of treatment. A comprehensive geriatric assessment is a crucial element within the multidisciplinary dialogue. Since limited knowledge is available on the optimal non-operative treatment strategy, these patients should be treated by dedicated multidisciplinary rectal cancer experts with special interest in the elderly and frail. The aim of this narrative review was to discuss a multidisciplinary patient-centred treatment approach and provide a practical suggestion of a successfully implemented clinical care pathway.
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Affiliation(s)
- Stijn H. J. Ketelaers
- Department of Surgery, Catharina Hospital, P.O. Box 1350, 5602 ZA Eindhoven, The Netherlands; (J.L.T.); (J.G.B.); (H.J.T.R.); (J.W.A.B.)
| | - Anne Jacobs
- Department of Gerontology and Geriatrics, Catharina Hospital, P.O. Box 1350, 5602 ZA Eindhoven, The Netherlands;
| | - An-Sofie E. Verrijssen
- Department of Radiation Oncology, Catharina Hospital, P.O. Box 1350, 5602 ZA Eindhoven, The Netherlands; (A.-S.E.V.); (J.S.C.)
| | - Jeltsje S. Cnossen
- Department of Radiation Oncology, Catharina Hospital, P.O. Box 1350, 5602 ZA Eindhoven, The Netherlands; (A.-S.E.V.); (J.S.C.)
| | - Irene E. G. van Hellemond
- Department of Medical Oncology, Catharina Hospital, P.O. Box 1350, 5602 ZA Eindhoven, The Netherlands; (I.E.G.v.H.); (G.-J.M.C.)
| | - Geert-Jan M. Creemers
- Department of Medical Oncology, Catharina Hospital, P.O. Box 1350, 5602 ZA Eindhoven, The Netherlands; (I.E.G.v.H.); (G.-J.M.C.)
| | - Ramon-Michel Schreuder
- Department of Gastroenterology, Catharina Hospital, P.O. Box 1350, 5602 ZA Eindhoven, The Netherlands;
| | - Harm J. Scholten
- Department of Anaesthesiology, Catharina Hospital, P.O. Box 1350, 5602 ZA Eindhoven, The Netherlands;
| | - Jip L. Tolenaar
- Department of Surgery, Catharina Hospital, P.O. Box 1350, 5602 ZA Eindhoven, The Netherlands; (J.L.T.); (J.G.B.); (H.J.T.R.); (J.W.A.B.)
| | - Johanne G. Bloemen
- Department of Surgery, Catharina Hospital, P.O. Box 1350, 5602 ZA Eindhoven, The Netherlands; (J.L.T.); (J.G.B.); (H.J.T.R.); (J.W.A.B.)
| | - Harm J. T. Rutten
- Department of Surgery, Catharina Hospital, P.O. Box 1350, 5602 ZA Eindhoven, The Netherlands; (J.L.T.); (J.G.B.); (H.J.T.R.); (J.W.A.B.)
- GROW, School for Oncology and Reproduction, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands
| | - Jacobus W. A. Burger
- Department of Surgery, Catharina Hospital, P.O. Box 1350, 5602 ZA Eindhoven, The Netherlands; (J.L.T.); (J.G.B.); (H.J.T.R.); (J.W.A.B.)
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Kim JK, Marco MR, Roxburgh CSD, Chen CT, Cercek A, Strombom P, Temple LKF, Nash GM, Guillem JG, Paty PB, Yaeger R, Stadler ZK, Gonen M, Segal NH, Reidy DL, Varghese A, Shia J, Vakiani E, Wu AJ, Romesser PB, Crane CH, Gollub MJ, Saltz L, Smith JJ, Weiser MR, Patil S, Garcia-Aguilar J. Survival After Induction Chemotherapy and Chemoradiation Versus Chemoradiation and Adjuvant Chemotherapy for Locally Advanced Rectal Cancer. Oncologist 2022; 27:380-388. [PMID: 35278070 PMCID: PMC9074984 DOI: 10.1093/oncolo/oyac025] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2021] [Accepted: 12/07/2021] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND Total neoadjuvant therapy (TNT) improves tumor response in locally advanced rectal cancer (LARC) patients compared to neoadjuvant chemoradiotherapy alone. The effect of TNT on patient survival has not been fully investigated. MATERIALS AND METHODS This was a retrospective case series of patients with LARC at a comprehensive cancer center. Three hundred and eleven patients received chemoradiotherapy (chemoRT) as the sole neoadjuvant treatment and planned adjuvant chemotherapy, and 313 received TNT (induction fluorouracil and oxaliplatin-based chemotherapy followed by chemoradiotherapy in the neoadjuvant setting). These patients then underwent total mesorectal excision or were entered in a watch-and-wait protocol. The proportion of patients with complete response (CR) after neoadjuvant therapy (defined as pathological CR or clinical CR sustained for 2 years) was compared by the χ2 test. Disease-free survival (DFS), local recurrence-free survival, distant metastasis-free survival, and overall survival were assessed by Kaplan-Meier analysis and log-rank test. Cox regression models were used to further evaluate DFS. RESULTS The rate of CR was 20% for chemoRT and 27% for TNT (P=.05). DFS, local recurrence-free survival, metastasis-free survival, and overall survival were no different. Disease-free survival was not associated with the type of neoadjuvant treatment (hazard ratio [HR] 1.3; 95% confidence interval [CI] 0.93-1.80; P = .12). CONCLUSIONS Although TNT does not prolong survival than neoadjuvant chemoradiotherapy plus intended postoperative chemotherapy, the higher response rate associated with TNT may create opportunities to preserve the rectum in more patients with LARC.
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Affiliation(s)
- Jin K Kim
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Michael R Marco
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | | | - Chin-Tung Chen
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Andrea Cercek
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Paul Strombom
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Larissa K F Temple
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Garrett M Nash
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Jose G Guillem
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Philip B Paty
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Rona Yaeger
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Zsofia K Stadler
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Mithat Gonen
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Neil H Segal
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Diane L Reidy
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Anna Varghese
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Jinru Shia
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Efsevia Vakiani
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Abraham J Wu
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Paul B Romesser
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Christopher H Crane
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Marc J Gollub
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Leonard Saltz
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - J Joshua Smith
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Martin R Weiser
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Sujata Patil
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Julio Garcia-Aguilar
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
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Abstract
The management of localized rectal cancer requires a multidisciplinary approach to optimize outcomes, reduce morbidity and prevent under or overtreatments. While early stages may obtain benefit of local resections without any additional therapies, locally advanced rectal cancer becomes a challenge defining the better sequential strategy of surgery, radiotherapy and chemotherapy. The latest results of international phase III studies have positioned the total neoadjuvant therapy as a potential new standard of care in high risk rectal cancers, however, the best schedule is still not well defined.
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The Evolving Neoadjuvant Treatment Paradigm for Patients with Locoregional mismatch Repair Proficient Rectal Cancer. Curr Treat Options Oncol 2022; 23:453-473. [PMID: 35312962 DOI: 10.1007/s11864-022-00961-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/31/2022] [Indexed: 12/29/2022]
Abstract
OPINION STATEMENT The standard of care for locally advanced rectal cancer (LARC) has included preoperative chemoradiation, total mesorectal excision surgery and post operative adjuvant chemotherapy based on histopathology. The current therapeutic landscape in LARC has many different options with different directions of travel - depending on the goal of treatment. Enthusiasm for delivering total neoadjuvant therapy (TNT) for patients with locally advanced rectal cancer (LARC) is increasing in the light of recently published randomised phase III trials - RAPIDO and PRODIGE-23. There is a wide diversity of different potential schedules and a multitude of approaches, which include induction neoadjuvant chemotherapy (NACT) with a range of chemotherapy options (CAPEOX, FOLFOX, FOLFOXIRI) and a varying duration of 6-18 weeks, or consolidation NACT. These schedules either precede or follow short-course preoperative radiation therapy (SCPRT) using 5 × 5Gy or long-course chemoradiation (LCCRT) using 45-60Gy respectively. The different strategies of induction and consolidation neoadjuvant chemotherapy have been compared and have similar long-term outcomes, but consolidation chemotherapy may facilitate organ-sparing. The results are driving novel paradigms with both intensification and de-intensification treatment strategies. The ideal combination, sequence or duration of such a TNT approach remains undefined. As yet, there are no robust clinical, genetic, molecular, immune or imaging features (alone or integrated), which either direct or aid these choices. Currently, the selection of neoadjuvant treatment is driven by the impact on avoidance or feasibility of surgery or reducing the risk of metastases rather than prevention of local recurrence. Most believe that TNT will improve overall survival, despite the present lack of evidence. Both the inherent heterogeneity in LARC and the observed range of different responses underline the need for response biomarkers to individually tailor therapy rather than 'a one size fits all' approach.
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Bauer PS, Chapman WC, Atallah C, Makhdoom BA, Damle A, Smith RK, Wise PE, Glasgow SC, Silviera ML, Hunt SR, Mutch MG. Perioperative Complications After Proctectomy for Rectal Cancer: Does Neoadjuvant Regimen Matter? Ann Surg 2022; 275:e428-e432. [PMID: 32209914 PMCID: PMC8245013 DOI: 10.1097/sla.0000000000003885] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
OBJECTIVE Investigate the association between neoadjuvant treatment strategy and perioperative complications in patients undergoing proctectomy for nonmetastatic rectal cancer. SUMMARY OF BACKGROUND DATA Neoadjuvant SC-TNT is an alternative to neoadjuvant CRT for rectal cancer. Some have argued that short-course radiation and extended radiation-to-surgery intervals increase operative difficulty and complication risk. However, the association between SC-TNT and surgical complications has not been previously investigated. METHODS This single-center retrospective cohort study included patients undergoing total mesorectal excision for nonmetastatic rectal cancer after SC-TNT or CRT between 2010 and 2018. Univariate analysis of severe POM and multiple secondary outcomes, including overall POM, intraoperative complications, and resection margins, was performed. Logistic regression of severe POM was also performed. RESULTS Of 415 included patients, 156 (38%) received SC-TNT and 259 (62%) received CRT. The cohorts were largely similar, though patients with higher tumors (69.9% vs 47.5%, P < 0.0001) or node-positive disease (76.9% vs 62.6%, P = 0.004) were more likely to receive SC-TNT. We found no difference in incidence of severe POM (9.6% SC-TNT vs 12.0% CRT, P = 0.46) or overall POM (39.7% SC-TNT vs 37.5% CRT, P = 0.64) between cohorts. Neoadjuvant regimen was also not associated with a difference in severe POM (odds ratio 0.42, 95% confidence interval 0.04-4.70, P = 0.48) in multivariate analysis. There was no significant association between neoadjuvant regimen and any secondary outcome. CONCLUSION In rectal cancer patients treated with SC-TNT and proctectomy, we found no significant association with POM compared to patients undergoing CRT. SC-TNT does not significantly increase the risk of POM compared to CRT.
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Affiliation(s)
- Philip S Bauer
- Washington University School of Medicine, Department of Surgery, Section of Colon and Rectal Surgery, St. Louis, MO
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Wu H, Fan C, Fang C, Huang L, Li Y, Zhou Z. Preoperative short-course radiotherapy followed by consolidation chemotherapy for treatment with locally advanced rectal cancer: a meta-analysis. Radiat Oncol 2022; 17:14. [PMID: 35073940 PMCID: PMC8785003 DOI: 10.1186/s13014-021-01974-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2021] [Accepted: 12/21/2021] [Indexed: 11/11/2022] Open
Abstract
Abstract
Background
The addition of consolidation chemotherapy to preoperative short-course radiotherapy during the prolonged interval between the completion of radiation and surgery in locally advanced rectal cancer (LARC) could enhance pathologic response and might act on potential micrometastasis. We performed this meta-analysis to evaluate whether short-course radiotherapy followed by consolidation chemotherapy (SCRT/CCT) could be a neoadjuvant treatment option compared with conventional long-course chemoradiotherapy (LCCRT).
Methods
We searched the PubMed, EMBASE, MEDLINE, and Cochrane Library databases. The primary endpoints were pathological outcomes, and the secondary endpoints included survival rate, sphincter preservation rate, R0 resection rate and toxicity. RevMan 5.3 was used to calculate pooled risk ratio (RRs) and 95% confidence intervals (CIs).
Results
A total of seven eligible studies and 1865 participants were included in this meta-analysis. Compared with the LCCRT, SCRT/CCT increased pathologic complete response (pCR) rate [RR = 1.74, 95% CI (1.41, 2.15), P < 0.01] and led to a lower proportion of patients with adjuvant pathologic tumor stage 3–4 (ypT3-4) disease [RR = 0.88, 95% CI (0.80, 0.97), P = 0.01] or lymph node positive (ypN +) disease [RR = 0.83, 95% CI (0.71, 0.98), P = 0.02]. In addition, the disease-free survival (DFS) was better in SCRT/CCT group [RR = 1.10, 95% CI (1.02, 1.18), P = 0.01], while overall survival rate and toxicity and surgical procedures were similar between two groups.
Conclusion
Based on better pathological outcomes and DFS in SCRT/CCT group, we recommended preoperative short-course radiotherapy followed by consolidation chemotherapy as the optional neoadjuvant treatment for LARC.
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Kirilovsky A, Sissy CE, Zeitoun G, Marliot F, Haicheur N, Lagorce-Pagès C, Taieb J, Karoui M, Custers P, Dizdarevic E, Iseas S, Hansen TF, Jensen LH, Beets G, Gérard JP, Castillo-Martin M, Figueiredo N, Habr-Gama A, Perez R, Galon J, Pagès F. The "Immunoscore" in rectal cancer: could we search quality beyond quantity of life? Oncotarget 2022; 13:18-31. [PMID: 35018217 PMCID: PMC8734641 DOI: 10.18632/oncotarget.28100] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2021] [Accepted: 09/26/2021] [Indexed: 12/24/2022] Open
Abstract
Because of the function and anatomical environment of the rectum, therapeutic strategies for local advanced rectal cancer (LARC) must deal with two challenging stressors that are a high-risk of local and distal recurrences and a high-risk of poor quality of life (QoL). Over the last three decades, advances in screening tests, therapies, and combined-modality treatment options and strategies have improved the prognosis of patients with LARC. However, owing to the heterogeneous nature of LARC and genetic status, the patient may not respond to a specific therapy and may be at increased risk of side-effects without the life-prolonging benefit. Indeed, each therapy can cause its own side-effects, which may worsen by a combination of treatments resulting in long-term poor QoL. In LARC, QoL has become even more essential with the increasing incidence of rectal cancer in young individuals. Herein, we analyzed the value of the Immunoscore-Biopsy (performed on tumor biopsy at diagnosis) in predicting outcomes, alone or in association with clinical and imaging data, for each therapy used in LARC.
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Affiliation(s)
- Amos Kirilovsky
- Laboratory of Integrative Cancer Immunology, INSERM, Paris, France.,Equipe Labellisée Ligue Contre le Cancer, Paris, France.,Centre de Recherche des Cordeliers, Sorbonne Université, Université de Paris, Paris, France.,Immunomonitoring Platform, Laboratory of Immunology, Assistance Publique-Hôpitaux de Paris (AP-HP), Georges Pompidou European Hospital, Paris, France.,These authors contributed equally to this work
| | - Carine El Sissy
- Laboratory of Integrative Cancer Immunology, INSERM, Paris, France.,Equipe Labellisée Ligue Contre le Cancer, Paris, France.,Centre de Recherche des Cordeliers, Sorbonne Université, Université de Paris, Paris, France.,Immunomonitoring Platform, Laboratory of Immunology, Assistance Publique-Hôpitaux de Paris (AP-HP), Georges Pompidou European Hospital, Paris, France.,These authors contributed equally to this work
| | - Guy Zeitoun
- Immunomonitoring Platform, Laboratory of Immunology, Assistance Publique-Hôpitaux de Paris (AP-HP), Georges Pompidou European Hospital, Paris, France.,These authors contributed equally to this work
| | - Florence Marliot
- Laboratory of Integrative Cancer Immunology, INSERM, Paris, France.,Equipe Labellisée Ligue Contre le Cancer, Paris, France.,Centre de Recherche des Cordeliers, Sorbonne Université, Université de Paris, Paris, France.,Immunomonitoring Platform, Laboratory of Immunology, Assistance Publique-Hôpitaux de Paris (AP-HP), Georges Pompidou European Hospital, Paris, France
| | - Nacilla Haicheur
- Immunomonitoring Platform, Laboratory of Immunology, Assistance Publique-Hôpitaux de Paris (AP-HP), Georges Pompidou European Hospital, Paris, France
| | - Christine Lagorce-Pagès
- Laboratory of Integrative Cancer Immunology, INSERM, Paris, France.,Equipe Labellisée Ligue Contre le Cancer, Paris, France.,Centre de Recherche des Cordeliers, Sorbonne Université, Université de Paris, Paris, France.,Department of Pathology, AP-HP, Georges Pompidou European Hospital, Paris, France
| | - Julien Taieb
- Department of Gastroenterology and Gastrointestinal Oncology, AP-HP, Georges Pompidou European Hospital, Université de Paris, Paris, France
| | - Mehdi Karoui
- Department of Digestive Surgery, AP-HP, Georges Pompidou European Hospital, Université de Paris, Paris, France
| | - Petra Custers
- Department of Surgery, Netherlands Cancer Institute - Antoni van Leeuwenhoek, Amsterdam, The Netherlands.,GROW School for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands
| | - Edina Dizdarevic
- Department of Oncology, Vejle Hospital, University Hospital of Southern Denmark, Vejle, Denmark.,Danish Colorectal Cancer Center South, Vejle Hospital, Vejle, Denmark
| | - Soledad Iseas
- Oncology Unit, Gastroenterology Hospital, Dr. Carlos Bonorino Udaondo, Ciudad Autónoma de Buenos Aires, Argentina
| | - Torben Frøstrup Hansen
- Department of Oncology, Vejle Hospital, University Hospital of Southern Denmark, Vejle, Denmark.,Danish Colorectal Cancer Center South, Vejle Hospital, Vejle, Denmark
| | - Lars Henrik Jensen
- Department of Oncology, Vejle Hospital, University Hospital of Southern Denmark, Vejle, Denmark.,Danish Colorectal Cancer Center South, Vejle Hospital, Vejle, Denmark
| | - Geerard Beets
- Department of Surgery, Netherlands Cancer Institute - Antoni van Leeuwenhoek, Amsterdam, The Netherlands.,GROW School for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands
| | - Jean Pierre Gérard
- Department of Radiation Oncology, Centre Antoine Lacassagne, Nice Sophia-Antipolis University, Nice, France
| | - Mireia Castillo-Martin
- Service of Pathology, Champalimaud Foundation Biobank (CFB)/Champalimaud Centre for the Unknown/Champalimaud Foundation, Lisbon, Portugal
| | - Nuno Figueiredo
- Colorectal Surgery, Digestive Department, Champalimaud Foundation, Lisbon, Portugal.,Colorectal Surgery, Lusiadas Hospital Lisboa, Lisbon, Portugal
| | - Angelita Habr-Gama
- Department of Colorectal Surgery, Angelita & Joaquim Gama Institute, São Paulo, Brazil
| | - Rodrigo Perez
- Department of Colorectal Surgery, Angelita & Joaquim Gama Institute, São Paulo, Brazil
| | - Jérôme Galon
- Laboratory of Integrative Cancer Immunology, INSERM, Paris, France.,Equipe Labellisée Ligue Contre le Cancer, Paris, France.,Centre de Recherche des Cordeliers, Sorbonne Université, Université de Paris, Paris, France
| | - Franck Pagès
- Laboratory of Integrative Cancer Immunology, INSERM, Paris, France.,Equipe Labellisée Ligue Contre le Cancer, Paris, France.,Centre de Recherche des Cordeliers, Sorbonne Université, Université de Paris, Paris, France.,Immunomonitoring Platform, Laboratory of Immunology, Assistance Publique-Hôpitaux de Paris (AP-HP), Georges Pompidou European Hospital, Paris, France
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Zhang C, Zhao S, Wang X. A Postsurgical Prognostic Nomogram for Locally Advanced Rectosigmoid Cancer to Assist in Patient Selection for Adjuvant Chemotherapy. Front Oncol 2022; 11:772482. [PMID: 35004292 PMCID: PMC8739949 DOI: 10.3389/fonc.2021.772482] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2021] [Accepted: 12/06/2021] [Indexed: 11/25/2022] Open
Abstract
Background The perioperative treatment model for locally advanced rectosigmoid junction cancer (LARSC) has not been finalized; whether this model should refer to the treatment model for rectal cancer remains controversial. Methods We screened 10,188 patients with stage II/III rectosigmoid junction adenocarcinoma who underwent surgery between 2004 and 2016 from the National Cancer Institute Surveillance, Epidemiology, and End Results database. Among them, 4,960 did not receive adjuvant chemotherapy, while 5,228 did receive adjuvant chemotherapy. Propensity score matching was used to balance the two groups for confounding factors, and the Kaplan-Meier method and log-rank test were used for survival analysis. Cox proportional hazards regression analysis was used to identify independent prognostic factors and build a predictive nomogram of survival for LARSC. X-tile software was used to divide the patients into three groups (low, medium, and high) according to their risk scores. 726 patients in our hospital were included for external validation. Results LARSC patients did not show a benefit from neoadjuvant radiotherapy (P>0.05). After further excluding patients who received neoadjuvant radiotherapy, multivariate analysis found that age, grade, tumor size, T stage, and log odds of positive lymph nodes were independent prognostic factors for patients without adjuvant chemotherapy and were included in the nomogram. The C-index of the model was 0.690 (95% confidence interval: 0.668–0.712). We divided the patients into low, moderate, and high risk subgroups based on prediction scores of the nomogram. We found that adjuvant chemotherapy did not improve the prognosis of low risk patients, while moderate and high risk patients benefited from adjuvant therapy. External validation data found that moderate, and high risk patients also benefited from AT. Conclusion Direct surgery plus adjuvant chemotherapy may be the best perioperative treatment for LARSC. Moreover, adjuvant chemotherapy is only recommended for moderate and high risk patients as it did not benefit low risk patients.
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Affiliation(s)
- Chao Zhang
- Department of Gastrointestinal Nutrition and Hernia Surgery, The Second Hospital of Jilin University, Changchun, China
| | - Shutao Zhao
- Department of Gastrointestinal Nutrition and Hernia Surgery, The Second Hospital of Jilin University, Changchun, China
| | - Xudong Wang
- Department of Gastrointestinal Nutrition and Hernia Surgery, The Second Hospital of Jilin University, Changchun, China
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Prabhakaran S, Yang TWW, Johnson N, Bell S, Chin M, Simpson P, Carne P, Farmer C, Skinner S, Warrier SK, Kong JCH. Latest evidence on the management of early‐stage and locally advanced rectal cancer: a narrative review. ANZ J Surg 2022; 92:365-372. [DOI: 10.1111/ans.17429] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2021] [Revised: 11/21/2021] [Accepted: 12/10/2021] [Indexed: 02/03/2023]
Affiliation(s)
- Swetha Prabhakaran
- Department of Colorectal Surgery Alfred Health Melbourne Victoria Australia
| | | | - Nicholas Johnson
- Department of Colorectal Surgery Alfred Health Melbourne Victoria Australia
| | - Stephen Bell
- Department of Colorectal Surgery Alfred Health Melbourne Victoria Australia
- Central Clinical School Monash University Melbourne Victoria Australia
| | - Martin Chin
- Department of Colorectal Surgery Alfred Health Melbourne Victoria Australia
- Central Clinical School Monash University Melbourne Victoria Australia
| | - Paul Simpson
- Department of Colorectal Surgery Alfred Health Melbourne Victoria Australia
- Central Clinical School Monash University Melbourne Victoria Australia
| | - Peter Carne
- Department of Colorectal Surgery Alfred Health Melbourne Victoria Australia
- Central Clinical School Monash University Melbourne Victoria Australia
| | - Chip Farmer
- Department of Colorectal Surgery Alfred Health Melbourne Victoria Australia
- Central Clinical School Monash University Melbourne Victoria Australia
| | - Stewart Skinner
- Department of Colorectal Surgery Alfred Health Melbourne Victoria Australia
- Central Clinical School Monash University Melbourne Victoria Australia
| | - Satish K Warrier
- Department of Colorectal Surgery Alfred Health Melbourne Victoria Australia
- Central Clinical School Monash University Melbourne Victoria Australia
- Division of Cancer Surgery Peter MacCallum Cancer Centre Melbourne Victoria Australia
- The Sir Peter MacCallum Centre Department of Oncology The University of Melbourne Parkville Victoria Australia
| | - Joseph CH Kong
- Department of Colorectal Surgery Alfred Health Melbourne Victoria Australia
- Central Clinical School Monash University Melbourne Victoria Australia
- Division of Cancer Surgery Peter MacCallum Cancer Centre Melbourne Victoria Australia
- The Sir Peter MacCallum Centre Department of Oncology The University of Melbourne Parkville Victoria Australia
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Locally Advanced Rectal Cancer: What We Learned in the Last Two Decades and the Future Perspectives. J Gastrointest Cancer 2022; 54:188-203. [PMID: 34981341 DOI: 10.1007/s12029-021-00794-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/20/2021] [Indexed: 12/13/2022]
Abstract
The advancement in surgical techniques, optimization of systemic chemoradiotherapy, and development of refined diagnostic and imaging modalities have brought a phenomenal shift in the treatment of the locally advanced rectal cancer. Although each therapeutic option has shown substantial progress in their field, it is finding their ideal amalgamation which has baffled the clinician and researchers alike. In the effort to identifying the perfect salutary treatment plan, we have even shifted our attention from the trimodal approach to non-operative "watchful waiting" to more recent individualized care. In this article, we acknowledge the scientific progress in the management of locally advanced rectal cancer and compare the opportunities as well as the obstacles while implementing them clinically. We also explore the current challenges and controversies surrounding the multidisciplinary approach and highlight the new trends and recent advances with an ultimate goal to improve the patients' quality of life.
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Johnson D, Li L, Lee KC, Lam KO, Wong KH, Ho WM, Ma B. Total Neoadjuvant Therapy for High Risk Rectal Cancer in Western and Asian Populations – Current Evidence and Clinical Applications. Clin Colorectal Cancer 2021; 21:45-54. [DOI: 10.1016/j.clcc.2021.12.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2021] [Revised: 12/14/2021] [Accepted: 12/21/2021] [Indexed: 11/26/2022]
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Feng W, Yu B, Zhang Z, Li J, Wang Y. Current status of total neoadjuvant therapy for locally advanced rectal cancer. Asia Pac J Clin Oncol 2021; 18:546-559. [PMID: 34818447 DOI: 10.1111/ajco.13640] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Accepted: 07/05/2021] [Indexed: 12/21/2022]
Abstract
Neoadjuvant chemoradiotherapy (nCRT) plus total mesorectal excision (TME) has been the standard regimen for treatment of patients with locally advanced rectal cancer (LARC), because it significantly reduces the rate of local recurrence and enables sphincter preservation. However, distant metastasis remains the major reason for treatment failure, and the value of postoperative chemotherapy is still controversial. Recent studies have examined the use of total neoadjuvant therapy (TNT), defined as induction and/or consolidation chemotherapy (CONCT) with radiotherapy (RT) or nCRT prior to surgery. The results indicated that TNT may increase the rates of chemotherapy compliance and pathological complete response (pCR), and probably improve the success rate of sphincter preservation surgery. TNT may also improve disease-free survival and overall survival, and even reduce the rate of relapse. Here, we critically appraise the existing literature on three different TNT schemes used for LARC patients.
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Affiliation(s)
- Wei Feng
- Department of Radiation Oncology, Cancer Hospital of the University of Chinese Academy of Sciences, Hangzhou, China.,Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou, China
| | - Bin Yu
- The Second Department of Surgery, Hebei Medical University Fourth Affiliated Hospital and Hebei Provincial Tumor Hospital, Shijiazhuang, China
| | - Zhenya Zhang
- The Second Department of Surgery, Hebei Medical University Fourth Affiliated Hospital and Hebei Provincial Tumor Hospital, Shijiazhuang, China
| | - Juan Li
- Department of Radiation Oncology, Hebei Medical University Fourth Affiliated Hospital and Hebei Provincial Tumor Hospital & Hebei Clinical Research Center for Radiation Oncology, Shijiazhuang, China
| | - Yuxiang Wang
- Department of Radiation Oncology, Hebei Medical University Fourth Affiliated Hospital and Hebei Provincial Tumor Hospital & Hebei Clinical Research Center for Radiation Oncology, Shijiazhuang, China
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44
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Shulman RM, Meyer JE. Current Trends in the Treatment of Locally Advanced Rectal Cancer: Where We Are and How We Got Here. CURRENT COLORECTAL CANCER REPORTS 2021. [DOI: 10.1007/s11888-021-00471-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
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45
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Liu S, Jiang T, Xiao L, Yang S, Liu Q, Gao Y, Chen G, Xiao W. Total Neoadjuvant Therapy (TNT) versus Standard Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer: A Systematic Review and Meta-Analysis. Oncologist 2021; 26:e1555-e1566. [PMID: 33987952 PMCID: PMC8417863 DOI: 10.1002/onco.13824] [Citation(s) in RCA: 120] [Impact Index Per Article: 30.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2020] [Accepted: 04/08/2021] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND Total neoadjuvant therapy (TNT) is a novel approach for locally advanced rectal cancer (LARC), which attempts to deliver both systemic chemotherapy and neoadjuvant chemoradiotherapy prior to surgery. However, its efficacy and safety remain controversial in randomized controlled trials (RCTs). We conducted this meta-analysis to assess such concerns. MATERIALS AND METHODS Head-to-head phase II/III RCTs were searched in Embase, PubMed, Web of Science, and the Cochrane Library, as well as other sources. The primary endpoint was pathologic complete response (pCR). Secondary endpoints were disease-free survival (DFS), overall survival (OS), local recurrence-free survival, distant metastasis-free survival, and the R0 resection rate. RESULTS Eight phase II/III RCTs involving 2,196 patients with LARC were assessed. The primary analysis demonstrated a statistically significant improvement in the pCR rate for TNT treatment (odds ratio, 1.77; 95% confidence interval [CI], 1.28-2.45; p = .0005). TNT treatment also showed improvements in DFS and OS outcomes compared with standard chemoradiotherapy (hazard ratio [HR], 0.83; 95% CI, 0.72-0.96; p = .03 and HR, 0.88; 95% CI, 0.74-1.05; p = .15). In addition, TNT treatment showed significant efficacy in reducing the risk of distant metastasis (HR, 0.81; 95% CI, 0.68-0.95; p = .012). CONCLUSION The overall pCR rate may be improved with TNT compared with standard treatment. The TNT strategy may also improve DFS and OS and reduce the risk of distant metastasis. IMPLICATIONS FOR PRACTICE Locally advanced rectal cancer (LARC) is a relatively common disease, with a poor prognosis because of its high metastatic potential. The role of total neoadjuvant therapy (TNT) has always been controversial. This meta-analysis found that TNT in LARC is associated with a significant improvement in overall pathologic complete response rate, disease-free survival, overall survival, and distant metastasis-free survival compared with standard treatment. TNT is a promising strategy for LARC, especially for patients who have little desire for surgery.
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Affiliation(s)
- Shuang Liu
- Departments of Radiation Oncology, Sun Yat‐sen University Cancer CenterGuangzhouPeople's Republic of China
- Sun Yat‐sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer MedicineGuangzhouPeople's Republic of China
| | - Ting Jiang
- Departments of Radiation Oncology, Sun Yat‐sen University Cancer CenterGuangzhouPeople's Republic of China
- Sun Yat‐sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer MedicineGuangzhouPeople's Republic of China
| | - Lin Xiao
- Department of Oncology, Section II, Jiangmen Central Hospital, Affiliated Jiangmen Hospital of Sun Yat‐sen UniversityJiangmenPeople's Republic of China
| | - Shanfei Yang
- Departments of Radiation Oncology, Sun Yat‐sen University Cancer CenterGuangzhouPeople's Republic of China
- Sun Yat‐sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer MedicineGuangzhouPeople's Republic of China
| | - Qing Liu
- Sun Yat‐sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer MedicineGuangzhouPeople's Republic of China
- Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat‐sen UniversityGuangzhouPeople's Republic of China
| | - Yuanhong Gao
- Departments of Radiation Oncology, Sun Yat‐sen University Cancer CenterGuangzhouPeople's Republic of China
- Sun Yat‐sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer MedicineGuangzhouPeople's Republic of China
| | - Gong Chen
- Department of Colorectal Surgery, Sun Yat‐sen University Cancer CenterGuangzhouPeople's Republic of China
- Sun Yat‐sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer MedicineGuangzhouPeople's Republic of China
| | - Weiwei Xiao
- Departments of Radiation Oncology, Sun Yat‐sen University Cancer CenterGuangzhouPeople's Republic of China
- Sun Yat‐sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer MedicineGuangzhouPeople's Republic of China
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[Neoadjuvant treatment for rectal cancer]. Bull Cancer 2021; 108:855-867. [PMID: 34140155 DOI: 10.1016/j.bulcan.2021.03.018] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2021] [Revised: 03/22/2021] [Accepted: 03/30/2021] [Indexed: 02/01/2023]
Abstract
The management of patients with locally advanced rectal cancer has improved significantly in the past few years with preoperative radiotherapy (RT) and total mesorectal excision. The rate of local recurrence is now around 5 % while the risk of metastatic recurrence has not been reduced which is about 30 %. The benefit of adjuvant chemotherapy remains questionable apart from patients with ypN+tumor after preoperative chemoradiotherapy (CRT) for whom FOLFOX is an option. In recent years, several therapeutic trials have evaluated the benefit of extending the time between the end of RT and surgery and/or the benefit of neoadjuvant chemotherapy, administered as induction (before RT) or in consolidation (after RT and before surgery). The first results of two positive phase 3 trials, PRODIGE 23 and RAPIDO, have been reported in 2020. The two regimens evaluated in these trials are markedly different but have shown that neoadjuvant chemotherapy significantly reduces the risk of distant metastasis. Current developments largely related to a de-escalation of therapy: organ conservation according to a "Watch and Wait" strategy or local resection of the scar, administration of neoadjuvant chemotherapy without RT. These therapeutic strategies have not yet been validated but should be in the news tomorrow. The purpose of this review is to present recent data reported in patients with locally advanced rectal cancer.
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Voogt ELK, Schaap DP, van den Berg K, Nieuwenhuijzen GAP, Bloemen JG, Creemers GJ, Willems J, Cnossen JS, Peulen HMU, Nederend J, van Lijnschoten G, Burger JWA, Rutten HJT. Improved response rate in patients with prognostically poor locally advanced rectal cancer after treatment with induction chemotherapy and chemoradiotherapy when compared with chemoradiotherapy alone: A matched case-control study. Eur J Surg Oncol 2021; 47:2429-2435. [PMID: 34030921 DOI: 10.1016/j.ejso.2021.05.017] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Revised: 04/16/2021] [Accepted: 05/07/2021] [Indexed: 02/07/2023] Open
Abstract
INTRODUCTION The addition of induction chemotherapy (ICT) to neoadjuvant chemoradiotherapy (CRT) has the potential to improve outcomes in patients with locally advanced rectal cancer (LARC). However, patient selection is essential to prevent overtreatment. This study compared the complete response (CR) rate after treatment with and without ICT of LARC patients with prognostically poor characteristics. METHODS All LARC patients who were treated with neoadjuvant CRT, whether or not preceded by ICT, and who underwent surgery or were considered for a wait-and-see strategy between January 2016 and March 2020 in the Catharina Hospital Eindhoven, were retrospectively selected. LARC was defined as any T4 tumour, or a T2/T3 tumour with extramural venous invasion and/or tumour deposits and/or N2 lymph node status, and/or mesorectal fascia involvement (T3 tumours only). Case-control matching was performed based on the aforementioned characteristics. RESULTS Of 242 patients, 178 (74%) received CRT (CRT-group) and 64 patients (26%) received ICT followed by CRT (ICT-group). In the ICT-group, 3 patients (5%) did not receive the minimum of three cycles. In addition, in this selected cohort, compliance with radiotherapy was 100% in the ICT-group and 97% in the CRT-group. The CR rate was 30% in the ICT-group and 15% in the CRT-group (p = 0.011). After case-control matching, the CR rate was 28% and 9%, respectively (p = 0.013). CONCLUSION Treatment including ICT seemed well tolerated and resulted in a high CR rate. Hence, this treatment strategy may facilitate organ preservation and improve survival in LARC patients with prognostically poor characteristics.
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Affiliation(s)
- E L K Voogt
- Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands.
| | - D P Schaap
- Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands
| | - K van den Berg
- Department of Medical Oncology, Catharina Hospital, Eindhoven, the Netherlands
| | | | - J G Bloemen
- Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands
| | - G J Creemers
- Department of Medical Oncology, Catharina Hospital, Eindhoven, the Netherlands
| | - J Willems
- Department of Medical Oncology, Catharina Hospital, Eindhoven, the Netherlands
| | - J S Cnossen
- Department of Radiation Oncology, Catharina Hospital, Eindhoven, the Netherlands
| | - H M U Peulen
- Department of Radiation Oncology, Catharina Hospital, Eindhoven, the Netherlands
| | - J Nederend
- Department of Radiology, Catharina Hospital, Eindhoven, the Netherlands
| | - G van Lijnschoten
- Department of Pathology, PAMM Laboratory for Pathology and Medical Microbiology, Eindhoven, the Netherlands
| | - J W A Burger
- Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands
| | - H J T Rutten
- Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands; GROW School for Oncology and Developmental Biology, Maastricht University, Maastricht, the Netherlands
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PelvEx Collaborative, Voogt ELK, Nordkamp S, Aalbers AGJ, Buffart T, Creemers GJ, Marijnen CAM, Verhoef C, Havenga K, Holman FA, Kusters M, Marinelli AWKS, Melenhorst J, Abdul Aziz N, Abecasis N, Abraham-Nordling M, Akiyoshi T, Alberda W, Albert M, Andric M, Angenete E, Antoniou A, Auer R, Austin KK, Aziz O, Baker RP, Bali M, Baseckas G, Bebington B, Bedford M, Bednarski BK, Beets GL, Beets-Tan RGH, Berbée M, Berg J, Berg PL, Beynon J, Biondo S, Bloemen JG, Boyle K, Bordeianou L, Bremers AB, Brunner M, Buchwald P, Bui A, Burgess A, Burling D, Burns E, Campain N, Carvalhal S, Castro L, Caycedo-Marulanda A, Ceha HM, Chan KKL, Chang GJ, Chang M, Chew MH, Chok AK, Chong P, Christensen HK, Clouston H, Codd M, Collins D, Colquhoun AJ, Corr A, Coscia M, Cosimelli M, Coyne PE, Crobach ASLP, Crolla RMPH, Croner RS, Damjanovic L, Daniels IR, Davies M, Davies RJ, Delaney CP, de Roos MAJ, de Wilt JHW, den Hartogh MD, Denost Q, Deseyne P, Deutsch C, de Vos tot Nederveen Cappel R, de Vries M, Dieters M, Dietz D, Domingo S, Doukas M, Dozois EJ, Duff M, Eglinton T, Enrique-Navascues JM, Espin-Basany E, Evans MD, Eyjólfsdóttir B, Fahy M, Fearnhead NS, Feshtali S, Flatmark K, Fleming F, et alPelvEx Collaborative, Voogt ELK, Nordkamp S, Aalbers AGJ, Buffart T, Creemers GJ, Marijnen CAM, Verhoef C, Havenga K, Holman FA, Kusters M, Marinelli AWKS, Melenhorst J, Abdul Aziz N, Abecasis N, Abraham-Nordling M, Akiyoshi T, Alberda W, Albert M, Andric M, Angenete E, Antoniou A, Auer R, Austin KK, Aziz O, Baker RP, Bali M, Baseckas G, Bebington B, Bedford M, Bednarski BK, Beets GL, Beets-Tan RGH, Berbée M, Berg J, Berg PL, Beynon J, Biondo S, Bloemen JG, Boyle K, Bordeianou L, Bremers AB, Brunner M, Buchwald P, Bui A, Burgess A, Burling D, Burns E, Campain N, Carvalhal S, Castro L, Caycedo-Marulanda A, Ceha HM, Chan KKL, Chang GJ, Chang M, Chew MH, Chok AK, Chong P, Christensen HK, Clouston H, Codd M, Collins D, Colquhoun AJ, Corr A, Coscia M, Cosimelli M, Coyne PE, Crobach ASLP, Crolla RMPH, Croner RS, Damjanovic L, Daniels IR, Davies M, Davies RJ, Delaney CP, de Roos MAJ, de Wilt JHW, den Hartogh MD, Denost Q, Deseyne P, Deutsch C, de Vos tot Nederveen Cappel R, de Vries M, Dieters M, Dietz D, Domingo S, Doukas M, Dozois EJ, Duff M, Eglinton T, Enrique-Navascues JM, Espin-Basany E, Evans MD, Eyjólfsdóttir B, Fahy M, Fearnhead NS, Feshtali S, Flatmark K, Fleming F, Folkesson J, Frizelle FA, Frödin JE, Gallego MA, Garcia-Granero E, Garcia-Sabrido JL, Geboes K, Gentilini L, George ML, George V, Ghouti L, Giner F, Ginther N, Glyn T, Glynn R, Golda T, Grabsch HI, Griffiths B, Harris DA, Hagemans JAW, Hanchanale V, Harji DP, Helewa RM, Helgason H, Hellawell G, Heriot AG, Heyman S, Hochman D, Hoff C, Hohenberger W, Holm T, Hompes R, Horsthuis K, Hospers G, Houwers J, Iversen H, Jenkins JT, Kaffenberger S, Kandaswamy GV, Kapur S, Kanemitsu Y, Kats-Ugurlu G, Kelley SR, Keller DS, Kelly ME, Keymeulen K, Khan MS, Kim H, Kim HJ, Koh CE, Kok NFM, Kokelaar R, Kontovounisios C, Kristensen HØ, Kroon HM, Kumar S, Lago V, Lakkis Z, Lamberg T, Larsen SG, Larson DW, Law WL, Laurberg S, Lee PJ, Leseman-Hoogenboom MM, Limbert M, Lydrup ML, Lyons A, Lynch AC, Mantyh C, Mathis KL, Margues CFS, Martling A, Meijer OWM, Meijerink WJHJ, Merchea A, Merkel S, Mehta AM, McArthur DR, McDermott FD, McGrath JS, Malde S, Mirnezami A, Monson JRT, Morton JR, Nederend J, Negoi I, Neto JWM, Ng JL, Nguyen B, Nielsen MB, Nieuwenhuijzen GAP, Nilsson PJ, Nilsson ML, Oei S, Oliver A, O’Dwyer ST, Oppedijk V, Palmer G, Pappou E, Park J, Patsouras D, Pellino G, Peterson AC, Peulen HMU, Poggioli G, Proud D, Quinn M, Quyn A, Rajendran N, Radwan RW, Rasheed S, Rasmussen PC, Rausa E, Regenbogen SE, Renehan A, Richir MC, Rocha R, Rochester M, Rohila J, Rothbarth J, Rottoli M, Roxburgh C, Rozema T, Safar B, Sagar PM, Sahai A, Saklani A, Sammour T, Sayyed R, Schizas AMP, Schwarzkopf E, Scripcariu V, Selvasekar C, Shaikh I, Shida D, Simpson A, Skeie-Jensen T, Slangen JJG, Smart NJ, Smart P, Smith JJ, Snaebjornsson P, Solbakken AM, Solomon MJ, Sørensen MM, Sorrentino L, Speetjens FM, Spillenaar Bilgen EJ, Steele SR, Steffens D, Stitzenberg K, Stocchi L, Stylianides NA, Swartling T, Sumrien H, Sutton PA, Swartking T, Tan EJ, Taylor C, Tekkis PP, Teras J, Terpstra V, Thurairaja R, Toh EL, Tsarkov P, Tsukada Y, Tsukamoto S, Tuech JJ, Turner WH, Tuynman JB, van Duyn EB, van Grevenstein WMU, van Grieken NCT, van Iersel L, van Lijnschoten G, van Meerten E, van Ramshorst GH, Westreenen HLV, van Zoggel D, Vasquez-Jimenez W, Velema LA, Verdaasdonk E, Verheul HMW, Versteeg KS, Vizzielli G, Uehara K, Wakeman C, Warrier S, Wasmuth HH, Weber K, Weiser MR, Wheeler JMD, Wijffels NAT, Wild J, Willems JMWE, Wilson M, Winter DC, Wolthuis A, Wumkes ML, Yano H, Yip B, Yip J, Yoo RN, Zappa MA, Zimmerman DDE, Rutten HJT, Burger JWA. Induction chemotherapy followed by chemoradiotherapy versus chemoradiotherapy alone as neoadjuvant treatment for locally recurrent rectal cancer: study protocol of a multicentre, open-label, parallel-arms, randomized controlled study (PelvEx II). BJS Open 2021; 5:zrab029. [PMID: 34089596 PMCID: PMC8179511 DOI: 10.1093/bjsopen/zrab029] [Show More Authors] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2020] [Revised: 01/26/2021] [Accepted: 03/03/2021] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND A resection with clear margins (R0 resection) is the most important prognostic factor in patients with locally recurrent rectal cancer (LRRC). However, this is achieved in only 60 per cent of patients. The aim of this study is to investigate whether the addition of induction chemotherapy to neoadjuvant chemo(re)irradiation improves the R0 resection rate in LRRC. METHODS This multicentre, international, open-label, phase III, parallel-arms study will enrol 364 patients with resectable LRRC after previous partial or total mesorectal resection without synchronous distant metastases or recent chemo- and/or radiotherapy treatment. Patients will be randomized to receive either induction chemotherapy (three 3-week cycles of CAPOX (capecitabine, oxaliplatin), four 2-week cycles of FOLFOX (5-fluorouracil, leucovorin, oxaliplatin) or FOLFORI (5-fluorouracil, leucovorin, irinotecan)) followed by neoadjuvant chemoradiotherapy and surgery (experimental arm) or neoadjuvant chemoradiotherapy and surgery alone (control arm). Tumours will be restaged using MRI and, in the experimental arm, a further cycle of CAPOX or two cycles of FOLFOX/FOLFIRI will be administered before chemoradiotherapy in case of stable or responsive disease. The radiotherapy dose will be 25 × 2.0 Gy or 28 × 1.8 Gy in radiotherapy-naive patients, and 15 × 2.0 Gy in previously irradiated patients. The concomitant chemotherapy agent will be capecitabine administered twice daily at a dose of 825 mg/m2 on radiotherapy days. The primary endpoint of the study is the R0 resection rate. Secondary endpoints are long-term oncological outcomes, radiological and pathological response, toxicity, postoperative complications, costs, and quality of life. DISCUSSION This trial protocol describes the PelvEx II study. PelvEx II, designed as a multicentre, open-label, phase III, parallel-arms study, is the first randomized study to compare induction chemotherapy followed by neoadjuvant chemo(re)irradiation and surgery with neoadjuvant chemo(re)irradiation and surgery alone in patients with locally recurrent rectal cancer, with the aim of improving the number of R0 resections.
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Hanna CR, O'Cathail SM, Graham J, Adams R, Roxburgh CS. Immune Checkpoint Inhibition as a Strategy in the Neoadjuvant Treatment of Locally Advanced Rectal Cancer. JOURNAL OF IMMUNOTHERAPY AND PRECISION ONCOLOGY 2021; 4:86-104. [PMID: 35663532 PMCID: PMC9153256 DOI: 10.36401/jipo-20-31] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/10/2020] [Revised: 12/22/2020] [Accepted: 12/23/2020] [Indexed: 06/15/2023]
Abstract
The treatment of locally advanced rectal cancer (LARC) has seen major advances over the past 3 decades, with multimodality treatment now standard of care. Combining surgical resection with radiotherapy and/or chemotherapy can reduce local recurrence from around 20% to approximately 5%. Despite improvements in local control, distant recurrence and subsequent survival rates have not changed. Immune checkpoint inhibitors have improved patient outcomes in several solid tumor types in the neoadjuvant, adjuvant, and advanced disease setting; however, in colorectal cancer, most clinical trials have been performed in the metastatic setting and the benefits confined to microsatellite instability-high tumors. In this article, we review the current preclinical and clinical evidence for using immune checkpoint inhibition in the treatment of LARC and discuss the rationale for specifically exploring the use of this therapy in the neoadjuvant setting. We summarize and discuss relevant clinical trials that are currently in setup and recruiting to test this treatment strategy and reflect on unanswered questions that still need to be addressed within future research efforts.
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Affiliation(s)
- Catherine R. Hanna
- Cancer Research United Kingdom Clinical Trials Unit, Glasgow, Scotland
- Institute of Cancer Sciences, University of Glasgow, Glasgow, Scotland
- Beatson West of Scotland Cancer Centre, Glasgow, Scotland
| | - Séan M. O'Cathail
- Institute of Cancer Sciences, University of Glasgow, Glasgow, Scotland
- Beatson West of Scotland Cancer Centre, Glasgow, Scotland
| | - Janet Graham
- Institute of Cancer Sciences, University of Glasgow, Glasgow, Scotland
- Beatson West of Scotland Cancer Centre, Glasgow, Scotland
| | - Richard Adams
- Centre for Trials Research, Cardiff University and Velindre Cancer Centre, Cardiff, Wales
| | - Campbell S.D. Roxburgh
- Institute of Cancer Sciences, University of Glasgow, Glasgow, Scotland
- Glasgow Royal Infirmary, Glasgow, Scotland
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Kong JC, Soucisse M, Michael M, Tie J, Ngan SY, Leong T, McCormick J, Warrier SK, Heriot AG. Total Neoadjuvant Therapy in Locally Advanced Rectal Cancer: A Systematic Review and Metaanalysis of Oncological and Operative Outcomes. Ann Surg Oncol 2021; 28:7476-7486. [PMID: 33891203 DOI: 10.1245/s10434-021-09837-8] [Citation(s) in RCA: 50] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2021] [Accepted: 02/24/2021] [Indexed: 11/18/2022]
Abstract
BACKGROUND Total neoadjuvant therapy in rectal cancer refers to the administration of chemoradiotherapy plus chemotherapy before surgery. Recent studies have shown improved pathological complete response and disease-free survival with this approach. However, survival benefits remain unproven. Our objective is to present a metaanalysis of oncological outcomes of total neoadjuvant therapy in locally advanced rectal cancer. PATIENTS AND METHODS A comprehensive search was performed on PubMed, Medline, and Google Scholars. Studies comparing total neoadjuvant therapy with standard neoadjuvant chemoradiotherapy were included. Data extracted from the individual studies were pooled and a metaanalysis performed. The outcomes of interest are the rate of complete pathological response, nodal response, resection margin, anal preservation, anastomotic leak, local recurrence, distant recurrence, disease-free survival, and overall survival. RESULTS There were 15 comparative studies with 2437 patients in the neoadjuvant chemoradiotherapy group and 2284 in the total neoadjuvant therapy group. The pooled complete pathological response was 22.3% in the total neoadjuvant therapy group, compared with 14.2% in the standard neoadjuvant chemoradiotherapy group (p < 0.001). Even though there was no difference in local recurrence rate, there was a significantly lower rate of distant recurrence (OR 0.81, p = 0.02), and better 3-year disease-free survival (70.6% vs. 65.3%, respectively, p < 0.001) and overall survival (84.9% vs. 82.3%, respectively, p = 0.006), favoring the total neoadjuvant therapy group. Due to significant heterogeneity in the study protocols, there remains uncertainty on the ideal chemotherapy/radiotherapy sequence. CONCLUSIONS This study provides supporting evidence on the favorable immediate and intermediate oncological outcomes with the use of total neoadjuvant therapy for locally advanced rectal cancer.
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Affiliation(s)
- Joseph C Kong
- Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia. .,Division of Cancer Research, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia. .,Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC, Australia.
| | - Mikael Soucisse
- Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
| | - Michael Michael
- Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC, Australia.,Division of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
| | - Jeanne Tie
- Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC, Australia.,Division of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
| | - Samuel Y Ngan
- Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC, Australia.,Division of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
| | - Trevor Leong
- Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC, Australia.,Division of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
| | - Jacob McCormick
- Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
| | - Satish K Warrier
- Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.,Division of Cancer Research, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.,Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC, Australia
| | - Alexander G Heriot
- Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.,Division of Cancer Research, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.,Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC, Australia
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