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Yang Y, Lam W, Lyu Z, Ouyang K, Chen R, Wang J, Wu D, Yang Z, Li Y. Predicting the surgical benefit of primary tumor resection in patients with stage IV colorectal cancer. Asian J Surg 2024; 47:4735-4743. [PMID: 38609833 DOI: 10.1016/j.asjsur.2024.03.179] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2023] [Revised: 03/12/2024] [Accepted: 03/28/2024] [Indexed: 04/14/2024] Open
Abstract
BACKGROUND There exists continuous controversy regarding the benefit of primary tumor resection (PTR) for stage IV colorectal cancer (CRC) patients. Little is known about how to predict the patients' benefit from PTR. This study aimed to develop a tool for surgical benefit prediction. METHODS Stage IV CRC patients diagnosed between 2010 and 2015 from the Surveillance, Epidemiology and End Results database were included. Patients receiving PTR who survived longer than the median cancer-specific survival (CSS) time of those who did not undergo PTR were considered to benefit from surgery. Logistic regression analysis identified prognostic factors influencing surgical benefit, based on which a nomogram was constructed. The data of patients who underwent PTR from our institution was used for external validation. A user-friendly webserver was then built for convenient clinical use. RESULTS The median CSS of the PTR group was 23 months, significantly longer than that of the non-PTR group (7 months, P < 0.001). In the PTR group, 23.3% of patients did not benefit from surgery. Logistic regression analysis identified age, marital status, tumor location, CEA level, chemotherapy, metastasectomy, tumor size, tumor deposits, number of examined lymph nodes, N stage, histological grade and number of distant metastases as independently associated with surgical benefit. The established prognostic nomogram demonstrated satisfactory performance in both the internal and external validation. CONCLUSION PTR was associated with prolonged CSS in stage IV CRC. The proposed nomogram could be used as an evidenced-based platform for risk-to-benefit assessment to select appropriate patients for undergoing PTR.
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Affiliation(s)
- Yuesheng Yang
- Shantou University Medical College, Shantou, 515041, Guangdong Province, PR China; Department of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, Guangdong Province, PR China
| | - Waiting Lam
- Department of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, Guangdong Province, PR China; Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Science, Guangzhou, 510080, Guangdong Province, PR China
| | - Zejian Lyu
- Department of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, Guangdong Province, PR China
| | - Kaibo Ouyang
- Shantou University Medical College, Shantou, 515041, Guangdong Province, PR China; Department of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, Guangdong Province, PR China
| | - Ruijain Chen
- Shantou University Medical College, Shantou, 515041, Guangdong Province, PR China; Department of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, Guangdong Province, PR China
| | - Junjiang Wang
- Department of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, Guangdong Province, PR China
| | - Deqing Wu
- Department of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, Guangdong Province, PR China
| | - Zifeng Yang
- Department of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, Guangdong Province, PR China.
| | - Yong Li
- Department of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, Guangdong Province, PR China; The Second School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, Guangdong Province, PR China.
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van der Kruijssen DEW, Elias SG, van de Ven PM, van Rooijen KL, Lam-Boer J', Mol L, Punt CJA, Sommeijer DW, Tanis PJ, Nielsen JD, Yilmaz MK, van Riel JMGH, Wasowiz-Kemps DK, Loosveld OJL, van der Schelling GP, de Groot JWB, van Westreenen HL, Jakobsen HL, Fromm AL, Hamberg P, Verseveld M, Jaensch C, Liposits GI, van Duijvendijk P, Oulad Hadj J, van der Hoeven JAB, Trajkovic M, de Wilt JHW, Koopman M. Upfront resection versus no resection of the primary tumor in patients with synchronous metastatic colorectal cancer: the randomized phase III CAIRO4 study conducted by the Dutch Colorectal Cancer Group and the Danish Colorectal Cancer Group. Ann Oncol 2024; 35:769-779. [PMID: 38852675 DOI: 10.1016/j.annonc.2024.06.001] [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: 02/05/2024] [Revised: 05/11/2024] [Accepted: 06/02/2024] [Indexed: 06/11/2024] Open
Abstract
BACKGROUND Upfront primary tumor resection (PTR) has been associated with longer overall survival (OS) in patients with synchronous unresectable metastatic colorectal cancer (mCRC) in retrospective analyses. The aim of the CAIRO4 study was to investigate whether the addition of upfront PTR to systemic therapy resulted in a survival benefit in patients with synchronous mCRC without severe symptoms of their primary tumor. PATIENTS AND METHODS This randomized phase III trial was conducted in 45 hospitals in The Netherlands and Denmark. Eligibility criteria included previously untreated mCRC, unresectable metastases, and no severe symptoms of the primary tumor. Patients were randomized (1 : 1) to upfront PTR followed by systemic therapy or systemic therapy without upfront PTR. Systemic therapy consisted of first-line fluoropyrimidine-based chemotherapy with bevacizumab in both arms. Primary endpoint was OS in the intention-to-treat population. The study was registered at ClinicalTrials.gov, NCT01606098. RESULTS Between August 2012 and February 2021, 206 patients were randomized. In the intention-to-treat analysis, 204 patients were included (n = 103 without upfront PTR, n = 101 with upfront PTR) of whom 116 were men (57%) with median age of 65 years (interquartile range 59-71 years). Median follow-up was 69.4 months. Median OS in the arm without upfront PTR was 18.3 months (95% confidence interval 16.0-22.2 months) compared with 20.1 months (95% confidence interval 17.0-25.1 months) in the upfront PTR arm (P = 0.32). The number of grade 3-4 events was 71 (72%) in the arm without upfront PTR and 61 (65%) in the upfront PTR arm (P = 0.33). Three deaths (3%) possibly related to treatment were reported in the arm without upfront PTR and four (4%) in the upfront PTR arm. CONCLUSIONS Addition of upfront PTR to palliative systemic therapy in patients with synchronous mCRC without severe symptoms of the primary tumor does not result in a survival benefit. This practice should no longer be considered standard of care.
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Affiliation(s)
- D E W van der Kruijssen
- Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht
| | - S G Elias
- Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht
| | - P M van de Ven
- Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht
| | - K L van Rooijen
- Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht
| | - J 't Lam-Boer
- Department of Surgery, Radboud University Medical Center, Nijmegen; Department of Surgery, Netherlands Cancer Institute, Amsterdam
| | - L Mol
- Clinical Research Department, Netherlands Comprehensive Cancer Organisation (IKNL), Utrecht
| | - C J A Punt
- Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht
| | - D W Sommeijer
- Department of Medical Oncology, Amsterdam University Medical Center, Amsterdam; Department of Medical Oncology, Flevo Hospital, Almere
| | - P J Tanis
- Department of Surgery, Amsterdam University Medical Center, Amsterdam; Department of Surgery, Erasmus Medical Center, Rotterdam, The Netherlands
| | - J D Nielsen
- Department of Surgery, Aalborg University Hospital, Aalborg, Denmark
| | - M K Yilmaz
- Department of Medical Oncology, Aalborg University Hospital, Aalborg, Denmark
| | - J M G H van Riel
- Department of Medical Oncology, Elisabeth-TweeSteden Hospital, Tilburg
| | | | | | | | - J W B de Groot
- Department of Medical Oncology, Isala Hospital, Zwolle, The Netherlands
| | | | - H L Jakobsen
- Department of Surgery, Herlev and Gentofte Hospital, Herlev, Denmark
| | - A L Fromm
- Department of Medical Oncology, Herlev and Gentofte Hospital, Herlev, Denmark
| | - P Hamberg
- Department of Medical Oncology, Franciscus Gasthuis & Vlietland, Rotterdam, The Netherlands
| | - M Verseveld
- Department of Surgery, Franciscus Gasthuis & Vlietland, Rotterdam, The Netherlands
| | - C Jaensch
- Department of Surgery, Regional Hospital Gødstrup, Herning, Denmark
| | - G I Liposits
- Department of Medical Oncology, Regional Hospital Gødstrup, Herning, Denmark
| | | | - J Oulad Hadj
- Department of Medical Oncology, Gelre Hospital, Apeldoorn
| | | | - M Trajkovic
- Department of Medical Oncology, Albert Schweitzer Hospital, Dordrecht, The Netherlands
| | - J H W de Wilt
- Department of Surgery, Radboud University Medical Center, Nijmegen
| | - M Koopman
- Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht.
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Pécsi B, Mangel LC. The Real-Life Impact of Primary Tumor Resection of Synchronous Metastatic Colorectal Cancer-From a Clinical Oncologic Point of View. Cancers (Basel) 2024; 16:1460. [PMID: 38672540 PMCID: PMC11047864 DOI: 10.3390/cancers16081460] [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: 02/24/2024] [Revised: 04/03/2024] [Accepted: 04/09/2024] [Indexed: 04/28/2024] Open
Abstract
AIM The complex medical care of synchronous metastatic colorectal (smCRC) patients requires prudent multidisciplinary planning and treatments due to various challenges caused by the primary tumor and its metastases. The role of primary tumor resection (PTR) is currently uncertain; strong arguments exist for and against it. We aimed to define its effect and find its best place in our therapeutic methodology. METHOD We performed retrospective data analysis to investigate the clinical course of 449 smCRC patients, considering treatment modalities and the location of the primary tumor and comparing the clinical results of the patients with or without PTR between 1 January 2013 and 31 December 2018 at the Institute of Oncotherapy of the University of Pécs. RESULTS A total of 63.5% of the 449 smCRC patients had PTR. Comparing their data to those whose primary tumor remained intact (IPT), we observed significant differences in median progression-free survival with first-line chemotherapy (mPFS1) (301 vs. 259 days; p < 0.0001; 1 y PFS 39.2% vs. 26.6%; OR 0.56 (95% CI 0.36-0.87)) and median overall survival (mOS) (760 vs. 495 days; p < 0.0001; 2 y OS 52.4 vs. 26.9%; OR 0.33 (95% CI 0.33-0.53)), respectively. However, in the PTR group, the average ECOG performance status was significantly better (0.98 vs. 1.1; p = 0.0456), and the use of molecularly targeted agents (MTA) (45.3 vs. 28.7%; p = 0.0005) and rate of metastasis ablation (MA) (21.8 vs. 1.2%; p < 0.0001) were also higher, which might explain the difference partially. Excluding the patients receiving MTA and MA from the comparison, the effect of PTR remained evident, as the mOS differences in the reduced PTR subgroup compared to the reduced IPT subgroup were still strongly significant (675 vs. 459 days; p = 0.0009; 2 y OS 45.9 vs. 24.1%; OR 0.37 (95% CI 0.18-0.79). Further subgroup analysis revealed that the site of the primary tumor also had a major impact on the outcome considering only the IPT patients; shorter mOS was observed in the extrapelvic IPT subgroup in contrast with the intrapelvic IPT group (422 vs. 584 days; p = 0.0026; 2 y OS 18.2 vs. 35.9%; OR 0.39 (95% CI 0.18-0.89)). Finally, as a remarkable finding, it should be emphasized that there were no differences in OS between the smCRC PTR subgroup and metachronous mCRC patients (mOS 760 vs. 710 days, p = 0.7504, 2 y OS OR 0.85 (95% CI 0.58-1.26)). CONCLUSIONS The role of PTR in smCRC is still not professionally justified. Our survey found that most patients had benefited from PTR. Nevertheless, further prospective trials are needed to clarify the optimal treatment sequence of smCRC patients and understand this cancer disease's inherent biology.
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Affiliation(s)
- Balázs Pécsi
- Institute of Oncotherapy, Clinical Center and Medical School, University of Pécs, 7624 Pécs, Hungary
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Verheij FS, Yuval JB, Kok NFM, Lin ST, Qin LX, Omer DM, Thompson HM, Wei IH, Widmar M, Pappou EP, Weiser MR, Nash GM, Smith JJ, Paty PB, Beets GL, Garcia-Aguilar J. Nonoperative management of the primary tumor in patients with unresectable stage IV colon cancer treated with systemic chemotherapy: Higher complication rates for left-sided colon tumors. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2024; 50:107294. [PMID: 38039906 PMCID: PMC10841609 DOI: 10.1016/j.ejso.2023.107294] [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: 07/30/2023] [Revised: 11/02/2023] [Accepted: 11/17/2023] [Indexed: 12/03/2023]
Abstract
INTRODUCTION Treatment of the primary tumor in asymptomatic patients with unresectable colorectal metastases remains controversial. METHODS Data from patients with synchronous stage IV colon cancer and an untreated primary tumor who started treatment aimed at metastatic disease at a specialized cancer center between 2014 and 2018 were analyzed retrospectively. Main outcome was primary tumor-related complications comparing left-sided and right-sided colon cancer. A competing-risk regression model was used to identify predictors of complications. RESULTS Of 523 patients with metastatic colon cancer at presentation, 221 started treatment aimed at metastatic disease; these patients constituted the study cohort. The primary tumor was left-sided in 109 patients (49%) and right-sided in 112 patients (51%). In total, 46 patients (21%) developed a complication that required invasive intervention. Complications occurred more frequently in patients with left-sided tumors than in patients with right-sided tumors (29% vs 13%, P = 0.003). Eighteen patients (8%) underwent non-surgical intervention. Six patients (33%) failed non-surgical management and underwent surgery. Of 34 patients (15%) who underwent surgical intervention, 20 underwent an emergency colectomy and 14 underwent diversion with a permanent stoma. Overall, 10% of patients ended up with a permanent stoma. In competing-risk analysis, only left-sided primary tumor (hazard ratio 2.62; 95% CI 1.40-4.89; P = 0.003) was significantly associated with primary tumor-related complications requiring invasive intervention. CONCLUSIONS Patients with asymptomatic metastatic left-sided tumors have a higher risk for primary tumor-related complications than patients with right-sided tumors. Close monitoring and early surgical rescue should be considered for patients with left-sided colon cancer who are managed nonoperatively.
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Affiliation(s)
- Floris S Verheij
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Surgical Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands; GROW School for Oncology and Reproduction, Maastricht University, Maastricht, the Netherlands
| | - Jonathan B Yuval
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Niels F M Kok
- Department of Surgical Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - Sabrina T Lin
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Li-Xuan Qin
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Dana M Omer
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Hannah M Thompson
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Iris H Wei
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Maria Widmar
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Emmanouil P Pappou
- 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
| | - Garrett M Nash
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - J Joshua Smith
- 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
| | - Geerard L Beets
- Department of Surgical Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands; GROW School for Oncology and Reproduction, Maastricht University, Maastricht, the Netherlands
| | - Julio Garcia-Aguilar
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
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Fanotto V, Rossini D, Casagrande M, Bergamo F, Spagnoletti A, Santini D, Antoniotti C, Cupini S, Daniel F, Nasca V, Vetere G, Zaniboni A, Borelli B, Carullo M, Conca V, Passardi A, Tamburini E, Masi G, Pella N, Cremolini C. Primary Tumor Resection in Synchronous Metastatic Colorectal Cancer Patients Treated with Upfront Chemotherapy plus Bevacizumab: A Pooled Analysis of TRIBE and TRIBE2 Studies. Cancers (Basel) 2023; 15:5451. [PMID: 38001711 PMCID: PMC10670103 DOI: 10.3390/cancers15225451] [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: 10/07/2023] [Revised: 11/08/2023] [Accepted: 11/11/2023] [Indexed: 11/26/2023] Open
Abstract
BACKGROUND The decision to resect or not the primary tumor in asymptomatic patients with synchronous metastatic colorectal cancer (mCRC) is a complex and challenging issue for oncologists, especially when an antiangiogenic-based therapy is planned. METHODS Patients enrolled in the phase III TRIBE and TRIBE2 studies that compared upfront FOLFOXIRI + bevacizumab to FOLFIRI or FOLFOX + bevacizumab, respectively, were included. We assessed the association of primary tumor resection (PTR) with progression-free survival (PFS), overall survival (OS), response rate (ORR), rate of grade > 2 adverse events (AEs), and serious gastrointestinal and surgical AEs in the overall population and according to the treatment arm. RESULTS Of the 999 patients included, 513 (51%) underwent PTR at baseline. Longer PFS and OS were observed in resected patients compared to those with unresected primary tumors: 11.2 vs. 10.0 months (p < 0.001) and 26.6 vs. 22.5 (p < 0.001), respectively. In multivariate models, PTR was confirmed as an independent prognostic factor for better PFS (p = 0.032) and OS (p = 0.018). Patients with PTR experienced a higher incidence of grade 3 or 4 diarrhea (p = 0.055) and lower incidence of anemia (p = 0.053), perforation (p = 0.015), and serious gastrointestinal and surgical AEs (p < 0.001). No statistically significant differences were noted in incidence of bleeding (p = 0.39). The benefit of FOLFOXIRI + bevacizumab in terms of PFS (p for interaction: 0.46), OS (p for interaction: 0.80), ORR (p for interaction: 0.36), and incidence of grade 3 or 4 AEs was independent of PTR. CONCLUSIONS PTR at baseline was independently associated with good prognosis in synchronous mCRC patients and with lower incidence of serious gastrointestinal and surgical AEs during upfront chemotherapy plus bevacizumab. The benefit and toxicity profile of FOLFOXIRI plus bevacizumab was independent of PTR.
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Affiliation(s)
- Valentina Fanotto
- Department of Oncology, Academic Hospital of Udine, Azienda Sanitaria Universitaria Friuli Centrale (ASUFC), 33100 Udine, Italy; (V.F.); (M.C.); (N.P.)
| | - Daniele Rossini
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Savi 10, 56126 Pisa, Italy; (D.R.); (C.A.); (G.V.); (B.B.); (M.C.); (V.C.); (G.M.)
- UO Oncologia 2 Universitaria, Azienda Ospedaliero-Universitaria Pisana, Via Roma 67, 56126 Pisa, Italy
| | - Mariaelena Casagrande
- Department of Oncology, Academic Hospital of Udine, Azienda Sanitaria Universitaria Friuli Centrale (ASUFC), 33100 Udine, Italy; (V.F.); (M.C.); (N.P.)
| | - Francesca Bergamo
- Medical Oncology 1, Veneto Institute of Oncology IOV—IRCCS, 35128 Padua, Italy; (F.B.); (F.D.)
| | - Andrea Spagnoletti
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale Dei Tumori, 20133 Milan, Italy; (A.S.); (V.N.)
| | - Daniele Santini
- Medical Oncology Unit A, Policlinico Umberto I, Sapienza University of Rome, 00161 Rome, Italy;
| | - Carlotta Antoniotti
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Savi 10, 56126 Pisa, Italy; (D.R.); (C.A.); (G.V.); (B.B.); (M.C.); (V.C.); (G.M.)
- UO Oncologia 2 Universitaria, Azienda Ospedaliero-Universitaria Pisana, Via Roma 67, 56126 Pisa, Italy
| | - Samanta Cupini
- Department of Oncology, Division of Medical Oncology, Azienda USL Toscana Nord Ovest, 57124 Livorno, Italy;
| | - Francesca Daniel
- Medical Oncology 1, Veneto Institute of Oncology IOV—IRCCS, 35128 Padua, Italy; (F.B.); (F.D.)
| | - Vincenzo Nasca
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale Dei Tumori, 20133 Milan, Italy; (A.S.); (V.N.)
| | - Guglielmo Vetere
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Savi 10, 56126 Pisa, Italy; (D.R.); (C.A.); (G.V.); (B.B.); (M.C.); (V.C.); (G.M.)
- UO Oncologia 2 Universitaria, Azienda Ospedaliero-Universitaria Pisana, Via Roma 67, 56126 Pisa, Italy
| | - Alberto Zaniboni
- Oncology Department, Istituto Ospedaliero Fondazione Poliambulanza, 25124 Brescia, Italy;
| | - Beatrice Borelli
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Savi 10, 56126 Pisa, Italy; (D.R.); (C.A.); (G.V.); (B.B.); (M.C.); (V.C.); (G.M.)
- UO Oncologia 2 Universitaria, Azienda Ospedaliero-Universitaria Pisana, Via Roma 67, 56126 Pisa, Italy
| | - Martina Carullo
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Savi 10, 56126 Pisa, Italy; (D.R.); (C.A.); (G.V.); (B.B.); (M.C.); (V.C.); (G.M.)
- UO Oncologia 2 Universitaria, Azienda Ospedaliero-Universitaria Pisana, Via Roma 67, 56126 Pisa, Italy
| | - Veronica Conca
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Savi 10, 56126 Pisa, Italy; (D.R.); (C.A.); (G.V.); (B.B.); (M.C.); (V.C.); (G.M.)
- UO Oncologia 2 Universitaria, Azienda Ospedaliero-Universitaria Pisana, Via Roma 67, 56126 Pisa, Italy
| | - Alessandro Passardi
- Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014 Meldola, Italy;
| | - Emiliano Tamburini
- Oncology Department and Palliative Care, Cardinale Panico Tricase City Hospital, 73039 Tricase, Italy;
| | - Gianluca Masi
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Savi 10, 56126 Pisa, Italy; (D.R.); (C.A.); (G.V.); (B.B.); (M.C.); (V.C.); (G.M.)
- UO Oncologia 2 Universitaria, Azienda Ospedaliero-Universitaria Pisana, Via Roma 67, 56126 Pisa, Italy
| | - Nicoletta Pella
- Department of Oncology, Academic Hospital of Udine, Azienda Sanitaria Universitaria Friuli Centrale (ASUFC), 33100 Udine, Italy; (V.F.); (M.C.); (N.P.)
| | - Chiara Cremolini
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Savi 10, 56126 Pisa, Italy; (D.R.); (C.A.); (G.V.); (B.B.); (M.C.); (V.C.); (G.M.)
- UO Oncologia 2 Universitaria, Azienda Ospedaliero-Universitaria Pisana, Via Roma 67, 56126 Pisa, Italy
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Shin JE, An HJ, Shim BY, Kim H, Park HS, Cho HM, Kye BH, Yoo RN, Moon JY, Kim SH, Lee J, Lee HC, Jung JH, Lee KM, Lee JM. Clinical Outcomes of Upfront Primary Tumor Resection in Synchronous Unresectable Metastatic Colorectal Cancer. Cancers (Basel) 2023; 15:5057. [PMID: 37894424 PMCID: PMC10605032 DOI: 10.3390/cancers15205057] [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: 08/16/2023] [Revised: 10/01/2023] [Accepted: 10/17/2023] [Indexed: 10/29/2023] Open
Abstract
The role of upfront primary tumor resection (PTR) in patients with unresectable metastatic colorectal cancer without severe symptoms remains controversial. We retrospectively analyzed the role of PTR in overall survival (OS) in this population. Among the 205 patients who enrolled, the PTR group (n = 42) showed better performance (p = 0.061), had higher frequencies of right-sided origin (p = 0.058), the T4 stage (p = 0.003), the M1a stage (p = 0.012), and <2 organ metastases (p = 0.002), and received fewer targeted agents (p = 0.011) than the chemotherapy group (n = 163). The PTR group showed a trend for longer OS (20.5 versus 16.0 months, p = 0.064) but was not related to OS in Cox regression multivariate analysis (p = 0.220). The male sex (p = 0.061), a good performance status (p = 0.078), the T3 stage (p = 0.060), the M1a stage (p = 0.042), <2 organ metastases (p = 0.035), an RAS wild tumor (p = 0.054), and the administration of targeted agents (p = 0.037), especially bevacizumab (p = 0.067), seemed to be related to PTR benefits. Upfront PTR could be considered beneficial in some subgroups, but these findings require larger studies to verify.
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Affiliation(s)
- Ji Eun Shin
- Division of Oncology, Department of Internal Medicine, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Suwon 16247, Republic of Korea; (J.E.S.); (B.Y.S.); (H.K.); (H.S.P.)
| | - Ho Jung An
- Division of Oncology, Department of Internal Medicine, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Suwon 16247, Republic of Korea; (J.E.S.); (B.Y.S.); (H.K.); (H.S.P.)
| | - Byoung Yong Shim
- Division of Oncology, Department of Internal Medicine, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Suwon 16247, Republic of Korea; (J.E.S.); (B.Y.S.); (H.K.); (H.S.P.)
| | - Hyunho Kim
- Division of Oncology, Department of Internal Medicine, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Suwon 16247, Republic of Korea; (J.E.S.); (B.Y.S.); (H.K.); (H.S.P.)
| | - Hyung Soon Park
- Division of Oncology, Department of Internal Medicine, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Suwon 16247, Republic of Korea; (J.E.S.); (B.Y.S.); (H.K.); (H.S.P.)
| | - Hyeon-Min Cho
- Department of Surgery, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Suwon 16247, Republic of Korea; (H.-M.C.); (B.-H.K.); (R.N.Y.); (J.-Y.M.)
| | - Bong-Hyeon Kye
- Department of Surgery, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Suwon 16247, Republic of Korea; (H.-M.C.); (B.-H.K.); (R.N.Y.); (J.-Y.M.)
| | - Ri Na Yoo
- Department of Surgery, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Suwon 16247, Republic of Korea; (H.-M.C.); (B.-H.K.); (R.N.Y.); (J.-Y.M.)
| | - Ji-Yeon Moon
- Department of Surgery, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Suwon 16247, Republic of Korea; (H.-M.C.); (B.-H.K.); (R.N.Y.); (J.-Y.M.)
| | - Sung Hwan Kim
- Department of Radiation Oncology, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Suwon 16247, Republic of Korea; (S.H.K.); (J.L.); (H.C.L.)
| | - Jonghoon Lee
- Department of Radiation Oncology, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Suwon 16247, Republic of Korea; (S.H.K.); (J.L.); (H.C.L.)
| | - Hyo Chun Lee
- Department of Radiation Oncology, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Suwon 16247, Republic of Korea; (S.H.K.); (J.L.); (H.C.L.)
| | - Ji-Han Jung
- Department of Hospital Pathology, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Suwon 16247, Republic of Korea;
| | - Kang-Moon Lee
- Division of Gastroenterology, Department of Internal Medicine, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Suwon 16247, Republic of Korea; (K.-M.L.); (J.M.L.)
| | - Ji Min Lee
- Division of Gastroenterology, Department of Internal Medicine, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Suwon 16247, Republic of Korea; (K.-M.L.); (J.M.L.)
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Muzellec L, Campion L, Bachet JB, Taieb J, Fremont E, Senellart H, Moreau J, Bouché O, Garric M, Guimbaud R, Greilsamer C, Bodère A, Lièvre A, Girot P, Edeline J, Tougeron D, Bennouna J, Touchefeu Y. Prognostic score for synchronous metastatic rectal cancer: A real-world study. Dig Liver Dis 2023; 55:1411-1416. [PMID: 37005173 DOI: 10.1016/j.dld.2023.03.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2021] [Revised: 03/10/2023] [Accepted: 03/16/2023] [Indexed: 04/04/2023]
Abstract
BACKGROUND Prognostic factors of metastatic rectal cancer are not well known. AIM The objective of this study was to identify prognostic factors of overall survival (OS) in a cohort of patients with non-resectable synchronous metastatic rectal cancer. METHODS Patients were retrospectively enrolled from 18 French centres. Univariate and multivariate analyses were performed to identify prognostic factors for OS. A simple score was derived from this a development cohort RESULTS: A total of 243 patients with metastatic rectal cancer were included in the study. Median OS was 24.4 months, 95% CI [19.4-27.2]. Among patients with non-resected metastases (n=141), six independent prognostic factors associated with better OS were identified in multivariate analysis: primary tumour surgery, WHO score 0-1, middle or upper rectal tumour, lung metastases only, systemic chemotherapy and targeted agent in first line. A prognostic score individualized three groups, each factor counting for one point in the score (<3, = 3 et > 3). Their median OS were respectively 27.9 months, 95% CI [21.7-35.1], 17.1 months [11.9-19.7] (HR2/1=2.08, 95%, CI [1.31-3.30], p2/1=0.002) and 9.1 months [4.9-11.7] (HR3/2=2.32, 95% CI [1.38-3.92], p3/2=0.001). CONCLUSION A prognostic score for non-resectable synchronous metastatic rectal cancer can be proposed to classify patients in three prognostic groups.
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Affiliation(s)
- Léa Muzellec
- Nantes Université, CHU Nantes, Institut des Maladies de l'Appareil Digestif (IMAD), Hépato-Gastroentérologie, Inserm CIC 1413, F-44000 Nantes, France
| | - Loïc Campion
- Biometrics, Institut de Cancérologie de l'Ouest, Saint Herblain 44800, France; CRCINA, University of Nantes, INSERM UMR1232, CNRS-ERL6001, 44000 Nantes, France
| | - Jean-Baptiste Bachet
- Department of Gastroenterology and Digestive Oncology, Assistance publique-Hôpitaux de Paris, Groupe hospitalier Pitié Salpêtrière, France
| | - Julien Taieb
- Department of Gastroenterology and Digestive Oncology, Université Paris Descartes, Hopital Européen Georges Pompidou, Paris, France
| | - Elodie Fremont
- Department of Gastroenterology, Centre Hospitalier Universitaire de Poitiers, France
| | - Hélène Senellart
- Medical Oncology department, Institut de Cancérologie de l'Ouest, Saint Herblain, France
| | - Johanna Moreau
- Department of Gastroenterology and Digestive Oncology, Hôpital Robert Debré, CHU Reims, France
| | - Olivier Bouché
- Department of Gastroenterology and Digestive Oncology, Hôpital Robert Debré, CHU Reims, France
| | - Marie Garric
- Oncologie Médicale Digestive, CHU de Toulouse, Toulouse, France
| | - Rosine Guimbaud
- Oncologie Médicale Digestive, CHU de Toulouse, Toulouse, France
| | | | - Anaïs Bodère
- Department of Gastroenterology and Digestive Oncology, Centre Hospitalier Universitaire de Rennes, France
| | - Astrid Lièvre
- Department of Gastroenterology and Digestive Oncology, Centre Hospitalier Universitaire de Rennes, France
| | - Paul Girot
- Nantes Université, CHU Nantes, Institut des Maladies de l'Appareil Digestif (IMAD), Hépato-Gastroentérologie, Inserm CIC 1413, F-44000 Nantes, France
| | - Julien Edeline
- Medical Oncology department, Centre Eugène Marquis, Rennes, France
| | - David Tougeron
- Department of Gastroenterology, Centre Hospitalier Universitaire de Poitiers, France
| | - Jaafar Bennouna
- Department of Medical Oncology, Hospital Foch, F-92150 Suresnes, France
| | - Yann Touchefeu
- Nantes Université, CHU Nantes, Institut des Maladies de l'Appareil Digestif (IMAD), Hépato-Gastroentérologie, Inserm CIC 1413, F-44000 Nantes, France.
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Li S, Ji L, Huang J, Wang Y, Liu P, Zhang W, Lou Z. The impact of primary tumor resection for asymptomatic colorectal cancer patients with unresectable metastases: a systematic review and meta-analysis. Int J Colorectal Dis 2023; 38:214. [PMID: 37581775 DOI: 10.1007/s00384-023-04500-y] [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] [Accepted: 07/29/2023] [Indexed: 08/16/2023]
Abstract
BACKGROUND Whether patients with asymptomatic primary tumors and unresectable metastases of colorectal cancer (CRC) should undergo primary tumor resection (PTR) remains controversial. This study aims to determine the appropriateness of PTR for these individuals by evaluating a number of outcome measures. METHODS A systematic literature search was performed. Outcome measures included overall survival, emergency surgery rates, incidence of postoperative complications, time to initiate chemotherapy, conversion rates, and chemotherapy-related toxicities. RESULTS Patients who received PTR in addition to chemotherapy had a better overall survival rate than those who only received chemotherapy (HR = 0.62, 95%CI, 0.50-0.78, I2 = 84%, p < 0.00001). In the RCT subgroup, there were no significant differences with a HR of 0.72 (95%CI, 0.45-1.13, I2 = 17%, p = 0.15). More patients in the chemotherapy alone group could be converted to resectable status (OR = 0.47, 95%CI, 0.27-0.82, I2 = 0%, p = 0.008), but the incidence of emergency surgery was 23% (95%CI, 17-29%, I2 = 14%). The risk of chemotherapy-related toxicity was not significantly higher in the PTR group (OR = 1.5, 95%CI, 0.94-2.43, p = 0.09, I2 = 0%), with a 7% incidence of postoperative complications (95%CI, 0-14%, p = 0.05, I2 = 0%). The time to initiate chemotherapy after PTR was approximately 33.06 days (95%CI, 25.55-40.58, I2 = 0%). CONCLUSION PTR plus chemotherapy may be associated with improved survival in asymptomatic CRC patients with unresectable metastases. However, PTR did not provide a significant survival benefit in the subgroup of RCTs. Additionally, PTR did not result in a significantly increased risk of chemotherapy-related toxicity, with a postoperative complication rate of approximately 7%, and chemotherapy could be initiated at approximately 33.06 days after PTR. Compared with the PTR plus chemotherapy, chemotherapy alone could result in a significantly higher conversion rate. However, about 23% of patients receiving chemotherapy alone required emergency surgery for primary tumor-related symptoms. The above results needed to be validated in future larger prospective randomized trials.
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Affiliation(s)
- Shuyuan Li
- Department of Colorectal Surgery, the first affiliated Hospital of Naval Medical University, 168 Changhai Road, Yangpu District, Shanghai, China
| | - Liqiang Ji
- Department of Colorectal Surgery, the first affiliated Hospital of Naval Medical University, 168 Changhai Road, Yangpu District, Shanghai, China
| | - Jie Huang
- The first affiliated Hospital of Naval Medical University, Shanghai, China
| | - Ye Wang
- Department of Colorectal Surgery, the first affiliated Hospital of Naval Medical University, 168 Changhai Road, Yangpu District, Shanghai, China
| | - Peng Liu
- Department of Colorectal Surgery, the first affiliated Hospital of Naval Medical University, 168 Changhai Road, Yangpu District, Shanghai, China
| | - Wei Zhang
- Department of Colorectal Surgery, the first affiliated Hospital of Naval Medical University, 168 Changhai Road, Yangpu District, Shanghai, China
| | - Zheng Lou
- Department of Colorectal Surgery, the first affiliated Hospital of Naval Medical University, 168 Changhai Road, Yangpu District, Shanghai, China.
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9
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Bai J, Yang M, Liu Z, Efetov S, Kayaalp C, Dulskas A, Shaw D, Wang X. Primary tumor resection in colorectal cancer patients with unresectable distant metastases: a minireview. Front Oncol 2023; 13:1138407. [PMID: 37182188 PMCID: PMC10172590 DOI: 10.3389/fonc.2023.1138407] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2023] [Accepted: 04/12/2023] [Indexed: 05/16/2023] Open
Abstract
Colorectal cancer (CRC) is the second most common cause of cancer-related death among both men and women worldwide and the third most common cancer overall. About 20% of patients diagnosed with CRC were discovered to have distant metastatic lesions, the majority of which were located in the liver. For the optimum treatment of CRC patients with hepatic metastases, interventional radiologists, medical oncologists, and surgeons must all collaborate. The surgical excision of the primary tumor is an important part of CRC treatment since it has been found to be curative in cases of CRC with minimal metastases. However, given the evidence to date was gathered from retrospective data, there is still controversy over the effectiveness of primary tumor resection (PTR) in improving the median overall survival (OS) and quality of life. Patients who have hepatic metastases make up a very tiny fraction of those who are candidates for resection. With a focus on the PTR, this minireview attempted to review the current advancements in the treatment options for hepatic colorectal metastatic illness. This evaluation also included information on PTR's risks when performed on individuals with stage IV CRC.
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Affiliation(s)
- Junge Bai
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ming Yang
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zheng Liu
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Sergey Efetov
- Clinic of Coloproctology and Minimally Invasive Surgery, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
| | - Cuneyt Kayaalp
- Department of Gastrointestinal Surgery, Yeditepe University, Istanbul, Türkiye
| | - Audrius Dulskas
- Department of Abdominal and General Surgery and Oncology, National Cancer Institute, Vilnius, Lithuania
- Faculty of Medicine, Institute of Clinical Medicine, Vilnius University, Vilnius, Lithuania
| | - Darcy Shaw
- Colorectal Surgery Associates, Kansas City University, Kansas, MO, United States
| | - Xishan Wang
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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10
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Fanotto V, Salani F, Vivaldi C, Scartozzi M, Ribero D, Puzzoni M, Montagnani F, Leone F, Vasile E, Bencivenga M, De Manzoni G, Basile D, Fornaro L, Masi G, Aprile G. Primary Tumor Resection for Metastatic Colorectal, Gastric and Pancreatic Cancer Patients: In Search of Scientific Evidence to Inform Clinical Practice. Cancers (Basel) 2023; 15:cancers15030900. [PMID: 36765854 PMCID: PMC9913845 DOI: 10.3390/cancers15030900] [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: 12/23/2022] [Revised: 01/24/2023] [Accepted: 01/28/2023] [Indexed: 02/05/2023] Open
Abstract
The management of the primary tumor in metastatic colorectal, gastric and pancreatic cancer patients may be challenging. Indeed, primary tumor progression could be associated with severe symptoms, compromising the quality of life and the feasibility of effective systemic therapy, and might result in life-threatening complications. While retrospective series have suggested that surgery on the primary tumor may confer a survival advantage even in asymptomatic patients, randomized trials seem not to definitively support this hypothesis. We discuss the evidence for and against primary tumor resection for patients with metastatic gastrointestinal (colorectal, gastric and pancreatic) cancers treated with systemic therapies and put in context the pros and cons of the onco-surgical approach in the time of precision oncology. We also evaluate current ongoing trials on this topic, anticipating how these will influence both research and everyday practice.
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Affiliation(s)
- Valentina Fanotto
- Department of Oncology, Academic Hospital of Udine, Azienda Sanitaria Universitaria Friuli Centrale (ASUFC), Piazzale Santa Maria della Misericordia, 33100 Udine, Italy
| | - Francesca Salani
- Unit of Oncology 2, Azienda Ospedaliero-Universitaria Pisana, 56126 Pisa, Italy
- Institute of Interdisciplinary Research “Health Science”, Scuola Superiore Sant’Anna, Piazza Martiri della Libertà 33, 56124 Pisa, Italy
| | - Caterina Vivaldi
- Unit of Oncology 2, Azienda Ospedaliero-Universitaria Pisana, 56126 Pisa, Italy
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy
| | - Mario Scartozzi
- Unit of Medical Oncology, University Hospital, University of Cagliari, 09124 Cagliari, Italy
| | - Dario Ribero
- Division of General and Oncologic Surgery Multimedica, A.O. Santa Croce e Carle, 12100 Cuneo, Italy
| | - Marco Puzzoni
- Unit of Medical Oncology, University Hospital, University of Cagliari, 09124 Cagliari, Italy
| | - Francesco Montagnani
- Department of Oncology, Azienda Sanitaria Locale di Biella, 13900 Ponderano, Italy
| | - Francesco Leone
- Department of Oncology, Azienda Sanitaria Locale di Biella, 13900 Ponderano, Italy
| | - Enrico Vasile
- Unit of Oncology 2, Azienda Ospedaliero-Universitaria Pisana, 56126 Pisa, Italy
| | - Maria Bencivenga
- General and Upper GI Surgery Division, Verona University (VR), 37134 Verona, Italy
| | - Giovanni De Manzoni
- General and Upper GI Surgery Division, Verona University (VR), 37134 Verona, Italy
| | - Debora Basile
- Department of Oncology, San Bortolo General Hospital, ULSS 8 Berica-Vicenza, 36100 Vicenza, Italy
| | - Lorenzo Fornaro
- Unit of Oncology 2, Azienda Ospedaliero-Universitaria Pisana, 56126 Pisa, Italy
- Correspondence: ; Tel.: +39-050992466
| | - Gianluca Masi
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy
| | - Giuseppe Aprile
- Department of Oncology, San Bortolo General Hospital, ULSS 8 Berica-Vicenza, 36100 Vicenza, Italy
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Survival Outcomes after Elective or Emergency Surgery for Synchronous Stage IV Colorectal Cancer. Biomedicines 2022; 10:biomedicines10123114. [PMID: 36551870 PMCID: PMC9775222 DOI: 10.3390/biomedicines10123114] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2022] [Revised: 11/29/2022] [Accepted: 11/29/2022] [Indexed: 12/12/2022] Open
Abstract
Patients with stage IV colorectal cancer (CRC) who have not undergone primary tumor resection (PTR) are at risk of sudden medical emergencies. Despite the ongoing controversy over the necessity and timing of PTR in patients with stage IV CRC, studies comparing the survival outcomes of elective and emergency surgery in this population are scarce. This is a retrospective study conducted at a single institute. The patients were divided into two groups: the elective surgery (ELS) group (n = 46) and the emergency surgery (EMS) group (n = 26). The primary outcome was 2-year overall survival (OS). During a median follow-up period of 27.0 months, the 2-year OS was significantly better in the ELS group (80% vs. 42.9%, p = 0.002). No significant differences were observed in the 2-year relapse-free survival and 30-day postoperative complication rates. Planning and performing elective surgery could help increase the survival rate of patients with synchronous stage IV CRC, especially those that undergo simultaneous or staged metastasectomy.
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12
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Rim CH, Cho WK, Lee JH, Kim YS, Suh YG, Kim KH, Chie EK, Ahn YC, The Oligometastasis Working Group, Korea Cancer Association. Role of Local Treatment for Oligometastasis: A Comparability-Based Meta-Analysis. Cancer Res Treat 2022; 54:953-969. [PMID: 35989655 PMCID: PMC9582460 DOI: 10.4143/crt.2022.329] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Accepted: 08/13/2022] [Indexed: 11/21/2022] Open
Abstract
PURPOSE We intend to investigate the oncological efficacy and feasibility of local consolidative therapy (LCT) through a meta-analysis method. MATERIALS AND METHODS Four databases including PubMed, MEDLINE, Embase, and Cochrane library were searched. Target studies are controlled trials comparing outcomes of LCT versus a control group. Primary endpoints are overall survival (OS) and progression-free survival (PFS). RESULTS A total of 54 studies involving 7,242 patients were included. Pooled analyses showed that the LCT arm could achieve improved OS with pooled odds ratio of 2.896 (95% confidence interval [CI], 2.377 to 3.528; p < 0.001). Regarding PFS, pooled analyses showed pooled odds ratio of 3.045 (95% CI, 2.356 to 3.937; p < 0.001) in favor of the LCT arm. In the subgroup analyses including the studies with reliable comparability (e.g. randomized studies or intentionally matched studies without significant favorable prognosticator in LCT arms), pooled odds ratio was 2.548 (95% CI, 1.808 to 3.591; p < 0.001) favoring the LCT arm regarding OS. Regarding PFS, pooled OR was 2.656 (95% CI, 1.713 to 4.120; p < 0.001) which also favored the LCT arm. Subgroup analyses limited to the randomized controlled trials (RCT) were also performed and pooled odds ratios on OS and PFS were 1.535 (95% CI, 1.082 to 2.177; p=0.016) and 1.668 (95% CI, 1.187 to 2.344; p=0.003). The rates of grade ≥ 3 complications related to LCT was mostly low (< 10%) and not significantly higher compared to the control arm. CONCLUSION Pooled analyses results of all included studies, selected studies with reliable comparability, and RCT's demonstrated the survival benefit of LCT. These consistent results suggest that LCT was beneficial to the patients with oligometastasis.
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Affiliation(s)
- Chai Hong Rim
- Department of Radiation Oncology, Korea University Ansan Hospital, Korea University College of Medicine, Ansan,
Korea
| | - Won Kyung Cho
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul,
Korea
| | - Jong Hoon Lee
- Department of Radiation Oncology, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Suwon,
Korea
| | - Young Seok Kim
- Department of Radiation Oncology, Asan Medical Center, Ulsan University College of Medicine, Seoul,
Korea
| | - Yang-Gun Suh
- Proton Therapy Center, Research Institute and Hospital, National Cancer Center, Goyang,
Korea
| | - Kyung Hwan Kim
- Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul,
Korea
| | - Eui Kyu Chie
- Department of Radiation Oncology, Seoul National University College of Medicine, Seoul,
Korea
| | - Yong Chan Ahn
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul,
Korea
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Yang Y, Yang Z, Lyu Z, Wang J, Wu D, Li Y. Predicting Surgical Benefit for Primary Tumor Resection in Patients with Stage IV Colorectal Cancer.. [DOI: 10.21203/rs.3.rs-2031087/v1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Abstract
Purpose
There exists continuous controversy regarding the effect of primary tumor resection (PTR) for stage IV colorectal cancer (CRC) patients. Little is known about how to predict the patients’ survival benefit from PTR. This study aimed to develop a tool for surgical benefit prediction.
Methods
Stage IV CRC patients diagnosed between 2010 and 2015 from the Surveillance, Epidemiology, and End Results database were included. After propensity score matching, patients receiving PTR that survived longer than the median cancer-specific survival (CSS) time of those who did not undergo PTR were considered to benefit from surgery. Logistic regression analysis identified prognostic factors influencing the surgical benefit, based on which a nomogram was constructed. A user-friendly webserver was then built for convenient clinical use. The predictive model was assessed using Harrell’s concordance index, calibration plot, receiver operative curve and decision curve analysis.
Results
The median CSS of the PTR group was 23 months, which was significantly longer than the non-PTR group (12 months, P < 0.001). In the PTR group, 32.9% of patients did not benefit from surgery. Logistic regression analysis identified age, tumor location, CEA level, histological grade, number of distant metastasis, and preoperative chemotherapy independently associated with surgical benefit. The established prognostic nomogram demonstrated satisfactory performance.
Conclusion
PTR was associated with prolonged survival in stage IV CRC. The proposed nomogram could be used as a risk-to-benefit assessment evidenced-based platform for selecting appropriate patients to undergo PTR.
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Affiliation(s)
| | | | | | | | - Deqing Wu
- Guangdong Provincial People's Hospital
| | - Yong Li
- Guangdong Provincial People's Hospital
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14
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Qiao Y, Qiao Y, Li H, Fu J, You S. Survival benefit of primary and metastatic tumor resection for colon cancer with liver metastases: A population based, propensity score-matched study. Front Surg 2022; 9:959826. [PMID: 36111222 PMCID: PMC9468248 DOI: 10.3389/fsurg.2022.959826] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2022] [Accepted: 08/08/2022] [Indexed: 11/16/2022] Open
Abstract
Background Colon cancer remains one of the most common malignancies and we aimed to evaluate whether surgery has an effect on the survival of metastatic colon patients. Methods We analyzed 7,583 metastatic colon patients from the Surveillance, Epidemiology, between January 2010 and December 2015. Using Cox proportional hazards models and Kaplan-Meier curves, the overall survival rate (OS) and cancer-specific survival rate and End Results (SEER) registry (CSS) months (m) were evaluated with corresponding 95% confidence intervals (95% CIs). Propensity score matching (PSM) was performed to adjust for potential baseline confounding of all comparison groups. Results In general, receiving both primary and metastatic tumor resection (PMTR) remarkably improved OS and CSS compared with only primary tumor resection (PTR) after PS matching (PSM) (P < 0.05), with a significantly improved OS (HR = 0.74, 95%CI = 0.69–0.80) and CSS (HR = 0.71, 95%CI = 0.66–0.76) in all stage M1 colon patients. The stratification analysis indicated a significant difference between OS and CSS in M1a and M1b stages. After PSM, PMTR was found to be associated with remarkably improved OS and CSS for patients with liver metastases but not associated with OS and CSS of patients with lung metastases in both M1a and M1b stage. Conclusions The results from this large SEER cohort supported PMTR might improve the survival of colon patients with liver metastases on the basis of chemotherapy.
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Affiliation(s)
- Yunfeng Qiao
- First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Yunfeng Qiao
- Cancer Center, Faculty of Health Sciences, University of Macau, Macau, China
| | - Huijun Li
- Department of Imaging Medicine, Taikang Tongji (Wuhan) Hospital, Wuhan, China
| | - Jinge Fu
- Department of Anorectal Surgery, Weishi Central Hospital, Kaifeng, China
| | - Shuping You
- Department of Anus and Bowel Surgery, Jingmen No. 2 People's Hospital, Jingmen, China
- Correspondence: Shuping You
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15
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Cheng X, Li Y, Chen D, Xu X, Liu F, Zhao F. Primary Tumor Resection Provides Survival Benefits for Patients with Synchronous Brain Metastases from Colorectal Cancer. Diagnostics (Basel) 2022; 12:1586. [PMID: 35885491 PMCID: PMC9322496 DOI: 10.3390/diagnostics12071586] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2022] [Revised: 06/22/2022] [Accepted: 06/27/2022] [Indexed: 02/01/2023] Open
Abstract
Background: Brain metastases (BMs), particularly synchronous brain metastases, in colorectal cancer (CRC) patients are uncommon. The survival benefit of primary tumor resection (PTR) in patients with metastatic colorectal cancer is controversial. Whether PTR can bring survival benefits to patients with BMs of CRC has not been reported. Methods: From 2010 to 2016, 581 CRC patients with BMs from the Surveillance, Epidemiology, and End Results (SEER) database were divided into PTR and non-PTR groups. The log-rank test was used to compare the survival distributions. The Kaplan-Meier method was used to estimate survival. By controlling additional prognostic factors, a Cox proportional multivariate regression analysis was used to estimate the survival benefit of PTR. Results: The median overall survival for CRC patients with synchronous BMs was 3 months, with a 1-year survival rate of 27.2% and a 2-year survival rate of 12.8%. The PTR group contained 171 patients (29.4%), whereas the non-PTR group had 410 patients (70.6%). Patients who underwent PTR had a 1-year survival rate of 40.2% compared to 21.7% in those who did not (p < 0.0001). Cox proportional analysis showed that patients ≥60 years (hazard ratio [HR] 1.718, 95% confidence interval [CI] 1.423−2.075, p < 0.0001) had a shorter OS than patients < 60 years of age. OS was better in CEA-negative than in CEA-positive patients (HR 0.652, 95% CI 0.472−0.899, p = 0.009). Patients in whom the primary tumor was removed had considerably improved prognoses (HR 0.654, 95% CI 0.531−0.805, p < 0.0001). Subgroup analysis revealed that the PTR group achieved a survival advantage except for patients with CEA negative. Conclusions: Patients with synchronous BMs from CRC may benefit from primary tumor resection (PTR). Age, CEA level, and PTR were independent prognostic risk factors for CRC patients with synchronous BMs.
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Affiliation(s)
- Xiaofei Cheng
- Department of Colorectal Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; (X.C.); (D.C.); (X.X.)
| | - Yanqing Li
- Department of Pathology, The Second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou 310009, China;
| | - Dong Chen
- Department of Colorectal Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; (X.C.); (D.C.); (X.X.)
| | - Xiangming Xu
- Department of Colorectal Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; (X.C.); (D.C.); (X.X.)
| | - Fanlong Liu
- Department of Colorectal Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; (X.C.); (D.C.); (X.X.)
| | - Feng Zhao
- Department of Radiation Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
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Cheng X, Li Y, Chen D, Xu X, Liu F, Zhao F. Nomogram Predicting the Survival of Young-Onset Patients with Colorectal Cancer Liver Metastases. Diagnostics (Basel) 2022; 12:1395. [PMID: 35741205 PMCID: PMC9221975 DOI: 10.3390/diagnostics12061395] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2022] [Revised: 05/22/2022] [Accepted: 05/27/2022] [Indexed: 02/04/2023] Open
Abstract
Background: Although the global prevalence of colorectal cancer (CRC) is decreasing, there has been an increase in incidence among young-onset individuals, in whom the disease is associated with specific pathological characteristics, liver metastases, and a poor prognosis. Methods: From 2010 to 2016, 1874 young-onset patients with colorectal cancer liver metastases (CRLM) from the Surveillance, Epidemiology, and End Results (SEER) database were randomly allocated to training and validation cohorts. Multivariate Cox analysis was used to identify independent prognostic variables, and a nomogram was created to predict cancer-specific survival (CSS) and overall survival (OS). Receiver operating characteristic (ROC) curve, C-index, area under the curve (AUC), and calibration curve analyses were used to determine nomogram accuracy and reliability. Results: Factors independently associated with young-onset CRLM CSS included primary tumor location, the degree of differentiation, histology, M stage, N stage, preoperative carcinoembryonic antigen level, and surgery (all p < 0.05). The C-indices of the CSS nomogram for the training and validation sets (compared to TNM stage) were 0.709 and 0.635, and 0.735 and 0.663, respectively. The AUC values for 1-, 3-, and 5-year OS were 0.707, 0.708, and 0.755 in the training cohort and 0.765, 0.735, and 0.737 in the validation cohort, respectively; therefore, the nomogram had high sensitivity, and was superior to TNM staging. The calibration curves for the training and validation sets were relatively consistent. In addition, a similar result was observed with OS. Conclusions: We developed a unique nomogram incorporating clinical and pathological characteristics to predict the survival of young-onset patients with CRLM. This may serve as an early warning system allowing doctors to devise more effective treatment regimens.
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Affiliation(s)
- Xiaofei Cheng
- Department of Colorectal Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; (X.C.); (D.C.); (X.X.)
| | - Yanqing Li
- Department of Pathology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China;
| | - Dong Chen
- Department of Colorectal Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; (X.C.); (D.C.); (X.X.)
| | - Xiangming Xu
- Department of Colorectal Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; (X.C.); (D.C.); (X.X.)
| | - Fanlong Liu
- Department of Colorectal Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; (X.C.); (D.C.); (X.X.)
| | - Feng Zhao
- Department of Radiation Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
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Newhook TE, Vauthey JN. Colorectal liver metastases: state-of-the-art management and surgical approaches. Langenbecks Arch Surg 2022; 407:1765-1778. [DOI: 10.1007/s00423-022-02496-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Accepted: 03/10/2022] [Indexed: 02/06/2023]
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Rasbach E, Birgin E, Betzler A, Rahbari NN, Reissfelder C. Therapiestrategien beim synchron metastasierten Kolonkarzinom. COLOPROCTOLOGY 2022. [DOI: 10.1007/s00053-022-00601-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
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Schwartzberg DM, Valente MA. Surgical Dilemmas Associated with Malignant Large Bowel Obstructions. Clin Colon Rectal Surg 2022; 35:197-203. [PMID: 35966387 PMCID: PMC9374526 DOI: 10.1055/s-0042-1742589] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/27/2023]
Abstract
Despite an increase in screening colonoscopy, with the objective to decrease the incidence of colorectal cancer, a third of patients will present with an obstructing cancer. Malignant large bowel obstructions (MLBO) pose a challenging workup and treatment paradigm where an oncologic primary tumor resection must be balanced with relieving the obstruction, functional outcomes, palliation, and consideration for adjuvant therapy. A thorough work up with cross-sectional imaging and medical optimization should be attempted; however, patients may present in extremis and require emergent intervention. The onset of MLBO can be insidious, but result in electrolyte derangements, perforation, small bowel obstruction, hemorrhage, and ischemia. Self-expandable metallic stents have been used as palliation or as a bridge to surgery and have allowed for minimally invasive surgical options as well as a decrease in stoma rates. Patients with signs of colon ischemia or perforation require emergent surgery, which is associated with an increase in stoma formation, morbidity, mortality, and a decrease in overall survival.
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Affiliation(s)
- David M. Schwartzberg
- Mather Colorectal Surgery, Mather Hospital-Northwell Health, Port Jefferson, New York
| | - Michael A. Valente
- Department of Colorectal Surgery, Cleveland Clinic Foundation, Cleveland, Ohio,Address for correspondence Michael A. Valente, DO, FACS, FASCRS Department of Colorectal Surgery, Digestive Disease Institute9500 Euclid Avenue, A30, Cleveland, OH 44195
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Liang Z, Liu Z, Huang C, Chen X, Zhang Z, Xiang M, Hu W, Wang J, Feng X, Yao X. The role of upfront primary tumor resection in asymptomatic patients with unresectable stage IV colorectal cancer: A systematic review and meta-analysis. Front Surg 2022; 9:1047373. [PMID: 36684350 PMCID: PMC9857770 DOI: 10.3389/fsurg.2022.1047373] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2022] [Accepted: 12/01/2022] [Indexed: 01/09/2023] Open
Abstract
BACKGROUND Controversy exists over the role of upfront primary tumor resection (PTR) in asymptomatic patients with unresectable stage IV colorectal cancer (CRC). The purpose of this study was to evaluate the effect of upfront PTR on survival outcomes and adverse outcomes. METHODS Searches were conducted on PubMed, EMBASE, Web of Science, and Cochrane Library from inception to August 2021. Studies comparing survival outcomes with or without adverse outcomes between PTR and non-PTR treatments were included. Review Manager 5.3 was applied for meta-analyses with a random-effects model whenever possible. RESULTS Overall, 20 studies with 3,088 patients were finally included in this systematic review. Compared with non-PTR, upfront PTR was associated with better 3-year (HR: 0.69, 95% CI, 0.57-0.83, P = 0.0001) and 5-year overall survival (OS) (HR: 0.77, 95% CI, 0.62-0.95, P = 0.01), while subgroup analysis indicated that there was no significant difference between upfront PTR and upfront chemotherapy (CT) group. In addition, grade 3 or higher adverse effects due to CT were more frequent in the PTR group with marginal significance (OR: 1.74, 95% CI, 0.99-3.06, P = 0.05), and other adverse outcomes were comparable. CONCLUSIONS PTR might be related to improved OS for asymptomatic patients with unresectable stage IV CRC, whereas receiving upfront CT is a rational alternative without detrimental influence on survival or adverse outcomes compared with upfront PTR. SYSTEMATIC REVIEW REGISTRATION https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=272675.
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Affiliation(s)
- Zongyu Liang
- Department of Gastrointestinal Surgery, Second Department of General Surgery, The Sixth Affiliated Hospital, School of Medicine, South China University of Technology, Foshan, China
- Department of Gastrointestinal Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
- Shantou University Medical College, Shantou, China
- Guangdong Provincial People’s Hospital Ganzhou Hospital (Ganzhou Municipal Hospital), Ganzhou, China
| | - Zhiyuan Liu
- Department of Gastrointestinal Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
- Shantou University Medical College, Shantou, China
- Guangdong Provincial People’s Hospital Ganzhou Hospital (Ganzhou Municipal Hospital), Ganzhou, China
| | - Chengzhi Huang
- Department of Gastrointestinal Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
- Guangdong Provincial People’s Hospital Ganzhou Hospital (Ganzhou Municipal Hospital), Ganzhou, China
- School of Medicine, South China University of Technology, Guangzhou, China
| | - Xin Chen
- Department of Gastrointestinal Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
- Shantou University Medical College, Shantou, China
- Guangdong Provincial People’s Hospital Ganzhou Hospital (Ganzhou Municipal Hospital), Ganzhou, China
| | - Zhaojun Zhang
- Department of Gastrointestinal Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
- Guangdong Provincial People’s Hospital Ganzhou Hospital (Ganzhou Municipal Hospital), Ganzhou, China
- School of Biology and Biological Engineering, South China University of Technology, Guangzhou, China
| | - Meijuan Xiang
- Department of Gastrointestinal Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
- Guangdong Provincial People’s Hospital Ganzhou Hospital (Ganzhou Municipal Hospital), Ganzhou, China
- School of Biology and Biological Engineering, South China University of Technology, Guangzhou, China
| | - Weixian Hu
- Department of Gastrointestinal Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Junjiang Wang
- Department of Gastrointestinal Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
- Shantou University Medical College, Shantou, China
- School of Medicine, South China University of Technology, Guangzhou, China
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China
| | - Xingyu Feng
- Department of Gastrointestinal Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
- Correspondence: Xingyu Feng ; Xueqing Yao
| | - Xueqing Yao
- Department of Gastrointestinal Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
- Shantou University Medical College, Shantou, China
- Guangdong Provincial People’s Hospital Ganzhou Hospital (Ganzhou Municipal Hospital), Ganzhou, China
- School of Medicine, South China University of Technology, Guangzhou, China
- School of Biology and Biological Engineering, South China University of Technology, Guangzhou, China
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China
- Correspondence: Xingyu Feng ; Xueqing Yao
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van der Kruijssen DEW, Elias SG, Vink GR, van Rooijen KL, 't Lam-Boer J, Mol L, Punt CJA, de Wilt JHW, Koopman M. Sixty-Day Mortality of Patients With Metastatic Colorectal Cancer Randomized to Systemic Treatment vs Primary Tumor Resection Followed by Systemic Treatment: The CAIRO4 Phase 3 Randomized Clinical Trial. JAMA Surg 2021; 156:1093-1101. [PMID: 34613339 DOI: 10.1001/jamasurg.2021.4992] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
Importance The role of primary tumor resection (PTR) in synchronous patients with metastatic colorectal cancer (mCRC) who had unresectable metastases and few or absent symptoms of their primary tumor is unclear. Studying subgroups with low postoperative mortality may identify patients who potentially benefit from PTR. Objective To determine the difference in 60-day mortality between patients randomized to systemic treatment only vs PTR followed by systemic treatment, and to explore risk factors associated with 60-day mortality. Design, Setting, and Participants CAIRO4 is a randomized phase 3 trial initiated in 2012 in which patients with mCRC were randomized to systemic treatment only or PTR followed by systemic treatment with palliative intent. This multicenter study was conducted by the Danish and Dutch Colorectal Cancer Group in general and academic hospitals in Denmark and the Netherlands. Patients included between August 2012 and December 2019 with histologically proven colorectal cancer, unresectable metastases, and a primary tumor with few or absent symptoms were eligible. Interventions Systemic treatment, consisting of fluoropyrimidine-based chemotherapy with bevacizumab vs PTR followed by fluoropyrimidine-based chemotherapy with bevacizumab. Main Outcomes and Measures The aim of the current analysis was to compare 60-day mortality rates in both treatment arms. A secondary aim was the identification of risk factors for 60-day mortality in the treatment arms. These aims were not predefined in the study protocol. Results A total of 196 patients were included in the intention-to-treat analysis (112 [57%] men; median [IQR] age, 65 [59-70] years). Sixty-day mortality was 3% (95% CI, 1%-9%) in the systemic treatment arm and 11% (95% CI, 6%-19%) in the PTR arm (P = .03). In a per-protocol analysis, 60-day mortality was 2% (95% CI, 1%-7%) vs 10% (95% CI, 5%-18%; P = .048). Patients with elevated serum levels of lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, and/or neutrophils who were randomized to PTR had a significantly higher 60-day mortality than patients without these characteristics. Conclusions and Relevance Patients with mCRC who were randomized to PTR followed by systemic treatment had a higher 60-day mortality than patients randomized to systemic treatment. Especially patients randomized to the PTR arm with elevated serum levels of lactate dehydrogenase, neutrophils, aspartate aminotransferase, and/or alanine aminotransferase were at high risk of postoperative mortality. Final study results on overall survival have to be awaited. Trial Registration ClinicalTrials.gov Identifier: NCT01606098.
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Affiliation(s)
- Dave E W van der Kruijssen
- Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
| | - Sjoerd G Elias
- Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
| | - Geraldine R Vink
- Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.,Department of Research and Development, Netherlands Comprehensive Cancer Organisation (IKNL), Utrecht, the Netherlands
| | - Karlijn L van Rooijen
- Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
| | - Jorine 't Lam-Boer
- Department of Surgery, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Linda Mol
- Clinical Research Department, Netherlands Comprehensive Cancer Organisation (IKNL), Utrecht, the Netherlands
| | - Cornelis J A Punt
- Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
| | - Johannes H W de Wilt
- Department of Surgery, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Miriam Koopman
- Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
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Primary Tumor-Related Complications Among Patients With Unresectable Stage IV Colorectal Cancer in the Era of Targeted Therapy: A Competing Risk Regression Analysis. Dis Colon Rectum 2021; 64:1074-1082. [PMID: 34397558 DOI: 10.1097/dcr.0000000000002010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND Whether prolonged survival with current chemotherapy using molecular target agents has changed the rate of primary tumor-related complications in patients with unresectable stage IV colorectal cancer is unclear. OBJECTIVE This study aimed to investigate the rate of primary tumor-related complications among patients receiving targeted therapy as compared with patients receiving chemotherapy without molecular target agents. DESIGN This was a retrospective review of data from a prospectively maintained database. SETTINGS The study was conducted at a high-volume multidisciplinary tertiary cancer center in Japan. PATIENTS Subjects were 352 consecutive patients with unresectable stage IV colorectal cancer who received systemic chemotherapy without primary tumor resection from 2001 to 2015. Patients were categorized into nontargeted and targeted groups according to the use of molecular target agents. MAIN OUTCOME MEASURES Complication rates attributed to primary tumors were measured. RESULTS Of the 352 patients, 159 were categorized into the nontargeted group and 193 patients into the targeted group. Competing risk-adjusted univariate analysis revealed that the primary tumor-related complication rates in the nontargeted group were 6.9% (95% CI, 3.8%-11.9%) at 1 year and 8.2% (95% CI, 4.8%-13.8%) at 2 years, whereas the targeted group had complication rates of 11.5% (95% CI, 7.5%-16.6%) at 1 year and 16.7% (95% CI, 12.4%-23.3%) at 2 years. Multivariate analysis revealed that the targeted group was ≈2 times more likely to have primary tumor-related complications (subdistribution HR = 2.04 (95% CI, 1.12-4.01); p = 0.020). Median survival time was 12.0 months in the nontargeted group and 24.1 months in the targeted group (p < 0.001). LIMITATIONS This study was limited by the retrospective design. CONCLUSIONS Targeted therapy was associated with a significantly increased risk of primary tumor-related complications during chemotherapy. However, targeted therapy also improved overall survival, making it a tolerable therapy. See Video Abstract at http://links.lww.com/DCR/B536. COMPLICACIONES PRIMARIAS RELACIONADAS CON EL TUMOR ENTRE PACIENTES CON CNCER COLORRECTAL EN ESTADIO IV IRRESECABLE EN LA ERA DE LA TERAPIA DIRIGIDA UN ANLISIS DE REGRESIN DEL RIESGO COMPETITIVO ANTECEDENTES:No está claro si la supervivencia prolongada con la quimioterapia actual utilizando agentes moleculares dirigidos ha cambiado la tasa de complicaciones relacionadas con el tumor primario en pacientes con cáncer colorrectal en estadio IV irresecable.OBJETIVO:Este estudio tuvo como objetivo investigar la tasa de complicaciones relacionadas con el tumor primario entre los pacientes que reciben terapia dirigida, en comparación con pacientes que reciben quimioterapia sin agentes moleculares dirigidos.DISEÑO:Revisión retrospectiva de datos de una base de datos mantenida prospectivamente.ESCENARIO CLINICO:Centro oncológico de tercer nivel multidisciplinario de alto volumen en Japón.PACIENTES:352 pacientes consecutivos con cáncer colorrectal en estadio IV irresecable que recibieron quimioterapia sistémica sin resección del tumor primario entre 2001 y 2015. Los pacientes se clasificaron en grupos dirigidos y no dirigidos según el uso de agentes moleculares dirigidos.PRINCIPALES MEDIDAS DE VALORACION:Tasas de complicaciones debidas a tumores primarios.RESULTADOS:De los 352 pacientes, 159 se clasificaron en el grupo no dirigido y 193 pacientes en el grupo dirigido. El análisis univariado ajustado al riesgo competitivo reveló que las tasas de complicaciones primarias relacionadas con el tumor en el grupo no dirigido fueron del 6,9% (intervalo de confianza (IC) del 95%, 3,8 - 11,9%) al año y del 8,2% (IC del 95%, 4,8%). - 13,8%) a los dos años, mientras que el grupo dirigido tuvo tasas de complicaciones del 11,5% (IC del 95%, 7,5 - 16,6%) al año y del 16,7% (IC del 95%, 12,4 - 23,3%) a los dos años. El análisis multivariado reveló que el grupo dirigido tenía aproximadamente dos veces más probabilidades de tener complicaciones relacionadas con el tumor primario (razón de riesgo de subdistribución, 2,04; IC del 95%, 1,12 a 4,01; p = 0,020). La mediana del tiempo de supervivencia fue de 12,0 meses en el grupo no dirigido y de 24,1 meses en el grupo dirigido (p <0,001).LIMITACIONES:Este estudio estuvo limitado por el diseño retrospectivo.CONCLUSIONES:La terapia dirigida se asoció con un riesgo significativamente mayor de complicaciones relacionadas con el tumor primario durante la quimioterapia. Sin embargo, la terapia dirigida también mejoró la SG, convirtiéndola en una terapia tolerable. Consulte Video Resumen en http://links.lww.com/DCR/B536.
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Impact of Primary Tumor Resection on Mortality in Patients with Stage IV Colorectal Cancer with Unresectable Metastases: A Multicenter Retrospective Cohort Study. World J Surg 2021; 45:3230-3239. [PMID: 34223985 DOI: 10.1007/s00268-021-06233-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/18/2021] [Indexed: 12/24/2022]
Abstract
BACKGROUND Primary tumor resection (PTR) before commencing systemic chemotherapy in patients with stage IV colorectal cancer and unresectable metastases (mCRC) remains controversial. This study aimed to assess whether PTR before systemic chemotherapy is associated with mortality in mCRC patients, after adjusting for confounding factors, such as the severity of the primary tumor and metastatic lesions. METHODS We analyzed hospital-based cancer registries from nine designated cancer hospitals in Fukushima Prefecture, Japan. Patients were divided into two groups (PTR and non-PTR), based on whether PTR was performed as initial therapy for mCRC or not. The primary outcome was all-cause mortality. Kaplan-Meier survival analysis was performed, and survival estimates were compared using the log-rank test. Adjusted hazard ratios were calculated using Cox regression to adjust for confounding factors. All tests were two-sided; P-values < 0.05 were considered statistically significant. RESULTS Between 2008 and 2015, 616 mCRC patients were included (PTR: 414 [67.2%]; non-PTR: 202 [32.8%]). The median follow-up time was 18.0 (interquartile range [IQR]: 8.4-29.7) months, and 492 patients (79.9%) died during the study period. Median overall survival in the PTR and non-PTR groups was 23.9 (IQR: 12.2-39.9) and 12.3 (IQR: 6.2-23.8) months, respectively (P < 0.001, log-rank test). PTR was significantly associated with improved overall survival (adjusted hazard ratio: 0.51; 95% confidence interval: 0.42-0.64, P < 0.001). CONCLUSIONS PTR before systemic chemotherapy in patients with mCRC was associated with improved survival.
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Prognostic value of regional lymph node involvement in patients with metastatic colorectal cancer: palliative versus curative resection. World J Surg Oncol 2021; 19:150. [PMID: 33985521 PMCID: PMC8120831 DOI: 10.1186/s12957-021-02260-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Accepted: 05/05/2021] [Indexed: 12/11/2022] Open
Abstract
Background Approximately 20% of patients with colorectal cancer are initially diagnosed with stage IV disease. This study aims to examine the role of regional lymph node (LN) status in metastatic colorectal cancer (mCRC) with respect to clinicopathologic features and survival outcomes. Methods We investigated 1147 patients diagnosed with mCRC and had undergone surgical resection of the primary CRC. A total of 167 patients were placed in the LN-negative (LN−) group and another 980 in the LN-positive (LN+) group. Results LN+ patients exhibited a significantly higher rate of T4 tumors (p = 0.008), poorly differentiated adenocarcinoma (p < 0.001), lymphovascular invasion (p < 0.001), and perineural invasion (p < 0.001) than those in the LN− group. LN− patients had a significantly higher rate of lung metastasis (p < 0.001), whereas the rate of peritoneal seeding (p < 0.001) and systemic node metastasis (p < 0.001) was both significantly higher in the LN+ group. The 5-year overall survival (OS) in the LN+ group was significantly poorer than that in the LN− group (LN− vs. LN+ 23.2% vs. 18.1%; p = 0.040). In patients with curative resection, the 5-year OS rate has no significant difference between the two groups (LN− vs. LN+ 19.5% vs. 24.3%; p = 0.890). Conclusions Metastatic CRC patients with LN+ who underwent primary tumor resection may present with more high-risk pathological features, more peritoneal seeding, and systemic node metastasis, but less lung metastasis than LN− patients. LN+ patients had poorer long-term outcomes compared with that in LN− patients. Nevertheless, with curative resection, LN+ patients could have similar survival outcomes as LN− patients.
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Rim CH, Shin IS, Park S, Lee HY. Benefits of local consolidative treatment in oligometastases of solid cancers: a stepwise-hierarchical pooled analysis and systematic review. NPJ Precis Oncol 2021; 5:2. [PMID: 33479481 PMCID: PMC7820397 DOI: 10.1038/s41698-020-00141-4] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2020] [Accepted: 12/01/2020] [Indexed: 01/29/2023] Open
Abstract
We conducted a meta-analysis of articles published in PubMed, MEDLINE, EMBASE, and Cochrane library to investigate the effectiveness of local consolidative therapy (LCT) against oligometastases. Data from randomized controlled trials (RCTs), balanced studies, and all studies combined were analyzed in a hierarchical manner. Pooled analyses of 31 studies (including seven randomized trials) investigating the effectiveness of LCT on overall survival revealed odds ratios of 3.04, 2.56, and 1.41 for all studies, balanced studies, and RCTs, respectively (all p < 0.05). The benefit of LCT was more prominent in patients with non-small cell lung and colorectal cancers than in those with prostate and small cell lung cancers. Moreover, the benefit of LCT was smaller in patients with high metastatic burdens (p = 0.054). In four of 12 studies with available information, additional grade ≥3 toxicities due to LCTs were reported. Overall, LCT is beneficial for patients with oligometastases, although such benefits are less evident in RCTs than in observational studies. Appropriate LCTs should be carefully selected considering their feasibility, disease type, and metastatic burden.
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Affiliation(s)
- Chai Hong Rim
- grid.222754.40000 0001 0840 2678Department of Radiation Oncology, Ansan Hospital, Korea University Medical College, Ansan, Gyeonggi-do Republic of Korea
| | - In-Soo Shin
- grid.255168.d0000 0001 0671 5021Graduate school of Education, Dongguk University, Seoul, Korea
| | - Sunmin Park
- grid.222754.40000 0001 0840 2678Department of Radiation Oncology, Ansan Hospital, Korea University Medical College, Ansan, Gyeonggi-do Republic of Korea
| | - Hye Yoon Lee
- grid.222754.40000 0001 0840 2678Department of General Surgery, Ansan Hospital, Korea University Medical College, Ansan, Gyeonggi-do Republic of Korea
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Alese OB, Zakka K, Huo X, Jiang R, Shaib WL, Akce M, Behera M, Sullivan P, Wu C, El-Rayes BF. Perioperative therapy in metastatic colorectal cancer: Pattern of use and survival outcomes. J Surg Oncol 2020; 123:596-605. [PMID: 33125756 DOI: 10.1002/jso.26278] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2020] [Revised: 10/09/2020] [Accepted: 10/12/2020] [Indexed: 12/24/2022]
Abstract
BACKGROUND Multimodality therapy of metastatic colorectal cancer (mCRC) is currently considered the standard of care. The aim of this study was to evaluate the impact of perioperative therapy on surgical resection in mCRC. METHODS The National Cancer Database was analyzed for affected patients between 2004 and 2013. Univariate and multivariate analyses were done to identify factors associated with patient outcomes. Kaplan-Meier analysis and Cox proportional hazards models were used for the association between patient characteristics and survival. RESULTS About 61,940 patients with mCRC were identified. Mean age = 63.4 years (SD ± 14). About 69% had a colon primary and 32% had only one metastatic site. Only 49% of those who underwent surgery for both primary and metastatic sites received postoperative chemotherapy (p < .001). Negative prognostic factors included no chemotherapy received (hazard ratio [HR], 2.32; 2.27-2.37; p < .001), more than three metastatic sites (HR, 2.28; 2.09-2.48; p < .001), year of diagnosis between 2004 and 2008 (HR, 1.71; 1.15-1.20; p < .001) and colon tumor location with right worse than left-sided (HR, 1.21; 1.19-1.24; p < .001). Five-year overall survival for resection of the primary and metastatic site (28.2%) was higher than for no surgical treatment (4.7%). CONCLUSION Perioperative therapy was associated with improved survival, following resection of metastatic sites or primary tumor.
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Affiliation(s)
- Olatunji B Alese
- Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia, USA
| | - Katerina Zakka
- Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia, USA
| | - Xingyue Huo
- Winship Research Informatics, Emory University, Atlanta, Georgia, USA
| | - Renjian Jiang
- Winship Research Informatics, Emory University, Atlanta, Georgia, USA
| | - Walid L Shaib
- Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia, USA
| | - Mehmet Akce
- Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia, USA
| | - Madhusmita Behera
- Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia, USA.,Winship Research Informatics, Emory University, Atlanta, Georgia, USA
| | - Patrick Sullivan
- Division of General and GI Surgery, Department of Surgery, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Christina Wu
- Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia, USA
| | - Bassel F El-Rayes
- Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia, USA
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Huang Y, Ge K, Fu G, Chu J, Wei W. Efficacy of Primary Tumor Resection in Metastatic Colorectal Cancer. Med Sci Monit 2020; 26:e923501. [PMID: 32859887 PMCID: PMC7477930 DOI: 10.12659/msm.923501] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2020] [Accepted: 05/11/2020] [Indexed: 11/09/2022] Open
Abstract
BACKGROUND The aim of this study was to evaluate the survival benefit of palliative primary tumor resection in colorectal cancer (CRC) patients with unresectable metastases. MATERIAL AND METHODS Clinicopathological characteristics of eligible patients who underwent surgery to remove the primary tumor and those who did not between 2004 and 2013 were compared. We also evaluated the association between survival and different clinicopathologic characteristics in metastatic CRC. RESULTS The percentage of patients undergoing surgical resection of the primary tumor was higher during the earlier years and trended toward less use of surgery in later years. Palliative primary tumor resection was strongly associated with better cause-specific survival (hazard ratio=0.403, 95% confidence interval=0.389 to 0.417, P<0.001). CONCLUSIONS We added new strong evidence supporting the survival benefit of palliative resection, which should be confirmed in future randomized controlled trials.
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Affiliation(s)
- Yong Huang
- Department of General Surgery, Jiangdu People’s Hospital Affiliated to Medical College of Yangzhou University, Yangzhou, Jiangsu, P.R. China
| | - Kuanxue Ge
- Department of Gastroenterology, Jiangdu People’s Hospital Affiliated to Medical College of Yangzhou University, Yangzhou, Jiangsu, P.R. China
| | - Guangshun Fu
- Department of General Surgery, Jiangdu People’s Hospital Affiliated to Medical College of Yangzhou University, Yangzhou, Jiangsu, P.R. China
| | - Junfeng Chu
- Department of Radiotherapy, Jiangdu People’s Hospital Affiliated to Medical College of Yangzhou University, Yangzhou, Jiangsu, P.R. China
| | - Wei Wei
- Department of General Surgery, Jiangdu People’s Hospital Affiliated to Medical College of Yangzhou University, Yangzhou, Jiangsu, P.R. China
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Yang Y, Lu Y, Jiang W, Zhu J, Yan S. Individualized prediction of survival benefit from primary tumor resection for patients with unresectable metastatic colorectal cancer. World J Surg Oncol 2020; 18:193. [PMID: 32746835 PMCID: PMC7401291 DOI: 10.1186/s12957-020-01972-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2020] [Accepted: 07/28/2020] [Indexed: 12/14/2022] Open
Abstract
Background The impact of primary tumor resection (PTR) on the prognosis of unresectable metastatic colorectal cancer (mCRC) patients remains debatable. We aimed to develop several prognostic nomograms which could be useful in predicting whether patients might benefit from PTR or not. Methods Patients diagnosed as mCRC without resected metastasis were identified from the Surveillance Epidemiology and End Results database and randomly assigned into two groups: a training cohort (6369 patients) and a validation cohort (2774 patients). Univariate and multivariable Cox analyses were performed to identify the independent predictors and construct nomograms that could independently predict the overall survival (OS) of unresectable mCRC patients in PTR and non-PTR groups, respectively. The performance of these nomograms was assessed by the concordance index (C-index), calibration curves, and decision curve analysis (DCA). Results Based on the result of univariate and multivariable Cox analyses, two nomograms were respectively constructed to predict the 1-year OS rates of unresectable mCRC patients when receiving PTR and not. The first one included age, gender, tumor grade, proximal colon, N stage, CEA, chemotherapy, radiotherapy, histology type, brain metastasis, liver metastasis, lung metastasis, and bone metastasis. The second nomogram included age, race, tumor grade, primary site, CEA, chemotherapy, brain metastasis, and bone metastasis. These nomograms showed favorable sensitivity with the C-index range of 0.700–0.725. The calibration curves and DCAs also exhibited adequate fit and ideal net benefits in prognosis prediction and clinical application. Conclusions These practical prognosis nomograms could assist clinicians in making appropriate treatment decisions to effectively manage the disease.
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Affiliation(s)
- Yi Yang
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, 899 Pinghai Road, Suzhou, 215006, Jiangsu, China
| | - Yujie Lu
- Department of Oncology, The First Affiliated Hospital of Soochow University, 899 Pinghai Road, Suzhou, 215006, Jiangsu, China
| | - Wen Jiang
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, 899 Pinghai Road, Suzhou, 215006, Jiangsu, China
| | - Jinzhou Zhu
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, 899 Pinghai Road, Suzhou, 215006, Jiangsu, China
| | - Su Yan
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, 899 Pinghai Road, Suzhou, 215006, Jiangsu, China.
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Chen X, Hu W, Huang C, Liang W, Zhang J, Wu D, Lv Z, Li Y, Luo Y, Liang Z, Wang M, Wang J, Yao X. Survival outcome of palliative primary tumor resection for colorectal cancer patients with synchronous liver and/or lung metastases: A retrospective cohort study in the SEER database by propensity score matching analysis. Int J Surg 2020; 80:135-152. [PMID: 32634480 DOI: 10.1016/j.ijsu.2020.06.024] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2020] [Revised: 06/09/2020] [Accepted: 06/13/2020] [Indexed: 01/05/2023]
Abstract
BACKGROUND There is a great matter of controversies whether some of these synchronous metastatic colorectal cancer patients can benefit from palliative primary tumor resection (pPTR) and there is still no reported randomized control trial to address this issue. METHODS Patients with microscopically proven metastatic colorectal cancer were identified within the SEER database (2010-2016). Patients were propensity matched 1:1 into pPTR and non-surgery groups and among the matched cohort, the univariable and multivariable Cox proportional hazards regression models were performed to identify predictors of survival. Median survival was calculated by using the Kaplan-Meier method. RESULTS Of 21,405 colorectal cancer patients diagnosed with synchronous liver and/or lung metastases, 7386 were identified in the matched cohort. The median overall survival was 12.0 months, 22.0 months in the non-surgery, surgery groups, respectively (p < 0.001) and the corresponding median cancer-specific survival was 13.0 months, 22.0 months, respectively (p < 0.001). Multivariable Cox regression analysis demonstrated that surgery was independently associated with improved overall survival (hazard ratio, 0.531) as well as cancer-specific survival (hazard ratio, 0.516). In stratified analyses by primary site and patterns of distant metastases, those patients with pPTR had better prognosis. In addition, stratified analysis revealed that trimodality therapy was linked with the greatest therapeutic effect followed by addition of chemotherapy to pPTR. CONCLUSIONS pPTR may offer some therapeutic benefits among carefully selected patients, and surgery-based multimodality therapy was associated with better survival.
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Affiliation(s)
- Xianzhe Chen
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, China; Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, 510080, China.
| | - Weixian Hu
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, China; Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, 510080, China.
| | - Chengzhi Huang
- Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, 510080, China; School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510006, China.
| | - Weijun Liang
- Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, 510080, China; Medical College of Shantou University, Shantou, Guangdong, 515000, China.
| | - Jie Zhang
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, China; Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, 510080, China.
| | - Deqing Wu
- Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, 510080, China.
| | - Zejian Lv
- Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, 510080, China.
| | - Yong Li
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, China; Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, 510080, China; Medical College of Shantou University, Shantou, Guangdong, 515000, China; School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510006, China.
| | - Yuwen Luo
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, China; Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, 510080, China.
| | - Zongyu Liang
- Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, 510080, China; Medical College of Shantou University, Shantou, Guangdong, 515000, China.
| | - Minjia Wang
- Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, 510080, China; School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510006, China.
| | - Junjiang Wang
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, China; Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, 510080, China.
| | - Xueqing Yao
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, China; Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, 510080, China; Medical College of Shantou University, Shantou, Guangdong, 515000, China; School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510006, China.
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Breugom A, Bastiaannet E, Guren M, Kørner H, Boelens P, Dekker F, Kapiteijn E, Gelderblom H, Larsen I, Liefers G, van de Velde C. Treatment strategies and overall survival for incurable metastatic colorectal cancer – A EURECCA international comparison including 21,196 patients from the Netherlands and Norway. Eur J Surg Oncol 2020; 46:1167-1173. [DOI: 10.1016/j.ejso.2020.02.005] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2019] [Revised: 01/15/2020] [Accepted: 02/10/2020] [Indexed: 12/26/2022] Open
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Xu J, Ma T, Ye Y, Pan Z, Lu D, Pan F, Peng W, Sun G. Surgery on primary tumor shows survival benefit in selected stage IV colon cancer patients: A real-world study based on SEER database. J Cancer 2020; 11:3567-3579. [PMID: 32284753 PMCID: PMC7150453 DOI: 10.7150/jca.43518] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2019] [Accepted: 03/02/2020] [Indexed: 12/16/2022] Open
Abstract
Objectives: Most patients with stage IV colon cancer did not have the opportunity for curative surgery, only selected patients could benefit from surgery. This study aimed to determine whether surgery on the primary tumor (SPT) should be performed in patients with stage IV colon cancer and how to select patients for SPT. Methods: This study included 48,933 patients with stage IV colon cancer who were identified in the Surveillance, Epidemiology and End Results (SEER) database between 1998 and 2015. Propensity score matching (PSM) analysis was adopted to balance baseline differences between SPT and non-surgery groups. Kaplan-Meier (K-M) curves were utilized to compare the overall survival (OS). Prognostic nomograms were generated to predict survival based on pre- and post-operative risk factors. Patients were divided into low, middle, and high mortality risk subsets for OS by X-tile analyses based on scores derived from above nomograms. Results: Patients with SPT had a significantly longer OS than those without surgery, regardless of the metastatic sites and diagnostic years. Nomograms, according to the pre- and post-operative risk factors, showed moderate discrimination (all C-indexes above 0.7). Based on X-tile analyses, low mortality risk subset (post-operative score ≤ 22.3, preoperative score ≤ 9.7) recommended for SPT, and high mortality risk was not. Conclusions: SPT led to prolonged survival in stage IV colon cancer. Our nomograms would help to select suitable patients for SPT.
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Affiliation(s)
- Jing Xu
- Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province 230000, China
| | - Tai Ma
- Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province 230000, China
| | - Yuanzi Ye
- Department of Pathology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province 230000, China
| | - Zhipeng Pan
- Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province 230000, China
| | - Donghui Lu
- Department of Radiology, The 901st Hospital of the Joint Logistics Support Force of PLA, Hefei, Anhui Province 230031, China
| | - Faming Pan
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui Province 230000, China
| | - Wanren Peng
- Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province 230000, China
| | - Guoping Sun
- Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province 230000, China
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Ergun Y, Bal O, Dogan M, Ucar G, Dirikoc M, Acikgoz Y, Bacaksiz F, Uncu D. Does primary tumor resection contribute to overall survival in unresectable synchronous metastatic colorectal cancer? JOURNAL OF RESEARCH IN MEDICAL SCIENCES : THE OFFICIAL JOURNAL OF ISFAHAN UNIVERSITY OF MEDICAL SCIENCES 2020; 25:14. [PMID: 32174986 PMCID: PMC7053176 DOI: 10.4103/jrms.jrms_1056_18] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/31/2018] [Revised: 02/15/2019] [Accepted: 11/22/2019] [Indexed: 12/17/2022]
Abstract
BACKGROUND Primary tumor resection (PTR) in metastatic colorectal cancer (mCRC) has not been suggested by guidelines, since new systemic chemotherapy options have improved overall survival. However, the effect of PTR is still controversial in mCRC. In this study, we aimed to evaluate the effect of PTR on survival in unresectable mCRC. MATERIALS AND METHODS Two hundred and fifty-two patients with unresectable mCRC were screened retrospectively between January 2007 and December 2017 and a total of 147 patients who met inclusion criteria were included. The patients with emergency or elective PTR and the patients without surgery were compared for baseline features and overall survival. RESULTS The median follow-up time was 15.6 months (range; 1.2-78.9) in whole patients. There were 91 patients in nonsurgical (NS) group and 56 patients in PTR group. The median overall survival was significantly longer in PTR group compared NS group (21.8 vs. 17.0 months, P = 0.01), but it was not associated to better overall survival in multivariate Cox analysis (hazard ratio: 0.65, 95% confidence interval: 0.41-1.02, P = 0.06). There was no significant difference in overall survival between emergency and elective surgery subgroups (22.9 vs. 16.1 months, respectively, P = 0.9). CONCLUSION PTR did not offer an overall survival benefit in this study. Although it is debated, we think that it is better to start treatment with chemotherapy and biological agent combinations in patients with asymptomatic mCRC. Thus, the patients can be protected from the morbidity and mortality of the surgery.
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Affiliation(s)
- Yakup Ergun
- Department of Medical Oncology, Ankara Numune Training and Research Hospital, Ankara, Turkey
| | - Oznur Bal
- Department of Medical Oncology, Ankara Numune Training and Research Hospital, Ankara, Turkey
| | - Mutlu Dogan
- Department of Medical Oncology, Ankara Numune Training and Research Hospital, Ankara, Turkey
| | - Gokhan Ucar
- Department of Medical Oncology, Ankara Numune Training and Research Hospital, Ankara, Turkey
| | - Merve Dirikoc
- Department of Medical Oncology, Ankara Numune Training and Research Hospital, Ankara, Turkey
| | - Yusuf Acikgoz
- Department of Medical Oncology, Ankara Numune Training and Research Hospital, Ankara, Turkey
| | - Ferhat Bacaksiz
- Department of Gastroenterology, Yuksek Ihtisas Training and Research Hospital, Ankara, Turkey
| | - Dogan Uncu
- Department of Medical Oncology, Ankara Numune Training and Research Hospital, Ankara, Turkey
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Lillemoe HA, Vauthey JN. Surgical approach to synchronous colorectal liver metastases: staged, combined, or reverse strategy. Hepatobiliary Surg Nutr 2020; 9:25-34. [PMID: 32140476 DOI: 10.21037/hbsn.2019.05.14] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
An increasing number of patients with colorectal cancer (CRC) are presenting with synchronous disease to the liver. The optimal surgical approach for this complex patient group is controversial, but ultimately depends on individual patient characteristics and institutional practices. Surgical strategies include the traditional staged approach, a combined colorectal and liver resection, or a liver-first reverse approach. In this review, the authors will provide an overview of each strategy, including case examples demonstrating the benefits of the more recently described liver-first approach, while arguing for individualized planning and multidisciplinary discussion for every patient.
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Affiliation(s)
- Heather A Lillemoe
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Jean-Nicolas Vauthey
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
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Fiori E, Lamazza A, Sterpetti AV, Crocetti D, DE Felice F, DI Muzio M, Mingoli A, Sapienza P, DE Toma G. Quality of Life for Patients With Incurable Stage IV Colorectal Cancer: Randomized Controlled Trial Comparing Resection Versus Endoscopic Stenting. In Vivo 2019; 33:2065-2070. [PMID: 31662539 PMCID: PMC6899085 DOI: 10.21873/invivo.11705] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2019] [Revised: 09/09/2019] [Accepted: 09/11/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND/AIM A prospective randomized open label parallel trial, comparing the quality of life (QoL) after endoscopic placement of a self-expandable metal stent or primary tumor resection, in patients with stage IV colorectal cancer was performed. PATIENTS AND METHODS Thirty-three patients affected with stage IV colorectal cancer and unresectable metastases were randomly assigned into two groups: Group 1 (16 patients), that underwent self-expandable metal stent positioning and Group 2 (17 patients), in which primary tumor resection was performed. Karnofsky performance scale and QoL assessment using the EQ-5D-5L™ questionnaire was administered before treatment and thereafter at 1, 3 and 6 months. RESULTS At 1 month, index values showed a statistically significant deterioration of the QoL in patients of Group 2 when compared to those of Group 1 (p=0.001; 95%CI=0.065-0.211) whereas, at 6 months, index values showed a statistically significant deterioration of the QoL in patients of Group 1 (p<0.025; 95%CI=0.017-0.238). CONCLUSION QoL in patients affected with stage IV colorectal cancer has a bimodal fluctuation pattern: at 1-month it was better in patients that received stent, but at 6-months it was significantly better in patients submitted to surgical resection.
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Affiliation(s)
- Enrico Fiori
- Department of Surgery "Pietro Valdoni", "Sapienza" University of Rome, Rome, Italy
| | - Antonietta Lamazza
- Department of Surgery "Pietro Valdoni", "Sapienza" University of Rome, Rome, Italy
| | - Antonio V Sterpetti
- Department of Surgery "Pietro Valdoni", "Sapienza" University of Rome, Rome, Italy
| | - Daniele Crocetti
- Department of Surgery "Pietro Valdoni", "Sapienza" University of Rome, Rome, Italy
| | - Francesca DE Felice
- Department of Radiology, Radiotherapy, Oncology and Anatomopathology, "Sapienza" University of Rome, Rome, Italy
| | - Marco DI Muzio
- Department of Clinical and Molecular Medicine, "Sapienza" University of Rome, Rome, Italy
| | - Andrea Mingoli
- Department of Surgery "Pietro Valdoni", "Sapienza" University of Rome, Rome, Italy
| | - Paolo Sapienza
- Department of Surgery "Pietro Valdoni", "Sapienza" University of Rome, Rome, Italy
| | - Giorgio DE Toma
- Department of Surgery "Pietro Valdoni", "Sapienza" University of Rome, Rome, Italy
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Leijssen LGJ, Dinaux AM, Kunitake H, Bordeianou LG, Berger DL. The impact of postoperative morbidity on survival in patients with metastatic colon and rectal cancer. J Surg Oncol 2019; 120:460-472. [PMID: 31276213 DOI: 10.1002/jso.25610] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2019] [Accepted: 06/13/2019] [Indexed: 12/16/2022]
Abstract
INTRODUCTION Avoiding postoperative morbidity is essential in patients with advanced cancer. To further improve treatment in stage IV colorectal cancer, knowledge about risk factors which effect short- and long-term outcomes is important. METHODS All stage IV colon and rectal cancer who underwent elective surgery between 2004 and 2015 were included (n = 345). We compared resectable colon and rectal patients, and unresectable colon and rectal cancer patients. RESULTS Median follow-up duration was 22.2 (unresectable) and 56.7 months (resectable) with no difference in tumor location. Colon cancer patients were more often considered unresectable (P < .001). Rectal procedures were correlated with a higher morbidity rate and a longer surgical duration (P < .001). In the resectable cohort, obese patients, open procedures and prolonged surgery were independently associated with postoperative complications. Considering the palliative group, neoadjuvant treatment and age were correlated with worse outcomes. Morbidity was not associated with long-term outcomes in the resectable cohort. However, unresectable patients who developed respiratory (hazard ratio [HR]: 7.53) or cardiac (HR: 3.75) complications and patients with an American Society of Anesthesiologists-score III to IV (HR: 1.51) had an impaired survival. CONCLUSION Our results emphasize the need for an adequate preoperative assessment to identify patients at risk for postoperative complications and impaired survival.
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Affiliation(s)
- Lieve G J Leijssen
- Department of General and Gastrointestinal Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | - Anne M Dinaux
- Department of General and Gastrointestinal Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | - Hiroko Kunitake
- Department of General and Gastrointestinal Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | - Liliane G Bordeianou
- Department of General and Gastrointestinal Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | - David L Berger
- Department of General and Gastrointestinal Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
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36
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Wang X, Mao M, Xu G, Lin F, Sun P, Baklaushev VP, Chekhonin VP, Peltzer K, Zhang J, Zhang C. The incidence, associated factors, and predictive nomogram for early death in stage IV colorectal cancer. Int J Colorectal Dis 2019; 34:1189-1201. [PMID: 31089875 DOI: 10.1007/s00384-019-03306-1] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/25/2019] [Indexed: 02/04/2023]
Abstract
PURPOSE The purpose of the present study was to investigate the incidence and associated factors for early death in stage IV colorectal cancer (CRC) and to construct the predictive nomogram. METHODS Patients with stage IV CRC, who had been diagnosed between 2010 and 2014 in the Surveillance, Epidemiology, and End Results datasets, were eligible for this retrospective cohort study. The univariable and multivariable logistic regression models were conducted to determine the associated factors for early death (survival time ≤ 3 months). The predictive nomogram was constructed and the internal validation was performed. RESULTS Ten thousand two hundred sixty-three out of 36,461 (28.1%) eligible patients resulted in all causes of early death (25.8% for cancer-specific early death and 2.3% for non-cancer early death). Advanced age, marital status, right colon, poor differentiation, higher N stage, and bone metastasis were positively associated with all causes of early death, cancer-specific early death, and non-cancer early death, while higher T stage, positive carcinoembryonic antigen, and distant metastases (bone, lung, liver, and brain) were only positively associated with all causes of early death and cancer-specific early death. The calibration curve for all causes of early death, cancer-specific early death, and non-cancer early death showed the prediction curve closely approximated at the 45° line and the areas under the curve were 75.7% (95% CI, 74.9-76.4%), 75.9% (95% CI, 75.1-76.6%), and 76.9% (95% CI, 76.3-77.6%), respectively. CONCLUSIONS The nomogram was calibrated to predict all causes of early death development, cancer-specific early death development, and non-cancer early death development. These findings can be utilized in early screening and to tailor targeted treatment regimens for stage IV CRC patients.
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Affiliation(s)
- Xin Wang
- Department of Epidemiology and Biostatistics, First Affiliated Hospital, Army Medical University, Chongqing, China
| | - Min Mao
- Department of Pathology and Southwest Cancer Center, First Affiliated Hospital, Army Medical University, Chongqing, China
| | - Guijun Xu
- Department of Bone and Soft Tissue Tumors, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Huanhu Xi Road, Tianjin, 300060, China
| | - Feng Lin
- Department of Bone and Soft Tissue Tumors, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Huanhu Xi Road, Tianjin, 300060, China
| | - Peng Sun
- Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
- Department of Colorectal Surgery, National Cancer Center, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Vladimir P Baklaushev
- Federal Research and Clinical Center of Specialized Medical Care and Medical Technologies, Federal Biomedical Agency of the Russian Federation, Moscow, Russian Federation
| | - Vladimir P Chekhonin
- Department of Basic and Applied Neurobiology, Federal Medical Research Center for Psychiatry and Narcology, Moscow, Russian Federation
| | - Karl Peltzer
- Department of Research and Innovation, University of Limpopo, Turfloop, Mankweng, South Africa
| | - Jin Zhang
- Department of Bone and Soft Tissue Tumors, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Huanhu Xi Road, Tianjin, 300060, China.
| | - Chao Zhang
- Department of Bone and Soft Tissue Tumors, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Huanhu Xi Road, Tianjin, 300060, China.
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37
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Lorimer PD, Motz BM, Kirks RC, Han Y, Symanowski JT, Hwang JJ, Salo JC, Hill JS. Frequency of unplanned surgery in patients with stage IV colorectal cancer receiving palliative chemotherapy with an intact primary: An analysis of SEER‐Medicare. J Surg Oncol 2019; 120:407-414. [DOI: 10.1002/jso.25508] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2019] [Accepted: 05/05/2019] [Indexed: 12/19/2022]
Affiliation(s)
- Patrick D. Lorimer
- Department of Surgery, Carolinas Medical CenterLevine Cancer Institute Charlotte North Carolina
| | - Benjamin M. Motz
- Department of Surgery, Carolinas Medical CenterLevine Cancer Institute Charlotte North Carolina
| | - Russell C. Kirks
- Department of Surgery, Carolinas Medical CenterLevine Cancer Institute Charlotte North Carolina
| | - Yimei Han
- Department of Biostatistics, Carolinas Medical CenterLevine Cancer Institute Charlotte North Carolina
| | - James T. Symanowski
- Department of Biostatistics, Carolinas Medical CenterLevine Cancer Institute Charlotte North Carolina
| | - Jimmy J. Hwang
- Department of Surgery, Carolinas Medical CenterLevine Cancer Institute Charlotte North Carolina
| | - Jonathan C. Salo
- Department of Surgery, Carolinas Medical CenterLevine Cancer Institute Charlotte North Carolina
| | - Joshua S. Hill
- Department of Surgery, Carolinas Medical CenterLevine Cancer Institute Charlotte North Carolina
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38
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Simillis C, Kalakouti E, Afxentiou T, Kontovounisios C, Smith JJ, Cunningham D, Adamina M, Tekkis PP. Primary Tumor Resection in Patients with Incurable Localized or Metastatic Colorectal Cancer: A Systematic Review and Meta-analysis. World J Surg 2019; 43:1829-1840. [DOI: 10.1007/s00268-019-04984-2] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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Renz P, Wegner RE, Hasan S, Brookover R, Finley G, Monga D, Raj M, McCormick J, Kirichenko A. Survival Outcomes After Surgical Management of the Primary Tumor With and Without Radiotherapy for Metastatic Rectal Adenocarcinoma: A National Cancer Database (NCDB) Analysis. Clin Colorectal Cancer 2019; 18:e237-e243. [PMID: 30905549 DOI: 10.1016/j.clcc.2018.12.005] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2018] [Revised: 12/21/2018] [Accepted: 12/24/2018] [Indexed: 12/26/2022]
Abstract
BACKGROUND With advances in systemic therapies, the role of primary tumor resection may be of increased importance in patients with metastatic rectal cancer. The role of combining pelvic radiotherapy with surgical resection in the metastatic setting is unknown. We utilized the National Cancer Database to examine outcomes in patients with metastatic rectal adenocarcinoma with primary tumor resection with and without pelvic radiotherapy. MATERIALS AND METHODS We queried the National Cancer Database from 2004 to 2014 for patients with stage IV rectal adenocarcinoma receiving chemotherapy. We identified 4051 patients in that group that had primary tumor resection. Patients were then stratified by receipt of pelvic radiotherapy (yes = 1882; no = 2169) Univariable and multivariable analyses identified characteristics predictive of overall survival. Propensity-adjusted Cox proportional hazard ratios for survival were used to account for indication bias. RESULTS The median patient age was 63 years (range, 18-90 years) with a median follow-up of 32.3 months (range, 3.02-151.29 months). There were proportionately more patients with T3/T4 disease or N1 disease in the surgery plus radiotherapy arm. The median survival was 46.3 months versus 35.3 months in favor of addition of radiotherapy (P < .001). The 2- and 5-year overall survival was 68.4% and 24.8% for surgical resection alone compared with 77.2% and 39.6% for surgery + radiotherapy. On propensity-adjusted multivariable analysis, radiotherapy was associated with a statistically significant reduction in risk of death (hazard ratio, 0.722; 95% confidence interval, 0.0665-0.784). CONCLUSION This analysis indicates that in patients with metastatic rectal adenocarcinoma receiving chemotherapy, pelvic radiotherapy in addition to primary tumor resection may be of significant benefit.
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Affiliation(s)
- Paul Renz
- Division of Radiation Oncology, Allegheny Health Network Cancer Institute, Pittsburgh, PA
| | - Rodney E Wegner
- Division of Radiation Oncology, Allegheny Health Network Cancer Institute, Pittsburgh, PA.
| | - Shaakir Hasan
- Division of Radiation Oncology, Allegheny Health Network Cancer Institute, Pittsburgh, PA
| | - Robert Brookover
- Division of Surgical Oncology, Allegheny Health Network Cancer Institute, Pittsburgh, PA
| | - Gene Finley
- Division of Medical Oncology, Allegheny Health Network Cancer Institute, Pittsburgh, PA
| | - Dulabh Monga
- Division of Medical Oncology, Allegheny Health Network Cancer Institute, Pittsburgh, PA
| | - Moses Raj
- Division of Medical Oncology, Allegheny Health Network Cancer Institute, Pittsburgh, PA
| | - James McCormick
- Division of Surgical Oncology, Allegheny Health Network Cancer Institute, Pittsburgh, PA
| | - Alexander Kirichenko
- Division of Radiation Oncology, Allegheny Health Network Cancer Institute, Pittsburgh, PA
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40
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Abdel-Halim M, Wu H, Poustie M, Beveridge A, Scott N, Mitchell PJ. Survival after non-resection of colorectal cancer: the argument for including non-operatives in consultant outcome reporting in the UK. Ann R Coll Surg Engl 2018; 101:126-132. [PMID: 30354186 DOI: 10.1308/rcsann.2018.0180] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
INTRODUCTION Although the mainstay of colorectal cancer treatment remains operative, a significant proportion of patients end up without surgery. This is because they are either deemed to have no oncological benefit from the resection (too much disease) or to be unfit for major surgery (too frail). The aim of this study was to assess the proportion and survival of these two groups among the totality of practice in a tertiary unit and to discuss the implications on the conceptual understanding of outcome measures. METHODS Data was collected over two study periods with the total duration of four years. Patient demographics, comorbidities, cancer staging and management pathways were all recorded. The primary endpoint was all-cause mortality. RESULTS The total of 909 patients were examined. In the 29% who did not undergo resectional surgery, 6.5% had too little disease, 13.8% had too much disease, while 8.7% were deemed too frail. The highest two-year mortality was observed in the too much (83.2%) and too frail (75.9%) groups, whereas in patients with too little cancer the rate was 5.1%, and in those undergoing a resection it was 19.2% (P < 0.001). CONCLUSIONS The study has expectedly shown poor survival in the too much and too frail groups. We believe that understanding the prognosis in these subgroups is vital, as it informs complex decisions on whether to operate. Moreover, an overall reporting taking into account the proportion of these groups in an multidisciplinary team practice (the non-surgical index) is proposed to render individual surgeon's mortality results meaningful as a comparative measure.
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Affiliation(s)
- M Abdel-Halim
- Department of Colorectal Surgery, Lancashire Teaching Hospitals NHS Foundation Trust, Royal Preston Hospital, Fulwood , Preston , UK
| | - H Wu
- Department of Colorectal Surgery, Lancashire Teaching Hospitals NHS Foundation Trust, Royal Preston Hospital, Fulwood , Preston , UK
| | - M Poustie
- Department of Colorectal Surgery, Lancashire Teaching Hospitals NHS Foundation Trust, Royal Preston Hospital, Fulwood , Preston , UK
| | - A Beveridge
- Department of Colorectal Surgery, Lancashire Teaching Hospitals NHS Foundation Trust, Royal Preston Hospital, Fulwood , Preston , UK
| | - N Scott
- Department of Colorectal Surgery, Lancashire Teaching Hospitals NHS Foundation Trust, Royal Preston Hospital, Fulwood , Preston , UK
| | - P J Mitchell
- Department of Colorectal Surgery, Lancashire Teaching Hospitals NHS Foundation Trust, Royal Preston Hospital, Fulwood , Preston , UK
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To resect or not to resect: The hamletic dilemma of primary tumor resection in patients with asymptomatic stage IV colorectal cancer. Crit Rev Oncol Hematol 2018; 132:154-160. [PMID: 30447921 DOI: 10.1016/j.critrevonc.2018.10.001] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2018] [Accepted: 10/05/2018] [Indexed: 02/07/2023] Open
Abstract
Primary tumor resection (PTR) in advanced asymptomatic colorectal cancer (CRC) has been a matter of intense debate for long time. With the advances in systemic treatments, this practice has decreased over the years, although it remains still pervasive. Although the removal of primary tumor has been extensively interrogated both in retrospective and prospective studies, it still remains a clinical conundrum. There are many arguments for and against PTR in CRC both from the preclinical and the clinical point of view. Two scoring models have been published aiming at identifying patients who are suitable candidate for PTR, but they deserve further investigations in larger datasets. While awaiting the results of ongoing randomized clinical trials (RCTs) on this controversial topic, both upfront systemic treatment and PTR followed by chemotherapy should be considered valid options in patients with asymptomatic mCRC. Clinical selection and a shared-decision making approach are the keys to success.
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Harji DP, Vallance A, Selgimann J, Bach S, Mohamed F, Brown J, Fearnhead N. A systematic analysis highlighting deficiencies in reported outcomes for patients with stage IV colorectal cancer undergoing palliative resection of the primary tumour. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2018; 44:1469-1478. [PMID: 30007475 DOI: 10.1016/j.ejso.2018.06.012] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2018] [Revised: 05/24/2018] [Accepted: 06/11/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND Management of the primary tumour in the presence of unresectable metastatic colorectal cancer (mCRC) is controversial. The role of primary tumour resection (PTR) has been investigated by a number of retrospective cohort studies, with a number on going randomised controlled trials. The aim of this study was to identify the clinical and patient-reported outcomes currently reported in studies that evaluate the role of PTR in mCRC. METHODS Literature searches were performed in MEDLINE (via OvidSP) (1966-June 2017), EMBASE (via OvidSP) and the Cochrane Library using terms related to colorectal cancer and primary tumour resection. All studies documenting outcomes following palliative PTR were included. Eligible articles were assessed using the Risk of Bias In Non-Randomised Studies of Intervention (ROBINS-I) tool. RESULTS Of 11,209 studies screened, 59 non-randomised studies reporting outcomes on 331,157 patients were included. Patient characteristics regarding performance status and co-morbidity were recorded in 26 (44.1%) and 17 (28.8%) studies. The chemotherapy regime used was reported in 27 (45.8%) studies. The operative setting and the operative approach was reported in 42 (71%) and 14 (23.7%) studies. Post-operative mortality and morbidity were reported in 33 (55.9%) and 35 (59.3%) studies. Overall survival was reported in 49 (83.1%) studies, with 5 different definitions identified. Quality of life was only reported in 1 (1.7%) study. CONCLUSION This study demonstrates significant heterogeneity in the selection and definition of outcomes reported following PTR in mCRC. There is significant heterogeneity with a significant under-reporting of important outcomes such as treatment related adverse events and patient reported outcomes.
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Affiliation(s)
- Deena P Harji
- Newcastle Centre of Bowel Disease, Royal Victoria Infirmary, Newcastle upon Tyne, UK; Clinical Trials Research Unit, University of Leeds, UK.
| | - Abigail Vallance
- Clinical Effectiveness Unit, Royal College of Surgeons, London, UK
| | - Jenny Selgimann
- Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK
| | - Simon Bach
- Department of Surgery, University Hospitals Birmingham, Birmingham, UK
| | - Faheez Mohamed
- Peritoneal Malignancy Institute, North Hampshire Hospital, Hampshire Hospital Foundation Trust, Basingstoke, UK
| | - Julia Brown
- Clinical Trials Research Unit, University of Leeds, UK
| | - Nicola Fearnhead
- Department of Colorectal Surgery, Addenbrooke's Hospital, Cambridge, UK
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Korkmaz L, Coşkun HŞ, Dane F, Karabulut B, Karaağaç M, Çabuk D, Karabulut S, Aykan NF, Doruk H, Avcı N, Turhal NS, Artaç M. Kras-mutation influences outcomes for palliative primary tumor resection in advanced colorectal cancer-a Turkish Oncology Group study. Surg Oncol 2018; 27:485-489. [PMID: 30217306 DOI: 10.1016/j.suronc.2018.05.032] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2017] [Revised: 05/28/2018] [Accepted: 05/29/2018] [Indexed: 02/05/2023]
Abstract
PURPOSE We aimed to investigate the prognostic effect of primary tumor resection (PTR) prior to bevacizumab-based treatments in unresectable metastatic colorectal cancer (mCRC). METHODS We retrospectively collected 341 mCRC cases with unresectable metastases at diagnosis. PTR was performed in 210 cases (the surgery group) and the other patients (n = 131) were followed without PTR (the no-surgery group). All the patients were treated with bevacizumab combined chemotherapy regimens. RESULTS The median progression free survival (PFS) of the surgery group was 10.4 months (95% CI: 8.9-11.9), which was significantly better than that of the no-surgery group (7.6 months, 95% CI: 6.4-8.8, P=0.000). The median overall survival (OS) of the surgery group was longer than that of the no-surgery group (27.4 months vs. 18.3 months, respectively, P=0.000). The median PFS and OS of the surgery group were 10.4 months and 28.2 months, which were significantly longer than that of the no-surgery group in Kras-mutant patients (7.8 months and 18.3 months; P=0.004, P=0.028, respectively). There was no difference in terms of PFS and OS between the surgery and the no-surgery groups in Kras-wild type patients. CONCLUSION Palliative PTR may improve the survival outcomes for unresectable mCRC patients. PTR may be preferred, particularly in Kras-mutant patients.
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Affiliation(s)
- Levent Korkmaz
- Department of Medical Oncology, NecmettinErbakan University, Meram Faculty of Medicine, Konya, Turkey
| | - Hasan Şenol Coşkun
- Department of Medical Oncology, Akdeniz University Faculty of Medicine, Antalya, Turkey
| | - Faysal Dane
- Department of Medical Oncology, Marmara University Faculty of Medicine, Istanbul, Turkey
| | - Bülent Karabulut
- Department of Medical Oncology, Ege University Faculty of Medicine, Izmir, Turkey
| | - Mustafa Karaağaç
- Department of Medical Oncology, NecmettinErbakan University, Meram Faculty of Medicine, Konya, Turkey
| | - Devrim Çabuk
- Department of Medical Oncology, Kocaeli University Faculty of Medicine, Kocaeli, Turkey
| | - Senem Karabulut
- Department of Medical Oncology, Istanbul University, Istanbul Medical Faculty, Istanbul, Turkey
| | - Nuri Faruk Aykan
- Department of Medical Oncology, Istanbul University, Istanbul Medical Faculty, Istanbul, Turkey
| | - Hatice Doruk
- Department of Medical Oncology, Acıbadem Bursa Hospital, Bursa, Turkey
| | - Nilüfer Avcı
- Department of Medical Oncology, Ali Osman Sönmez Oncology Hospital, Bursa, Turkey
| | | | - Mehmet Artaç
- Department of Medical Oncology, NecmettinErbakan University, Meram Faculty of Medicine, Konya, Turkey.
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Akagi T, Inomata M, Hasegawa S, Kinjo Y, Ito M, Fukunaga Y, Kanazawa A, Idani H, Yamamoto S, Otsuka K, Endo S, Watanabe M. Short- and long-term outcomes following laparoscopic palliative resection for patients with incurable, asymptomatic stage IV colorectal cancer: A multicenter study in Japan. JOURNAL OF THE ANUS RECTUM AND COLON 2018; 1:125-130. [PMID: 31583312 PMCID: PMC6768683 DOI: 10.23922/jarc.2017-012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/24/2017] [Accepted: 07/20/2017] [Indexed: 11/30/2022]
Abstract
OBJECTIVE This retrospective multicenter study compared short- and long-term results between Japanese patients with asymptomatic stage IV colorectal cancer who underwent palliative laparoscopic surgery (LS) versus those who underwent conventional open surgery (OS). METHODS Among 968 patients treated for stage IV colorectal cancer from January 2006 to December 2007 in 41 surgical units that were participating in the Japan Society of Laparoscopic Colorectal Surgery group, we studied 398 patients who received palliative resection of their asymptomatic primary colorectal tumor. RESULTS We analyzed data from patients undergoing LS (LS group, n=106) and OS (OS group, n=292). Fourteen (13.2%) LS group patients were converted to OS. Although the differences between groups for postoperative complications were not significant, the mean time to solid food intake and postoperative length of hospital stay for the LS group were significantly shorter than those for the OS group (2 vs. 3 days, p<0.0001; 13 vs. 16 days, p<0.0001, respectively). The LS group patients experienced a longer median survival time than that of the OS group (24.5 vs. 23.9 months, p=0.0357). CONCLUSIONS Laparoscopic palliative resection (LS) offers advantages for short-term outcomes and no disadvantages for long-term outcomes. The use of laparoscopic procedures to treat asymptomatic, incurable stage IV colorectal cancer appears to be acceptable.
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Affiliation(s)
- Tomonori Akagi
- Department of Gastroenterological & Pediatric Surgery, Oita University Faculty of Medicine, Oita, Japan
| | - Masafumi Inomata
- Department of Gastroenterological & Pediatric Surgery, Oita University Faculty of Medicine, Oita, Japan
| | | | - Yousuke Kinjo
- Department of Surgery, Kyoto University, Kyoto, Japan
| | - Masaaki Ito
- Department of Colorectal and Pelvic Surgery, National Cancer Center Hospital East, Chiba, Japan
| | - Yosuke Fukunaga
- Department of Gastroenterological Surgery, Cancer Institute Hospital, Tokyo, Japan
| | - Akiyoshi Kanazawa
- Department of Gastroenterology, Osaka Red Cross Hospital, Osaka, Japan
| | - Hitoshi Idani
- Department of Surgery, Fukuyama City Hospital, Fukuyama, Japan
| | - Seiichiro Yamamoto
- Division of Colorectal Surgery, National Cancer Center Hospital, Tokyo, Japan
| | - Koki Otsuka
- Department of Surgery, Iwate Medical University, Iwate, Japan
| | - Shungo Endo
- Department of Surgery, Showa University School of Medicine, Yokohama Northern Hospital, Yokohama, Japan
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Maroney S, de Paz CC, Reeves ME, Garberoglio C, Raskin E, Senthil M, Namm JP, Solomon N. Benefit of Surgical Resection of the Primary Tumor in Patients Undergoing Chemotherapy for Stage IV Colorectal Cancer with Unresected Metastasis. J Gastrointest Surg 2018; 22:460-466. [PMID: 29124549 DOI: 10.1007/s11605-017-3617-5] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2017] [Accepted: 10/24/2017] [Indexed: 01/31/2023]
Abstract
PURPOSE Resection of the primary tumor in patients with unresected metastatic colorectal cancer is controversial, and often performed only for palliation of symptoms. Our goal was to determine if resection of the primary tumor in this patient population is associated with improved survival. METHODS This is a retrospective cohort study of the National Cancer Data Base from 2004 to 2012. The study population included all patients with synchronous metastatic colorectal adenocarcinoma who were treated with systemic chemotherapy. The study groups were patients who underwent definitive surgery for the primary tumor and those who did not. Patients were excluded if they had surgical intervention on the sites of metastasis or pathology other than adenocarcinoma. Primary outcome was overall survival. RESULTS Of the 65,543 patients with unresected stage IV colorectal adenocarcinoma undergoing chemotherapy, 55% underwent surgical resection of the primary site. Patients who underwent surgical resection of the primary tumor had improved median survival compared to patients treated with chemotherapy alone (22 vs 13 months, p < .0001). The surgical survival benefit was present for patients who were treated with either multi-agent or single-agent chemotherapy (23 vs 14 months, p < 0.001; 19 vs 9 months, p < 0.001). Surgical resection of the primary tumor was also associated with improved survival when using multivariate analysis with propensity score matching (OR = 0.863; 95% CI [0.805-.924]; HR = 0.914; 95% CI [0.888-0.942]). CONCLUSIONS Our results show that in patients with synchronous unresected stage IV colorectal adenocarcinoma undergoing single- or multi-agent chemotherapy, after adjusting for confounding variables, definitive resection of the primary site was associated with improved overall survival. Large randomized controlled trials are needed to determine if there is a causal relationship between surgery and increased overall survival in this patient population.
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Affiliation(s)
- Sean Maroney
- Department of Surgery, Loma Linda University Health, 11175 Campus Street, Suite 21108, Loma Linda, CA, 92350, USA.
| | | | - Mark E Reeves
- Department of Surgery, Loma Linda University Health, 11234 Anderson St, Loma Linda, CA, 92354, USA
| | - Carlos Garberoglio
- Department of Surgery, Loma Linda University Health, 11234 Anderson St, Loma Linda, CA, 92354, USA
| | - Elizabeth Raskin
- Department of Surgery, Loma Linda University Health, 11234 Anderson St, Loma Linda, CA, 92354, USA
| | - Maheswari Senthil
- Department of Surgery, Loma Linda University Health, 11234 Anderson St, Loma Linda, CA, 92354, USA
| | - Jukes P Namm
- Department of Surgery, Loma Linda University Health, 11234 Anderson St, Loma Linda, CA, 92354, USA
| | - Naveenraj Solomon
- Department of Surgery, Loma Linda University Health, 11234 Anderson St, Loma Linda, CA, 92354, USA
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van Rooijen KL, Shi Q, Goey KKH, Meyers J, Heinemann V, Diaz-Rubio E, Aranda E, Falcone A, Green E, de Gramont A, Sargent DJ, Punt CJA, Koopman M. Prognostic value of primary tumour resection in synchronous metastatic colorectal cancer: Individual patient data analysis of first-line randomised trials from the ARCAD database. Eur J Cancer 2018; 91:99-106. [PMID: 29353165 DOI: 10.1016/j.ejca.2017.12.014] [Citation(s) in RCA: 62] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2017] [Accepted: 12/07/2017] [Indexed: 12/11/2022]
Abstract
Indication for primary tumour resection (PTR) in asymptomatic metastatic colorectal cancer (mCRC) patients is unclear. Previous retrospective analyses suggest a survival benefit for patients who underwent PTR. The aim was to evaluate the prognostic value of PTR in patients with synchronous mCRC by analysis of recent large RCTs including systemic therapy with modern targeted agents. Individual patient data (IPD) of 3423 patients enrolled into 8 randomised controlled trials (RCTs) with first-line systemic therapy in the ARCAD (Aide et Recherche en Cancérologie Digestive) database were analysed. The number of patients with unresected synchronous mCRC, resected synchronous mCRC and metachronous mCRC was 710 (21%), 1705 (50%) and 1008 (29%), respectively. Adjusting for age, gender, performance status (PS) and prior chemotherapy, the unresected group had a significantly worse median overall survival (16.4 m) compared with the synchronous resected (22.2 m; hazard ratio [HR] 1.60, 95% CI 1.43-1.78) and metachronous (22.4 m; HR 1.81, 95% CI 1.58-2.07) groups. Similarly, median progression-free survival was significantly worse for the unresected group compared with the synchronous resected (HR 1.31, 95% CI 1.19-1.44) and metachronous (HR 1.47, 95% CI 1.30-1.66) groups. In a multivariate analysis, the observed associations remained significant. This largest IPD analysis of mCRC trials to date demonstrates an improved survival in synchronous mCRC patients after PTR. These results may be subject to bias since reasons for (non)resection were not available. Until results of ongoing RCTs are available, both upfront PTR followed by systemic treatment and upfront systemic treatment are considered appropriate treatment strategies.
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Affiliation(s)
- K L van Rooijen
- Department of Medical Oncology, University Medical Center Utrecht, University of Utrecht, Utrecht, The Netherlands
| | - Q Shi
- Department of Health Science Research, Mayo Clinic, Rochester, USA
| | - K K H Goey
- Department of Medical Oncology, University Medical Center Utrecht, University of Utrecht, Utrecht, The Netherlands
| | - J Meyers
- Department of Health Science Research, Mayo Clinic, Rochester, USA
| | - V Heinemann
- Department of Medical Oncology and Comprehensive Cancer Center, Munich, Germany
| | - E Diaz-Rubio
- Cancer Translational Unit, Hospital Clinico San Carlos, Universidad Complutense, Madrid, Spain
| | - E Aranda
- Department of Medical Oncology, UCO, Maimonides Institute of Biomedical Research (IMIBIC), CIBERONC, Instituto de Salud Carlos III, Córdoba, Spain
| | - A Falcone
- Department of Medical Oncology, University of Pisa, Pisa, Italy
| | - E Green
- Department of Health Science Research, Mayo Clinic, Rochester, USA
| | - A de Gramont
- Department of Medical Oncology, Franco-British Institute, Levallois-Perret, France
| | - D J Sargent
- Department of Health Science Research, Mayo Clinic, Rochester, USA
| | - C J A Punt
- Department of Medical Oncology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
| | - M Koopman
- Department of Medical Oncology, University Medical Center Utrecht, University of Utrecht, Utrecht, The Netherlands.
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Abstract
The impressive advances in breast cancer treatment observed in recent years also apply to the metastatic setting, where a subset of patients with favorable metastatic disease enjoy long-term survival with systemic therapy. In patients with distant disease, the primary tumor in the breast has not classically been though to merit specific locoregional therapy. However, about 6% of Stage IV patients in the USA and up to 20% in limited resource environments present with synchronous distant metastases at the time of initial diagnosis. For this group, who have an intact primary tumor, retrospective studies suggest that local therapy for the primary site may be beneficial. However, these retrospective analyses are biased in that women receiving local therapy to the primary site were younger and had biologically favorable tumors and lower volume metastatic disease. Two completed randomized clinical trials have shown conflicting results, and others are ongoing. In this chapter, we discuss the results of these studies through the present day and summarize their conclusions and their implications for clinical management.
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Morikawa T, Inada R, Nagasaka T, Mori Y, Kishimoto H, Kawai T, Umeda Y, Mishima H, Goel A, Fujiwara T. BRAF V600E mutation is a predictive indicator of upfront chemotherapy for stage IV colorectal cancer. Oncol Lett 2017; 15:2195-2201. [PMID: 29434925 PMCID: PMC5776948 DOI: 10.3892/ol.2017.7553] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2016] [Accepted: 02/07/2017] [Indexed: 12/16/2022] Open
Abstract
In stage IV colorectal cancer (CRC), initial resection of the primary tumor is considered to be an important strategy for improving disease outcome. However, there is no consensus on the timing as to when the surgical intervention of the primary tumor should occur. The present study hypothesizes that genetic profiles in CRC may indicate the appropriate treatment strategies for patients with stage IV CRC, and a cohort of 113 patients with stage IV CRC resected primary lesions at various periods were analyzed for the presence of mutations in the KRAS, exon 2, and BRAF genes, exon 15, and for the microsatellite instability status of the tumor. These data were additionally correlated with various clinicopathological features. Although BRAF-mutant was revealed to be an independent negative prognostic factor in stage IV CRC (HR, 8.42; 95% confidence interval, 2.72–26.02), BRAF-mutant samples exhibited better prognoses if they were treated with chemotherapy prior to tumor resection. Thus, the presence of BRAF mutations provides a compelling rationale for the establishment of intensive upfront chemotherapy to improve survival in stage IV CRC.
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Affiliation(s)
- Tatsuya Morikawa
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Chūgoku 700-8558, Japan
| | - Ryo Inada
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Chūgoku 700-8558, Japan
| | - Takeshi Nagasaka
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Chūgoku 700-8558, Japan
| | - Yoshiko Mori
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Chūgoku 700-8558, Japan
| | - Hiroyuki Kishimoto
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Chūgoku 700-8558, Japan
| | - Takashi Kawai
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Chūgoku 700-8558, Japan
| | - Yuzo Umeda
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Chūgoku 700-8558, Japan
| | - Hideyuki Mishima
- Cancer Center, Aichi Medical University, Nagakute, Aichi 480-1195, Japan
| | - Ajay Goel
- Center for Gastrointestinal Research and Translational Genomics and Oncology, Baylor Scott & White Research Institute and Charles A Sammons Cancer Center, Baylor University Medical Center, Dallas, TX 75246, USA
| | - Toshiyoshi Fujiwara
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Chūgoku 700-8558, Japan
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49
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Nitsche U, Stöß C, Stecher L, Wilhelm D, Friess H, Ceyhan GO. Meta-analysis of outcomes following resection of the primary tumour in patients presenting with metastatic colorectal cancer. Br J Surg 2017; 105:784-796. [PMID: 29088493 DOI: 10.1002/bjs.10682] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2017] [Revised: 06/01/2017] [Accepted: 07/07/2017] [Indexed: 12/15/2022]
Abstract
BACKGROUND It is not clear whether resection of the primary tumour (when there are metastases) alters survival and/or whether resection is associated with increased morbidity. This systematic review and meta-analysis assessed the prognostic value of primary tumour resection in patients presenting with metastatic colorectal cancer. METHODS A systematic review of MEDLINE/PubMed was performed on 12 March 2016, with no language or date restrictions, for studies comparing primary tumour resection versus conservative treatment without primary tumour resection for metastatic colorectal cancer. The quality of the studies was assessed using the MINORS and STROBE criteria. Differences in survival, morbidity and mortality between groups were estimated using random-effects meta-analysis. RESULTS Of 37 412 initially screened articles, 56 retrospective studies with 148 151 patients met the inclusion criteria. Primary tumour resection led to an improvement in overall survival of 7·76 (95 per cent c.i. 5·96 to 9·56) months (risk ratio (RR) for overall survival 0·50, 95 per cent c.i. 0·47 to 0·53), but did not significantly reduce the risk of obstruction (RR 0·50, 95 per cent c.i. 0·16 to 1·53) or bleeding (RR 1·19, 0·48 to 2·97). Neither was the morbidity risk altered (RR 1·14, 0·77 to 1·68). Heterogeneity between the studies was high, with a calculated I2 of more than 50 per cent for most outcomes. CONCLUSION Primary tumour resection may provide a modest survival advantage in patients presenting with metastatic colorectal cancer.
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Affiliation(s)
- U Nitsche
- Department of Surgery, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
| | - C Stöß
- Department of Surgery, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
| | - L Stecher
- Institute of Medical Statistics and Epidemiology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
| | - D Wilhelm
- Department of Surgery, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
| | - H Friess
- Department of Surgery, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
| | - G O Ceyhan
- Department of Surgery, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
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50
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Kim IH, Lee JE, Yang JH, Jeong JW, Ro S, Lee MA. Clinical significance of changes in systemic inflammatory markers and carcinoembryonic antigen levels in predicting metastatic colorectal cancer prognosis and chemotherapy response. Asia Pac J Clin Oncol 2017; 14:239-246. [PMID: 29044941 DOI: 10.1111/ajco.12784] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2017] [Accepted: 08/28/2017] [Indexed: 12/19/2022]
Abstract
AIM Metastatic colorectal cancer (mCRC) is associated with poor prognosis, and biomarkers are required for predicting survival and chemotherapy response. This study aimed to evaluate the significance of changes in systemic inflammatory markers and carcinoembryonic antigen (CEA) levels in predicting mCRC prognosis and chemotherapy response. METHODS In this retrospective study, 503 patients who received first-line palliative chemotherapy for mCRC between 2008 and 2014 at a tertiary hospital in Korea were evaluated. Changes in neutrophil-to-lymphocyte ratio (NLR) and modified Glasgow prognostic score (mGPS) were divided into low-to-low, high-to-low, low-to-high and high-to-high groups. The CEA response was defined as CEA-complete response (CEA normalization), CEA-partial response (≥50% decrease in CEA levels), CEA-progressive disease (≥50% increase in CEA levels) and CEA-stable disease. Overall survival (OS) and progression-free survival (PFS) were evaluated according to NLR, mGPS and CEA levels. RESULTS High prechemotherapy NLR, mGPS and CEA levels independently predicted poor survival and chemotherapy response. Continuously high NLR or change to high NLR was also associated with poor OS and PFS; however, continuously low NLR or reduced NLR showed good prognosis. CEA response was also an independent prognostic marker for OS and PFS. High NLR and mGPS were correlated with elevated CEA levels. CONCLUSION Inflammatory marker levels were significantly associated with CEA levels. The prechemotherapy levels of systemic inflammatory markers and CEA were associated with OS or PFS. The change patterns in NLR and CEA levels can be utilized as prognostic and predictive markers for chemotherapy response.
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Affiliation(s)
- In-Ho Kim
- Division of Medical Oncology, Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea.,Cancer Research Institute, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Ji Eun Lee
- Division of Medical Oncology, Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea.,Cancer Research Institute, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Ji Hyun Yang
- Division of Medical Oncology, Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea.,Cancer Research Institute, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Joon Won Jeong
- Division of Medical Oncology, Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea.,Cancer Research Institute, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Sangmi Ro
- Division of Medical Oncology, Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea.,Cancer Research Institute, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Myung Ah Lee
- Division of Medical Oncology, Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea.,Cancer Research Institute, The Catholic University of Korea College of Medicine, Seoul, Korea
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