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1
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Basile G, Bandini M, Li R, Poch MA, Necchi A, Spiess PE. Gold standard nephroureterectomy, chemoprophylaxis and surveillance in upper tract urothelial carcinoma. Curr Opin Urol 2024:00042307-990000000-00208. [PMID: 39529478 DOI: 10.1097/mou.0000000000001247] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2024]
Abstract
PURPOSE OF REVIEW The purpose of this review is to summarize the most recent evidence on surgical management, strategies to reduce tumor recurrence, and surveillance regimens in patients diagnosed with upper tract urothelial carcinoma (UTUC) and elected for radical treatment. RECENT FINDINGS Minimally invasive surgery is gaining momentum in the surgical management of UTUC. Chemoprophylaxis is still the gold standard to reduce intravesical recurrence after radical nephroureterectomy (RNU). Novel surveillance strategies have been proposed to adapt follow-up regimens to patients' characteristics. SUMMARY Minimally invasive surgery has been associated with comparable oncological outcomes to the open approach while improving postoperative morbidity. In these cases, bladder cuff excision (BCE) is mostly performed by an extravesical approach, that demonstrates a noninferiority compared to the intravesical one in terms of oncological outcomes. Although lymphadenectomy is recommended in patients with high-risk tumors, its benefits are still unclear. Currently, there is a lack of recent prospective trials on chemoprophylaxis to reduce intravesical recurrence post RNU, making single-dose postoperative chemotherapy instillation the standard treatment. Although novel risk stratification models were released by international urological guidelines, their validity is mainly nonevidence-based. Risk-adapted follow-up strategies incorporating cystoscopy and cross-sectional imaging accounting for individual patient factors should be implemented.
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Affiliation(s)
- Giuseppe Basile
- Vita-Salute San Raffaele University, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Marco Bandini
- Vita-Salute San Raffaele University, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Roger Li
- Department of Genitourinary Oncology, Moffitt Cancer Center, Tampa, Florida, USA
| | - Michael A Poch
- Department of Genitourinary Oncology, Moffitt Cancer Center, Tampa, Florida, USA
| | - Andrea Necchi
- Department of Medical Oncology, IRCCS San Raffaele Hospital, Milan, Italy
| | - Philippe E Spiess
- Department of Genitourinary Oncology, Moffitt Cancer Center, Tampa, Florida, USA
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2
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Head DJ, Raman JD. Kidney-Sparing Surgery for Upper Tract Urothelial Carcinoma-Modalities, Outcomes, and Limitations. J Clin Med 2024; 13:6593. [PMID: 39518735 PMCID: PMC11546368 DOI: 10.3390/jcm13216593] [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: 09/03/2024] [Revised: 10/23/2024] [Accepted: 10/28/2024] [Indexed: 11/16/2024] Open
Abstract
Upper tract urothelial carcinoma (UTUC) accounts for 5-10% of urothelial cancers and is associated with high morbidity and mortality. Increasing incidence of UTUC has been observed since the 1970's, alongside the evolution of advance imaging techniques, precision biopsy equipment, and risk stratification models. The high morbidity of radical nephroureterectomy (RNU) which is still the gold-standard treatment for high-risk UTUC, has driven the development of kidney-sparing surgery alternatives for low-risk UTUC. Now, several treatment approaches have outcomes comparable to RNU for low-risk UTUC and guidelines are recommending kidney-sparing surgery for favorable low-risk disease. The main categories of kidney-sparing surgery include segmental ureterectomy, endoscopic ablation, chemoablation, and vascular-targeted phototherapy. These treatments are highly nuanced making them difficult to compare, but for most cases of favorable low-grade disease, we recommend endoscopic laser ablation with optional adjuvant intracavitary therapy. Adverse events associated with kidney-sparing surgery include ureteral stricture, bleeding requiring transfusion, and bladder recurrence of UTUC. Limitations of kidney-sparing surgery include appropriate tissue sampling (contributing to under-grading and under-staging), higher rates of ipsilateral recurrence, and potential for grade and stage progression. Collectively, these may subsequently necessitate RNU. Here, we review the technical variations and evidence behind kidney-sparing therapies as well as their practicality in the real world.
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Affiliation(s)
| | - Jay D. Raman
- Department of Urology, Penn State Health Milton S. Hershey Medical Center, Hershey, PA 17033, USA
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3
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Dłubak A, Karwacki J, Logoń K, Tomecka P, Brawańska K, Krajewski W, Szydełko T, Małkiewicz B. Lymph Node Dissection in Upper Tract Urothelial Carcinoma: Current Status and Future Perspectives. Curr Oncol Rep 2023; 25:1327-1344. [PMID: 37801187 PMCID: PMC10640513 DOI: 10.1007/s11912-023-01460-y] [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] [Accepted: 09/04/2023] [Indexed: 10/07/2023]
Abstract
PURPOSE OF REVIEW This narrative review aims to evaluate the role of lymph node dissection (LND) in upper tract urothelial carcinoma (UTUC) and its implications for staging and management outcomes, as well as future perspectives. RECENT FINDINGS Multiple studies have demonstrated the limitations of conventional imaging techniques in accurately localizing lymph node metastasis (LNM) in UTUC. While 18F-fluorodeoxyglucose positron emission tomography with computed tomography (18FDG-PET/CT) shows promise for preoperative LNM detection, its specificity is low. Alternative methods such as choline PET/CT and sentinel lymph node detection are under consideration but require further investigation. Additionally, various preoperative factors associated with LNM hold potential for predicting nodal involvement, thereby improving nodal staging and oncologic outcomes of LND. Several surgical approaches, including segmental ureterectomy and robot-assisted nephroureterectomy, provide a possibility for LND, while minimizing morbidity. LND remains the primary nodal staging tool for UTUC, but its therapeutic benefit is still uncertain. Advances in imaging techniques and preoperative risk assessment show promise in improving LNM detection. Further research and multi-center studies are needed to comprehensively assess the advantages and limitations of LND in UTUC, as well as the long-term outcomes of alternative staging and treatment strategies.
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Affiliation(s)
- Andrzej Dłubak
- Department of Minimally Invasive and Robotic Urology, University Center of Excellence in Urology, Wroclaw Medical University, 50-556, Wroclaw, Poland
| | - Jakub Karwacki
- Department of Minimally Invasive and Robotic Urology, University Center of Excellence in Urology, Wroclaw Medical University, 50-556, Wroclaw, Poland
| | - Katarzyna Logoń
- Department of Minimally Invasive and Robotic Urology, University Center of Excellence in Urology, Wroclaw Medical University, 50-556, Wroclaw, Poland
| | - Paulina Tomecka
- Department of Minimally Invasive and Robotic Urology, University Center of Excellence in Urology, Wroclaw Medical University, 50-556, Wroclaw, Poland
| | - Kinga Brawańska
- Department of Minimally Invasive and Robotic Urology, University Center of Excellence in Urology, Wroclaw Medical University, 50-556, Wroclaw, Poland
| | - Wojciech Krajewski
- Department of Minimally Invasive and Robotic Urology, University Center of Excellence in Urology, Wroclaw Medical University, 50-556, Wroclaw, Poland
| | - Tomasz Szydełko
- Department of Minimally Invasive and Robotic Urology, University Center of Excellence in Urology, Wroclaw Medical University, 50-556, Wroclaw, Poland
| | - Bartosz Małkiewicz
- Department of Minimally Invasive and Robotic Urology, University Center of Excellence in Urology, Wroclaw Medical University, 50-556, Wroclaw, Poland.
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4
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Franco A, Ditonno F, Feng C, Manfredi C, Sturgis MR, Farooqi M, Del Giudice F, Coogan C, Ferro M, Zhang C, Wu Z, Yang B, Wang L, Autorino R. Minimally Invasive Radical Nephroureterectomy: 5-Year Update of Techniques and Outcomes. Cancers (Basel) 2023; 15:4585. [PMID: 37760553 PMCID: PMC10527300 DOI: 10.3390/cancers15184585] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2023] [Revised: 09/07/2023] [Accepted: 09/11/2023] [Indexed: 09/29/2023] Open
Abstract
The gold standard treatment for non-metastatic upper tract urothelial cancer (UTUC) is represented by radical nephroureterectomy (RNU). The choice of surgical technique in performing UTUC surgery continues to depend on several factors, including the location and extent of the tumor, the patient's overall health, and very importantly, the surgeon's skill, experience, and preference. Although open and laparoscopic approaches are well-established treatments, evidence regarding robot-assisted radical nephroureterectomy (RANU) is growing. Aim of our study was to perform a critical review on the evidence of the last 5 years regarding surgical techniques and outcomes of minimally invasive RNU, mostly focusing on RANU. Reported oncological and function outcomes suggest that minimally invasive RNU is safe and effective, showing similar survival rates compared to the open approach.
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Affiliation(s)
- Antonio Franco
- Department of Urology, Rush University, Chicago, IL 60612, USA; (A.F.); (F.D.); (C.F.); (C.M.); (M.R.S.); (M.F.); (C.C.)
- Department of Urology, Sant’Andrea Hospital, Sapienza University, 00189 Rome, Italy
| | - Francesco Ditonno
- Department of Urology, Rush University, Chicago, IL 60612, USA; (A.F.); (F.D.); (C.F.); (C.M.); (M.R.S.); (M.F.); (C.C.)
- Department of Urology, Azienda Ospedaliera Universitaria Integrata Verona, University of Verona, 37126 Verona, Italy
| | - Carol Feng
- Department of Urology, Rush University, Chicago, IL 60612, USA; (A.F.); (F.D.); (C.F.); (C.M.); (M.R.S.); (M.F.); (C.C.)
| | - Celeste Manfredi
- Department of Urology, Rush University, Chicago, IL 60612, USA; (A.F.); (F.D.); (C.F.); (C.M.); (M.R.S.); (M.F.); (C.C.)
- Urology Unit, Department of Woman, Child and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
| | - Morgan R. Sturgis
- Department of Urology, Rush University, Chicago, IL 60612, USA; (A.F.); (F.D.); (C.F.); (C.M.); (M.R.S.); (M.F.); (C.C.)
| | - Mustafa Farooqi
- Department of Urology, Rush University, Chicago, IL 60612, USA; (A.F.); (F.D.); (C.F.); (C.M.); (M.R.S.); (M.F.); (C.C.)
| | - Francesco Del Giudice
- Department of Maternal Infant and Urologic Sciences, Policlinico Umberto I Hospital, “Sapienza” University of Rome, 00161 Rome, Italy;
| | - Christopher Coogan
- Department of Urology, Rush University, Chicago, IL 60612, USA; (A.F.); (F.D.); (C.F.); (C.M.); (M.R.S.); (M.F.); (C.C.)
| | - Matteo Ferro
- Division of Urology, European Institute of Oncology (IEO), IRCCS, 20141 Milan, Italy;
| | - Chao Zhang
- Department of Urology, Changhai Hospital, Naval Medical University, Shanghai 200433, China; (C.Z.); (Z.W.); (B.Y.); (L.W.)
| | - Zhenjie Wu
- Department of Urology, Changhai Hospital, Naval Medical University, Shanghai 200433, China; (C.Z.); (Z.W.); (B.Y.); (L.W.)
| | - Bo Yang
- Department of Urology, Changhai Hospital, Naval Medical University, Shanghai 200433, China; (C.Z.); (Z.W.); (B.Y.); (L.W.)
| | - Linhui Wang
- Department of Urology, Changhai Hospital, Naval Medical University, Shanghai 200433, China; (C.Z.); (Z.W.); (B.Y.); (L.W.)
| | - Riccardo Autorino
- Department of Urology, Rush University, Chicago, IL 60612, USA; (A.F.); (F.D.); (C.F.); (C.M.); (M.R.S.); (M.F.); (C.C.)
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5
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Lin CY, Weng HY, Tai TY, Wu HC, Chen WC, Chen CH, Huang CY, Lo CW, Yu CC, Tsai CY, Wu WC, Jiang YH, Lee YK, Hsueh TY, Chiu AW, Chiang BJ, Huang HC, Chen IHA, Chen YT, Lin WY, Wu CC, Tsai YC, Lee HY, Li WM. Clinical Efficacy of Adjuvant Chemotherapy in Advanced Upper Tract Urothelial Carcinoma (pT3-T4): Real-World Data from the Taiwan Upper Tract Urothelial Carcinoma Collaboration Group. J Pers Med 2022; 12:jpm12020226. [PMID: 35207714 PMCID: PMC8877034 DOI: 10.3390/jpm12020226] [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: 11/20/2021] [Revised: 01/09/2022] [Accepted: 01/28/2022] [Indexed: 02/01/2023] Open
Abstract
The clinical efficacy of adjuvant chemotherapy in upper tract urothelial carcinoma (UTUC) is unclear. We aimed to assess the therapeutic outcomes of adjuvant chemotherapy in patients with advanced UTUC (pT3-T4) after radical nephroureterectomy (RNU). We retrospectively reviewed the data of 2108 patients from the Taiwan UTUC Collaboration Group between 1988 and 2018. Comprehensive clinical features, pathological characteristics, and survival outcomes were recorded. Univariate and multivariate Cox proportional hazards models were used to evaluate overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS). Of the 533 patients with advanced UTUC included, 161 (30.2%) received adjuvant chemotherapy. In the multivariate analysis, adjuvant chemotherapy was significantly associated with a reduced risk of overall death (hazard ratio (HR), 0.599; 95% confidence interval (CI), 0.419–0.857; p = 0.005), cancer-specific mortality (HR, 0.598; 95% CI, 0.391–0.914; p = 0.018), and cancer recurrence (HR, 0.456; 95% CI, 0.310–0.673; p < 0.001). The Kaplan–Meier survival analysis revealed that patients receiving adjuvant chemotherapy had significantly better five-year OS (64% vs. 50%, p = 0.002), CSS (70% vs. 62%, p = 0.043), and DFS (60% vs. 48%, p = 0.002) rates compared to those who did not receive adjuvant chemotherapy. In conclusion, adjuvant chemotherapy after RNU had significant therapeutic benefits on OS, CSS, and DFS in advanced UTUC.
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Affiliation(s)
- Chung-Yu Lin
- Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan; (C.-Y.L.); (H.-Y.L.)
| | - Han-Yu Weng
- Department of Urology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan; (H.-Y.W.); (T.-Y.T.)
| | - Ta-Yao Tai
- Department of Urology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan; (H.-Y.W.); (T.-Y.T.)
| | - Hsi-Chin Wu
- Department of Urology, China Medical University Hospital, Taichung 404, Taiwan; (H.-C.W.); (W.-C.C.)
- School of Medicine, China Medical University, Taichung 404, Taiwan
- Department of Urology, China Medical University Beigang Hospital, Yunlin 651, Taiwan
| | - Wen-Chi Chen
- Department of Urology, China Medical University Hospital, Taichung 404, Taiwan; (H.-C.W.); (W.-C.C.)
- Graduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung 404, Taiwan
| | - Chung-Hsin Chen
- Department of Urology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei 100, Taiwan; (C.-H.C.); (C.-Y.H.)
| | - Chao-Yuan Huang
- Department of Urology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei 100, Taiwan; (C.-H.C.); (C.-Y.H.)
| | - Chi-Wen Lo
- Division of Urology, Department of Surgery, Taipei Tzu Chi Hospital, The Buddhist Medical Foundation, New Taipei City 231, Taiwan; (C.-W.L.); (C.-C.Y.)
| | - Chih-Chin Yu
- Division of Urology, Department of Surgery, Taipei Tzu Chi Hospital, The Buddhist Medical Foundation, New Taipei City 231, Taiwan; (C.-W.L.); (C.-C.Y.)
- School of Medicine, Buddhist Tzu Chi University, Hualien 970, Taiwan
| | - Chung-You Tsai
- Division of Urology, Department of Surgery, Far Eastern Memorial Hospital, New Taipei City 220, Taiwan; (C.-Y.T.); (W.-C.W.)
- Department of Healthcare Information and Management, Ming Chuan University, Taipei 111, Taiwan
| | - Wei-Che Wu
- Division of Urology, Department of Surgery, Far Eastern Memorial Hospital, New Taipei City 220, Taiwan; (C.-Y.T.); (W.-C.W.)
- Institute of Biomedical Engineering, National Taiwan University, Taipei 106, Taiwan
| | - Yuan-Hong Jiang
- Department of Urology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, Hualien 970, Taiwan; (Y.-H.J.); (Y.-K.L.)
| | - Yu-Khun Lee
- Department of Urology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, Hualien 970, Taiwan; (Y.-H.J.); (Y.-K.L.)
| | - Thomas Y. Hsueh
- Division of Urology, Department of Surgery, Taipei City Hospital Renai Branch, Taipei 106, Taiwan;
- Department of Urology, School of Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan
| | - Allen W. Chiu
- College of Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan;
| | - Bing-Juin Chiang
- College of Medicine, Fu-Jen Catholic University, New Taipei City 242, Taiwan;
- Division of Urology, Department of Surgery, Cardinal Tien Hospital, New Taipei City 231, Taiwan;
- Department of Life Science, College of Science, National Taiwan Normal University, Taipei 116, Taiwan
| | - Hsu-Che Huang
- Division of Urology, Department of Surgery, Cardinal Tien Hospital, New Taipei City 231, Taiwan;
- Department of Life Science, College of Science, National Taiwan Normal University, Taipei 116, Taiwan
| | - I-Hsuan Alan Chen
- Division of Urology, Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan;
| | - Yung-Tai Chen
- Department of Urology, Taiwan Adventist Hospital, Taipei 105, Taiwan;
| | - Wei-Yu Lin
- Division of Urology, Department of Surgery, Chang Gung Memorial Hospital, Chia-Yi 613, Taiwan;
- Chang Gung University of Science and Technology, Chia-Yi 613, Taiwan
- Department of Medicine, Chang Gung University, Taoyuan 333, Taiwan
| | - Chia-Chang Wu
- Department of Urology, Shuang Ho Hospital, Taipei Medical University, New Taipei City 235, Taiwan;
- Department of Urology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan;
- TMU Research Center of Urology and Kidney (TMU-RCUK), Taipei Medical University, Taipei 110, Taiwan
| | - Yao-Chou Tsai
- Department of Urology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan;
- Department of Urology, Taipei Medical University Hospital, Taipei Medical University, Taipei 110, Taiwan
| | - Hsiang-Ying Lee
- Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan; (C.-Y.L.); (H.-Y.L.)
- Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
| | - Wei-Ming Li
- Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan; (C.-Y.L.); (H.-Y.L.)
- Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
- Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung 807, Taiwan
- Department of Urology, Ministry of Health and Welfare, Pingtung Hospital, Pingtung 900, Taiwan
- Correspondence:
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Ricci AD, Rizzo A, Mollica V, Schiavina R, Fiorentino M, Brunocilla E, Ardizzoni A, Massari F. Platinum-based adjuvant chemotherapy for upper tract urothelial carcinoma: a change of paradigm? A meta-analysis of aggregate data. Anticancer Drugs 2022; 33:e61-e68. [PMID: 34387596 DOI: 10.1097/cad.0000000000001200] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
We performed a systematic review and meta-analysis to evaluate the role of platinum-based adjuvant chemotherapy (AC) in upper tract urothelial carcinoma. Eligible studies were identified using Pubmed/Medline, Cochrane library, Embase and meeting abstracts. Outcomes of interest included: overall survival (OS), cancer-specific survival (CSS) and disease-free survival (DFS). Platinum-based AC was associated with improved DFS, while the benefit in OS and CSS was not statistically significant compared to observation. Conversely, platinum-based AC showed a modest OS benefit in an analysis combing multivariable HRs with estimated HRs from Kaplan-Meier curves. Our results suggest that platinum-based AC is associated with improved DFS and a modest OS benefit in patients with locally advanced urothelial carcinomas.
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Affiliation(s)
| | - Alessandro Rizzo
- Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna
| | - Veronica Mollica
- Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna
| | | | | | | | - Andrea Ardizzoni
- Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna
| | - Francesco Massari
- Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna
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Barton GJ, Tan WP, Inman BA. The nephroureterectomy: a review of technique and current controversies. Transl Androl Urol 2020; 9:3168-3190. [PMID: 33457289 PMCID: PMC7807352 DOI: 10.21037/tau.2019.12.07] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/03/2022] Open
Abstract
The nephroureterectomy (NU) is the standard of care for invasive upper tract urothelial carcinoma (UTUC) and has been around for well over one hundred years. Since then new operative techniques have emerged, new technologies have developed, and the surgery continues to evolve and grow. In this article, we review the various surgical techniques, as well as present the literature surrounding current areas of debate surrounding the NU, including the lymphatic drainage of the upper urinary tract, management of UTUC involvement with the adrenals and caval thrombi, surgical management of the distal ureter, the use of intravesical chemotherapy as well as perioperative systemic chemotherapy, as well as various outcome measures. Although much has been studied about the NU, there still is a dearth of level 1 evidence and the field would benefit from further studies.
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Affiliation(s)
- Gregory J Barton
- Division of Urology, Duke University Medical Center, Durham, NC, USA
| | - Wei Phin Tan
- Division of Urology, Duke University Medical Center, Durham, NC, USA
| | - Brant A Inman
- Division of Urology, Duke University Medical Center, Durham, NC, USA.,Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA
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8
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Schuettfort VM, Pradere B, Quhal F, Mostafaei H, Laukhtina E, Mori K, Motlagh RS, Rink M, D'Andrea D, Abufaraj M, Karakiewicz PI, Shariat SF. Diagnostic challenges and treatment strategies in the management of upper-tract urothelial carcinoma. Turk J Urol 2020; 47:S33-S44. [PMID: 33052841 DOI: 10.5152/tud.2020.20392] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2020] [Accepted: 09/03/2020] [Indexed: 01/19/2023]
Abstract
Upper-tract urothelial carcinoma (UTUC) is a rare disease, posing many challenges for the treating physician due to the lack of strong evidence-based recommendations. However, novel molecular discoveries and a better understanding of the clinical behavior of the disease lead to a continuous evolution of therapeutic landscape in UTUC. The aim of the review is to provide a comprehensive update of the current diagnostic modalities and treatment strategies in UTUC with a special focus on recent developments and challenges. A comprehensive literature search including relevant articles up to August 2020 was performed using the MEDLINE/PubMed database. Despite several technological improvements, accurate staging and outcome prediction remain major challenges and hamper appropriate risk stratification. Kidney-sparing surgery can be offered in low risk UTUC; however, physician and patient must be aware of the high rate of recurrence and risk of progression due to tumor biology and understaging. The value and efficacy of intracavitary therapy in patients with UTUC remains unclear due to the lack of high-quality data. In high-risk diseases, radical nephroureterectomy with bladder cuff excision and template lymph node dissection is the standard of care. Perioperative systemic chemotherapy is today accepted as a novel standard for advanced cancers. In metastatic or unresectable disease, the therapeutic landscape is rapidly changing due to several novel agents, such as checkpoint inhibitors. While several diagnostic and treatment challenges remain, progress in endoscopic technology and molecular knowledge have ushered a new age in personalized management of UTUC. Novel accurate molecular and imaging biomarkers are, however, still needed to guide decision making as tissue acquisition remains suboptimal. Next generation sequencing and novel agents are promising to rapidly improve patient outcomes.
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Affiliation(s)
- Victor M Schuettfort
- Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.,Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Benjamin Pradere
- Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.,Department of Urology, University Hospital of Tours, Tours, France
| | - Fahad Quhal
- Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.,Department of Urology, King Fahad Specialist Hospital, Dammam, Saudi Arabia
| | - Hadi Mostafaei
- Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.,Research Center for Evidence Based Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Ekaterina Laukhtina
- Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.,Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russia
| | - Keiichiro Mori
- Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.,Department of Urology, The Jikei University School of Medicine, Tokyo, Japan
| | - Reza Sari Motlagh
- Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria
| | - Michael Rink
- Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - David D'Andrea
- Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria
| | - Mohammad Abufaraj
- Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.,Division of Urology, Department of Special Surgery, Jordan University Hospital, The University of Jordan, Amman, Jordan
| | - Pierre I Karakiewicz
- Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montreal Health Center, Montreal, Canada
| | - Shahrokh F Shariat
- Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.,Department of Urology, Weill Cornell Medical College, New York, New York, USA.,Department of Urology, University of Texas Southwestern, Dallas, Texas, USA.,Department of Urology, Second Faculty of Medicine, Charles University, Prague, Czech Republic.,Karl Landsteiner Institute of Urology and Andrology, Vienna, Austria.,European Association of Urology Research Foundation, Arnhem, Netherlands.,Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russia
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9
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Liu Z, Huang J, Li X, Huang C, Ye Y, Zhang J, Liu Z. The effectiveness of chemotherapy for patients with pT3N0M0 renal pelvic urothelial carcinomas: An inverse probability of treatment weighting comparison using Surveillance, Epidemiology, and End Results data. Cancer Med 2020; 9:5756-5766. [PMID: 32585775 PMCID: PMC7433845 DOI: 10.1002/cam4.3238] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2020] [Revised: 05/26/2020] [Accepted: 05/30/2020] [Indexed: 12/14/2022] Open
Abstract
Introduction Unlike the established evidence to use chemotherapy for urothelial carcinoma of the bladder, presently there are insufficient data to inform a recommendation on upper urinary tract urothelial carcinoma treatment. The prognosis for patients with stage T4 and positive lymph nodes is poor; however, primary tumors in the renal pelvis are associated with favorable prognoses compared to those located in the ureter. Our study aimed at investigating the effectiveness of chemotherapy in patients with pT3N0M0 renal pelvic urothelial carcinomas (RPUC) who have relative favorable prognosis. Methods Patients with pT3N0M0 tumors who underwent radical nephroureterectomy combined with bladder cuff excision between 2005 and 2014 and registered in the Surveillance, Epidemiology, and End Results database were eligible for inclusion (n = 939). Baseline characteristics between the chemotherapy and observation groups were controlled for with inverse probability of treatment weighting (IPTW)‐adjusted analysis. Results After the IPTW‐adjusted analysis, the 5‐year IPTW‐adjusted rates of overall survival (OS) for the chemotherapy and observation groups were 53.1% and 44.9%, respectively. The IPTW‐adjusted Kaplan‐Meier curves suggested that chemotherapy was associated with increased OS compared with observation (P = .028). In the IPTW‐adjusted Cox proportional hazards regression model, chemotherapy was associated with favorable survival benefits compared with observation (hazard ratio [HR] 0.71, 95% CI 0.52‐0.92, P = .031), and this was maintained after bootstrapping (HR 0.72, 95% CI 0.49‐0.93). Chemotherapy had a protective effect on OS benefits, which were found in a majority of the results of the subgroup analysis and were consistent with the main results (all P‐interactions > 0.05). Conclusion Chemotherapy may provide significant OS benefits for patients with pT3N0M0 RPUC. The results of our study could strengthen the evidence for using adjuvant chemotherapy in this rare group of patients.
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Affiliation(s)
- Zefu Liu
- Department of Urology, Cancer Center, Sun Yat-sen University, Guangzhou, China
| | - Jialing Huang
- Department of Medical Statistics, School of Public Health, Sun Yat-Sen University, Guangzhou, China
| | - Xiangdong Li
- Department of Urology, Cancer Center, Sun Yat-sen University, Guangzhou, China
| | - Chaowen Huang
- Department of Urology, Cancer Center, Sun Yat-sen University, Guangzhou, China
| | - Yunlin Ye
- Department of Urology, Cancer Center, Sun Yat-sen University, Guangzhou, China
| | - Jinxin Zhang
- Department of Medical Statistics, School of Public Health, Sun Yat-Sen University, Guangzhou, China
| | - Zhouwei Liu
- Department of Urology, Cancer Center, Sun Yat-sen University, Guangzhou, China
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Birtle A, Johnson M, Chester J, Jones R, Dolling D, Bryan RT, Harris C, Winterbottom A, Blacker A, Catto JWF, Chakraborti P, Donovan JL, Elliott PA, French A, Jagdev S, Jenkins B, Keeley FX, Kockelbergh R, Powles T, Wagstaff J, Wilson C, Todd R, Lewis R, Hall E. Adjuvant chemotherapy in upper tract urothelial carcinoma (the POUT trial): a phase 3, open-label, randomised controlled trial. Lancet 2020; 395:1268-1277. [PMID: 32145825 PMCID: PMC7181180 DOI: 10.1016/s0140-6736(20)30415-3] [Citation(s) in RCA: 344] [Impact Index Per Article: 68.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2020] [Revised: 02/07/2020] [Accepted: 02/11/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Urothelial carcinomas of the upper urinary tract (UTUCs) are rare, with poorer stage-for-stage prognosis than urothelial carcinomas of the urinary bladder. No international consensus exists on the benefit of adjuvant chemotherapy for patients with UTUCs after nephroureterectomy with curative intent. The POUT (Peri-Operative chemotherapy versus sUrveillance in upper Tract urothelial cancer) trial aimed to assess the efficacy of systemic platinum-based chemotherapy in patients with UTUCs. METHODS We did a phase 3, open-label, randomised controlled trial at 71 hospitals in the UK. We recruited patients with UTUC after nephroureterectomy staged as either pT2-T4 pN0-N3 M0 or pTany N1-3 M0. We randomly allocated participants centrally (1:1) to either surveillance or four 21-day cycles of chemotherapy, using a minimisation algorithm with a random element. Chemotherapy was either cisplatin (70 mg/m2) or carboplatin (area under the curve [AUC]4·5/AUC5, for glomerular filtration rate <50 mL/min only) administered intravenously on day 1 and gemcitabine (1000 mg/m2) administered intravenously on days 1 and 8; chemotherapy was initiated within 90 days of surgery. Follow-up included standard cystoscopic, radiological, and clinical assessments. The primary endpoint was disease-free survival analysed by intention to treat with a Peto-Haybittle stopping rule for (in)efficacy. The trial is registered with ClinicalTrials.gov, NCT01993979. A preplanned interim analysis met the efficacy criterion for early closure after recruitment of 261 participants. FINDINGS Between June 19, 2012, and Nov 8, 2017, we enrolled 261 participants from 57 of 71 open study sites. 132 patients were assigned chemotherapy and 129 surveillance. One participant allocated chemotherapy withdrew consent for data use after randomisation and was excluded from analyses. Adjuvant chemotherapy significantly improved disease-free survival (hazard ratio 0·45, 95% CI 0·30-0·68; p=0·0001) at a median follow-up of 30·3 months (IQR 18·0-47·5). 3-year event-free estimates were 71% (95% CI 61-78) and 46% (36-56) for chemotherapy and surveillance, respectively. 55 (44%) of 126 participants who started chemotherapy had acute grade 3 or worse treatment-emergent adverse events, which accorded with frequently reported events for the chemotherapy regimen. Five (4%) of 129 patients managed by surveillance had acute grade 3 or worse emergent adverse events. No treatment-related deaths were reported. INTERPRETATION Gemcitabine-platinum combination chemotherapy initiated within 90 days after nephroureterectomy significantly improved disease-free survival in patients with locally advanced UTUC. Adjuvant platinum-based chemotherapy should be considered a new standard of care after nephroureterectomy for this patient population. FUNDING Cancer Research UK.
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Affiliation(s)
- Alison Birtle
- Lancashire Teaching Hospitals NHS Foundation Trust, Preston, UK; University of Manchester, Manchester, UK.
| | - Mark Johnson
- Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle, UK
| | | | | | - David Dolling
- The Institute of Cancer Research, Clinical Trials and Statistics Unit, London, UK
| | | | | | - Andrew Winterbottom
- Patient and Public Involvement Representative, Fight Bladder Cancer, Chinnor, UK
| | - Anthony Blacker
- University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK
| | | | | | | | | | - Ann French
- Southend University Hospital NHS Foundation Trust, Southend, UK
| | | | - Benjamin Jenkins
- The Institute of Cancer Research, Clinical Trials and Statistics Unit, London, UK
| | | | | | | | | | | | - Rachel Todd
- The Institute of Cancer Research, Clinical Trials and Statistics Unit, London, UK
| | - Rebecca Lewis
- The Institute of Cancer Research, Clinical Trials and Statistics Unit, London, UK
| | - Emma Hall
- The Institute of Cancer Research, Clinical Trials and Statistics Unit, London, UK
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11
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Shields LBE, Kalebasty AR. Metastatic clear cell renal cell carcinoma in isolated retroperitoneal lymph node without evidence of primary tumor in kidneys: A case report. World J Clin Oncol 2020; 11:103-109. [PMID: 32133279 PMCID: PMC7046920 DOI: 10.5306/wjco.v11.i2.103] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2019] [Revised: 11/08/2019] [Accepted: 12/01/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Retroperitoneal lymph node dissection (RPLND) plays a diagnostic, therapeutic, and prognostic role in myriad urologic malignancies, including testicular carcinoma, renal cell carcinoma (RCC), and upper urinary tract urothelial carcinoma. RCC represents 2% of all cancers with approximately 25% of patients presenting with advanced disease. Clear cell RCC (CCRCC) is the most common RCC, accounting for 75%-80% of all RCC.
CASE SUMMARY A 71-year-old man presented with a history of benign prostatic hypertrophy. He was asymptomatic without any hematuria, pain, or other urinary symptoms. A computed tomography (CT) scan of the abdomen and pelvis showed a 1.8 cm left retroperitoneal lymph node. There was no evidence of renal pathology. A core biopsy was performed of the left para-aortic lymph node. Although the primary tumor site was unknown, the morphological and immunohistochemical features were most consistent with CCRCC. A RPLND was performed which revealed a single mass 5.5 cm in greatest dimension with extensive necrosis. The retroperitoneal lymph node was most compatible with CCRCC. A nephrectomy was not conducted as a renal mass had not been detected on any prior imaging studies. The patient did not receive any type of adjuvant therapy. The patient underwent surveillance with serial CT scans with contrast of the chest, abdomen, and pelvis for the next 5 years, all of which demonstrated no recurrent or metastatic disease and no evidence of retroperitoneal adenopathy.
CONCLUSION Our unique case emphasizes the therapeutic role of metastasectomy in metastatic CCRCC even in the absence of primary tumor in the kidneys.
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Affiliation(s)
- Lisa BE Shields
- Norton Neuroscience Institute, Norton Healthcare, Louisville, KY 40202, United States
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Nazzani S, Mazzone E, Preisser F, Tian Z, Mistretta FA, Shariat SF, Montanari E, Acquati P, Briganti A, Saad F, Carmignani L, Karakiewicz PI. Rates of lymph node invasion and their impact on cancer specific mortality in upper urinary tract urothelial carcinoma. Eur J Surg Oncol 2019; 45:1238-1245. [DOI: 10.1016/j.ejso.2018.12.004] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2018] [Revised: 11/14/2018] [Accepted: 12/07/2018] [Indexed: 12/19/2022] Open
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Abstract
OPINION STATEMENT Upper tract urothelial carcinoma (UTUC) is a rare genitourinary entity of the renal pelvis and the ureter characterized by a more aggressive disease phenotype when compared with urothelial carcinoma of the bladder (UCB) with more than half of UTUC cases presenting with invasive disease at diagnosis compared to 20% for bladder tumors. There is growing evidence suggesting that its distinct natural history from that of bladder cancer can be related to several genetic and epigenetic differences. Treatment of low-risk disease consists of kidney-sparing surgeries such as ureteroscopic and percutaneous treatments, segmental ureterectomy, and adjuvant topical and intracavitary chemo-immunotherapies. The standard of care for high-risk non-metastatic disease remains radical nephroureterectomy and bladder cuff excision with increasing utilization rates of minimally invasive approaches leading to reduced morbidity without compromising outcomes while the role of lymphadenectomy is still being investigated. The prognosis of UTUC has been stagnant over the past decade highlighting the need for further studies on the role of multimodal therapy (neoadjuvant/adjuvant chemotherapy, immunotherapy, targeted therapy) to optimize management and improve outcomes.
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EKMEKCİ S, KÜÇÜK Ü, DERE Y, ÇAKIR E, SAYAR HC, ERGANİ B, ÇAKMAK Ö, BOZKURT O, YÖRÜKOĞLU K. 8-armed octopus: Evaluation of clinicopathologic prognostic factors of urothelial carcinoma of the upper urinary system. Turk J Med Sci 2019; 49:153-161. [PMID: 30764592 PMCID: PMC7350879 DOI: 10.3906/sag-1805-51] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Background/aim This study was designed to determine the characteristic features of upper urinary system urothelial carcinomas (UUSUCs) and to evaluate the clinicopathological parameters associated with prognosis. Materials and methods A total of 74 cases of UUSUC were included, from three different centers. Demographic data and histopathological features such as tumor localization, concomitant tumor in the urinary system, distant metastasis with overall survival and disease-free survival obtained from the hospital records were evaluated retrospectively. Histopathologic prognostic features such as grade, perineural invasion, lymphovascular invasion, tumor necrosis, and surgical margin status were also evaluated. Results Seventy cases (94.6%) underwent open nephroureterectomy whereas 4 cases (5.4%) had laparoscopic nefroureterectomy. Thirty-eight (51.4%) cases were located in the pelvis, 7 (9.5%) in the ureter, 29 (39.2%) both in the pelvis and ureter. Fifty-six (75.7%) cases were alive; however, 18 (24.3%) patients were found to be dead. pTa, pT1, pT2, pT3, and pT4 tumors were reported in 16 (21.6%), 13 (17.6%), 4 (5.4%), 28 (37.8%), and 13 (17.6%) patients, respectively. Histopathologically, 17 cases (23%) were low-grade, 57 cases (77%) were high-grade. Statistically significant correlation was observed between overall survival and lymph node metastasis, distant metastasis, tumor necrosis, and differentiation by univariate analysis. Only distant metastasis was statistically associated with overall survival by multivariate analysis. We found no significant relationship between disease-free survival and all parameters. Conclusion Differentiation and necrosis of tumor, lymph node involvement, and presence of distant metastasis is associated with the overall survival of urothelial carcinoma of the upper urinary system.
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Affiliation(s)
- Sümeyye EKMEKCİ
- Department of Pathology, Health Sciences University Tepecik Training and Research Hospital, İzmirTurkey
| | - Ülkü KÜÇÜK
- Department of Pathology, Health Sciences University Tepecik Training and Research Hospital, İzmirTurkey
| | - Yelda DERE
- Department of Pathology, Faculty of Medicine, Muğla Sıtkı Koçman University, MuğlaTurkey
| | - Ebru ÇAKIR
- Department of Pathology, Atatürk Training and Research Hospital, Faculty of Medicine, Katip Çelebi University, İzmirTurkey
| | - Hatice Ceren SAYAR
- Department of Pathology, Health Sciences University Tepecik Training and Research Hospital, İzmirTurkey
| | - Batuhan ERGANİ
- Department of Urology, Health Sciences University Tepecik Training and Research Hospital, İzmirTurkey
| | - Özgür ÇAKMAK
- Department of Urology, Health Sciences University Tepecik Training and Research Hospital, İzmirTurkey
| | - Ozan BOZKURT
- Department of Urology, Faculty of Medicine, Dokuz Eylül University, İzmirTurkey
| | - Kutsal YÖRÜKOĞLU
- Department of Pathology, Faculty of Medicine, Dokuz Eylül University, IzmirTurkey
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