Bas W G van Rhijn1,2, Peter C Black3, Laura S Mertens4, Sarah M H Einerhand1, Anna J Black3, Homayoun Zargar5, Adrian S Fairey6,7, Colin P Dinney8, Maria C Mir9, Laura-Maria Krabbe10, Michael S Cookson11, Niels-Erik Jacobson7, Jeffrey S Montgomery12, Nikhil Vasdev13,14, Evan Y Yu15, Evanguelos Xylinas16, Wassim Kassouf17, Marc A Dall'Era18, Srikala S Sridhar19, Jonathan S McGrath20, Jonathan Aning14,20, Shahrokh F Shariat16,21, Jonathan L Wright15, Andrew C Thorpe14, Todd M Morgan12, Jeff M Holzbeierlein22, Trinity J Bivalacqua23, Scott North24, Daniel A Barocas25, Yair Lotan26, Petros Grivas15, Jorge A Garcia27, Andrew J Stephenson28, Jay B Shah29, Siamak Daneshmand6, Kamran Zargar-Shoshtari30, Philippe E Spiess30. 1. Department of Surgical Oncology (Urology), The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands. 2. Department of Urology, Caritas St Josef Medical Center, University of Regensburg, Regensburg, Germany. 3. Vancouver Prostate Centre, Vancouver, Canada. 4. Department of Surgical Oncology (Urology), The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands. l.mertens@nki.nl. 5. Department of Urology, Western Health, Melbourne, Australia. 6. USC/Norris Comprehensive Cancer Center, Institute of Urology, University of Southern California, Los Angeles, CA, USA. 7. University of Alberta, Edmonton, AB, Canada. 8. Department of Urology, MD Anderson Cancer Center, Houston, TX, USA. 9. Department of Urology, Fundacion Instituto Valenciano de Oncologia, Valencia, Spain. 10. Department of Urology, University of Münster, Münster, Germany. 11. Department of Urology, University of Oklahoma College of Medicine, Oklahoma City, OK, USA. 12. Department of Urology, University of Michigan Health System, Ann Arbor, MI, USA. 13. Hertfordshire and Bedfordshire Urological Cancer Centre, Department of Urology, Lister Hospital, Stevenage, UK. 14. Department of Urology, Freeman Hospital, Newcastle Upon Tyne, UK. 15. Division of Oncology, Department of Medicine, University of Washington School of Medicine and Fred Hutchinson Cancer Center, Seattle, WA, USA. 16. Department of Urology, Weill Cornell Medical College, Presbyterian Hospital New York, New York, NY, USA. 17. Department of Surgery (Division of Urology), McGill University Health Centre, Montreal, QC, Canada. 18. Department of Urology, David Medical Center, University of California at David, Sacramento, CA, USA. 19. Princess Margaret Hospital, Toronto, ON, Canada. 20. Department of Surgery, Exeter Surgical Health Services Research Unit, Royal Devon and Exeter NHS Trust, Exeter, UK. 21. Department of Urology, Vienna General Hospital, Medical University of Vienna, Vienna, Austria. 22. Department of Urology, University of Kansas Medical Center, Kansas City, KS, USA. 23. Division of Urology, University of Pennsylvania, Pennsylvania, PA, USA. 24. Cross Cancer Institute, Edmonton, AB, Canada. 25. Department of Urologic Surgery, Vanderbilt University Medical Center, Nashville, TN, USA. 26. Department of Urology, University of Texas Southern Medical Center, Dallas, TX, USA. 27. Department of Medicine, Case Comprehensive Cancer Center, Cleveland, USA. 28. Division of Urology, Rush University Medical Center, Chicago, IL, USA. 29. Department of Urology, Stanford University School of Medicine, Stanford, CA, USA. 30. Department of Genitourinary Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
Abstract
PURPOSE: Cisplatin-based chemotherapy followed by radical cystectomy (RC) is recommended in patients with muscle-invasive bladder cancer (MIBC). However, up to 50% of patients are cisplatin ineligible. The aim of this study was to compare clinical outcomes after ≥ 3 cycles of preoperative gemcitabine-carboplatin (gem-carbo) versus gemcitabine-cisplatin (gem-cis). METHODS: We identified 1865 patients treated at 19 centers between 2000 and 2013. Patients were included if they had received ≥ 3 cycles of neoadjuvant (cT2-4aN0M0) or induction (cTanyN + M0) gem-carbo or gem-cis followed by RC. RESULTS: We included 747 patients treated with gem-carbo (n = 147) or gem-cis (n = 600). Patients treated with gem-carbo had a higher Charlson Comorbidity Index (p = 0.016) and more clinically node-positive disease (32% versus 20%; p = 0.013). The complete pathological response (pCR; ypT0N0) rate did not significantly differ between gem-carbo and gem-cis (20.7% versus 22.1%; p = 0.73). Chemotherapeutic regimen was not significantly associated with pCR (OR 0.99 [95%CI 0.61-1.59]; p = 0.96), overall survival (OS) (HR 1.20 [95%CI 0.85-1.67]; p = 0.31), or cancer-specific survival (CSS) (HR 1.35 [95%CI 0.93-1.96]; p = 0.11). Median OS of patients treated with gem-carbo and gem-cis was 28.6 months (95%CI 18.1-39.1) and 45.1 months (95%CI 32.7-57.6) (p = 0.18), respectively. Median CSS of patients treated with gem-carbo and gem-cis was 28.8 months (95%CI 9.8-47.8) and 71.0 months (95%CI median not reached) (p = 0.02), respectively. Subanalyses of the neoadjuvant and induction setting did not show significant survival differences. CONCLUSION: Our results show that a subset of cisplatin-ineligible patients with MIBC achieve pCR on gem-carbo and that survival outcomes seem comparable to gem-cis provided patients are able to receive ≥ 3 cycles and undergo RC.
PURPOSE: Cisplatin-based chemotherapy followed by radical cystectomy (RC) is recommended in patients with muscle-invasive bladder cancer (MIBC). However, up to 50% of patients are cisplatin ineligible. The aim of this study was to compare clinical outcomes after ≥ 3 cycles of preoperative gemcitabine-carboplatin (gem-carbo) versus gemcitabine-cisplatin (gem-cis). METHODS: We identified 1865 patients treated at 19 centers between 2000 and 2013. Patients were included if they had received ≥ 3 cycles of neoadjuvant (cT2-4aN0M0) or induction (cTanyN + M0) gem-carbo or gem-cis followed by RC. RESULTS: We included 747 patients treated with gem-carbo (n = 147) or gem-cis (n = 600). Patients treated with gem-carbo had a higher Charlson Comorbidity Index (p = 0.016) and more clinically node-positive disease (32% versus 20%; p = 0.013). The complete pathological response (pCR; ypT0N0) rate did not significantly differ between gem-carbo and gem-cis (20.7% versus 22.1%; p = 0.73). Chemotherapeutic regimen was not significantly associated with pCR (OR 0.99 [95%CI 0.61-1.59]; p = 0.96), overall survival (OS) (HR 1.20 [95%CI 0.85-1.67]; p = 0.31), or cancer-specific survival (CSS) (HR 1.35 [95%CI 0.93-1.96]; p = 0.11). Median OS of patients treated with gem-carbo and gem-cis was 28.6 months (95%CI 18.1-39.1) and 45.1 months (95%CI 32.7-57.6) (p = 0.18), respectively. Median CSS of patients treated with gem-carbo and gem-cis was 28.8 months (95%CI 9.8-47.8) and 71.0 months (95%CI median not reached) (p = 0.02), respectively. Subanalyses of the neoadjuvant and induction setting did not show significant survival differences. CONCLUSION: Our results show that a subset of cisplatin-ineligible patients with MIBC achieve pCR on gem-carbo and that survival outcomes seem comparable to gem-cis provided patients are able to receive ≥ 3 cycles and undergo RC.
Authors: Matthew D Galsky; Noah M Hahn; Jonathan Rosenberg; Guru Sonpavde; Thomas Hutson; William K Oh; Robert Dreicer; Nicholas Vogelzang; Cora Sternberg; Dean F Bajorin; Joaquim Bellmunt Journal: Lancet Oncol Date: 2011-03 Impact factor: 41.316
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Authors: Thomas Powles; Michiel S van der Heijden; Daniel Castellano; Matthew D Galsky; Yohann Loriot; Daniel P Petrylak; Osamu Ogawa; Se Hoon Park; Jae-Lyun Lee; Ugo De Giorgi; Martin Bögemann; Aristotelis Bamias; Bernhard J Eigl; Howard Gurney; Som D Mukherjee; Yves Fradet; Iwona Skoneczna; Marinos Tsiatas; Andrey Novikov; Cristina Suárez; André P Fay; Ignacio Duran; Andrea Necchi; Sophie Wildsmith; Philip He; Natasha Angra; Ashok K Gupta; Wendy Levin; Joaquim Bellmunt Journal: Lancet Oncol Date: 2020-09-21 Impact factor: 41.316