Homayoun Zargar1, Patrick N Espiritu2, Adrian S Fairey3, Laura S Mertens4, Colin P Dinney5, Maria C Mir6, Laura-Maria Krabbe7, Michael S Cookson8, Niels-Erik Jacobsen9, Nilay M Gandhi10, Joshua Griffin11, Jeffrey S Montgomery12, Nikhil Vasdev13, Evan Y Yu14, David Youssef1, Evanguelos Xylinas15, Nicholas J Campain16, Wassim Kassouf17, Marc A Dall'Era18, Jo-An Seah19, Cesar E Ercole6, Simon Horenblas4, Srikala S Sridhar19, John S McGrath16, Jonathan Aning20, Shahrokh F Shariat21, Jonathan L Wright14, Andrew C Thorpe13, Todd M Morgan12, Jeff M Holzbeierlein11, Trinity J Bivalacqua10, Scott North22, Daniel A Barocas23, Yair Lotan7, Jorge A Garcia6, Andrew J Stephenson6, Jay B Shah5, Bas W van Rhijn4, Siamak Daneshmand24, Philippe E Spiess2, Peter C Black25. 1. Vancouver Prostate Centre, Vancouver, British Columbia, Canada. 2. Department of Genitourinary Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA. 3. USC/Norris Comprehensive Cancer Center, Institute of Urology, University of Southern California, Los Angeles, CA, USA; University of Alberta, Edmonton, Alberta, Canada. 4. Department of Urology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands. 5. Department of Urology, MD Anderson Cancer Center, Houston, TX, USA. 6. Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, USA. 7. Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA. 8. Department of Urology, University of Oklahoma College of Medicine, Oklahoma City, OK, USA. 9. University of Alberta, Edmonton, Alberta, Canada. 10. Department of Urology, The James Buchanan Brady Urological Institute, The Johns Hopkins School of Medicine, Baltimore, MD, USA. 11. Department of Urology, University of Kansas Medical Center, Kansas City, KS, USA. 12. Department of Urology, University of Michigan Health System, Ann Arbor, MI, USA. 13. Department of Urology, Freeman Hospital, Newcastle Upon Tyne, UK. 14. Department of Medicine, Division of Oncology, University of Washington School of Medicine and Fred Hutchinson Cancer Research Center, Seattle, WA, USA. 15. Department of Urology, Weill Cornell Medical College, Presbyterian Hospital, New York, NY, USA. 16. Department of Surgery, Exeter Surgical Health Services Research Unit, Royal Devon and Exeter NHS Trust, Exeter, UK. 17. Department of Surgery (Division of Urology), McGill University Health Center, Montreal, Quebec, Canada. 18. Department of Urology, University of California at Davis, Davis Medical Center, Sacramento, CA, USA. 19. Princess Margaret Hospital, Toronto, Ontario, Canada. 20. Department of Urology, Freeman Hospital, Newcastle Upon Tyne, UK; Department of Surgery, Exeter Surgical Health Services Research Unit, Royal Devon and Exeter NHS Trust, Exeter, UK. 21. Department of Urology, Weill Cornell Medical College, Presbyterian Hospital, New York, NY, USA; Department of Urology, Medical University of Vienna, Vienna General Hospital, Vienna, Austria. 22. Cross Cancer Institute, Edmonton, Alberta, Canada. 23. Department of Urologic Surgery, Vanderbilt University Medical Center, Nashville, TN, USA. 24. USC/Norris Comprehensive Cancer Center, Institute of Urology, University of Southern California, Los Angeles, CA, USA. 25. Vancouver Prostate Centre, Vancouver, British Columbia, Canada. Electronic address: pblack@mail.ubc.ca.
Abstract
BACKGROUND: The efficacy of neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (BCa) was established primarily with methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC), with complete response rates (pT0) as high as 38%. However, because of the comparable efficacy with better tolerability of gemcitabine and cisplatin (GC) in patients with metastatic disease, GC has become the most commonly used regimen in the neoadjuvant setting. OBJECTIVE: We aimed to assess real-world pathologic response rates to NAC with different regimens in a large, multicenter cohort. DESIGN, SETTING, AND PARTICIPANTS: Data were collected retrospectively at 19 centers on patients with clinical cT2-4aN0M0 urothelial carcinoma of the bladder who received at least three cycles of NAC, followed by radical cystectomy (RC), between 2000 and 2013. INTERVENTION: NAC and RC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was pathologic stage at cystectomy. Univariable and multivariable analyses were used to determine factors predictive of pT0N0 and ≤pT1N0 stages. RESULTS AND LIMITATIONS: Data were collected on 935 patients who met inclusion criteria. GC was used in the majority of the patients (n=602; 64.4%), followed by MVAC (n=183; 19.6%) and other regimens (n=144; 15.4%). The rates of pT0N0 and ≤pT1N0 pathologic response were 22.7% and 40.8%, respectively. The rate of pT0N0 disease for patients receiving GC was 23.9%, compared with 24.5% for MVAC (p=0.2). There was no difference between MVAC and GC in pT0N0 on multivariable analysis (odds ratio: 0.89 [95% confidence interval, 0.61-1.34]; p=0.6). CONCLUSIONS: Response rates to NAC were lower than those reported in prospective randomized trials, and we did not discern a difference between MVAC and GC. Without any evidence from randomized prospective trials, the best NAC regimen for invasive BCa remains to be determined. PATIENT SUMMARY: There was no apparent difference in the response rates to the two most common presurgical chemotherapy regimens for patients with bladder cancer.
BACKGROUND: The efficacy of neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (BCa) was established primarily with methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC), with complete response rates (pT0) as high as 38%. However, because of the comparable efficacy with better tolerability of gemcitabine and cisplatin (GC) in patients with metastatic disease, GC has become the most commonly used regimen in the neoadjuvant setting. OBJECTIVE: We aimed to assess real-world pathologic response rates to NAC with different regimens in a large, multicenter cohort. DESIGN, SETTING, AND PARTICIPANTS: Data were collected retrospectively at 19 centers on patients with clinical cT2-4aN0M0 urothelial carcinoma of the bladder who received at least three cycles of NAC, followed by radical cystectomy (RC), between 2000 and 2013. INTERVENTION: NAC and RC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was pathologic stage at cystectomy. Univariable and multivariable analyses were used to determine factors predictive of pT0N0 and ≤pT1N0 stages. RESULTS AND LIMITATIONS: Data were collected on 935 patients who met inclusion criteria. GC was used in the majority of the patients (n=602; 64.4%), followed by MVAC (n=183; 19.6%) and other regimens (n=144; 15.4%). The rates of pT0N0 and ≤pT1N0 pathologic response were 22.7% and 40.8%, respectively. The rate of pT0N0 disease for patients receiving GC was 23.9%, compared with 24.5% for MVAC (p=0.2). There was no difference between MVAC and GC in pT0N0 on multivariable analysis (odds ratio: 0.89 [95% confidence interval, 0.61-1.34]; p=0.6). CONCLUSIONS: Response rates to NAC were lower than those reported in prospective randomized trials, and we did not discern a difference between MVAC and GC. Without any evidence from randomized prospective trials, the best NAC regimen for invasive BCa remains to be determined. PATIENT SUMMARY: There was no apparent difference in the response rates to the two most common presurgical chemotherapy regimens for patients with bladder cancer.
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