ASCO 2018: Clinical Complete Response to Neoadjuvant Chemotherapy for Muscle-Invasive Bladder Cancer

Chicago, IL (UroToday.com) Over the past 15 years, results of several randomized controlled trials have cemented neoadjuvant platinum-based chemotherapy followed by radical cystectomy as the gold standard treatment for muscle-invasive bladder cancer (MIBC) [1,2]. Grossman and colleagues randomized 317 patients with stage T2-T4a bladder cancer to radical cystectomy alone vs three cycles of methotrexate, vinblastine, doxorubicin and cisplatin followed by radical cystectomy [1]. In the intention-to-treat analysis, the median OS among patients assigned to radical cystectomy alone was 46 months, compared with 77 months for patients assigned to combination therapy (p=0.06 two-sided stratified log-rank test).

Interestingly, in both groups of this trial, improved survival was seen among patients without residual cancer at the time of radical cystectomy (pT0). Given these findings, for those that experience complete response after neoadjuvant chemotherapy, there has been interest in foregoing the morbidity associated with radical cystectomy. At ASCO 2018 annual meeting, Dr. Mazza and colleagues presented results of a multi-institutional study of patients with a complete response to neoadjuvant chemotherapy who opted for surveillance only and did not undergo a post-neoadjuvant chemotherapy radical cystectomy.   

For this study, patients at Columbia University Medical Center and Memorial Sloan Kettering Cancer Center were prospectively enrolled and retrospectively reviewed (2001-2017). Eligible patients for this analysis included those with MIBC who underwent a radical TURBT (complete resection down to muscularis propria) followed by neoadjuvant chemotherapy, exhibited a complete response to chemotherapy, and opted for surveillance only. The authors defined a complete response as a negative (i) radical TURBT, (ii) urine cytology, and (iii) cross-sectional imaging. The patients were subsequently followed with physical exam, cystoscopy and cytology every 2-3 months, and cross-sectional imaging generally with a CT scan every 4-6 months for two years; after five years, cystoscopy and imaging were generally done annually. 

The cohort for this study included 148 patients, of which 119 (80%) were men, a median age of 62 (range 32-88) years, and a median follow-up of 55 (range 5-145) months. The neoadjuvant chemotherapy regimens comprised 31% MVAC, 63% gemcitabine and cisplatin, and 6% other platinum-based regimens. Among these patients, 71 (48%) recurred in the bladder, including 16 (11%) with muscle invasive disease and 55 with non-muscle invasive disease. Salvage radical cystectomy was performed in 12 patients with muscle invasive recurrence, of which cancer-specific death was prevented in nine (75%) patients. Salvage radical cystectomy was performed in 14 patients with non-muscle invasive recurrence, of which cancer-specific death was prevented in 13 patients (93%).  The 5-year disease-specific survival rate was 90%, overall survival rate was 86%, cystectomy-free survival rate was 76%, and recurrence-free survival rate was 64%. 

The Kaplan-Meier curve for DSS is as follows: 

Screen Shot 2018 06 02 at 11.59.20 AM

The strength of this study is the multi-institutional assessment of two large cancer center institutions, allowing pooling of patients and events to enable this study to be undertaken. A limitation is the potential for selection bias, given the retrospective analysis. If feasible, a trial randomizing patients with complete response after neoadjuvant chemotherapy to surveillance vs radical cystectomy would offer more definitive conclusions to the oncological safety of patients desiring bladder-sparing follow-up for chemotherapy-treated MIBC. Dr. Mazza concluded that based on these findings, favorable outcomes may be attained among patients with complete response to neoadjuvant chemotherapy who opt for surveillance only. He suggests that these patients should be highly selected and have close surveillance protocols. He highlights that future studies should aim to improve patient selection by identifying biomarkers predictive of invasive relapse and developing novel imaging methods for relapse detection. 

Presented By: Patrick M. Mazza, Department of Urology, Columbia University Medical Center, New York, NY 
Co-Authors: George W. Moran, Gen Li, Dennis J. Robins, Justin T. Matulay, Harry W. Herr, Christopher B. Anderson, James M. McKiernan; Department of Urology, Columbia University Medical Center, New York, NY; Columbia University College of Physicians and Surgeons, New York, NY; Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, NY; Memorial Sloan Kettering Cancer Center, New York, NY 

Written by: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre, Twitter: @zklaassen_md  at the 2018 ASCO Annual Meeting - June 1-5, 2018 – Chicago, IL USA

References: 
1. Grossman HB, Natale RB, Tangen CM, et al. Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. N Engl J Med 2003;349(9):859-866. 
2. Griffiths G, Hall R, Sylvester R, et al. International phase III trial assessing neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: long term results of the BA06 30894 trial. J Clin Oncol 2011;29(16):2171-2177.
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