Four versus 3 Cycles of Neoadjuvant Chemotherapy for Muscle-Invasive Bladder Cancer: Implications for Pathological Response and Survival
Hiten D. Patel, Sunil Patel, Enrique Blanco-Martinez, Jake Kuzbel, Victor S. Chen, Aleksander Druck, Elizabeth L. Koehne, Parth M. Patel, Chirag Doshi, Noah M. Hahn, Jean Hoffman‐Censits, Stephanie Berg, Trinity J. Bivalacqua, Max Kates, Marcus L. Quek
Abstract
PURPOSE: The ideal number of neoadjuvant chemotherapy (NAC) cycles for muscle-invasive bladder cancer is uncertain with 3 to 4 representing the standard of care (SOC). We compared ypT0 rates and survival between patients receiving 4 versus 3 cycles of NAC with evaluation of chemotherapy-related toxicity for correlation with tumor chemosensitivity and pathological response. MATERIALS AND METHODS: Patients receiving NAC followed by radical cystectomy for cT2-4N0M0 urothelial carcinoma from 2 institutions were included. Primary study groups included 4 cisplatin-based NAC cycles, 3 cisplatin-based NAC cycles, and nonSOC NAC (1-2 cycles or noncisplatin-based) to compare ypT0/≤ypT1 rates and survival. A cohort of patients not receiving NAC was included for pathological reference. RESULTS: Of 693 total patients, 318 (45.9%) received NAC. ypT0 and ≤ypT1 rates were 42/157 (26.8%) and 86/157 (54.8%) for 4 cycles, 38/114 (33.3%) and 71/114 (62.3%) for 3 cycles, and 6/47 (12.8%) and 13/47 (27.7%) for nonSOC (p=0.03 and p <0.01, respectively). Pathological response appeared higher among patients receiving 3 cycles due to toxicity (ypT0: 29/77 [37.7%]; ≤ypT1: 51/77 [66.2%]) but did not reach statistical significance. Toxicities leading to treatment modifications were thrombocytopenia (32.1%), neutropenia (27.2%), renal insufficiency (22.2%), and constitutional symptoms (18.5%). NonSOC patients had lower Kaplan-Meier survival (cT2-cT4N0M0: log-rank p=0.07; cT2N0M0: log-rank p=0.02). There were no statistically significant differences in survival between 4 and 3 cycles (HR 1.00 [95% CI 0.57-1.74], p=0.99). CONCLUSIONS: Patients completing 3 cycles of cisplatin-based NAC have similar pathologic response and short-term survival compared to 4 cycles. Further evaluation of patients experiencing toxicity as a potential marker of tumor chemosensitivity is needed.