Four versus 3 Cycles of Neoadjuvant Chemotherapy for Muscle-Invasive Bladder Cancer: Implications for Pathological Response and Survival

Hiten D. Patel, Sunil H. Patel, Enrique Blanco-Martinez, Jake Kuzbel, Victor S. Chen, Aleksander Druck, Elizabeth L. Koehne, Parth M. Patel, Chirag P. Doshi, Noah M. Hahn, Jean H. Hoffman-Censits, Stephanie Berg, Trinity J. Bivalacqua, Max Kates, Marcus L. Quek

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)77-85
Number of pages9
JournalJournal of Urology
Volume207
Issue number1
DOIs
StatePublished - Jan 1 2022

Keywords

  • drug-related side effects and adverse reactions
  • neoadjuvant therapy
  • pathology, surgical
  • survival
  • urinary bladder neoplasms

ASJC Scopus subject areas

  • Urology

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