Modeling 1-year Relapse-free Survival After Neoadjuvant Chemotherapy and Radical Cystectomy in Patients with Clinical T2–4N0M0 Urothelial Bladder Carcinoma: Endpoints for Phase 2 Trials

Abstract

Background: Several ongoing phase 2 trials are evaluating new neoadjuvant therapy regimens in patients with muscle-invasive bladder cancer (MIBC). The 1-yr recurrence-free survival (RFS) after radical cystectomy (RC), with or without perioperative chemotherapy, can be used to model statistical assumptions and interpret outcomes from these studies. Objective: To provide a benchmark for predicting 1-yr RFS in patients with cT2–4N0 MIBC. Design, setting, and participants: We identified 950 patients with clinical stage T2–4N0 MIBC undergoing RC at 27 centers between 1990 and 2016. We assessed 1-yr RFS rates for patients managed with no perioperative chemotherapy, neoadjuvant chemotherapy (NAC), adjuvant chemotherapy (AC), or NAC followed by AC. Cox regression analyses tested for 1-yr postsurgical RFS predictors. A Cox-based nomogram was developed to estimate 1-yr RFS and its accuracy was assessed in terms of Harrell's c-index, a calibration plot, and decision curve analysis. We report 1-yr RFS rates across the nomogram tertiles. Results and limitations: The 1-yr RFS rates were 67.9% (95% confidence interval [CI] 64–72) after no perioperative chemotherapy, 76.9% (95% CI 72–83%) after NAC, 77.8% (95% CI 71–85%) after AC, and 57% (95% CI 37–87) after NAC + AC. On multivariable analysis, positive surgical margins (p = 0.002), pT stage (p < 0.0001), and pN stage (p