Purpose: The PURE-01 study (NCT02736266) pioneered the neoadjuvant immune-checkpoint inhibitor (ICI) therapy before radical cystectomy (RC) in patients with muscle-invasive urothelial bladder carcinoma (MIBC). We herein present the survival outcomes after a median follow-up of three years. Patients and Methods: The intention-to-treat (ITT) population included 155 patients. Event-free survival (EFS) was defined as the time from pembrolizumab initiation until radiographic disease progression precluding RC, initiation of neoadjuvant chemotherapy, recurrence after RC, or death. Further outcomes were recurrence-free survival (RFS) post-RC and overall survival (OS). Multivariable Cox regression analyses for EFS were performed. Kaplan–Meier analyses compared EFS outcomes according with baseline programmed cell-death-ligand-1 (PD-L1) combined positive score (CPS) and according to the molecular subtypes. Results: After a median (interquartile range, IQR) follow-up of 39 (30–47) months, 36-month EFS and OS were 74.4% [95% confidence interval (CI), 67.8–81.7] and 83.8% (95% CI, 77.8–90.2) in the ITT population, respectively. Overall, 143 (92.3%) patients underwent RC. Within the cohort of patients who did not receive additional chemotherapy (N = 125), 36-month RFS was 96.3% (95% CI, 91.6–100) for patients achieving a ypT0N0, 96.1% (95% CI, 89–100) for ypT1/a/isN0, 74.9% (95% CI, 60.2–93) for ypT2–4N0, and 58.3% (95% CI, 36.2–94.1) for ypTanyN1–3 response. EFS was significantly stratified among PD-L1 tertiles (lower tertile: 59.7% vs. medium tertile: 76.7% vs. higher tertile: 89.8%, P = 0.0013). The claudin-low and basal/squamous subtypes displayed the lowest rates of events. Conclusions: At a median follow-up of three years, PURE-01 results further confirm the sustained efficacy of neoadjuvant pembrolizumab before RC. PD-L1 expression was the strongest predictor of sustained response post-RC.

Objective: To assess the impact of primary or progressive status on recurrence‐free survival ( RFS ), cancer‐specific mortality ( CSM ) and overall mortality ( OM ) after radical cystectomy ( RC ) for muscle‐ invasive bladder cancer ( MIBC ). Patients and Methods: A total of 768 consecutive patients underwent RC as treatment for MIBC at our institution between 2000 and 2012. Primary MIBC was defined as no previous history of bladder cancer and progressive was defined as recorded previous treated non‐ MIBC ( NMIBC ) that had progressed to MIBC . The median follow‐up was 85 (60–109) months. Univariate and multivariate Cox regression models were used to compare RFS , CSM and OM between these two cohorts. Results: In all, 475 (61.8%) patients had primary and 293 (38.2%) patients had progressive MIBC . There were no differences between the two groups in terms of demographics, pathological and peri‐operative complications (all P > 0.1). The 10‐year RFS , CSM and OM rates for primary vs progressive status were 43 vs 36% ( P = 0.01), 43 vs 37% ( P = 0.01), and 35 vs 28% ( P = 0.03), respectively. On multivariable Cox regression analyses, progressive status remained significantly associated with a higher rate of recurrence (hazard ratio [ HR ] 1.47, 95% confidence interval [ CI ] 1.12–1.79; P = 0.03), CSM ( HR 1.42, 95% CI 1.07–1.89; P = 0.01) and OM ( HR 1.42, 95% CI 1.13–1.65; P = 0.02). Conclusions: Among patients treated with RC for MIBC , progressive status was associated with a higher CSM , OM and recurrence rate after RC . The present study thus provides an impetus to improve risk sub‐stratification when bladder cancer is still at the NMIBC stage, be it through new biomarkers or improved imaging, as a subset of patients with NMIBC are likely to benefit from early RC .