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.

To provide a benchmark for predicting 1-yr RFS in patients with cT2-4N0 MIBC.

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.

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<.0001) were significantly associated with RFS, while NAC was not (p=0.6). The model including all these factors yielded a c-index of 0.76 (95% CI 0.72-0.79), good calibration, and a high net benefit. The 1-yr RFS rates across nomogram tertiles were 90.5% (95% CI 87-94%), 73.4% (95% CI 68-79%), and 51.1% (95% CI 45-58%), respectively. The results lack external validation.

Benchmark 1-yr RFS estimates for phase 2 design of new neoadjuvant trials are proposed and can be used for statistical assumptions, pending external validation.

Our prognostic model predicting 1-yr survival free from recurrence of bladder cancer after radical cystectomy, with or without standard chemotherapy, could provide an improvement to the quality of phase 2 clinical trial designs and interpretation of their results.

European urology oncology. 2018 Sep 07 [Epub]

Marco Bandini, Alberto Briganti, Elizabeth R Plimack, Günter Niegisch, Evan Y Yu, Aristotelis Bamias, Neeraj Agarwal, Srikala S Sridhar, Cora N Sternberg, Ulka Vaishampayan, Christine Théodore, Jonathan E Rosenberg, Joaquim Bellmunt, Matthew D Galsky, Francesco Montorsi, Andrea Necchi

Vita-Salute San Raffaele University and Department of Urology, IRCCS San Raffaele Hospital, Milan, Italy. Electronic address: ., Vita-Salute San Raffaele University and Department of Urology, IRCCS San Raffaele Hospital, Milan, Italy., Fox Chase Cancer Center, Philadelphia, PA, USA., Department of Urology, Heinrich-Heine University, Düsseldorf, Germany., Seattle Cancer Care Alliance, University of Washington, Seattle, WA, USA., University of Athens, Athens, Greece., Huntsman Cancer Institute (HCI), University of Utah, Salt Lake City, UT, USA., Cancer Clinical Research Unit (CCRU), Princess Margaret Cancer Centre, University Health Network, Toronto, Canada., Department of Medical Oncology, San Camillo Forlanini Hospital, Rome, Italy., Wayne State University/Karmanos Cancer Center, Detroit, MI, USA., Hospital Foch, Suresnes, France., Memorial Sloan-Kettering Cancer Center, New York, NY, USA., Bladder Cancer Center, Medicine, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA., Mount Sinai School of Medicine, Tisch Cancer Institute, New York, NY, USA., Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.