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 Journal Article


Authors: Bandini, M.; Briganti, A.; Plimack, E. R.; Niegisch, G.; Yu, E. Y.; Bamias, A.; Agarwal, N.; Sridhar, S. S.; Sternberg, C. N.; Vaishampayan, U.; Theodore, C.; Rosenberg, J. E.; Bellmunt, J.; Galsky, M. D.; Montorsi, F.; Necchi, A.
Article Title: 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, 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<.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. Conclusions: 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. Patient summary: 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. (C) 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.
Keywords: recurrence; bladder cancer; risk; adjuvant chemotherapy; urothelial carcinoma; perioperative chemotherapy; nomogram; stage; relapse-free survival; cancer
Journal Title: European Urology Oncology
Volume: 2
Issue: 3
ISSN: 2588-9311
Publisher: Elsevier BV  
Date Published: 2019-05-01
Start Page: 248
End Page: 256
Language: English
ACCESSION: WOS:000474612900003
DOI: 10.1016/j.euo.2018.08.009
PROVIDER: wos
PUBMED: 31200838
PMCID: PMC7552889
Notes: Article -- Source: Wos
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
  1. Jonathan Eric Rosenberg
    512 Rosenberg