Timely initiation of definitive treatment is critical in muscle-invasive bladder cancer (MIBC). While cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) is the standard of care, its real-world implementation remains limited. We evaluated the association between time-to-treatment initiation (TTI) and overall survival (OS) in MIBC.
Using the National Cancer Database (2004-2022), we identified cT2-T4aN0M0 urothelial MIBC patients treated with RC with/without NAC. Patients were stratified into four groups: upfront RC within 60 days, upfront RC beyond 60 days, NAC within 60 days followed by RC, and NAC beyond 60 days followed by RC. Inverse probability of treatment weighting (IPTW) was applied. Weighted Kaplan-Meier and IPTW-adjusted Cox models estimated OS, reported as hazard ratios (HRs) with 95% confidence intervals (CIs).
Among 16,517 eligible patients (median follow-up:49.7 months [IQR:20.8-95.2]), 39.1% underwent upfront RC within 60 days and 23.3% initiated NAC within 60 days. In cT2N0M0 disease, NAC initiated within 60 days was associated with improved OS compared with upfront RC ≤60 days (HR:0.79; 95%CI: 0.71-0.90; P<.001); delayed NAC showed no significant benefit (HR:0.83; 95%CI: 0.67-1.02; P=.08). In cT3-T4aN0M0 disease, delayed RC (>60 days) was associated with worse OS (HR:1.21; 95%CI: 1.03-1.41; P=.02); early NAC improved survival (HR:0.78; 95%CI: 0.67-0.92; P=.004). Sensitivity analyses confirmed consistent findings.
TTI is a critical determinant of survival in MIBC. NAC initiated within 60-days from diagnosis retains its survival benefit, whereas longer delays do not confer improved outcomes. These findings highlight the need for timely multidisciplinary coordination and streamlined care pathways in MIBC.
Clinical genitourinary cancer. 2026 Jun 05 [Epub ahead of print]
Andrea Piccolini, Marco Paciotti, Stephan M Korn, Zhiyu Qian, Pietro Brin, Klara Pohl, Hanna Zurl, Boyuan Xiao, Stuart Lipsitz, Mark A Preston, Giovanni Lughezzani, Nicolò M Buffi, Quoc-Dien Trinh, Alexander P Cole
Department of Urology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Center for Surgery and Public Health, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Urology, IRCCS Humanitas Research Hospital, Milan, Italy; Department of Biomedical Sciences, Humanitas University, Milan, Italy., Department of Urology, IRCCS Humanitas Research Hospital, Milan, Italy; Department of Biomedical Sciences, Humanitas University, Milan, Italy., Department of Urology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Center for Surgery and Public Health, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Urology, Medical University of Vienna, Vienna, Austria., Department of Urology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Center for Surgery and Public Health, Brigham and Women's Hospital, Harvard Medical School, Boston, MA., Department of Urology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Center for Surgery and Public Health, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Urology, Medical University of Graz, Graz, Austria., Boston University Chobanian and Avedisian School of Medicine, Boston, MA., Center for Surgery and Public Health, Brigham and Women's Hospital, Harvard Medical School, Boston, MA., Department of Urology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA., Department of Urology, University of Pittsburgh, Pittsburgh, PA., Department of Urology, MaineHealth Pen Bay Hospital, Rockport, ME; Tufts University School of Medicine, Boston, MA. Electronic address: .