The optimal postoperative management strategy for patients with muscle-invasive bladder cancer (MIBC) who achieve pathological complete response (pCR) after neoadjuvant therapy remains undefined. We aimed to compare disease-free survival (DFS) outcomes among 3 strategies: observation alone, adjuvant immune checkpoint inhibitor (ICI) continuation, and adjuvant enfortumab vedotin plus pembrolizumab (EV+P) continuation.
We conducted a comprehensive literature search of PubMed, Cochrane Library, Web of Science, Google Scholar, and ClinicalTrials.gov to identify prospective phase II or higher trials evaluating ICI-based or EV-containing neoadjuvant therapy for MIBC. Individual patient data were reconstructed from published Kaplan-Meier curves stratified by pCR status using the Guyot algorithm. DFS was compared using Kaplan-Meier analysis, Cox proportional hazards models, and restricted mean survival time (RMST) analysis.
Five trials reported survival data for pCR subgroups, yielding 534 patients: 226 observation, 211 ICI continuation, and 97 EV+P continuation. An estimated 74 DFS events were reconstructed (37 observation, 22 ICI, 15 EV+P). No significant differences in DFS were observed among groups (log-rank P = .12). Two-year DFS rates were 86.6%, 90.8%, and 86.6% for observation, ICI continuation, and EV+P continuation, respectively. Hazard ratios (HRs) for ICI continuation vs. observation (HR 0.64; 95% confidence intervals [CI], 0.38-1.08; P = .097) and EV+P vs. observation (HR 1.24; 95% CI, 0.67-2.27; P = .49) were not statistically significant. RMST analysis confirmed no significant differences at 12, 24, 36, and 48 months across all pairwise comparisons.
This exploratory analysis found no evidence that adjuvant therapy provides an additional survival benefit in MIBC patients achieving pCR; however, the limited number of events constrains power, and this absence of evidence should not be interpreted as evidence of no benefit. Given substantial heterogeneity in baseline patient characteristics and cisplatin eligibility across included trials, these findings require prospective validation before informing clinical practice.
Clinical genitourinary cancer. 2026 Jun 20 [Epub ahead of print]
Shugo Yajima, Soichiro Yoshida, Naoki Imasato, Wei Chen, Hiroyuki Sato, Akihiro Hirakawa, Hiroshi Fukushima, Hajime Tanaka, Hitoshi Masuda, Yasuhisa Fujii
Department of Urology, National Cancer Center Hospital East, Chiba, Japan; Department of Urology, Institute of Science Tokyo, Tokyo, Japan., Department of Urology, Institute of Science Tokyo, Tokyo, Japan. Electronic address: ., Department of Urology, National Cancer Center Hospital East, Chiba, Japan., Department of Urology, Institute of Science Tokyo, Tokyo, Japan., Department of Clinical Biostatistics, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Tokyo, Japan.