Comparison of Neoadjuvant Chemotherapy, Chemoimmunotherapy, and Upfront Radical Cystectomy in High-Risk Bladder...

Background: While radical cystectomy is standard for muscle-invasive bladder cancer (MIBC), micrometastasis-related recurrence is common. Cisplatin-based neoadjuvant therapy (NAT) confers modest benefits, while immune checkpoint inhibitors (ICIs) provide new efficacy-enhancing strategies. This study aims to compare the efficacy and safety of ICIs with chemotherapy (NAC-ICI), neoadjuvant chemotherapy (NAC), and no neoadjuvant therapy (NNAT). It also explores potential biomarkers predictive of NAT response and evaluates the real-world efficacy of NAC-IC. Method: This single-center retrospective analysis included 80 radical cystectomy patients, with 51 NNAT group and 29 in the NAT group. Survival outcomes were evaluated by Kaplan-Meier survival curves, with log-rank test and restricted mean survival time (RMST) for comparisons. Pathological responses were assessed by complete response (pCR) and downstaging (pDS). Treatment-related adverse events (TRAEs) and predictive hematological biomarkers were analyzed. Results: Kaplan-Meier curves showed NAT is non-significant survival advantage over NNAT (p = 0.30). The RMST analysis showed the NAC-ICI had significantly longer RMST than the NNAT (56.00 vs. 47.73 months; Δ = +8.27 months; p = 0.0008). Fisher's exact test showed that NAC-ICI had a numerically higher pCR rate (42.10%) than NAC (20.00%), but the difference was non-significant (p = 0.414) ROC analysis showed baseline platelet count (PLT) was a significant negative predictor of pCR after NAC-ICI. Conclusions: This study indicates potential feasibility and safety of NAT for MIBC patients. Chemoimmunotherapy trends toward better pathological and survival outcomes than chemotherapy alone, but no statistically significant differences were observed. Baseline PLT may be a potential prdictive biomarker.