Efficacy and safety analysis of disitamab vedotin combined with immunotherapy as neoadjuvant treatment to promote conversion to bladder preservation in bladder cancer: A retrospective comparative study with the GC combined with immunotherapy regimen.

INTRODUCTION: For cisplatin-eligible muscle-invasive bladder cancer, cisplatin-based neoadjuvant chemotherapy followed by radical cystectomy has been a standard approach. With the advent of more effective systemic therapies, bladder-preserving strategies after favorable response have become an area of increasing interest. METHODS: We retrospectively analyzed 46 patients with bladder cancer (BCG-unresponsive T1N0M0 and T2-4N0-2M0). Patients received neoadjuvant disitamab vedotin (DV) plus toripalimab (Group A, n = 23) or gemcitabine/cisplatin (GC) plus toripalimab (Group B, n = 23). The primary endpoint was strict clinical complete response (cCR). The main efficacy analysis was restricted to patients with T2-4 disease, whereas T1 outcomes were summarized descriptively. Exploratory propensity-score overlap weighting was performed in the full cohort. RESULTS: Among patients with T2-4 disease, strict cCR was achieved in 10 of 16 patients (62.5%) in Group A and 2 of 17 patients (11.8%) in Group B (P = 0.004). Strict cCR with initial bladder preservation was observed in 9 of 16 patients (56.3%) and 2 of 17 patients (11.8%), respectively. In the T1 subgroup, strict cCR rates were similar between the groups (85.7% vs. 83.3%). Exploratory overlap-weighted analyses of the full cohort showed weighted risk differences of 31.9 percentage points for strict cCR (95% confidence intervals, 7.1-56.7; P = 0.012) and 29.5 percentage points for strict cCR with initial bladder preservation (95% confidence intervals, 4.8-54.2; P = 0.019). The median follow-up duration for the overall cohort was 26.5 months. Among patients with strict cCR who were initially managed with bladder preservation, no muscle-invasive bladder recurrence or progression and no nodal or distant progression were observed. No adverse-event comparison remained statistically significant after false discovery rate adjustment. CONCLUSION: In this single-center retrospective cohort, DV plus toripalimab was associated with higher observed rates of strict cCR and strict cCR with initial bladder preservation than GC plus toripalimab among patients with T2-4 disease. These findings are hypothesis-generating and require validation in prospective multicenter studies with longer follow-up.