Disitamab vedotin (RC48-ADC) combined with immunotherapy as neoadjuvant therapy for localized muscle-invasive bladder cancer: a multicenter real-world study

Neoadjuvant cisplatin-based combination chemotherapy or perioperative durvalumab with neoadjuvant gemcitabine-cisplatin has been the primary treatment for localized muscle-invasive bladder cancer (MIBC). Nevertheless, many patients are either cisplatin-ineligible or relapse after standard therapy. This multicenter, retrospective real-world study evaluated disitamab vedotin (RC48) plus PD-1 inhibitors as neoadjuvant therapy for localized MIBC. Twenty-five patients (cT2-4aN0-2M0) received at least four cycles of RC48 (2.0 mg/kg, Q2W or Q3W) with toripalimab, tislelizumab, or pembrolizumab, followed by radical cystectomy. The pathological complete response rate was 48%, and the pathological downstaging rate was 88%. After a median follow-up of 17.0 months, 12-month disease-free and overall survival rates were 91.5% and 100%, respectively. HER2 overexpression (IHC 3+) was significantly associated with higher response (odds ratio [OR] = 6.75, 95% confidence interval [CI]: 1.16-39.20, p = 0.033), whereas advanced stage (>T2N0M0) predicted poorer outcomes (OR = 0.15, 95% CI: 0.03-0.86, p = 0.033). Treatment-related adverse events were manageable. These findings suggest that RC48 combined with PD-1 inhibitors is a promising neoadjuvant strategy for localized MIBC and warrants further validation in biomarker-selected populations.