Pathologic response with neoadjuvant chemotherapy, immunotherapy, and chemo-immunotherapy for muscle-invasive bladder cancer (MIBC): A systematic review and meta-analysis.

Abstract

531 Background: Neoadjuvant cisplatin-based chemotherapy (NAC) is established in the management of MIBC. Pathologic complete response (pCR, ypT0N0) and downstaging (<ypT2N0) are associated with long term survival in patients with MIBC. Several trials have evaluated neoadjuvant immunotherapy (NAI) and chemoimmunotherapy (NACI) for MIBC. We aimed to conduct a meta-analysis of available trials to compare the incidence of pathological response with NAC, NAI and NACI in MIBC patients undergoing radical cystectomy. Methods: Phase II/III clinical trials assessing neoadjuvant systemic therapies (NAC, NAI, or NACI) in patients with MIBC undergoing radical cystectomy were identified through a systematic search of MEDLINE and EMBASE. Outcomes of interest included pCR and pathological downstaging. A DerSimonian and Laird random-effect meta-analysis was conducted to estimate pooled incidence of events using the Freeman-Tukey transformation. Clopper-Pearson method was used to estimate the associated 95% confidence intervals (CI). Results: Of the 5357 records initially identified, 28 trials with a total of 2138 patients were considered eligible for inclusion. Neoadjuvant chemotherapy was assessed in 15 trials (1535 patients), NAI in 5 (288 patients), and NACI in 8 (315 patients). The pooled incidence of patients experiencing a pCR was 30.91% (95% CI: 26.54%-35.45%) with NAC, 30.92% (23.22%-39.14%) with NAI, and 42.25% (36.6%-48.0%) with NACI. The difference in pCR among these therapies was statistically significant (p <0.05). Similarly, the pooled incidence of achieving pathological downstaging was 40.91% (34.26%-47.72%) with NAC, 38.84% (26.73%-51.64%) with NAI, and 62.88% (57.22%-68.39%) with NACI. Consistently, there was statistically significant effect modification by the choice of neoadjuvant systemic therapy (p <0.01). The results were consistent across different clinically important subgroups (Table). Conclusions: NACI may achieve better pCR and pathological downstaging than NAC and NAI alone in MIBC patients which may potentially be associated with long-term survival. Definitive data from phase III trials are pending. [Table: see text]