Neoadjuvant PD-1/PD-L1 Inhibitors for Muscle-Invasive Bladder Cancer: A Meta-Analysis

Abstract

Neoadjuvant immune checkpoint inhibitors have emerged as a potential treatment option for muscle-invasive bladder cancer (MIBC), but their comparative efficacy and safety remain unclear. This meta-analysis evaluated pathological outcomes and adverse events of neoadjuvant PD-(L)1 inhibitors across different therapeutic approaches. A systematic search was conducted across multiple databases (PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, and Wanfang databases), from their inception to December 21, 2024, for studies investigating neoadjuvant PD-(L)1 inhibitors in patients with MIBC. Primary outcomes included pathological complete response (pCR), pathological partial response (pPR), downstaging (DS), and grade ≥3 immune-related adverse events (irAEs). Random-effects models were used to calculate pooled estimates, with subgroup analyses performed based on treatment strategy and inhibitor type. Twenty-nine studies were finally included, involving 33 treatment arms. The overall pooled pCR rate was 32.7% (95% confidence interval [CI]: 27.7%-37.7%), with PD-(L)1 inhibitors plus chemotherapy showing the highest rate (39.2%, 95% CI: 32.1%-46.3%), followed by dual checkpoint inhibition (27.6%, 95% CI: 15.5%-39.6%), and monotherapy (24.6%, 95% CI: 16.9%-32.3%). The overall pooled pPR was 45.3% (95% CI: 38.4%-52.2%), and DS rate was 62.9% (95% CI: 53.1%-72.8%). Grade ≥3 irAEs varied significantly by approach: 9.4% (95% CI: 6.0%-12.7%) for monotherapy, 24.9% (95% CI: 9.6%-40.2%) for dual checkpoint inhibition, and 14.2% (95% CI: 6.9%-21.5%) for combination with chemotherapy. Sensitivity analyses confirmed the robustness of these findings. Neoadjuvant PD-(L)1 inhibitors demonstrate promising efficacy in MIBC with acceptable toxicity profiles. Combination with chemotherapy provides the highest pathological response rates with moderate toxicity, while monotherapy offers a favorable safety profile that may benefit cisplatin-ineligible patients. These findings support the continued investigation of these approaches in ongoing Phase III trials.