The advancement of immune checkpoint inhibitors (ICIs) has expanded perioperative treatment options for urothelial carcinoma. We aimed to evaluate the effect of neoadjuvant ICI-based regimens on oncological outcomes in patients with muscle-invasive bladder cancer (MIBC).

In September 2024, we systematically searched MEDLINE, Embase, Web of Science, and ClinicalTrials.gov for studies on neoadjuvant therapies for MIBC. A proportion meta-analysis and network meta-analysis (NMA) using random-effect models were conducted to evaluate pooled pathological complete response (pCR) rates and to compare overall survival (OS) and adverse events (AEs). (PROSPERO: CRD42024587964)

In total, 12 randomized controlled trials (RCTs) (n = 5,004) and 35 non-RCTs (n = 2,964) were included. ICI-chemo combination therapy (40.6%) was associated with a significantly higher pCR rate compared to chemotherapy alone (17.9%) (p < 0.01). In the two included phase Ⅲ RCTs, comprising 1556 patients, there was no significant difference in OS between ddMVAC and Durvalumab + GC (HR: 1.06; 95% CI: 0.72-1.55; p = 0.8). ddMVAC significantly increased the risk of grade ≥3 anemia (RR: 2.81; 95% CI: 1.62-4.88) and asthenia (RR: 3.46; 95% CI: 1.68-7.14) compared to GC, while Durvalumab + GC did not. Limitations include data heterogeneity across studies and the limited number of studies included in the NMA.

The addition of ICIs to chemotherapy, in the neoadjuvant MIBC setting significantly increased pCR rates compared to chemotherapy alone. There was, however, no difference in OS between Durvalumab + GC and ddMVAC. Further studies are needed to clarify the OS benefit of ICI-based combination therapy compared to the current standard chemotherapy regimen.