Background: Muscle-invasive bladder cancer (MIBC) is an aggressive malignancy associated with high mortality. While neoadjuvant chemotherapy (NAC) remains the standard of care, its overall benefit is limited. The addition of immune checkpoint blockade (ICB) to NAC holds potential for improving patient outcomes. This study aimed to compare the pathological response and safety profile of NAC alone versus NAC combined with the programmed cell death protein 1 (PD-1) inhibitor tislelizumab (NAC+ICB) in a real-world cohort of MIBC patients.

Methods: A total of 153 MIBC patients treated between October 2021 and December 2024 were retrospectively reviewed. Among them, 88 received gemcitabine/cisplatin-based NAC, while 65 received the same regimen combined with the PD-1 inhibitor tislelizumab (NAC+ICB). The primary endpoints were pathological complete response (pCR, ypT0N0) and the incidence of grade ≥3 treatment-related adverse events (TRAEs). Multivariate logistic regression was applied to identify factors associated with pCR.

Results: The NAC+ICB group showed a significantly higher pCR rate compared to the NAC group (33.85% vs. 18.18%, p = 0.027). Pathological downstaging rate (≤ypT1N0) was also significantly higher in the combination group (58.46% vs. 38.64%, p = 0.015). The incidence of grade ≥3 TRAEs did not significantly differ between groups (41.54% vs. 38.64%, p = 0.717). Multivariate analysis revealed that lower platelet counts (OR = 0.960, p = 0.003), higher hemoglobin levels (OR = 1.229, p = 0.002), and lower total cholesterol levels (OR = 0.010, p = 0.004) were independently associated with a higher pCR rate in the NAC+ICB group.

Conclusion: Compared with chemotherapy alone, NAC combined with ICB significantly improves pathological response in MIBC patients without increasing severe adverse events, suggesting favorable efficacy and safety. This combination represents a novel strategy for perioperative optimization, though prospective studies are needed to validate its long-term survival benefits.