Efficacy and Safety of Immune Checkpoint Blockade in Locally Advanced or Metastatic Penile Cancer: A Systematic Review and Meta-Analysis.

Locally advanced or metastatic penile cancer (LA/mPC) is an aggressive and rare malignancy with limited treatment options. While promising, the role of Immune Checkpoint Blockade (ICB) in LA/mPC remains controversial. We performed a systematic review and meta-analysis to evaluate the efficacy and safety of ICB in patients with LA/mPC. A literature search was conducted in PubMed, Embase, and Cochrane (up to June 2025). The analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines (CRD420251070583). Proportional outcomes were pooled using a random-effects proportional meta-analysis, and hazard ratios (HR) were pooled using a random-effects model. We used the available Kaplan-Meier curves to recreate time-to-event data from the studies considered. Heterogeneity between studies was evaluated using the I metric and Cochran's Q test. A total of 12 cohorts (488 patients) were included in the analysis. The pooled Objective Response Rate in patients treated with ICB was 34.13% (95% CI, 20.62%-56.48%). Subgroup analysis demonstrated marked variability by treatment strategy, with an ORR of 60.7% for ICB plus chemotherapy versus 16.7% for ICB monotherapy (P < .01). At 12 months, pooled Progression-Free Survival (PFS) and Overall Survival (OS) rates were 62.64% (95% CI, 55.55%-70.63%) and 80.21% (95% CI, 74.11%-86.83%), respectively. The median PFS and OS were 5.7 months and 13.6 months, respectively. The pooled incidence of Immune-related Adverse Events was 40.36% (95% CI, 26.82%-60.74%) for any grade and 13.79% (95% CI, 7.67%-24.80%) for grade ≥ 3 events. ICB, particularly when combined with chemotherapy, shows signals of clinical activity in LA/mPC. However, due to high inter-study variability and the single-arm nature of the analysis, these findings are hypothesis-generating and require prospective, randomized, biomarker-driven validation.