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 I2 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.
Clinical genitourinary cancer. 2025 Dec 22 [Epub ahead of print]
Mariana Macambira Noronha, Luiz Felipe Costa de Almeida, Pedro Robson Costa Passos, Luís Felipe Leite da Silva, Anelise Poluboiarinov Cappellaro, Valbert Oliveira Costa Filho, Leonardo-Gil Santana, Changsu Lawrence Park, Erick Figueiredo Saldanha
Department of Medical Sciences, Universidade Federal do Ceará, CE, Brazil., Department of Medical Sciences, Universidade Federal Fluminense, RJ, Brazil., Department of Medical Sciences, Centro Universitário Maurício de Nassau de Barreiras, Barreiras, BA, Brazil., Department of Medical Oncolofy, Santé Cancer Center, SC, Brazil; Department of Medical Oncolofy, Latin American Cooperative Oncology Group (LACOG), Porto Alegre, Brazil., Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, ON, Canada; Department of Medicine, University of Toronto, Toronto, ON, Canada., Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, ON, Canada; Department of Medicine, University of Toronto, Toronto, ON, Canada; Harvard T. H. Chan School, Harvard University, Boston, MA. Electronic address: .
PubMed http://www.ncbi.nlm.nih.gov/pubmed/41571538