An update on the pharmacotherapy of penile cancer

Objective To review the current pharmacologic treatment landscape for penile squamous cell carcinoma (PSCC), with a focus on current pharmacotherapy and emerging therapeutic approaches. Data Sources An extensive Medline, Embase and Cochrane search of peer-reviewed sources reporting on pharmacotherapy of penile cancer was performed (1/1/2000-06/30/2025). Contribution of immune checkpoint inhibitors (ICIs) to the therapeutics of penile cancer was carefully considered. Data Summary This review highlights recent advances in the management of PSCC, covering key aspects of global epidemiology, molecular subtyping, guideline-based treatment by stage, and systemic therapeutic approaches. Particular attention is given to the growing role of immunotherapy in biomarker-selected populations and its potential to reshape the treatment landscape of this disease. For fit patients with advanced disease, platinum-based chemotherapy, particularly the paclitaxel-ifosfamide-cisplatin regimen (TIP), remains the standard first-line option, offering reasonable response rates albeit with significant toxicity. In contrast, ICIs have emerged as valuable alternatives. Cemiplimab and pembrolizumab have shown durable responses in this setting, with the added benefit of improved tolerability and quality of life. Conclusions Despite its rarity, penile squamous cell carcinoma (PSCC) remains a therapeutically challenging malignancy. Randomized clinical trials with ICIs are being awaited. We believe that clinical trials to test the addition of these agents to a backbone of platinum-based chemotherapy are also warranted. Continued global collaboration and prospective trials are essential to refine stage-based management, improve access to specialized care, and integrate precision oncology to the bedside of patients with PSCC.