Current Management and Investigational Therapeutic Strategies in Penile Squamous Cell Carcinoma: A Narrative Review

Penile squamous cell carcinoma (PSCC) is a rare and aggressive genitourinary malignancy requiring integrated multidisciplinary management. This narrative review provides an updated overview of the diagnostic and therapeutic pathway of PSCC from localized disease, where surgery remains the cornerstone of treatment, to locally advanced disease, where multimodal strategies integrating chemotherapy and radiotherapy with surgery are required, and finally to metastatic disease, where systemic therapy becomes the mainstay of treatment. Platinum-based chemotherapy remains the established systemic backbone for advanced PSCC, whereas immune checkpoint inhibitors, chemo-immunotherapy combinations, targeted therapies, antibody-drug conjugates, vaccines, and adoptive cellular therapies represent investigational strategies supported by preliminary evidence. Although these approaches have shown early signals of activity, their routine integration into clinical practice remains limited by small and heterogeneous studies, the lack of definitive randomized evidence, and the need for prospective validation in well-defined clinical and molecular subgroups. The aim of this review is therefore to provide a stage-adapted and multidisciplinary overview of therapeutic strategies for the contemporary management of PSCC.