Systemic treatment of penile squamous cell carcinoma—hurdles and hopes of preclinical models and clinical regimens: a narrative review

Despite contemporary research efforts, the prognosis of penile squamous cell carcinoma (PeSCC) has not significantly improved over the past decade. Despite frequently encountered patient-related delayed medical consultations impairing outcomes, several other aspects contribute to the lack of advancement in the treatment of this condition. One essential reason is that translational research, a prerequisite for the clinically successful disease management, is still at an early stage in PeSCC as compared to many other malignancies. Preclinical experimental models are indispensable for the evaluation of tumor biology and identification of genomic alterations. However, since neither commercial PeSCC cell lines are available nor xenograft models sustainably established, such analyses are challenging in this field of research. In addition, systemic therapies are less effective and toxic without decisive breakthroughs over recent years. Current systemic management of PeSCC is based on protocols that have been investigated in small series of only up to 30 patients. Thus, there is an unmet medical need for new approaches necessitating research efforts to develop more efficacious systemic strategies. This review aims to highlight the current state of knowledge in the molecular alterations involved in the etiology and ensuing steps for cancer progression, existing preclinical models of translational research, clinically relevant systemic protocols, and ongoing clinical trials.