Genetics and penile cancer: recent developments and implications.

PURPOSE OF REVIEW: We summarize the recent developments in the molecular landscape of penile squamous cell carcinoma (PSCC). RECENT FINDINGS: Recent genomic studies have demonstrated a molecular convergence of PSCC with other squamous cell carcinomas (SCCs) from different organ sites. Similarly, human papillomavirus (HPV)-related PSCCs appear to have epigenetic and genomic similarities with other HPV-related cancers. This could have implications on future HPV-related cancer trial design. Growing efforts to characterize recurrent gene alterations in PSCC have expanded our understanding over the past years, showing a predominance of tumor suppressor gene alterations such as TP53 and NOTCH1. In addition, these studies have demonstrated that at least 30% of PSCC cases have targetable gene alterations. Further, the similar tumor mutational burden with other SCCs and the relatively high rates of programmed death-1 (PD-1) positive expression in PSCC constitute the rationale for investigation of PD-1 inhibition in ongoing clinical trials. Multiple studies have identified potential epigenetic and RNA signatures predictive of metastasis or survival, but these still require validation in larger cohorts. SUMMARY: PSCC appears to be genomicaly similar to other SCCs and HPV-related cancers. This provides the rationale and opportunity to include a rare tumor like PSCC in future 'basket type' trials using novel agents targeting multiple SCCs that may exhibit similar biology.