LAUSR

Introduction Prognosis for patients with lymph node positive or metastatic penile squamous cell carcinoma remains poor. Chemotherapy with paclitaxel, ifosfamide, and cisplatin (TIP regimen) is recommended as a first-line option in this cohort of patients. No standard preferred subsequent-line therapy exists for patients with relapsed or refractory penile carcinoma following TIP chemotherapy. Molecular pathogenesis of penile cancer can be subdivided into human papilloma virus-dependent and human papilloma virus-independent pathways. Recent studies have demonstrated increased expression of programmed death ligand-1 in some penile tumors, commonly those that are human papilloma virus-negative. Given the rarity of penile carcinoma in industrialized countries and lack of effective therapies, checkpoint inhibitors may be an attractive treatment option for this subset of patients. Case report We report a case of metastatic penile cancer refractory to TIP chemotherapy, with a dramatic treatment response to ipilimumab and nivolumab. Molecular profiling of this tumor showed a high programmed death ligand-1 expression, high tumor mutational burden, high microsatellite instability, and alterations in DNA mismatch repair genes. Discussion This case highlights another dimension of information that may be gained with molecular genomic profiling of penile tumors, providing insight into the biologic behavior of this neoplasm and assessing for predictive biomarkers of response to immune checkpoint inhibitors.