Clinical Presentation and Surgical Management of Penile Carcinoma: A Retrospective Case Series from a Tertiary Referral Center.

Background and Clinical Significance: Penile carcinoma is a rare malignancy in developed countries, yet it remains associated with significant morbidity due to its aggressive local behavior and potential for lymphatic dissemination. Human Papillomavirus (HPV) infection plays a central role in its pathogenesis, while lymph node involvement represents the most important prognostic factor. Case Presentation: In this retrospective case series (n = 3), we evaluated three representative patients treated at a tertiary referral center in Romania between August 2020 and December 2024. Clinical, pathological, and therapeutic data were analyzed, with emphasis on tumor stage, nodal involvement, surgical management, and follow-up outcomes. Immunohistochemical analysis, including p16 expression, was performed to assess HPV-related tumor profiles. Conclusions: Three representative cases illustrating distinct clinical scenarios were included. Patients with localized disease and negative lymph nodes achieved favorable long-term outcomes, including 3-year disease-free survival (documented follow-up through December 2023; follow-up data beyond 2023 were unavailable, capping documented disease-free follow-up at 36 months). In contrast, advanced disease with nodal metastasis was associated with poor prognosis despite aggressive multimodal treatment. Immunohistochemical profiling revealed both HPV-associated and HPV-independent tumor patterns, which appeared to correlate with clinical outcomes. A case of locally advanced disease demonstrated that radical surgical intervention combined with adjuvant therapy may achieve prolonged recurrence-free survival. Penile carcinoma requires prompt diagnosis and individualized management.