Introduction: Penile cancer (PC) is a rare neoplasm, mostly in developed countries. Herewith, we evaluate the main prognostic factors of patients with PC undergoing surgery. Methods: This is a retrospective analysis of prognostic factors of overall survival in 65 patients with PC treated at a tertiary referral center over the last 15 years (2004–2018). Results: Almost half (48%) of the patients were diagnosed at an advanced local stage pT3/4. Thirty-eight (58%) patients underwent inguinal lymphadenectomy, and 25 (66%) were negative for lymph node (LN) invasion. Overall survival was 80% at a median follow-up of 31 months. In the multivariate analysis, the main factors of poor prognosis were nodal staging (pN) (p = 0.008) and perineural invasion (p = 0.023). The presence of LN metastasis and perineural invasion in the primary tumor increased the risk of death by 29 (hazard ratio 29.0, 95% confidence interval 2.4–354.2) and 13 (hazard ratio 12.7, 95% confidence interval 1.4–112.0) times, respectively. Discussion/Conclusion: Late diagnosis of PC has a negative impact on overall survival, as nodal invasion correlates with survival. Despite the high number of negative inguinal lymphadenectomy, we continue to advocate aggressive surgical treatment of this disease due to the poor prognosis associated with LN metastasis.

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