Lymphovascular Invasion Predicts Cancer-specific Mortality in Penile Localized Squamous Cell Carcinoma

Introduction: Lymphovascular invasion (LVI) is a predictor of unfavorable stage at presentation in squamous cell carcinoma of the penis (SCCP). However, it is unknown if LVI may also predict cancer-specific mortality (CSM), especially in patients with localized SCCP in whom important differences in the treated natural history may exist. We addressed this knowledge gap in localized (T1b-T2N0M0) SCCP patients treated with penectomy. Methods: Within the Surveillance, Epidemiology, and End Results database (SEER 2010-2021), we identified localized SCCP patients treated with penectomy in whom LVI status was available. Kaplan-Meier analyses and multivariable Cox regression models (CRM) addressed CSM. Covariates consisted of age at diagnosis, T stage, penectomy type, and race/ethnicity. Results: Of 685 localized SCCP patients, 144 (21%) were LVI-positive. At three-years of follow-up CSM-free survival rates were 85% versus 69% in respectively LVI-negative versus LVI-positive patients (P < 0.001), which resulted in a univariable hazard ratio [HR] of 2.5 (P < 0.01). After multivariable adjustment in Cox regression models, LVI-positive status independently predicted a 2.6-fold higher CSM (P < 0.001). In subgroup analyses, LVI also independently predicted higher CSM in T1b (HR = 3.0; P = 0.01), as well as in T2 (HR= 2.5; P < 0.001) SCCP patients. Conclusion: In localized SCCP patients, LVI is a highly significant independent predictor of higher CSM in both T1b and T2 stages and may warrant consideration for use in clinical practice.