Predictors of Local Recurrence and its Impact on Survival after Glansectomy for Penile Cancer: Time to Challenge the Dogma?

OBJECTIVE To identify predictive pathological factors for local recurrence (LR) and study its impact on survival in patients treated with glansectomy for penile squamous cell carcinoma (pSCC). PATIENTS AND METHODS We retrospectively studied patients treated with glansectomy at international, high-volume reference centers. We analyzed histopathological predictors of LR, stratified patients in risk groups based on the number of risk factors present and studied the impact of LR on survival outcomes using Kaplan-Meier survival analysis and stepwise Cox proportional hazards regression models. Subsequently, we performed sensitivity analyses excluding margin-positive cases, pT3 disease and cN+ disease or all of these factors. RESULTS Across 9 institutions, 897 patients were included of which 94 experienced LR. On multivariable analysis, presence of high-grade disease and pT3 stage were independent predictors of LR. LR-free survival rates significantly differed according to the number of risk factors present with a HR of 1.90 (95%CI 1.17-3.07, p=0.01) for the intermediate-risk (1 risk factor) and 6.11 (95%CI 3.47-10.77, p<0.001) for the high-risk group (2 risk factors), using the low-risk group (no risk factors) as reference. Patients who experienced LR had significantly worse OS (HR 2.89, 95%CI 2.02-4.14, p<0.001) and CSS (HR 5.64, 95%CI 3.45-9.22, p<0.001). LR (HR 3.82, 95%CI 2.14-6.8, p<0.001), lymphovascular invasion and cN-status were significant predictors of decreased CSS. LR remained a strong predictor of both OS and CSS in all sensitivity analyses. CONCLUSIONS Pathological T3 stage and presence of high-grade disease are independent histopathological predictors of LR after glansectomy for primary pSCC, which allows for risk stratification in three risk groups with significantly different risk of developing LR. Additionally, LR is related to poor OS and CSS, indicating that LR is a manifestation of underlying aggressive disease and clearly challenging the dogma of using OSS whenever possible since survival is unaffected by higher LR rates.