Investigating Risk Factors for Delayed Melanoma Recurrence Beyond 5 Years Post‐Primary Tumor Diagnosis

BACKGROUND: Patients undergoing treatment for cutaneous melanoma are generally considered cured after a period of 5 years, since most recurrences manifest within three to 5 years. However, some patients can present with a delayed recurrence of melanoma beyond a 10-year timeframe. OBJECTIVE: To identify clinicopathologic factors associated with survival in patients with cutaneous melanoma who developed metastatic recurrence at least 5 years after primary diagnosis. METHODS: We conducted a retrospective single-center cohort study of 30 patients with cutaneous melanoma developing metastatic recurrence at least 5 years post-diagnosis. The cohort contained 18 women and 12 men (mean age 50.2; range 25-76). Variables included age, sex, BRAF status, site, melanoma subtype, Breslow thickness, ulceration, Clark level, regression, and recurrence localization. Overall survival (OS), progression-free survival (PFS), and post-recurrence survival (PRS) were evaluated via Cox proportional hazards models. RESULTS: Mean OS, PFS, and PRS were 168.7, 130.4, and 43.7 months, respectively. Eight patients (27%) died. Tumors averaged 2.61 mm Breslow thickness; 50.0% were BRAF-mutant, 53.3% ulcerated, and 50.0% truncal. Recurrences were locoregional (cutaneous, subcutaneous, in-transit, nodal) in eight (26.7%) and distant in 21 (70.0%); one lacked data. Female sex predicted better univariate OS (HR 0.055, 95% CI 0.01-0.47; p = 0.008) and multivariate PFS (HR 0.364, 95% CI 0.14-0.93; p = 0.035). Increasing age predicted shorter multivariate PFS (HR 1.072, 95% CI 1.03-1.12; p = 0.001). Histologic regression (HR 3.557, 95% CI 1.04-12.17; p = 0.043) and BRAF status (HR 0.413, 95% CI 0.18-0.94; p = 0.034) independently impacted PFS. Kaplan-Meier showed longer OS and PFS in women, and longer PFS in patients younger than 50 years. CONCLUSIONS: Delayed recurrence can manifest over a decade post-diagnosis. Female sex and younger age correlate with favorable survival. These findings underscore the necessity of continued clinical vigilance and patient counseling beyond 10 years, although larger cohorts are needed to validate late-recurrence risk stratification.