Abstract
IMPORTANCE: The lymphatic and the hematogenous pathways have been proposed for disease progression in cutaneous melanoma, but association with recurrence has not been studied separately to date. OBJECTIVE: To identify the risk factors associated with lymphatic and hematogenous metastasis. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study included 1177 patients with malignant melanoma treated at Instituto Valenciano de Oncología, València, Spain. Data were retrieved from the melanoma database from January 1, 2000, through December 31, 2015, and analyzed from June 1 to 30, 2018. EXPOSURE: Malignant melanoma at stages I to II. MAIN OUTCOMES AND MEASURES: Analyses of survival free of lymphatic and hematogenous metastasis were performed using Kaplan-Meier curves and Cox proportional hazards regression. RESULTS: For the 1177 patients included in the study analysis (51.1% women; median age at diagnosis, 55 years [interquartile range, 42-68 years), median follow-up was 75 months (interquartile range, 33-121 months); 108 (9.2%) developed lymphatic metastasis, and 108 (9.2%) developed hematogenous metastasis. In the multivariate analysis, being older than 55 years (hazard ratio [HR], 1.9; 95% CI, 1.2-3.1), tumor in the head/neck (HR, 1.7; 95% CI, 1.0-2.9) and acral locations (HR, 2.4; 95% CI, 1.3-4.5), greater Breslow thickness (HR for >4.00 mm, 5.4; 95% CI, 2.4-12.4), and presence of vascular invasion (HR, 3.2; 95% CI, 0.9-10.6) were associated with lymphatic spreading. Hematogenous metastasis was associated with greater Breslow thickness (HR for >4.00 mm, 10.4; 95% CI, 3.6-29.7), the absence of regression (HR, 0.1; 95% CI, 0.0-1.0), TERT promoter mutations (HR, 2.9; 95% CI, 1.5-5.7), and BRAF mutations (HR, 1.9; 95% CI, 1.1-3.6). CONCLUSIONS AND RELEVANCE: Risk factors associated with lymphatic and hematogenous metastasis differ. Follow-up and adjuvant treatment strategies may therefore need to be adapted to individual clinical, histopathologic, and molecular characteristics.