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Original Investigation
May 1, 2019

Risk Factors for Lymphatic and Hematogenous Dissemination in Patients With Stages I to II Cutaneous Melanoma

Author Affiliations
  • 1Department of Dermatology, Instituto Valenciano de Oncología, València, Spain
  • 2School of Medicine, Universidad Católica de Valencia San Vicente Mártir, València, Spain
  • 3Department of Pathology, Instituto Valenciano de Oncología, València, Spain
  • 4Laboratory of Molecular Biology, Instituto Valenciano de Oncología, València, Spain
  • 5Department of Medical Oncology, Instituto Valenciano de Oncología, València, Spain
  • 6Division of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany
JAMA Dermatol. 2019;155(6):679-687. doi:10.1001/jamadermatol.2019.0069
Key Points

Question  What are the specific risk factors for recurrence of lymphatic and hematogenous dissemination among patients with stages I to II melanoma?

Findings  In this cohort study of 1177 patients with melanoma, age, site of primary tumor, tumor thickness, and vascular invasion were associated with lymphatic recurrence, whereas thickness, absence of regression, TERT promoter, and BRAF mutation were associated with hematogenous metastasis.

Meaning  With validation, these findings suggest that follow-up and adjuvant treatment strategies should be adapted to individual clinical, histopathologic, and molecular characteristics.

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.

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