Clinical and Pathologic Factors Associated with Distant Metastasis and Survival in Patients with Thin Primary Cutaneous Melanoma

Abstract

Approximately 3-5% of patients with thin (≤ 1 mm) cutaneous melanomas develop distant metastases. We sought to identify clinical and pathologic factors associated with distant metastasis and survival in a large number of patients with thin melanoma treated at a single institution. We identified patients with a single invasive melanoma ≤ 1 mm in thickness diagnosed between January 1983 and December 2003 who developed distant metastasis (cases), and matched patients with no recorded recurrence during follow-up (control subjects). Cases and control subjects were matched for age, sex, and year of primary melanoma diagnosis. Associations of clinical and pathologic parameters with distant metastasis-free survival and melanoma-specific survival were analyzed. A total of 178 cases and 178 control subjects were identified. Factors associated with development of distant metastasis were: increasing Breslow thickness (P < 0.001), increasing Clark level of invasion (P < 0.001), increasing mitotic rate (P = 0.001), ulceration (P = 0.025), and American Joint Committee on Cancer T subcategory (P < 0.001). Multivariable models including Breslow thickness (but not Clark level) showed that factors independently associated with poorer distant metastasis-free survival were increasing age [hazard ratio (HR) 1.01, 95% confidence interval (CI) 1.00-1.02]; increasing Breslow thickness (HR 3.21, 95% CI 1.73-5.94, and HR 3.77, 95% CI 2.11-6.74 for 0.51-0.75 mm and 0.76-1.00 mm, respectively, compared with 0.01-0.50 mm); ulceration (HR 1.87, 95% CI 1.14-3.06) and mitotic rate (HR 1.13, 95% CI 1.05-1.21). Similar associations with melanoma-specific survival were found. Clinical and pathologic predictors of distant metastasis and survival identified in this large study of patients with thin primary cutaneous melanomas will enable more accurate stratification of risk of distant metastasis and poor survival in such patients, and will assist in formulating clinical management and follow-up regimens based on the level of risk.