Tumor Mitotic Rate and Association with Recurrence in Sentinel Lymph Node Negative Stage II Melanoma Patients

Tumor mitotic rate (TMR) is a known prognostic variable in thin melanoma patients. Its significance in stage II melanoma patients is yet to be demonstrated. Retrospective analysis of a prospective melanoma database from 9/1997 to 7/2015 was performed. All stage II melanoma, with documented TMR, and six months of follow-up were included. We evaluated the association of clinicopathologic variables, TMR, as a continuous and categorical variable with recurrence-free survival (RFS) and overall survival (OS) using Cox proportional hazards modeling. We used a statistical model, X-tile, to develop optimal categorizations of TMR. A total of 265 patient characteristics are included in this study. Recurrences occurred in 82 (30.9%) patients, including 5 local, 41 regional, and 36 distant patients. In multivariate model, ulceration, Breslow, and continuous TMR were associated with worse RFS\OS. Continuous TMR demonstrated worse RFS (hazards ratio [HR] 1.02 (1.00-1.05)) and OS (HR 1.02 (1.00-1.04)), whereas dichotomized TMR (≥1 vs <1) was not significant. TMR >10.4 mitoses/mm2 has a 5-year RFS\OS of 27.2 and 44.3 per cent, respectively, compared with 57.4 and 71.4 per cent, respectively, for TMR <3.2 mitoses/mm2. Continuous TMR predicts incidence of recurrence in stage II melanoma. We propose a new categorization method developed by statistical modeling for optimal stratification that may guide surveillance for this disparate patient population.