J. L. Evans1, R. J. Vidri1,2, D. C. MacGillivray1, T. L. Fitzgerald1 1Tufts University School Of Medicine – Maine Medical Center,Surgery,Portland, ME, USA 2St. Mary’s Regional Medical Center,Surgery,Lewiston, ME, USA
Introduction:
The prognostic significance of tumor mitotic rate (TMR) for patients with localized melanoma has engendered significant controversy. Although several small studies have validated TMR as a prognostic marker for this disease, TMR is no longer incorporated in the AJCC staging paradigm. To better define TMR as an independent predictor of disease-specific survival for localized melanoma, we performed a cohort study utilizing an administrative cancer database.
Methods:
Patients diagnosed with localized cutaneous melanoma from 2010 to 2014 were identified from the SEER registry. TMR was then categorized into three groups based on the number of mitoses: 0-3 mitoses/mm2 (Group 1), 4-10 mitoses/mm2 (Group 2), and >10 mitoses/mm2 (Group 3). Five-year disease-specific survival for stage and TMR category were calculated using the Kaplan-Meier method, groups were compared using the log-rank test. Multivariate analysis was performed using Cox proportional hazards model. (Using JMP 13. Cary, NC: SAS Institute Inc.)
Results:
A total of 71,235 patients were included; the majority were white (94.7%), male (58.5%), and had Stage I disease (79.0%). When analyzed both as a categorical and a continuous variable, TMR was associated with disease-specific survival for all TNM stages. Univariate analysis demonstrated that 5-year disease-specific survival decreased with increasing TMR in Groups 1, 2, and 3 for Stage I (98.31%, 90.90%, 79.74%; p<0.0001), Stage II (86.07%, 74.17%, 72.85%; p<0.0001), and Stage III melanoma (72.52%, 58.58%, 49.65%, p<0.0001). Multivariate analysis controlling for age, race, sex, primary site, ulceration, and Breslow thickness revealed an increased mortality risk for those melanoma with 4-10 mitosis/mm2 and more than 10 mitosis/mm2, when compared to those with 0-3 mitosis/mm2: Stage I (RR=3.00 and 6.90 p<0.0001), Stage II (RR=1.37 and 1.63, p=0.0002), and Stage III disease (RR=1.33 and 1.46 p=0.0004). When analyzed as a continuous variable in this model, each unit increase in TMR increased the risk of death by 22% in Stage I (p<0.0001), 5% in Stage II (p<0.0001), and 4% in Stage III melanoma (p<0.0001).
Conclusion:
This retrospective cohort study, the largest to date; suggests that tumor mitotic rate is a strong, and independent predictor of disease-specific survival in melanoma. While the literature has previously demonstrated the prognostic value of TMR in Stage I disease, the present study expands upon this knowledge by demonstrating a similar relationship in Stage II and III melanoma.
