Clinical and Histopathological Predictors of Disease Progression in Stage II Cutaneous Melanoma

The recent approval of pembrolizumab and nivolumab for the adjuvant treatment of stage IIB-IIC cutaneous melanoma (CM) significantly improved the relapse-free survival probability of this patient population. Real-life data suggest that not all stage IIB and IIC CM patients will invariably undergo disease progression. There is a growing need for accurate patients' selection for whom adjuvant therapy is expected to be beneficial. The aim of this study was to investigate the baseline clinical and histopathological features associated with tumor recurrence in stage II CM patients in an Italian tertiary referral center.

Patients' clinical features and histopathological tumor characteristics were recorded at the time of melanoma diagnosis. Non-recurrent patients were defined based on a ≥5-year follow-up period; time to disease recurrence was calculated as the time from the diagnosis of the primary tumor until first evidence of melanoma relapse.

A total of 103 stage II CM patients, with a median follow-up of 6.2 years, were included. Twenty-one of 103 (20.4%) patients recurred, of whom 15/21 (71.4%) showed disease progression to stage IV disease. Breslow thickness was significantly associated with CM recurrence, with a 70% increased probability of melanoma relapse per each unit increase in Breslow thickness (mm) (OR = 1.7; 95% CI: 1.05-2.7; p = 0.029). Histopathological evidence of ulceration and the mitotic rate did not show a significant association with melanoma progression. Breslow thickness was also associated with a reduced time from melanoma diagnosis to recurrence per each unit increase (mm) (p = 0.032) and with shorter disease-free survival probability (HR: 1.47; 95% CI: 1.05-2.06; p = 0.025).

Breslow thickness is a relevant prognostic factor for CM recurrence. Further studies are needed to identify novel prognostic biomarkers.