BACKGROUND AND AIMS: Stage III cutaneous melanoma affects a heterogeneous group of patients. AJCC staging subdivides stage III according to micro- or macroscopic lymph nodes or in transit/cutaneous locoregional metastasis, without accounting for whether locoregional involvement is identified at diagnosis or post-progression. Information on potential divergent behavior among these subgroups is lacking.

The aim of the study is to analyze the differences in survival of melanoma patients with stages IIIB-IIID at diagnosis vs stages IIIB-IIID after relapse.

MATERIALS AND METHOD: We conducted a cohort study with patients diagnosed with cutaneous melanoma between 1998 and 2022. Patients in stage III (AJCC 8th) were identified and divided into 2 cohorts: initial stages IIIB-D (iSIII) and stages IIIB-D during progression (pSIII). We analyzed the clinical and histopathological characteristics and performed Cox regression analysis for melanoma specific survival (MSS) and overall survival (OS).

RESULTS: Of Of the 939 patients included, 608 had incident stage III (iSIII) melanoma and 331 had progressive stage III (pSIII) melanoma. Primary melanomas in the iSIII cohort showed greater Breslow thickness and higher mitotic indices and were more frequently ulcerated than those in the pSIII group (P < .001). Multivariable Cox regression analysis showed a slightly worse MSS and OS for patients in the pSIII cohort with an HR of 1.32 (95%CI, 1.05-1.66; p = 0.017) and an HR of 1.40 (95%CI, 1.14-1.72; p = 0.001) respectively.

CONCLUSIONS: Although patients from the pSIII cohort initially exhibited primary tumors with fewer aggressive features than primary tumors of the iSIII, after progression to stage III they showed a slightly worse MSS and OS than the iSIII cohort.