Advanced Melanomas Are Not Prognostically Equal: A Proposal for Substratification

ABSTRACT: Cutaneous melanoma represents a small proportion of skin cancers but accounts for most skin cancer-related deaths. Breslow thickness is the main prognostic factor; however, the AJCC system does not differentiate the prognostic subgroups within T4 melanomas (>4 mm). The aim of this study was to evaluate the prognosis of patients with thick and ultrathick melanomas using Breslow thickness cutoffs of 6 and 8 mm and assess the need for T4 substratification. This retrospective study analyzed 117 eligible cases of primary cutaneous melanoma diagnosed at a Brazilian cancer referral center (2008-2021). Cases were categorized according to the Breslow cutoffs of 6 and 8 mm. Ultrathick melanomas showed markedly shorter median survival than thick melanomas at both cutoffs: 22 versus 53.5 months (6 mm; P < 0.0001) and 16 versus 49 months (8 mm; P < 0.0001). In multivariate analysis, patients with melanomas >8 mm had an approximately 2.8-fold higher hazard of death than those with melanomas >4-8 mm (HR 2.822, 95% CI, 1.029-7.737; P = 0.0438), whereas the 6-mm cutoff was not independently associated with overall survival. These findings support the substratification of AJCC T4 melanomas to include a subgroup of tumors >8 mm, improving risk assessment and follow-up strategies.