Primary tumor location and mortality in melanoma: Considerations for future staging systems

Wei et al. reported an association between primary tumor location (PTL) and mortality in patients with cutaneous malignant melanoma, highlighting a higher mortality risk for head and neck (HN) melanomas. Although these findings support the potential prognostic relevance of PTL, several considerations warrant attention before tumor location is incorporated into future risk-stratification or staging systems. First, the study period spans substantial changes in melanoma management, whereas the SEER database lacks detailed information on immunotherapy and targeted therapy. Consequently, systemic therapy exposure represents a potential unmeasured confounder, and its contribution to the observed association between PTL and mortality cannot be determined. Second, the substantial proportion of missing tumor thickness data may introduce selection bias and affect the representativeness and generalizability of complete-case analyses, without necessarily indicating that patients with missing data constitute a higher-risk subgroup. Third, grouping all HN melanomas into a single anatomical category may obscure clinically relevant subsite heterogeneity. The attenuation of the HN prognostic disadvantage in higher T-stage or thicker tumors further supports investigation of interactions between anatomical location and tumor thickness, but does not establish a subsite-specific mechanism. Future studies incorporating systemic therapy exposure, detailed HN subsite classification, and validation in diverse populations are needed to clarify the independent prognostic contribution of PTL before its integration into future melanoma staging frameworks.