Management of Melanoma in Advanced Age: A Comprehensive Literature Review of Tumor Biology, Systemic Therapies and Geriatric Challenges.

Background: Melanoma disproportionately affects older adults, who account for a growing share of cases as populations age. Its incidence rises with age, and the number of ultra-octogenarians (≥85 years) is expected to triple by 2050, particularly in high-incidence regions such as Australia, North America and Europe. Moreover, older adults frequently present with substantial comorbidities, making management complex and complicating treatment decisions. Methods: This comprehensive review summarizes evidence concerning the clinicopathological characteristics, treatment patterns, systemic therapy outcomes, and geriatric considerations relevant to patients aged 75 years or older with melanoma. PubMed/MEDLINE was searched from January 2000 to March 2026. Reference lists of eligible articles and relevant reviews were examined to identify additional studies. Priority was given to studies reporting age-stratified outcomes for patients aged at least 75 years. Because relatively few studies reported outcomes specifically for patients aged ≥75 years, evidence using thresholds of ≥65, ≥70, or ≥80 years was included when directly relevant. Age thresholds are reported for each study and should not be considered interchangeable. Results: Most evidence specific to patients aged ≥75 years derives from retrospective cohorts and registries. Compared with younger patients, elderly patients more often present with melanomas of the head, neck, hands and feet, a higher prevalence of the nodular subtype, greater Breslow thickness, higher mitotic rates and lower tumor-infiltrating lymphocyte density. Diagnosis is frequently delayed due to difficulties with self-examination, visual impairment, benign age-related skin changes and social factors. Despite presenting such a high-risk disease, older patients are less likely than their younger counterparts to receive immunotherapy or BRAF/MEK-targeted agents. This treatment gap may reflect comorbidities, altered pharmacokinetics, concerns about toxicity, under-representation in pivotal trials, and limited caregiver support. Available real-world data suggest that the efficacy of immune checkpoint inhibitors and targeted therapies is comparable to that in younger adults, although treatment selection, discontinuation, hospitalization, and dose modification differ across studies. Conclusions: Melanoma in older adults has distinct clinical and pathological patterns, but treatment evidence for patients aged ≥75 years remains limited and subjected to selection bias. Tailored, geriatric-informed treatment strategies integrating tumor biology, comorbidity, functional status and patient preferences are needed to optimize outcomes for patients aged 75 years and older.