Importance: The incidence of melanoma in situ (MIS) is increasing more rapidly than any invasive or in situ cancer in the US. Although more than half of melanomas diagnosed are MIS, information about long-term prognosis following a diagnosis of MIS remains unknown.
Objective: To evaluate mortality and factors associated with mortality after a diagnosis of MIS.
Design, setting, and participants: This population-based cohort study of adults with a diagnosis of first primary MIS from 2000 to 2018 included data from the US Surveillance, Epidemiology, and End Results Program, which were analyzed from July to September 2022.
Main outcomes and measures: Mortality after a diagnosis of MIS was evaluated using 15-year melanoma-specific survival, 15-year relative survival (ie, compared with similar individuals without MIS), and standardized mortality ratios (SMRs). Cox regression was used to estimate hazard ratios (HRs) for death by demographic and clinical characteristics.
Results: Among 137 872 patients with a first-and-only MIS, the mean (SD) age at diagnosis was 61.9 (16.5) years (64 027 women [46.4%]; 239 [0.2%] American Indian or Alaska Native, 606 [0.4%] Asian, 344 [0.2%] Black, 3348 [2.4%] Hispanic, and 133 335 [96.7%] White individuals). Mean (range) follow-up was 6.6 (0-18.9) years. The 15-year melanoma-specific survival was 98.4% (95% CI, 98.3%-98.5%), whereas the 15-year relative survival was 112.4% (95% CI, 112.0%-112.8%). The melanoma-specific SMR was 1.89 (95% CI, 1.77-2.02); however, the all-cause SMR was 0.68 (95% CI, 0.67-0.7). Risk of melanoma-specific mortality was higher for older patients (7.4% for those 80 years or older vs 1.4% for those aged 60-69 years; adjusted HR, 8.2; 95% CI, 6.7-10.0) and patients with acral lentiginous histology results (3.3% for acral lentiginous vs 0.9% for superficial spreading; HR, 5.3; 95% CI, 2.3-12.3). Of patients with primary MIS, 6751 (4.3%) experienced a second primary invasive melanoma and 11 628 (7.4%) experienced a second primary MIS. Compared with patients without a subsequent melanoma, the risk of melanoma-specific mortality was increased for those with a second primary invasive melanoma (adjusted HR, 4.1; 95% CI, 3.6-4.6) and was decreased for those with a second primary MIS (adjusted HR, 0.7; 95% CI, 0.6-0.9).
Conclusions and relevance: The results of this cohort study suggest that patients with a diagnosis of MIS have an increased but low risk of melanoma-specific mortality and live longer than people in the general population, suggesting that there is significant detection of low-risk disease among health-seeking individuals. Factors associated with death following MIS include older age (≥80 years) and subsequent primary invasive melanoma.