Low Risk of Melanoma-Specific Mortality Seen in Patients With MIS


The incidence rate of melanoma in situ (MIS) has sharply risen since 1975.

Patients with melanoma in situ (MIS) have an increased but low risk of melanoma-specific mortality, new results of a cohort study show.

Findings published in JAMA Dermatology also revealed these individuals live longer than the general population, “suggesting that there is significant detection of low-risk disease among health-seeking individuals,” authors wrote.

Being at least 80 years old and having subsequent primary invasive melanoma were associated with death following MIS in patients.

In the past 50 years, the incidence of cutaneous melanoma has rapidly increased, the researchers explained, with MIS—or stage 0 melanoma—disproportionately contributing to the heightened incidence. Since 1975, there has been a 50-fold increase in the incidence rate of MIS.

“Although MIS is not generally considered life threatening, patients with MIS are at increased risk of receiving diagnoses of subsequent melanomas (invasive and in situ); thus, these individuals warrant more frequent surveillance,” the researchers added. In addition, the natural history of MIS and its likelihood of progression are not clear, and little information exists regarding the link with melanoma-specific or all-cause mortality.

To help address this knowledge gap, investigators carried out a retrospective population-based cohort study using the Surveillance, Epidemiology, and End Results (SEER) Program. All participants were adults who received a diagnosis of first primary MIS between 2000 and 2018. Researchers analyzed the SEER data from July to September 2022, and they assessed mortality after diagnosis using 15-year melanoma-specific survival, 15-year relative survival (ie, compared with similar individuals without MIS), and standardized mortality ratios (SMRs).

A total of 137, 872 patients were included. Mean (SD) patient age was 61.9 (16.5) years, and the mean follow-up was approximately 6.6 years. Most participants were White.

Analyses revealed these results:

  • 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)
  • The risk of melanoma-specific mortality was higher for older patients, at 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, at 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 decreased for those with a second primary MIS (adjusted HR, 0.7; 95% CI, 0.6-0.9)

American Indian and Alaska Native patients groups were the only racial and ethnic categories linked with a higher 15-year melanoma-specific mortality after receiving a diagnosis of MIS compared with White patients.

“Taken together, these cancer survival statistics that demonstrated increased overall survival of patients with MIS compared with the general population suggest that in most cases, diagnosis of MIS is a risk factor for future melanoma diagnosis and rarely portends adverse outcomes,” the authors wrote.

However, because providers cannot predict which cases of MIS may progress to invasive melanoma, all are treated. Results also suggest interpreting MIS as cancer could contribute to overdiagnosis.

“In this context, relative survival statistics may be reassuring to patients, showing that the health-related decisions they made before receiving their diagnosis may have a greater positive association with their overall survival than the diagnosis itself,” the researchers added.

Data indicate that although the risk of a second melanoma may be concerning to patients with MIS, the diagnosis does not necessarily mean a patient will die younger.

“The melanoma cancer survival statistics reported in this cohort study are potentially important for patients and clinicians to accurately understand and put into perspective the risks associated with receiving a diagnosis of MIS,” the authors concluded.


Patel VR, Roberson ML, Pignone MP, Adamson AS. Risk of mortality after a diagnosis of melanoma in situ. JAMA Dermatol. Published online June 7, 2023. doi:10.1001/jamadermatol.2023.1494

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