Incidence of in Situ vs Invasive Melanoma: Testing the "Obligate Precursor" Hypothesis

Melanoma incidence has been rising in populations with predominantly European ancestry (White), speculated to be partly driven by heightened detection of indolent tumors. If in situ melanomas are destined to evolve to invasive cancers, detecting and removing them should deplete the pool of invasive lesions, and people with in situ melanoma should, on average, be younger than those with invasive melanoma.

We analyzed long-term incidence trends (1982-2018) for in situ and invasive melanomas in 3 predominantly White populations with high, medium, and low melanoma rates: Queensland (Australia), United States White, and Scotland. We calculated the incidence rate ratio (IRR) of in situ to invasive melanomas and estimated the contributions of age, period, and cohort effects. We compared age at diagnosis of in situ vs invasive melanomas overall and stratified by sex and anatomic site.

In all 3 populations, the in situ to invasive incidence rate ratio increased statistically significantly from less than 0.3 in 1982 to 1.95 (95% confidence interval [CI] = 1.88 to 2.02) in Queensland, 0.93 (95% CI = 0.90 to 0.96) in the US White population, and 0.58 (95% CI = 0.54 to 0.63) in Scotland in 2018. The mean age at diagnosis of in situ melanomas was the same or higher than invasive melanomas for almost all time periods among men and women and on all body sites except the lower limbs.

The increasing ratio of in situ to invasive melanoma incidence over time, together with the high (and increasing) mean age at diagnosis of in situ melanomas, is consistent with more indolent lesions coming to clinical attention than in previous eras.