Risk of Subsequent Primary Melanoma in 68,002 five-year survivors of childhood and adolescent cancer in Europe: The PanCareSurFup cohort study

BACKGROUND: Survivors of childhood cancer are at risk of subsequent primary melanoma (SPM), but the magnitude of the risk after different childhood cancer types and beyond age 50 remains inadequately characterised. We quantified risks in the largest cohort of childhood cancer survivors worldwide.

METHODS: The PanCareSurFup cohort includes 68,002 five-year childhood cancer survivors across Europe (diagnosed 1940 to 2008). SPM risks were quantified using standardised incidence ratios (SIRs), absolute excess risks (AERs), cumulative incidence and relative risks (RRs).

RESULTS: Over 1,239,675 person-years, 197 SPMs were ascertained whereas 84.9 were expected (SIR = 2.3, 95%CI = 2.0 to 2.7). Although the SIR decreased with attained age (P_trend<0.001), it remained increased at 2.1-fold (95%CI = 1.5 to 3.1) age 50+. By age 65, cumulative incidence was 1.2% (0.8% expected). Of all cancer types, heritable retinoblastoma survivors had the greatest risk (SIR = 16.5, 95% CI = 10.8 to 25.3; AER = 94.4, 95% CI = 59.9 to 148.9), with cumulative incidence of 3.3% at age 50 and 5.5% at age 60. Survivors treated with radiotherapy had a 70% greater risk than those treated without (RR = 1.7, 95% CI = 1.1 to 2.7) increasing to 4-fold age 50 + (RR = 3.9, 95%CI = 1.1 to 13.9). For chemotherapy, no significant association was found (RR‌=0.9, 95%CI = 0.5 to 1.6).

CONCLUSIONS: Childhood cancer survivors, particularly those with heritable retinoblastoma and those treated with radiotherapy, remain at increased risk of melanoma beyond age 50. Current survivorship guidelines focus principally on treatment history; however, our findings suggest that long-term follow-up guidelines should additionally include childhood cancer type and attained age as risk-stratifying factors, particularly where individual treatment records are unavailable.