Risk of Second Primary Cancers in Melanoma Survivors: A Retrospective Hospital-Based Cohort Study from Two Romanian Referral Centres

Abstract

Background and objectives: Melanoma survivors may develop additional primary malignancies, but data from Eastern European hospital cohorts are scarce. We aimed to estimate the observed incidence of second primary cancers (SPCs) within a Romanian referral-centre cohort, identify associated factors, and explore the association of SPC occurrence with overall survival. Methods: We conducted a retrospective, hospital-based cohort study of 394 patients with histopathologically confirmed cutaneous melanoma followed at two referral centres in Cluj-Napoca. Additional malignancies were counted as new primaries only when clinical and/or histopathological documentation distinguished them from recurrence or metastasis. Incidence density was expressed per 1000 person-years. Multivariable logistic regression assessed age, sex, residence, and Breslow thickness. Fixed-covariate Cox and Kaplan–Meier analyses were considered exploratory because of immortal-time and competing-risk limitations. Results: Over 1848 person-years, 79 patients (20.1%) developed at least one SPC (131 events; observed incidence 70.9/1000 person-years), most frequently cutaneous (53.6/1000 person-years). SPC occurrence increased with age (Cochran–Armitage Z = 5.63, p < 0.001); the Kaplan–Meier complement estimate reached 20.7% at five years. Age independently predicted SPC (OR 1.86 per decade, p < 0.001), whereas greater Breslow thickness was inversely associated (OR 0.86, p = 0.008). Actinic keratosis showed a strong unadjusted association (OR 6.64, p < 0.001) but was not included in the adjusted model. The fixed-status Cox model showed lower mortality among patients with an SPC (HR 0.36, p < 0.001), a finding vulnerable to detection and immortal-time bias. Conclusions: SPCs were frequent in this hospital cohort and predominantly cutaneous. Older age was an independent predictor, while actinic keratosis was a strong unadjusted marker. Prospective, population-based validation is needed before surveillance intensity is individualised.