Environmental pollution is associated with poorer survival in patients with adrenocortical carcinoma: findings from a national cohort study in Italy

Background The impact of environmental pollution on adrenocortical carcinoma (ACC) remains largely unexplored. Although a few studies have assessed the incidence of ACC in polluted areas, no data are available on clinical outcomes. Methods We carried out a retrospective multicentre cohort study in adult patients with ACC diagnosed in 12 referral centres in Italy (1990-2018). We stratified patients for (1) residence in sites officially classified as contaminated (NPCSs [National Priority Contaminated Sites]) or in non-contaminated areas and (2) urbanization, as a contextual proxy for environmental exposure. Outcomes were recurrence-free survival (RFS) and overall survival (OS). Results Among 336 patients, 250 had localized disease (stage I-III) and 86 metastatic disease (stage IV). Subgroups among patients with stage IV ACC were too small for a meaningful analysis. Among patients with localized ACC, 26 (10.4%) living in NPCSs had significantly shorter median RFS (13 vs 43 months; P = .011) and OS (67 vs 142 months; P = .016) compared to the 224 patients living in non-contaminated areas. At multivariable analysis, residence in NPCSs was independently associated with both recurrence (HR 1.89, 95% CI 1.13-3.16, P = .016) and death (HR 2.44, 95% CI 1.39-4.28, P = .002). No significant association was found between the level of urbanization and survival. Conclusions This study provides the first evidence that environmental pollution is associated with worse clinical outcomes in patients with ACC. By linking contaminated-area residence with prognosis, these findings raise the possibility that environmental exposures may contribute to the disease behaviour, highlighting a new direction for integrated epidemiological and biological research.