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.