Time trends in incidence, treatment, and survival of patients with adrenocortical carcinoma, a nationwide study

PURPOSE: We aimed to determine time trends in incidence, treatment, and survival of patients with adrenocortical carcinoma in the Netherlands. METHODS: All 685 adult patients with adrenocortical carcinoma diagnosed between 1993 and 2020 in the Netherlands were included, using the nationwide prospective Netherlands Cancer Registry. RESULTS: The median age-adjusted incidence rate based on the European Standard Population was 1.62 per million person-years [0.83-2.11] and was stable over time. We saw a gradual increase in stage III on diagnosis (13%-25%) with a stable proportion of stage IV (40%). The 5-year survival remained stable over time for stage I-II at 65% and stage III at 35%, whereas the survival for stage IV increased from 3% in 1993 through 1996 to 11% in 2017 through 2020. Since the Dutch Adrenal Network was founded in 2004, more patients were referred to an expert center (P < .001), which was associated with increased survival (adjusted HR 0.70; 95% CI, 0.57-0.85). Multivariate Cox regression showed increased survival in all stages when treated with adrenalectomy (adjusted HR 0.53; 95% CI, 0.43-0.65) and mitotane therapy (adjusted HR 0.73; 95% CI, 0.55-0.98). In stage IV disease, adrenalectomy, surgical control of disease, chemotherapy, and mitotane therapy were associated with increased survival. However, only 58% of mitotane users reached a therapeutic drug level and 59.5% discontinued treatment prematurely. CONCLUSION: The incidence of adrenocortical carcinoma is stable over time. The 5-year survival for stage I-III remained stable, whereas the survival for stage IV increased. Factors associated with increased survival are centralization of care, adrenalectomy, surgical control of disease, chemotherapy, and mitotane therapy.