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.