New findings on presentation and outcome of patients with adrenocortical cancer: results from a national cohort study

Abstract Context Due to the rarity of adrenocortical cancer (ACC), only a few population-based studies are available and they reported limited details in the characterization of patients and their treatment. Objective To describe in a nation-wide cohort the presentation of ACC patients, treatment strategies and potential prognostic factors. Methods Retrospective analysis of 512 ACC patients, diagnosed in twelve referral centers in Italy from January 1990 to June 2018. Results ACC diagnosed as incidentalomas accounted for overall 38.1% of cases, with a frequency that increases with age and with less aggressive pathological features than symptomatic tumors. Women (60.2%) were younger than men, had smaller tumors, which more frequently secreted hormones. Surgery was mainly done with an open approach (72%), and after surgical resection, 62.7% of patients started adjuvant mitotane therapy. Recurrence after tumor resection occurred in 56.2% of patients. In patients with localized disease, cortisol secretion, ENSAT stage III, Ki67% and Weiss score were associated with an increased risk of recurrence, while margin-free resection, open surgery and adjuvant mitotane treatment were associated with reduced risk. Death occurred in 38.1% of patients and recurrence-free survival (RFS) predicted overall survival (OS). In localized disease, age, cortisol secretion, Ki67%, ENSAT stage III, and recurrence were associated with increased risk of mortality. ACCs presenting as adrenal incidentalomas showed prolonged RFS and OS. Conclusions Our study shows that ACC is a sex-related disease and demonstrates that an incidental presentation is associated with a better outcome. Given the correlation between RFS and OS, RFS may be used as a surrogate end-point in clinical studies.