Current clinical management and outcome of patients with adrenal cortical carcinoma (ACC) with rare histological subtypes-an ENSAT cohort study

Background: In 2022, the World Health Organization (WHO) classified adrenal cortical carcinoma (ACC) into four subtypes: conventional, oncocytic, myxoid, and sarcomatoid. The differences in prognosis among these subtypes remain unclear. This European Network for the Study of Adrenal Tumours (ENSAT) multicentre study examines the differences not only in outcomes but also in the clinical management of patients with different ACC subtypes. Patients and methods: Patient characteristics and survival data were retrospectively collected and analysed using Kaplan–Meier, multivariate Cox regression, and matched propensity score analyses (1 : 3 ratio) to compare recurrence-free survival (RFS) and overall survival (OS) for each subtype against conventional ACC. RFS was investigated only in patients after R0 resection, whereas OS was evaluated in the whole cohort. Matching was done for sex, age, and ENSAT tumour stage. Results: The study included 1098 conventional, 179 oncocytic, 28 myxoid, and 10 sarcomatoid ACCs. RFS (in 653 conventional, 127 oncocytic, 15 myxoid, and 6 sarcomatoid ACCs) and OS (in all patients) were significantly longer in oncocytic ACC compared with the other groups, which was confirmed by multivariate Cox regression analyses {hazard ratio (HR) for RFS using conventional ACC as reference: oncocytic 0.47 [95% confidence interval (CI) 0.34-0.66], myxoid 0.92 (0.49-1.71), and sarcomatoid 0.83 (0.13-2.13) and for OS: oncocytic 0.37 (0.22-0.61), myxoid 1.02 (0.50-2.1), and sarcomatoid 0.82 (0.11-5.94)}. Similar results were seen after propensity score matching. RFS and OS were significantly longer in oncocytic ACC compared with the matched conventional ACC (RFS HR 0.41, 95% CI 0.29-0.55, P < 0.001; OS HR 0.35, 95% CI 0.24-0.52, P < 0.001).In metastatic oncocytic ACC, mitotane was similarly effective as in conventional tumours, but platinum-based chemotherapy seemed to result in longer progression-free survival. Conclusion: Stage-adjusted outcome in oncocytic ACC is better than in other subtypes.