Prognostic Role of Overt Hypercortisolism in Completely Operated Patients with Adrenocortical Cancer

BackgroundAlthough prognostic parameters are important to guide adjuvant treatment, very few have been identified in patients with completely resected adrenocortical carcinoma (ACC).ObjectiveTo assess the prognostic role of clinical symptoms of hypercortisolism in a large series of patients with completely resected ACC.Design, setting, and participantsA total of 524 patients followed at referral centers for ACC in Europe and the United States entered the study. Inclusion criteria were ≥18 yr of age, a histologic diagnosis of ACC, and complete surgery (R0). Exclusion criteria were a history of other malignancies and adjuvant systemic therapies other than mitotane.InterventionAll ACC patients were completely resected, and adjuvant mitotane therapy was prescribed at the discretion of the investigators.Outcome measurements and statistical analysisThe primary end point was overall survival (OS). The secondary end points were recurrence-free survival (RFS) and the efficacy of adjuvant mitotane therapy according to cortisol secretion.Results and limitationsOvert hypercortisolism was observed in 197 patients (37.6%). Patients with cortisol excess were younger (p = 0.002); no difference according to sex and tumor stage was observed. The median follow-up of the series was 50 mo. After adjustment for sex, age, tumor stage, and mitotane treatment, the prognostic significance of cortisol excess was highly significant for both RFS (hazard ratio [HR]: 1.30; 95% confidence interval [CI], 1.04–2.62; p = 0.02) and OS (HR: 1.55; 95% CI, 1.15–2.09; p = 0.004). Mitotane administration was associated with a reduction of disease progression (adjusted HR: 0.65; 95% CI, 0.49–0.86; p = 0.003) that did not differ according to the patient's secretory status. A major limitation is that only symptomatic patients were considered as having hypercortisolism, thus excluding information on the prognostic role of elevated cortisol levels in the absence of a clinical syndrome.ConclusionsClinically relevant hypercortisolism is a new prognostic factor in patients with completely resected ACC. The efficacy of adjuvant mitotane does not seem to be influenced by overt hypercortisolism.