Prognostic role of overt hypercortisolism in completely operated patients with adrenocortical cancer

Abstract

Background: Although prognostic parameters are important to guide adjuvant treatment, very few have been identified in patients with completely resected adrenocortical carcinoma (ACC).

Objective: To assess the prognostic role of clinical symptoms of hypercortisolism in a large series of patients with completely resected ACC.

Design, setting, and participants: A 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.

Intervention: All ACC patients were completely resected, and adjuvant mitotane therapy was prescribed at the discretion of the investigators.

Outcome measurements and statistical analysis: The 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 limitations: Overt 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.

Conclusions: Clinically 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.

Keywords: Adjuvant therapy; Adrenocortical cancer; Cushing syndrome; Mitotane.