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.

• Authors: Alfredo Berruti, Martin Fassnacht, Harm Haak, Tobias Else, Eric Baudin, Paola Sperone, Matthias Kroiss, Thomas Kerkhofs, Andrew R Williams, Arianna Ardito, Sophie Leboulleux, Marco Volante, Timo Deutschbein, Richards Feelders, Cristina Ronchi, Salvatore Grisanti, Hans Gelderblom, Francesco Porpiglia, Mauro Papotti, Gary D Hammer, Bruno Allolio, Massimo Terzolo
• Journal: European urology (Eur Urol) Vol. 65 Issue 4 Pg. 832-8 (Apr 2014) ISSN: 1873-7560 [Electronic] Switzerland
• PMID: 24268504 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Chemical References

• Antineoplastic Agents, Hormonal
• Mitotane

Topics

• Adolescent
• Adrenal Cortex Neoplasms (complications, surgery)
• Adrenocortical Carcinoma (complications, surgery)
• Adult
• Aged
• Antineoplastic Agents, Hormonal (therapeutic use)
• Cushing Syndrome (etiology, prevention & control)
• Female
• Humans
• Male
• Middle Aged
• Mitotane (therapeutic use)
• Prognosis
• Retrospective Studies
• Young Adult