Adrenocortical carcinoma (ACC) is a rare tumour characterized by a dismal prognosis. The most important predictor of outcome is the possibility to attain a complete resection and prognosis is extremely poor when complete surgical removal of ACC is not feasible. Most patients have resectable disease at presentation; however, fully half of the patients who have undergone complete removal of the tumour are destined to relapse. The high recurrence rate of ACC has prompted many investigators to consider the use of adjuvant therapy following radical resection of the tumour. Very recently, the results of a retrospective analysis, performed by our group, involving a large cohort of patients with ACC, who were followed for up to 10 years at different institutions in Italy and Germany, demonstrated that recurrence-free survival was significantly prolonged in the mitotane group, as compared with untreated patients, who had a significantly higher risk of recurrence than those receiving mitotane. Multivariate analysis indicated that shorter disease-free survival was associated with older age and more advanced stage.
In contrast to our experience, Bertherat et al. did not observe a significant advantage with adjuvant mitotane after complete removal of ACC, even if survival of mitotane-treated patients was better in secreting ACC. They found that steroid secretion had a prognostic value: the poorer prognosis of cortisol-secreting tumours could be related to co-morbidity of Cushings syndrome. Alternatively, the pathophysiology of cortisol-secreting ACC may lead to the development of more aggressive tumours. It is also possible that the adrenolytic action of mitotane requires CYP11B activity within the tumour: this enzyme is probably expressed in cortisol-secreting tumours, accounting for the more potent effect of mitotane in such tumours.
To conclude, ACC is a rare disease with a high risk of relapse after radical surgery. In our centers, institution of adjuvant mitotane therapy following complete removal of ACC has become the standard of care, at least for patients at high risk of recurrence, as defined by advanced stage and/or high proliferation of ACC, as defined by elevated mitotic count or high Ki-67% index. A prospective randomised trial comparing the effect of mitotane versus observation in low-risk patients is currently ongoing.
25 - 29 Apr 2009
European Society of Endocrinology