Adjuvant mitotane therapy is beneficial in non-metastatic adrenocortical carcinoma at high risk of recurrence

Abstract

Objective Many patients with adrenocortical carcinoma (ACC) suffer from tumor recurrence despite radical surgery. Evidence on the post-operative use of mitotane is controversial and no predictors of response are available. We aimed to assess whether adjuvant mitotane treatment may prolong survival in patients with non-metastatic ACC following complete resection and whether ACC patients at high risk of recurrence may benefit from treatment. Design and methods We retrospectively reviewed data from 152 non-metastatic ACC patients followed at the San Luigi Gonzaga Hospital: 100 patients were treated with adjuvant mitotane and 52 patients were left untreated following surgery. We assessed a number of potential predictive factors of recurrence and death. Mitotane effect was explored stratifying patients by staging (stage I–II vs stage III), hormone secretion (yes vs no) and Ki67 index. Results The non-treated group had a higher risk of recurrence (HR: 2.79, 95%CI: 1.58–4.91; P < 0.001) than mitotane-treated group, while overall survival was not significantly different between groups. Hormone secretion, elevated Weiss score and elevated Ki67 index confer a higher risk of both recurrence and death and stage III ACC of death. Adjuvant mitotane treatment reduced significantly the risk of death in patients with elevated Ki67 index (P = 0.005) and in patients with stage III ACC (P = 0.02). Conclusions Adjuvant mitotane may prolong recurrence-free survival in radically resected ACC patients with acceptable toxicity and may also prolong overall survival in a subgroup of ACC patients at high risk of recurrence.

Open vs laparoscopic adrenalectomy for localized adrenocortical carcinoma

“…Moreover, the administration of adjuvant mitotane treatment to most of our patients with a high risk of tumour recurrence (ie Ki‐67 > 10%) probably had beneficial impact on the rate of tumour recurrence. This is in accordance with the recent study by Calabrese et al who demonstrated that adjuvant mitotane treatment might prolong RFS in ACC patients after radical tumour resection 20 . Furthermore, all patients from our cohort for whom the data on blood mitotane level were available reached and maintained the target mitotane concentration >14 mg/L which has been shown to be associated with a favourable response to adjuvant mitotane treatment 21 …”

Adjuvant Therapy in Adrenocortical Carcinoma: Reflections and Future Directions

“…Further support for adjuvant mitotane came from another recent retrospective study that included 152 patients with non-metastatic ACC (100 patients who received adjuvant mitotane and 52 who did not receive adjuvant therapy) who were stratified by disease stage (I-II vs III), hormone secretion (yes vs. no), and Ki-67 index. The recurrence risk was greater in patients who did not receive mitotane (HR, 2.79; 95% CI, 1.58-4.91) compared with those who did, but OS did not differ significantly between groups [59].…”

“…Cancers 2020, 12, x 6 of 12 mitotane (HR, 2.79; 95% CI, 1.58-4.91) compared with those who did, but OS did not differ significantly between groups [59].…”

Unwanted Hormonal and Metabolic Effects of Postoperative Adjuvant Mitotane Treatment for Adrenocortical Cancer

“…The topic of mitotane toxicity is of clinical interest considering that mitotane is still the backbone therapy for advanced ACC [15] and that the drug is also recommended as an adjuvant measure in ACC patients at high risk of recurrence following radical surgery [13,[20][21][22][23][24]. Drug toxicity is a compelling issue particularly in the adjuvant setting, since it may be more difficult to justify treatment-related problems in patients who are free of disease.…”