ENDOCRINE TUMOURS: Our experience with the management of patients with non-metastatic adrenocortical carcinoma

Abstract

Adrenocortical carcinoma (ACC) accounts for a minority of all malignant tumors in adults. Surgery remains the most important therapeutic option for non-metastatic ACC. Whether a subset of patients with small ACC may benefit from minimally invasive surgery remains a debated issue, but we believe that surgeon’s expertise is more important than surgical technique to determine outcome. However, even a state-of-the-art surgery cannot prevent disease recurrence that is determined mainly by specific tumor characteristics. We consider that the concomitant presence of the following features characterizes a cohort of patients at low risk of recurrence, i) R0 resection (microscopically free margin), ii) localized disease (stage I-II ACC), and iii) low grade tumor (ki-67 <10%). After the ADIUVO study, we do not recommend adjuvant mitotane as a routine measure for such patients, who can be managed with active surveillance thus sparing a toxic treatment. Patients at average risk of recurrence should be treated with adjuvant mitotane. For patients at very high risk of recurrence, defined as the presence of at least one of the following: Ki67 >30%, large venous tumor thrombus, R1 resection or stage IV ACC, we increasingly recommend to combine mitotane with four cycles of platinum-based chemotherapy. However, patients at moderate-to-high risk of recurrence should be ideally enrolled in the ongoing ADIUVO2 trial. We do not use frequently adjuvant radiotherapy of the tumor bed at our institutions, and we select for this treatment patients with microscopically, or macroscopically, incomplete resection. On long-term, prospective multicenter trials are required to improve patient care.

A Revised Version of the TNM Classification Leads to Optimized Predictive Performance in Patients with Adrenocortical Carcinoma

“…In this context, it would also be interesting to investigate the role of radiotherapy in adjuvant treatment according to tumor stage and prognostic assessment in randomized trials. Evidence suggests that patients with microscopic or macroscopic incomplete resection without evidence of distant metastases may benefit from radiotherapy, although randomized trials focusing on these specific subgroups are lacking 39 .…”

“…There was no significant difference in the primary endpoint of recurrence-free survival (RFS) or OS. The results suggest that mitotane should not be routinely administered to all patients to avoid potentially toxic treatment effects in these patients [39]. In this context, it would also be interesting to investigate the role of radiotherapy in adjuvant treatment according to tumor stage and prognostic assessment in randomized trials.…”

High expression of GMNN predicts malignant progression and poor prognosis in ACC

“…Mitotane is the only available drug approved for the treatment of advanced ACC. Considering the toxicity and side effects, it is very important to screen ACC patients who can benefit from mitotane [ 20 , 21 ]. However, there is still a lack of biomarkers for predicting the efficacy of mitotane in ACC.…”

Efficacy and safety of radiation therapy in advanced adrenocortical carcinoma

“…Almost all studies showed that adjuvant RT can reduce the risk of local recurrence. However, data are conflicting regarding overall recurrence-free and overall survival [33]. Nevertheless, these studies suggest that the majority of ACCs are sensitive to RT.…”