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Combination of mitotane and locoregional treatments in low-volume metastatic adrenocortical carcinoma.

PURPOSE
European and French guidelines for ENSAT stage IV low tumor burden or indolent adrenocortical carcinoma (ACC) recommend combination of mitotane and locoregional treatments (LRT) in first-line. Nevertheless, the benefit of LRT combination with mitotane has never been evaluated in this selected group of patients.


METHODS
A retrospective chart review was performed from 2003-2018 of patients with stage IV ACC with ≤2 tumoral organs who received mitotane in our center. Primary endpoint was the delay between mitotane initiation and first systemic chemotherapy. Secondary endpoints were progression-free survival (PFS) and overall survival (OS) from mitotane initiation. Adjusted analyses were performed on the main prognostic factors.


RESULTS
Out of 79 included patients, 48 (61%) patients were female and median age at stage IVA diagnosis was 49.8 years (interquartile-range:38.8-60.0). Metastatic sites were mainly lungs (76%) and liver (48%). Fifty-eight (73%) patients received LRT including adrenal bed radiotherapy (14 patients, 18%), surgery (37 patients, 47%) and/or interventional radiology n(35,44%). Median time between mitotane initiation and first chemotherapy administration was 9 months (Interquartile-range:4-18). Median PFS1 (first tumor-progression) was 6.0 months (CI95%:4.5-8.6). Median OS was 46 months (CI95%:41-68). PFS1, PFS2 and OS were statistically longer in the mitotane plus LRT group compared to the mitotane-only group (Hazard ratio (HR)=0.39 (CI95%:0.22-0.68), HR=0.35 (CI95%:0.20-0.63) and HR=0.27 (CI95%:0.14-0.50) respectively). Ten (13%) patients achieved complete response, all from mitotane plus LRT group.


CONCLUSION
Our results endorse European and French guidelines for stage IV ACC with ≤2 tumor-organs and favor the combination of mitotane and LRT as first-line treatment. For the first time, a significant number of complete responses were observed. Prospective studies are expected to confirm these findings.