Combination of Mitotane and Locoregional Treatments in Low-volume Metastatic Adrenocortical Carcinoma

CONTEXT: European and French guidelines for ENSAT stage IV low tumor burden or indolent adrenocortical carcinoma (ACC) recommend a combination of mitotane and locoregional treatments (LRT) as first-line treatment. Nevertheless, the benefit of LRT in combination with mitotane has never been evaluated in this selected group of patients. OBJECTIVE: This work aimed to evaluate the therapeutic strategy of LRT combined with mitotane in patients with low tumor burden stage IVA ACC. METHODS: A retrospective chart review was performed from 2003 to 2018 of patients with stage IV ACC with 2 or fewer tumoral organs who received mitotane in our center. The primary end point was the delay between mitotane initiation and first systemic chemotherapy. Secondary end points 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 the median age at stage IVA diagnosis was 49.8 years (interquartile range [IQR], 38.8-60.0 years). 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 (35 patients, 44%). Median time between mitotane initiation and first chemotherapy administration was 9 months (IQR, 4-18 months). Median PFS1 (first tumor-progression) was 6.0 months (95% CI, 4.5-8.6). Median OS was 46 months (95% CI, 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; 95% CI, 0.22-0.68; HR = 0.35; 95% CI, 0.20-0.63; and HR = 0.27; 95% CI, 0.14-0.50, respectively). Ten (13%) patients achieved complete response (CR), all from the mitotane plus LRT group. CONCLUSION: Our results endorse European and French guidelines for stage IV ACC with 2 or fewer tumor organs and favor the combination of mitotane and LRT as first-line treatment. For the first time, a significant number of CRs were observed. Prospective studies are expected to confirm these findings.