Impact of Adjuvant Radiotherapy and Mitotane on Survival in Localized Adrenocortical Carcinoma: A Retrospective Cohort Study.

OBJECTIVES: Adrenocortical carcinoma (ACC) is a rare, aggressive tumor with high recurrence rates after surgery. Although radiotherapy (RT) has historically been underutilized in ACC, modern RT techniques have renewed interest in its potential role for improving local control (LC). This study evaluated long-term outcomes and prognostic factors in high-risk localized ACC treated with adjuvant RT and mitotane.

METHODS: In this multicenter retrospective study, 23 patients with localized, high-risk ACC who underwent complete surgical resection followed by adjuvant RT between 2003 and 2023 were analyzed. All received mitotane, and 21.6% also received platinum-based chemotherapy. RT was delivered using image-guided IMRT or VMAT to a median dose of 50.4 Gy, targeting the tumor bed with or without regional lymphatics. Survival was estimated using the Kaplan-Meier method, and prognostic factors were assessed with Cox regression analyses.

RESULTS: At a median follow-up of 84.7 months, the 5-year LC, overall survival (OS), and disease-free survival (DFS) rates were 85.5%, 58.6%, and 45.6%. Locoregional recurrence occurred in two patients (8.6%), with isolated local failure in one (4.3%). Distant metastasis (DM) developed in 47.8% and was the predominant failure pattern. On univariable analysis, age > 55 years predicted worse OS and DFS, while female sex independently predicted inferior DFS. Treatment was well tolerated, with no grade ≥ 3 RT-related toxicities.

CONCLUSIONS: Adjuvant RT achieves excellent LC with minimal toxicity in high-risk localized ACC. These exploratory findings, limited by small cohort size, retrospective design, and absence of a comparator group, warrant confirmation in larger prospective multicenter studies.