From trial to practice: No survival benefit from adjuvant mitotane in low-risk adrenocortical carcinoma, insights from a nationwide cohort

Document Type

Conference Proceeding

Publication Date

3-1-2026

Publication Title

Eur Urol

Keywords

Urology & Nephrology

Abstract

Introduction & Objectives: The benefit of adjuvant mitotane in patients with surgically resected, low-risk adrenocortical carcinoma (ACC) remains uncertain. The randomized ADIUVO trial found no difference in recurrence-free survival between mitotane and surveillance groups; however, its interpretation is limited by reduced statistical power and small sample size. We aimed to evaluate the real-world use and outcomes of adjuvant mitotane in a large national cohort of patients with low-risk ACC. Materials & Methods: Using the National Cancer Database (2006–2022), we identified patients with localized ACC treated surgically. To define a low-risk population, we excluded those with positive surgical margins, metastatic disease, radiation therapy use, or tumors >60 mm. Tumor grade was inconsistently reported and Ki-67 data were unavailable, precluding their use for risk stratification. Adjuvant chemotherapy initiated within 120 days of surgery was considered mitotane use. Overall survival (OS) was estimated using the Kaplan–Meier method, while the independent impact of adjuvant mitotane on OS was assessed using multivariable Cox proportional hazards regression, adjusting for demographic, clinical, and socioeconomic factors. Results: Among 423 patients with resected low-risk ACC, median age was 57 years, and 61% were female. Adjuvant mitotane was administered in 19% of cases. Patients receiving mitotane had larger tumors (48 vs. 44 mm, p = 0.025) and were more frequently T3 stage (p = 0.03). Five-year OS was 65.3% (95% CI 59.8–71.2) after surgery alone and 63.5% (95% CI 52.9–76.4) with adjuvant therapy. In multivariable analysis, adjuvant mitotane was not an independent predictor of improved OS (HR 1.08, 95% CI 0.71–1.66, p = 0.7). Independent predictors of worse OS included older age (HR 1.03 per year, p < 0.001), higher comorbidity burden (Charlson–Deyo ≥1: HR 1.57, p = 0.02), and T3 stage vs. T1 (HR 2.41, p = 0.007). Conclusions: In this large, real-world cohort of surgically treated low-risk ACC, adjuvant mitotane was frequently used but did not confer a survival benefit. Increasing age, comorbidity, and advanced T stage were the strongest predictors of mortality. These findings reinforce that routine mitotane use in low-risk disease may not be justified and should be reserved for carefully selected higher-risk cases.

Volume

89

First Page

1

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