Disease stage is significantly associated with outcomes in pediatric patients with adrenocortical carcinoma (ACC), according to a study published in the Journal of Clinical Oncology.

“Excellent” outcomes were observed for patients with stage I and stage III ACC, but new treatment options are needed for patients with stage II and stage IV ACC, according to the study authors.

The ARAR0332 study (ClinicalTrials.gov Identifier: NCT00304070) is a prospective, risk-stratified interventional trial designed to evaluate clinical outcomes associated with different therapeutic approaches in pediatric patients with ACC.

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The study included 77 children with stage I (n=24), stage II (n=15), stage III (n=24), and stage IV (n=14) ACC. Roughly two-thirds of evaluable patients had germline TP53 mutations (41/62).

Patients with stage I (median age, 1.5 years), stage II (median age, 2 years), and stage III (median age, 3 years) disease were younger than patients with stage IV disease (median age, 13 years). 

Treatment for patients with stage I disease was tumor resection alone. Patients with stage II disease underwent tumor resection and retroperitoneal lymph node dissection.

Patients with stage III or IV disease were treated with 8 cycles of chemotherapy plus mitotane for 8 months, with surgery of the primary tumor and metastases done at the discretion of the treating team.

The 5-year event-free survival rates were 86.2% for the stage I group, 53.3% for stage II, 81% for stage III, and 7.1% for stage IV. The 5-year overall survival rates were 95.2%, 78.8%, 94.7%, and 15.6%, respectively.

The study authors noted that the combination of mitotane and chemotherapy was associated with high rates of toxicity, and one-third of patients with advanced disease were unable to complete the scheduled treatment.

In a univariate analysis, clinical outcomes were significantly associated with age, disease stage, presence of virilization, Cushing syndrome, hypertension, predicted p53 function, and the combination of TP53 and ATRX mutations.

In a multivariate analysis, only disease stage (P <.001) and patient age (P =.003) were significantly associated with outcomes.

According to the study authors, these results suggest that surgery provides “excellent” outcomes for patients with stage I ACC, but outcomes for patients with stage II disease are poor despite retroperitoneal lymph node dissection.

“Patients with stage III ACC have an excellent outcome combining surgery and chemotherapy,” the authors wrote. “Patients with stage IV ACC are older and have a poor outcome; new treatments should be explored for this high-risk group.”

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Rodriguez-Galindo C, Krailo MD, Pinto EM, et al. Treatment of Pediatric Adrenocortical Carcinoma With Surgery, Retroperitoneal Lymph Node Dissection, and Chemotherapy: The Children’s Oncology Group ARAR0332 Protocol. J Clin Oncol. 2021;39(22):2463-2473. doi:10.1200/JCO.20.02871