Adrenocortical Carcinoma in Childhood: A Systematic Review

SIMPLE SUMMARY: Pediatric adrenocortical tumors are rare. Little information is available on the incidence, risk factors, prognostic factors, treatment, and overall survival. In this systematic review, we performed a search of the current literature. The most common reported risk factors are age > 4 years, high pathological tumor score, and advanced stage in which prognosis is poor. Treatment options are surgery, radiation, or chemotherapy, but ongoing randomized trials are lacking. International prospective studies must be the next step to implement standardized clinical stratifications and risk-adapted therapeutic strategies. ABSTRACT: Adrenocortical tumors are rare in children. This systematic review summarizes the published evidence on pediatric adrenocortical carcinoma (ACC) to provide a basis for a better understanding of the disease, investigate new molecular biomarkers and therapeutic targets, and define which patients may benefit from a more aggressive therapeutic approach. We included 137 studies with 3680 ACC patients (~65% female) in our analysis. We found no randomized controlled trials, so this review mainly reflects retrospective data. Due to a specific mutation in the TP53 gene in ~80% of Brazilian patients, that cohort was analyzed separately from series from other countries. Hormone analysis was described in 2569 of the 2874 patients (89%). Most patients were diagnosed with localized disease, whereas 23% had metastasis at primary diagnosis. Only 72% of the patients achieved complete resection. In 334 children (23%), recurrent disease was reported: 81%—local recurrence, 19% (n = 65)—distant metastases at relapse. Patients < 4 years old had a different distribution of tumor stages and hormone activity and better overall survival (p < 0.001). Although therapeutic approaches are typically multimodal, no consensus is available on effective standard treatments for advanced ACC. Thus, knowledge regarding pediatric ACC is still scarce and international prospective studies are needed to implement standardized clinical stratifications and risk-adapted therapeutic strategies.