Locally Advanced Adrenocortical Carcinoma in Children and Adolescents—Enigmatic and Challenging Cases

SIMPLE SUMMARY: Pediatric COG stage II and III adrenocortical carcinoma (ACC) is one of the most unpredictable and challenging tumors in terms of prognosis and management. The EXPeRT/PARTNER recommendation suggested inclusion of the five-item microscopic score to guide management in these patients. In this study, we report on 18 pediatric ACC stage II and 37 stage III patients registered with the German MET studies. We explored the five-item microscopic and the pS-GRAS score to predict outcome. Three-year event-free survival estimates were 76.5% in stage II and 49.8% in stage III patients. In COG stage III patients, EFS was impaired for patients with unfavorable histology according to the five-item score. No differences were observed in stage II patients and in the pS-GRAS groups. Further research including molecular studies is needed to identify high-risk features in locally advanced pediatric ACC tumors. ABSTRACT: Background: Locally advanced tumors account for approximately 50% of children and adolescents with adrenocortical carcinoma (ACC), and of these, up to 50% relapse. We explored the five-item microscopic score and the pS-GRAS score for guiding management. Methods: Data from children and adolescents with COG stage II and III ACC registered in the MET studies were included. The five-item and pS-GRAS score were retrospectively calculated. Results: By December 2021, 55 patients with stage II and III (stage II n = 18, stage III n = 37) had been reported. Median age was 4.3 years [0.1–17.8], median duration of follow-up 6.0 years [0–16.7]. 3-year event-free survival (EFS) rate was 76.5% and 49.8% (p = 0.088), respectively. In stage II tumors, neither the five-item score (p = 0.872) nor pS-GRAS grouping (p = 0.218) had any effect as prognostic factors. In stage III patients, EFS was impaired in tumors with unfavorable histology according to the five-item score (100% vs. 30.8%, p = 0.018). No difference was observed for pS-GRAS groups (p = 0.798). Conclusions: In patients with COG stage III, but not stage II, the five-item score affected EFS. Further studies are needed to identify patients at risk in COG stage II.