Exploring heterogeneity of adrenal cortical tumors in children: The French pediatric rare tumor group (Fracture) experience

Introduction Pediatric adrenal cortical tumors are characterized by a wide spectrum of behavior. Questions remain regarding intermediate disease stages with isolated tumor rupture or relapse. Objectives To describe clinical characteristics, treatment strategy, and outcome of patients depending on disease stage, tumor rupture, or in case of a refractory tumor, to discuss optimal management. Material and methods Pediatric patients with histological material reviewed and treated between 2000 and 2018 in 23 French oncology centers were included. Results Among 95 cases, 59% of patients had stage I tumors (n = 55), 16% had stage II tumors (n = 16), 19% had stage III tumors (n = 17), and 5% had stage IV tumors (n = 5) (missing data: 2). Overall, 27% of patients (n = 25) had an unfavorable histology. Initial tumor resection was performed for 90% of patients (n = 86). Systemic therapies included mitotane in 20 cases and chemotherapy in 13 cases. Among 17 stage III patients, 12 had microscopic residual tumor due to an initial biopsy (n = 5), intraoperative rupture (n = 8), or surgical resection with microscopic residue or tumor spillage surgery (n = 1) (two patients with two modalities). After a median follow-up of 96 months (25-119), four early progressions and two relapses occurred. A total of seven patients died, including five of disease. Stage III diseases due to microscopic residual disease correlated with a worse prognosis: 5-year progression-free survival 44% (95% CI, 22-87%) versus 82% (95% CI, 73-91%) for the whole cohort (P < .0001). Among the 14 patients with refractory disease, only 3 were alive and free of disease after multimodal second-line therapy. Conclusions Stage III diseases due to a microscopic residual tumor have a dismal prognosis, arguing for the systematic use of adjuvant therapy. Patients with a relapsed disease should be included in experimental studies.