Use of Ovarian Tumor Markers in Prediction of Malignancy Risk in Pediatric and Adolescent Patients

INTRODUCTION: Pediatric and adolescent patients with ovarian masses undergo radiographic and serologic workup to determine malignancy risk before surgery. Commonly examined tumor markers for detecting malignancy among these patients are α-fetoprotein, β-human chorionic gonadotropin (β-HCG), cancer antigen-125, inhibin A, and lactate dehydrogenase. This study investigated the diagnostic performance of these tumor markers, individually and in combination, to assess malignancy risk in pediatric and adolescent patients with ovarian masses.

METHODS: This was a planned secondary analysis of a multi-institutional interventional study investigating a consensus-based, preoperative risk stratification algorithm in patients aged 6-21 y, undergoing surgery for an ovarian mass between August 2018 and February 2021 at 11 children's hospitals. All included patients underwent preoperative assessment with ≥ 1 tumor marker(s). Individual and all combinations of tumor marker performance were analyzed. A priori clinical consensus was that the optimal combination of tumor markers should minimize the misclassification of patients with malignancy (maximize negative predictive value).

RESULTS: Tumor markers were assessed in 309 out of the 519 patients, and malignancy was found in 25 patients. β-HCG was present among all the best-performing combinations. The most accurate combination was β-HCG/inhibin A/lactate dehydrogenase (accuracy = 0.951). Three combinations did not misclassify any malignant lesions as likely benign (100% negative predictive value), and the most accurate of these three combinations was α-fetoprotein/β-HCG/cancer antigen-125/inhibin A (accuracy = 0.862).

CONCLUSIONS: Tumor markers can support preoperative risk stratification for malignancy to determine which patients may benefit from ovary-sparing surgery and minimize those undergoing an unindicated oophorectomy or oophorectomy for benign disease.