A.M. Lin1, K.C. Bergus2, J. Bricker2, M. Fallat3, P. Hertweck2, G. Hewitt2, C. Lutz2, J. Aldrink2, C. Bence14, L. Breech4, P.A. Dillon5, C. Downward3, P.F. Ehrlich6, J.D. Fraser7, J. Grabowski8, M. Helmrath4, R.B. Hirschl6, R. Kabre8, D.R. Lal14, M. Landman9, C. Leys10, G. Mak11, T. Markel9, J.G. Pressey4, M. Raiji11, B. Rymeski4, J. Saito12, S.D. St. Peter13, L. Asti1, K. Deans1, P. Minneci1 1Nemours Children’s Hospital, Delaware Valley, DE, Surgery, Wilmington, DE, USA 2Nationwide Children’s Hospital, Surgery And Pediatric And Adolescent Gynecology, Columbus, OH, USA 3Norton Children’s Hospital, Pediatric Surgery And Gynecology, Louisville, KY, USA 4Cincinnati Children’s Hospital Medical Center, Pediatric Surgery, Cincinnati, OH, USA 5St. Louis Children’s Hospital, Surgery, St. Louis, MO, USA 6C.S. Mott Children’s Hospital, Pediatric Surgery, Ann Arbor, MI, USA 7Phoenix Children’s Hospital, Pediatric Surgery, Phoenix, AZ, USA 8Ann & Robert H. Lurie Children’s Hospital of Chicago, Pediatric Surgery, Chicago, IL, USA 9Riley Hospital for Children, Pediatric Surgery, Indianapolis, IN, USA 10American Family Children’s Hospital, Pediatric Surgery, Madison, WI, USA 11Comer Children’s Hospital, Pediatric Surgery, Chicago, IL, USA 12Children’s National Medical Center, General And Thoracic Surgery, Washington, DC, USA 13Children’s Mercy Hospital- University Of Missouri Kansas City, Pediatric Surgery, Kansas City, MO, USA 14Children’s Hospital Of Wisconsin, Pediatric Surgery, Milwaukee, WI, USA
Introduction:
Pediatric and adolescent patients with ovarian masses undergo radiographic and serologic evaluation to determine malignancy risk before surgery. Commonly examined tumor markers for detecting malignancy among these patients include α-fetoprotein (AFP), β-human chorionic gonadotropin (β-HCG), cancer antigen-125 (Ca-125), inhibin A, and lactate dehydrogenase (LDH). 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 years who underwent surgery for an ovarian mass between 8/2018-2/2021 at 11 children’s hospitals. All included patients underwent preoperative assessment with ≥1 tumor marker(s). Tumor markers were considered abnormal based on accepted cutoffs. Individual and all combinations of tumor marker performance were measured through point estimates of sensitivity, specificity, positive and negative predictive value (NPV), accuracy, and area under the receiver operating characteristic curve (AUC) in predicting malignancy based on final pathological diagnosis. AUC >0.9 was considered clinically meaningful. A priori clinical consensus was that the optimal combination of tumor markers should minimize the misclassification of patients with malignancy (maximize NPV).
Results:
Tumor markers were assessed in 309 patients out of the cohort of 519 treated and, among those assessed, 25 had a malignancy. The number of patients per combination of tumor markers ranged from 90 to 236. Seven combinations yielded AUC >0.9. The most accurate combination was β-HCG/Inhibin A/LDH (accuracy = 0.951; AUC = 0.939) (See Table 1). β-HCG was present among all the best performing combinations. Three combinations did not misclassify any malignant lesions as likely benign (100% NPV), and the most accurate of these was AFP/β-HCG/Ca-125/Inhibin A (accuracy = 0.862, AUC = 0.923).
Conclusion:
Tumor markers can support preoperative risk stratification for malignancy to determine which patients may benefit from ovary-sparing surgery and prevent unnecessary oophorectomy. The 5-tumor marker panel used in our algorithm did not have the highest accuracy. Three combinations satisfied the clinical criteria of 100% NPV (no malignancy misclassifications), and of which the most accurate combination consisted of AFP/β-HCG/Ca-125/Inhibin A. An optimal combination of tumor markers can be used to support preoperative risk assessment of ovarian masses in pediatric and adolescent patients.