Validation of ADNEX and IOTA two-step strategy and estimation of risk of complications during follow-up of adnexal masses in low-risk population

OBJECTIVES: To evaluate the ability of the Assessment of Different NEoplasias in the adneXa (ADNEX) model and the International Ovarian Tumour Analysis (IOTA) two-step strategy to predict malignancy in adnexal masses detected in an outpatient low-risk setting, and to estimate the risk of complications in masses with benign ultrasound morphology managed using clinical and ultrasound follow-up. METHODS: This single-center study was performed at Hospital Universitari Dexeus, Barcelona, Spain, using interim data from the ongoing prospective observational IOTA Phase-5 (IOTA5) study. The primary aim of the IOTA5 study is to describe the cumulative incidence of complications during follow-up of adnexal masses classified as benign on ultrasound examination. Consecutive patients with an adnexal mass detected between June 2012 and September 2016 in a private center offering screening for gynecological cancer were included and followed up until February 2020. Tumors were classified as benign or malignant based on histology (if patients underwent surgery) or the outcome of clinical and ultrasound follow-up at 12 (range, 10-14) months. Multiple imputation was used when outcomes were uncertain. The ability of the ADNEX model without CA125 and of the IOTA two-step strategy to distinguish benign from malignant masses was evaluated retrospectively using the prospectively collected data. We assessed performance with regard to discrimination (area under the receiver-operating-characteristics curve (AUC)), calibration, classification (sensitivity and specificity) and clinical utility (Net Benefit). In the group of patients with a mass judged to be benign who were selected for conservative management, we evaluated the occurrence of spontaneous resolution or any mass complication during the first 5 years of follow-up by assessing the cumulative incidence of malignancy, torsion, cyst rupture and minor mass complications (inflammation, infection or adhesions) and the time to occurrence of an event. RESULTS: A total of 2654 patients were recruited to the study. After application of exclusion criteria, 2039 patients with a newly detected mass were included for the model validation. Of those, 1684 (83%) masses were benign, 49 (2%) masses were malignant and, for 306 (15%) masses, the outcome was uncertain and therefore imputed. The AUC was 0.95 (95% CI, 0.89-0.98) for ADNEX without CA125 and 0.94 (95% CI, 0.88-0.97) for the two-step strategy. Calibration performance could not be mean