Benign descriptors and ADNEX in two‐step strategy to estimate risk of malignancy in ovarian tumors: retrospective validation in IOTA5 multicenter cohort

Abstract

Objective Previous work has suggested that the ultrasound‐based benign simple descriptors (BDs) can reliably exclude malignancy in a large proportion of women presenting with an adnexal mass. This study aimed to validate a modified version of the BDs and to validate a two‐step strategy to estimate the risk of malignancy, in which the modified BDs are followed by the Assessment of Different NEoplasias in the adneXa (ADNEX) model if modified BDs do not apply. Methods This was a retrospective analysis using data from the 2‐year interim analysis of the International Ovarian Tumor Analysis (IOTA) Phase‐5 study, in which consecutive patients with at least one adnexal mass were recruited irrespective of subsequent management (conservative or surgery). The main outcome was classification of tumors as benign or malignant, based on histology or on clinical and ultrasound information during 1 year of follow‐up. Multiple imputation was used when outcome based on follow‐up was uncertain according to predefined criteria. Results A total of 8519 patients were recruited at 36 centers between 2012 and 2015. We excluded patients who were already in follow‐up at recruitment and all patients from 19 centers that did not fulfil our criteria for good‐quality surgical and follow‐up data, leaving 4905 patients across 17 centers for statistical analysis. Overall, 3441 (70%) tumors were benign, 978 (20%) malignant and 486 (10%) uncertain. The modified BDs were applicable in 1798/4905 (37%) tumors, of which 1786 (99.3%) were benign. The two‐step strategy based on ADNEX without CA125 had an area under the receiver‐operating‐characteristics curve (AUC) of 0.94 (95% CI, 0.92–0.96). The risk of malignancy was slightly underestimated, but calibration varied between centers. A sensitivity analysis in which we expanded the definition of uncertain outcome resulted in 1419 (29%) tumors with uncertain outcome and an AUC of the two‐step strategy without CA125 of 0.93 (95% CI, 0.91–0.95). Conclusion A large proportion of adnexal masses can be classified as benign by the modified BDs. For the remaining masses, the ADNEX model can be used to estimate the risk of malignancy. This two‐step strategy is convenient for clinical use. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Conservative management of adnexal tumors: how to tell good from bad

“…Firstly, such studies are much harder to conduct as they require the recruited patients to attend for repeat visits and to comply with long-term follow-up. This point is well-illustrated by the current study, in which one of the main reasons for exclusion of participating centers from the data analysis was suboptimal data quality due to incomplete follow-up 1 . The other important issue is the lack of an agreed reference standard applicable to patients who are managed conservatively 6 .…”

“…In this issue of the Journal, Landolfo and colleagues from the International Ovarian Tumor Analysis (IOTA) collaboration 1 describe a novel model for non‐invasive diagnosis of ovarian cancer in an outpatient setting. The IOTA collaboration has been at the forefront of research into improving the accuracy of ultrasound assessment of adnexal tumors for more than two decades 2 .…”

“…ADNEX is the only model which takes this into consideration by incorporating the type of treatment center (oncology or non‐oncology units) in which patients are seen as one of the predictors 4 . However, no allowance was made in the original 4 or present 1 study for the low‐risk outpatient setting. This is relevant, as it has already been shown that using a test with a relatively high specificity and high positive predictive value could lead to a significantly higher proportion of false‐positive diagnoses of ovarian cancer when applied to a low‐risk population 6 .…”

“…In addition, the diagnostic models developed by experts may incorporate a degree of ultrasound skill which may appear trivial to the model's designers and yet not be prevalent among non‐specialist sonographers. As a result, there is a risk that more complex models, which involve subjective image analysis, such as O‐RADS 5 or the proposed two‐step strategy 1 , may not perform so well in their hands.…”

“…The two‐step strategy proposed by Landolfo et al 1 . is a welcome and important step in the right direction, which has the potential to better address the needs of patients and clinicians with an interest in the diagnosis and management of ovarian cancer.…”