Benign descriptors and ADNEX in two-step strategy to estimate risk of malignancy in ovarian tumors: retrospective validation on IOTA 5 multicenter cohort
C Landolfo 1 2 , T Bourne 1 3 4 , W Froyman 1 3 , B Van Calster 1 5 , J Ceusters 1 6 , A C Testa 2 7 , L Wynants 1 8 , P Sladkevicius 9 10 , C Van Holsbeke 11 , E Domali 12 , R Fruscio 13 , E Epstein 14 15 , D Franchi 16 , M J Kudla 17 , V Chiappa 18 , J L Alcazar 19 , F P G Leone 20 , F Buonomo 21 , M E Coccia 22 , S Guerriero 23 , N Deo 24 , L Jokubkiene 9 10 , L Savelli 25 , D Fischerova 26 , A Czekierdowski 27 , J Kaijser 28 , A Coosemans 6 , G Scambia 2 7 , I Vergote 3 6 , D Timmerman # 1 3 , L Valentin # 9 10
Objective: Previous work suggested that the ultrasound-based benign Simple Descriptors can reliably exclude malignancy in a large proportion of women presenting with an adnexal mass. We aim to validate a modified version of the Benign Simple Descriptors (BD), and we introduce a two-step strategy to estimate the risk of malignancy: if the BDs do not apply, the ADNEX model is used to estimate the risk of malignancy.
Methods: This is a retrospective analysis using the data from the 2-year interim analysis of the IOTA5 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 one year of follow-up. Multiple imputation was used when outcome based on follow-up was uncertain according to predefined criteria.
Results: 8519 patients were recruited at 36 centers between 2012 and 2015. We included all masses that were not already in follow-up at recruitment from 17 centers with good quality surgical and follow-up data, leaving 4905 patients for statistical analysis. 3441 (70%) tumors were benign, 978 (20%) malignant, and 486 (10%) uncertain. The BDs were applicable in 1798/4905 (37%) tumors, and 1786 (99.3%) of these were benign. The two-step strategy based on ADNEX without CA125 had an area under the receiver operating characteristic curve (AUC) of 0.94 (95% CI, 0.91-0.95). 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 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.