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.

Descriptores benignos y ADNEX en una estrategia de dos pasos para estimar el riesgo de malignidad de tumores ováricos: validación retrospectiva en la cohorte multicéntrica IOTA5 Objetivo Estudios previos han sugerido que los descriptores simples benignos (DB) basados en ecografías pueden excluir de forma fiable la malignidad en una gran proporción de mujeres que presentan una masa anexial. El objetivo de este estudio fue validar una versión modificada de los DB y validar una estrategia de dos pasos para estimar el riesgo de malignidad, en la que a los DB modificados les sigue el modelo de Evaluación de las Distintas Neoplasias en el modelo ADNEX si no se aplican los DB modificados. Métodos El estudio fue un análisis retrospectivo con datos del análisis provisional al cabo de 2 años del estudio Fase 5 del Análisis Internacional de Tumores de Ovario (IOTA, por sus siglas en inglés), en el que se reclutaron pacientes consecutivas con al menos una masa anexial, independientemente del tratamiento posterior (farmacológico o quirúrgico). El resultado principal fue la clasificación de los tumores como benignos o malignos, en función de la histología o de la información clínica y ecográfica durante 1 año de seguimiento. Se utilizó una imputación múltiple cuando el resultado basado en el seguimiento fue incierto según criterios predefinidos. Resultados Se reclutaron 8519 pacientes en 36 centros entre 2012 y 2015. Se excluyeron a las pacientes que ya estaban en seguimiento en el momento del reclutamiento y a todas las pacientes de 19 centros que no cumplían los criterios del estudio de datos quirúrgicos y de seguimiento de buena calidad, con lo que quedaron 4905 pacientes de 17 centros para el análisis estadístico. En total, 3441 (70%) tumores eran benignos, 978 (20%) malignos y 486 (10%) inciertos. Los DB modificados fueron aplicables a 1798/4905 (37%) tumores, de los cuales 1786 (99,3%) eran benignos. La estrategia de dos pasos basada en ADNEX sin CA125 tuvo un área bajo la curva de características operativas del receptor (ABC) de 0,94 (IC 95%, 0,92–0,96). El riesgo de malignidad se subestimó ligeramente, pero la calibración varió entre centros. Un análisis de sensibilidad en el que se amplió la definición de resultado incierto dio como resultado 1419 (29%) tumores con resultado incierto y un ABC de la estrategia de dos pasos sin CA125 de 0,93 (IC 95%, 0,91–0,95). Conclusión Una gran proporción de masas anexiales puede clasificarse como benignas mediante los DB modificados. Para estimar el riesgo de malignidad para las masas restantes puede utilizarse el modelo ADNEX. Esta estrategia de dos pasos es útil para el uso clínico.

1st Department of Gynecological Oncology and Gynecology Medical University of Lublin Lublin Poland

1st Department of Obstetrics and Gynecology Alexandra Hospital National and Kapodistrian University of Athens Athens Greece

Clinic of Obstetrics and Gynecology University of Milano Bicocca San Gerardo Hospital Monza Italy

Department of Biomedical Data Sciences Leiden University Medical Centre Leiden The Netherlands

Department of Clinical Science and Education Karolinska Institutet Stockholm Sweden

Department of Clinical Sciences Malmö Lund University Lund Sweden

Department of Development and Regeneration KU Leuven Leuven Belgium

Department of Epidemiology CAPHRI Care and Public Health Research Institute Maastricht University Maastricht The Netherlands

Department of Gynecologic Oncology National Cancer Institute of Milan Milan Italy

Department of Obstetrics and Gynecology Biomedical and Clinical Sciences Institute L Sacco University of Milan Milan Italy

Department of Obstetrics and Gynecology Clinica Universidad de Navarra School of Medicine Pamplona Spain

Department of Obstetrics and Gynecology Ikazia Hospital Rotterdam The Netherlands

Department of Obstetrics and Gynecology Skåne University Hospital Malmö Sweden

Department of Obstetrics and Gynecology Södersjukhuset Stockholm Sweden

Department of Obstetrics and Gynecology University Hospitals Leuven Leuven Belgium

Department of Obstetrics and Gynecology University of Cagliari Policlinico Universitario Duilio Casula Cagliari Italy

Department of Obstetrics and Gynecology University of Florence Florence Italy

Department of Obstetrics and Gynecology Whipps Cross Hospital London UK

Department of Obstetrics and Gynecology Ziekenhuis Oost Limburg Genk Belgium

Department of Perinatology and Oncological Gynecology Faculty of Medical Sciences Medical University of Silesia Katowice Poland

Department of Woman Child and Public Health Fondazione Policlinico Universitario A Gemelli IRCCS Rome Italy

Dipartimento Universitario Scienze della Vita e Sanità Pubblica Università Cattolica del Sacro Cuore Rome Italy

Gynecologic Oncology Centre Department of Obstetrics and Gynecology 1st Faculty of Medicine Charles University and General University Hospital Prague Prague Czech Republic

Gynecology and Physiopathology of Human Reproduction Unit Sant'Orsola Malpighi Hospital of Bologna Bologna Italy

Institute for Maternal and Child Health IRCCS 'Burlo Garofolo' Trieste Italy

Laboratory of Tumor Immunology and Immunotherapy Department of Oncology Leuven Cancer Institute KU Leuven Leuven Belgium

Preventive Gynecology Unit Division of Gynecology European Institute of Oncology IRCCS Milan Italy

Queen Charlotte's and Chelsea Hospital Imperial College Healthcare NHS Trust London UK

Ultrasound Obstet Gynecol. 2023 Feb;61(2):149-151. doi: 10.1002/uog.26158. PubMed

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