OBJECTIVE: To evaluate the performance of diagnostic prediction models for ovarian malignancy in all patients with an ovarian mass managed surgically or conservatively. DESIGN: Multicentre cohort study. SETTING: 36 oncology referral centres (tertiary centres with a specific gynaecological oncology unit) or other types of centre. PARTICIPANTS: Consecutive adult patients presenting with an adnexal mass between January 2012 and March 2015 and managed by surgery or follow-up. MAIN OUTCOME MEASURES: Overall and centre specific discrimination, calibration, and clinical utility of six prediction models for ovarian malignancy (risk of malignancy index (RMI), logistic regression model 2 (LR2), simple rules, simple rules risk model (SRRisk), assessment of different neoplasias in the adnexa (ADNEX) with or without CA125). ADNEX allows the risk of malignancy to be subdivided into risks of a borderline, stage I primary, stage II-IV primary, or secondary metastatic malignancy. The outcome was based on histology if patients underwent surgery, or on results of clinical and ultrasound follow-up at 12 (±2) months. Multiple imputation was used when outcome based on follow-up was uncertain. RESULTS: The primary analysis included 17 centres that met strict quality criteria for surgical and follow-up data (5717 of all 8519 patients). 812 patients (14%) had a mass that was already in follow-up at study recruitment, therefore 4905 patients were included in the statistical analysis. The outcome was benign in 3441 (70%) patients and malignant in 978 (20%). Uncertain outcomes (486, 10%) were most often explained by limited follow-up information. The overall area under the receiver operating characteristic curve was highest for ADNEX with CA125 (0.94, 95% confidence interval 0.92 to 0.96), ADNEX without CA125 (0.94, 0.91 to 0.95) and SRRisk (0.94, 0.91 to 0.95), and lowest for RMI (0.89, 0.85 to 0.92). Calibration varied among centres for all models, however the ADNEX models and SRRisk were the best calibrated. Calibration of the estimated risks for the tumour subtypes was good for ADNEX irrespective of whether or not CA125 was included as a predictor. Overall clinical utility (net benefit) was highest for the ADNEX models and SRRisk, and lowest for RMI. For patients who received at least one follow-up scan (n=1958), overall area under the receiver operating characteristic curve ranged from 0.76 (95% confidence interval 0.66 to 0.84) for RMI to 0.89 (0.81 to 0.94) for ADNEX with CA125. CONCLUSIONS: Our study found the ADNEX models and SRRisk are the best models to distinguish between benign and malignant masses in all patients presenting with an adnexal mass, including those managed conservatively. TRIAL REGISTRATION: ClinicalTrials.gov NCT01698632.

1st Department of Gynaecological Oncology and Gynaecology Medical University of Lublin Lublin Poland

1st Department of Obstetrics and Gynaecology Alexandra Hospital Medical School National and Kapodistrian University of Athens Athens Greece

Clinic of Obstetrics and Gynaecology University of Milan Bicocca San Gerardo Hospital Monza Italy

Department of Biomedical Data Sciences Leiden University Medical Centre Leiden 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 Herestraat 49 Box 805 3000 Leuven Belgium

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

Department of Experimental and Clinical Biomedical Sciences University of Florence Florence Italy

Department of Gynaecologic Oncology National Cancer Institute of Milan Milan Italy

Department of Life Science and Public Health Universita' Cattolica del Sacro Cuore Rome Italy

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

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

Department of Obstetrics and Gynaecology Ikazia Hospital Rotterdam Netherlands

Department of Obstetrics and Gynaecology Skåne University Hospital Malmö Sweden

Department of Obstetrics and Gynaecology Södersjukhuset Stockholm Sweden

Department of Obstetrics and Gynaecology University Hospitals Leuven Leuven Belgium

Department of Obstetrics and Gynaecology University of Bologna Bologna Italy

Department of Obstetrics and Gynaecology University of Cagliari Policlinico Universitario Duilio Casula Monserrato Cagliari Italy

Department of Obstetrics and Gynaecology Whipps Cross Hospital London UK

Department of Obstetrics and Gynaecology Ziekenhuis Oost Limburg Genk Belgium

Department of Perinatology and Oncological Gynaecology School of Health Sciences in Katowice Medical University of Silesia Katowice Poland

Department of Woman Child and Public Health Fondazione Policlinico Universitario Agostino Gemelli Istituto di Ricovero e Cura a Carattere Scientifico Rome Italy

EPI Centre KU Leuven Leuven Belgium

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

Institute for Maternal and Child Health IRCCS Burlo Garofolo Trieste Italy

Laboratory of Tumour Immunology and Immunotherapy Department of Oncology KU Leuven Leuven Belgium

Leuven Cancer Institute University Hospitals Leuven Leuven Belgium

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

Queen Charlotte's and Chelsea Hospital Imperial College London UK

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NCT01698632