BACKGROUND: To compare different ultrasound-based international ovarian tumour analysis (IOTA) strategies and risk of malignancy index (RMI) for ovarian cancer diagnosis using a meta-analysis approach of centre-specific data from IOTA3. METHODS: This prospective multicentre diagnostic accuracy study included 2403 patients with 1423 benign and 980 malignant adnexal masses from 2009 until 2012. All patients underwent standardised transvaginal ultrasonography. Test performance of RMI, subjective assessment (SA) of ultrasound findings, two IOTA risk models (LR1 and LR2), and strategies involving combinations of IOTA simple rules (SRs), simple descriptors (SDs) and LR2 with and without SA was estimated using a meta-analysis approach. Reference standard was histology after surgery. RESULTS: The areas under the receiver operator characteristic curves of LR1, LR2, SA and RMI were 0.930 (0.917-0.942), 0.918 (0.905-0.930), 0.914 (0.886-0.936) and 0.875 (0.853-0.894). Diagnostic one-step and two-step strategies using LR1, LR2, SR and SD achieved summary estimates for sensitivity 90-96%, specificity 74-79% and diagnostic odds ratio (DOR) 32.8-50.5. Adding SA when IOTA methods yielded equivocal results improved performance (DOR 57.6-75.7). Risk of Malignancy Index had sensitivity 67%, specificity 91% and DOR 17.5. CONCLUSIONS: This study shows all IOTA strategies had excellent diagnostic performance in comparison with RMI. The IOTA strategy chosen may be determined by clinical preference.

] KU Leuven Department of Development and Regeneration Herestraat 49 Box 7003 3000 Leuven Belgium [2] Department of Obstetrics and Gynaecology and Leuven Cancer Institute University Hospitals Leuven Herestraat 49 Box 7003 3000 Leuven Belgium

] KU Leuven Department of Development and Regeneration Herestraat 49 Box 7003 3000 Leuven Belgium [2] Department of Obstetrics and Gynaecology and Leuven Cancer Institute University Hospitals Leuven Herestraat 49 Box 7003 3000 Leuven Belgium [3] Department of Obstetrics and Gynaecology Queen Charlotte's and Chelsea Hospital Imperial College Du Cane Road London W12 0HS UK

] KU Leuven Department of Electrical Engineering Kasteelpark Arenberg 10 3001 Leuven Belgium [2] iMinds Future Health Department KU Leuven Kasteelpark Arenberg 10 3001 Leuven Belgium

1st Department of Gynecologic Oncology and Gynecology Medical University of Lublin ul Staszica 16 20 081 Lublin Poland

Department of Gynaecologic Oncology Catholic University of the Sacred Heart Largo Francesco Vito 8 Rome 00165 Italy

Department of Obstetrics and Gynaecology and Leuven Cancer Institute University Hospitals Leuven Herestraat 49 Box 7003 3000 Leuven Belgium

Department of Obstetrics and Gynaecology Azienda Ospedaliero Universitaria di Cagliari Strada Statale 554 Monserrato Cagliari 09045 Italy

Department of Obstetrics and Gynaecology Gynaecological Oncology Center Charles University Apolinarska 18 12000 Prague Czech Republic

Department of Obstetrics and Gynaecology Karolinska University Hospital Solna SE 17176 Stockholm Sweden

Department of Obstetrics and Gynaecology San Gerardo Hospital University of Milan Bicocca Via Pergolesi 33 20052 Monza Italy

Department of Obstetrics and Gynaecology Skåne University Hospital Malmö Lund University Södra Förstadsgatan 20502 Malmö Sweden

Department of Obstetrics and Gynaecology Ziekenhuis Oost Limburg Schiepse Bos 6 3600 Genk Belgium

Department of Obstetrics and Gynecology Clinical Sciences Institute L Sacco University of Milan Via G B Grassi 74 20157 Milan Italy

Gynaecology and Reproductive Medicine Unit S Orsola Malpighi Hospital University of Bologna Via Albertoni 15 Bologna 40138 Italy

KU Leuven Department of Development and Regeneration Herestraat 49 Box 7003 3000 Leuven Belgium

Preventive Gynaecology Unit Division of Gynaecology European Institute of Oncology Via Ripamonti 435 Milan 20141 Italy

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