Impact of multiparametric MRI on staging and management of patients with suspected or confirmed ovarian cancer Short title: MR in Ovarian Cancer (MROC study)

DESIGN: Prospective multicentre cohort diagnostic test accuracy study with internal pilot. Consenting women considered for surgery for suspected or proven ovarian cancer (OC) will have multiparametric MR (mpMR) & standard CT. Stage & management decisions will be recorded based on CT alone, CT/mpMR combined, and mpMR alone; mpMR may affect pathway if critical finding seen. SETTING: 10 UK gynae-oncology cancer centres TARGET POPULATION: Adult women with suspected OC (NICE guideline: Risk of Malignancy Index 1>250/ imaging) considered for surgery. Exclusion criteria: contraindication to MR; considered unfit for surgery HEALTH TECHNOLOGY INTERVENTION: mpMR as per Brief; chest to pelvis coverage: using small bowel suppression technique; T1&T2; diffusion-weighted imaging (DWI); dynamic contrast-enhanced (DCE) perfusion imaging; delayed peritoneal imaging COMPARATOR: CT (NICE standard of care) COST & OUTCOME MEASURES: All outcomes compare a) mpMR alone b) CT alone & c) mpMR with CT. Primary: Change in staging (as stipulated first in Brief):Difference in proportion of correct tumour stage. Reference: expert panel review of surgery, histology, cytology, all available imaging at 6 months. Secondary: 1) Change in patient management:Difference in proportion of women stratified correctly into i) surgery ii) no surgery. Management for each patient determined by two external blinded MDTs (as Brief). Reference:surgical/histology/imaging at 6 months. 2) Avoidance of unnecessary surgery: Proportion of correct imaging diagnosis of disease extent allowing successful surgery 3) Concordance (proportion of agreement) of imaging findings and MDT decisions for surgical resectability 4) Comparison of incremental cost & cost effectiveness accounting for categorisation into final surgical outcome, treatment costs and patient outcomes 5) Diagnostic accuracy of disease extent per patient and location 6) Substudy inter-rater agreement of MR 7) hospital stay, length of operation 8) prediction of which patients benefit from additional MR 9) comparison mpMR to conventional MR first 3 outcomes SAMPLE SIZE: 645 consenting women with suspected OC considered for surgery having mpMR and CT. 475 considered for primary surgery, 170 considered for delayed surgery. Primary outcome: Change in staging CT alone vs MR alone, 5% difference in correct staging (advanced vs non-advanced) based 96% MR vs CT 91%, (70% prevalence of OC), paired comparison proportions, 90% power, 5% significance, 10% LFU; Secondary: change in management CT alone vs MR alone. 6% increase in correct management (successful surgery); 78% CT vs 84% mpMR; expected reduction of women referred for unsuccessful surgery from 99 (CT) to 70 (MR) based on image results, 10% LFU. STATs HYPERLINK: in full plan. PROJECT TIMETABLE: 1) Develop protocol, CRF, database, ethics, contracting, mpMR QA (month 1-6) 2) Internal Pilot (month 7-12) assessing accrual in 3 centers; progression criteria: 30 patients/6 month 3) Recruitment (13-50) 24 patients/centre p.a. 4) Follow-up (month 51-56), complete MDTs, data retrieval, cleaning. 5) Analysis, write-up, dissemination, HTA monograph (month 57-60) TEAM: Multidisciplinary team expert in diagnostic test evaluation with academic/clinical radiologists, surgeons, medical oncologist, statistician, health economist, physicist, pathologist, patient rep.