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

Abstract: 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.

Lay abstract: Ovarian cancer causes more deaths in the UK than all other gynaecologic cancers combined. In >60% of patients, the cancer has already spread inside the abdomen by the time patients are diagnosed. The best treatment option at this time is surgical removal of all or most of the disease. Currently, a simple test called a CT scan (or Cat Scan) is used to identify where the disease is located and if surgery would be a suitable treatment option. However, CT cannot always separate diagnosis of benign (not cancer) from malignant (cancer) masses nor can it always reliably identify when it would be beneficial to operate, nor how far the cancer has spread. Because clinicians want to offer patients the chance of surgery when possible, women are given the benefit of any doubt if there is any uncertainty on the CT scan whether subsequent surgery will be successful; this means that 15–40% of patients are found to have inoperable disease at the time of surgery, gaining little benefit from surgery and chemotherapy is delayed. Additionally, in up to 30% of cases, suspected ovarian cancer turns out not to be cancer at all, and these women could have undergone less complex surgery or even avoided surgery and associated psychological distress if the CT scan was more accurate. It is possible that a different type of scan, called MR scan, may be more accurate than CT, especially a newer version “multi-parametric” MR (mpMR). Small studies suggest mpMR is better at discriminating ovarian cancer from non cancer (benign ovarian masses) and in seeing how much the disease has spread. This is important for planning the type of surgery and whether surgery will be successful in removing disease. Our study aims to determine whether women would benefit from having a pre-operative mpMR compared to CT scan recommended in NICE guidelines. We will approach women to have an extra mpMR scan if fit for surgery, aiming to recruit 645 women across 10 specialist NHS centres over 48 months. We will use MR methods and scanners that are available in the NHS. To prove that we can recruit women to the study, we will first pilot our research in 3 centres, progressing only if our minimum targets are met. We will determine how many women have important differences in disease stage and extent which would lead to different treatment planning if mpMR had been used instead of (or in combination with) standard CT. We have considered ethical issues arising if patients and their doctors are denied potentially important information from the mpMR scan done for research; this issue arose prominently in our patient consultation when planning our study. While mpMR is ’novel’ and unproven, and therefore the CT will determine the care for the patient primarily (as recommended by NICE), we will present the critical mpMR results to the doctors before surgery. We will give clear information when mpMR shows an important critical additional finding that could be used to benefit participants. We will undertake a cost-effectiveness analysis to understand the balance of cost to NHS & to patient benefit and will fund separately a psychological evaluation of women’s perceptions, expectations, and experience of the tests, as supported by our patient questionnaire. We have an excellent team, many having worked successfully together on other multi-center MRI studies (e.g.STREAMLINE, MAPPING). Senior support by HTA trialists, statistician and economist combines with world-class clinicians.

Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES;7.3 MANAGEMENT AND DECISION MAKING
Health categories: CANCER AND NEOPLASMS