Impact of Systematic Imaging for Follow up of Patients With Ovarian, Fallopian Tube or Primary Peritoneum Cancer

This is a randomized multi-center study. Randomization will be stratified on two major prognostic factors:

• The BRCA mutation (germline or somatic)
• the serous high or low grade histological subtype of histological se topical (defined according to morphological-well-differentiated criteria, low to moderate atypia, <3-4 mitoses/10 fields-and immunohistochemical-RO - strong p16/p53 low) At J0, after obtaining informed consent or within 7 days, patients will be randomized in one of the two arms (intervention group/standard group).

In the intervention arm, patients will perform a ca125 dosing ,/he4 dosage, a thoraco abdomino pelvic CT scan after contrast product injection and a full-body MRI (T2, DW and T1 sequences after fat saturation before and after gadolinium injection) with a maximum of 15 days between the two examinations, and will complete the HAD and EQ5D self-tests. A senior radiologist from each center will perform a prospective reading of each of the imaging. For any suspicious anomaly identified, the following criteria will be analyzed: Size, location, number, scalability, contrast taking after injection, MRI signal (T2, Diffusion, Dynamic Enhancement Curve). The RECIST criteria (version 1.1) will be applied.

In the standard arm, patients will perform a dosage of CA 125 (HE4 dosage), complete the HAD and EQ5D self-questionnaires, and the patient will be managed according to the INCa 2018 recommendations.

In the case of clinical abnormality (symptoms such as pain, transit changes, increased abdominal volume; or abnormality in clinical examination such as palpation of a mass, carcinosis nodule or suspicious adenopathy), marker elevation (CA125 >2N and/or 70 IU/L, HE4 > 140 pmol/L) and/or imaging (read by a senior at the center), the patient will be referred to the Multidisciplinary Consultation Meeting (PCR) for management according to the INCa 2018 recommendations.

In the case of a biopsy or surgery recommendation, it will be performed within a maximum of 2 months (according to the recommendations of good practice).

In common practice, the diagnosis of recurrence is often based on obvious imaging elements (RECIST criteria) without histological evidence. It is only in uncertain cases that a biopsy will be performed or a diagnostic surgery, so in this study it will be placed as in current practice without adding procedures that are not performed in common practice to start a new treatment.

In terms of the management of recidivism, this is the most complex element because it is difficult to homogenize all attitudes. Indeed, many studies are still underway to define the best ways to manage recurrences with contradictory results (such as DESKTOP III in favour of new complete secondary surgery and the study by Coleman et al published in the NEJM in 11/2019 which does not find this advantage). The purpose of this study is not to be not to define (or impose) optimal support (which has yet to be defined). In addition, this study is in real life and the modalities of care can change over the duration of the study.

We will therefore follow the main standard principles of the management of recidivism based on the characterization of platinosensitivity according to recurrence at less than 6 months, 6 to 12 months or more than 12 months of recidivism. Surgery will be considered if it is a localized recurrence, accessible for complete resection and less than 6 months delay compared to the last platinum chemotherapy (use of the AGO score).

Cost-utility analysis and AIB The economic assessment will be conducted in accordance with the recommendations of the HAS (updated) and the CHEERS collaboration, by measuring prospectively on the population study population the costs and outcomes at 24 months and extrapolating them over a lifetime.

We will carry out a cost utility study, based on the measurement of survival and quality of life from the EQ 5D. We will estimate a cost-utility incremental ratio and conduct a probabilistic sensitivity analysis to locate the systematic imaging surveillance strategy at cost-effectiveness.

For the economic assessment, we selected two perspectives, the collective perspective and the perspective of Medicare. The measurement of route efficiency will be based on an analysis of the different costs from a community perspective and an analysis of clinical effectiveness in real life and will be supplemented by a budgetary impact analysis from the perspective of Medicare. The time horizon for the main study ranges from inclusion to 2 years with secondary modelling over the whole life, with an annual discount of costs and benefits at 4% for the first 30 years, 1.5% then according to the latest recommendations of the HAS.

The data will be analyzed for all patients included in the study, based on the principle of the intention-to-treat analysis. We plan to perform sub-analyses based on BRCA (germinal or somatic) stratification and histological serous subtype.

The reference intervention is the usual management of patients with a dosage of CA 125 (OR/- dosage of HE4) and management according to the INCa 2018 recommendations according to the results. The procedure studied is also a dosage of CA125 (HE4 dosage), followed by a thoraco abdominopelvic CT scan after contrast product injection and a whole body MRI. Management will be decided on the basis of the results of the examinations