NRG-CC008: A nonrandomized prospective clinical trial comparing the non-inferiority of salpingectomy to salpingo-oophorectomy to reduce the risk of ovarian cancer among BRCA1 carriers [SOROCk].
Authors: Huh Warner King , Pugh Stephanie L. , Walker Joan L. , Pennington Kathryn , Jewell Elizabeth Lin , Havrilesky Laura J , Carter Jeanne , Muller Carolyn , Drapkin Ronny , Lankes Heather A. , Demora Lyudmila , Kachnic Lisa A. 
Published: June 2022

TPS10615 Background: Studies of ovarian cancer screening in the general population have not demonstrated a reduction in ovarian cancer mortality. High-grade pelvic serous carcinomas (HGSCs) have traditionally been thought to originate from the ovarian surface epithelium. However, more recent data strongly suggests that most HGSCs originate from precursor lesions found in the distal fallopian tube. Serous tubal intra-epithelial carcinoma (STIC) lesions are found in association with HGSCs in 50-60% of cases and other early serous precursor lesions can be identified in an additional 25% of cases. The Society of Gynecologic Oncology has recently issued recommendations that salpingectomy can be considered at the completion of childbearing in indiviuals at increased genetic risk of ovarian cancer who do not agree to salpingo-oophorectomy. They also indicated that approximately 30% of BRCA1 mutation carriers choose not to remove their ovaries, and the mean age at RRSO for those who do is in the late 40s, much later than recommended age per guidelines. The purpose of this study is to compare risk-reducing approaches in high-risk women with deleterious germline BRCA1mutations; specifically, to demonstrate the non-inferiority of bilateral salpingectomy compared to bilateral salpingo-oophorectomy to reduce the incidence of ovarian cancer among deleterious germline BRCA1mutation carriers. Methods: This is a non-randomized prospective trial to determine if bilateral salpingectomy is non-inferior to bilateral salpingo-oophorectomy in terms ovarian, primary peritoneal, and fallopian tube cancer risk among gBRCA1m carriers between 35 and 50 years old. Individuals choose the treatment they want to receive in collaboration with their physician(s). The primary endpoint is the time to development of incident HGSC, specifically ovarian, primary peritoneal, or fallopian tube cancers. Secondary endpoints include measurement of health-related quality of life, estrogen deprivation symptoms, sexual function, menopausal symptoms, cancer distress, Medical Decision Making, and adverse events. Results: As of 1/31/2022, 116 individuals have been enrolled into this trial. A recent amendment was put forward to allow the following individuals to also participate in this trial: 1) Individuals who are receiving hormonal therapy for maintenance therapy (eg, tamoxifen, AIs, etc), 2) Individuals with a history of any prior cancer and have completed chemotherapy, at least 30 days ago, and 3) Individuals who are considering Assisted Reproductive Technologies (eg, IVF). Furthermore, there is ongoing consideration of allowing general Ob/Gyn providers to recruit patients to this trial and perform procedures, with proper pathology training and sign off at their hospitals. NCI grant UG1CA189867. Clinical trial information: NCT04251052.