Background: Ovarian cancer (OC) – most lethal gynecologic malignancy - is rare among women with adnexal mass. Preventive adnexal surgery is a common practice, despite pathology confirming malignancy in only 10-15% of these cases. This motivates a surveillance-based clinical management paradigm to prognosticate the risk for malignancy and channel appropriately for surgery. We recently developed a multivariate index assay -MIA3G[1] - to assess risk for OC in women with adnexal mass. In a multi-center prospective surveillance trial, we assessed the concordance between preventive surgery and clinical management using MIA3G. Methods: MIA3G risk prediction uses a DNN algorithm which models 7 serum biomarkers (CA125, HE4, BM2, APO, FSH, TFR, PreAlbumin), age and menopausal status. With NPV of 99.7% (CI:99.2–99.9) it risk stratifies patients into low probability of malignancy or indeterminate. Across 11 centers, the MIA3G cohort comprised of 546 women (IQR:41-61yo) with symptomatic or asymptomatic masses and/or presence of HBOC variants. Serial blood draws were timed with clinic-visits and the ultimate one coincident with surgery. The objectives were: 1) prognosticate the MIA3G based preventive surgery pool and 2) establish concordance between the MIA3G probabilistic risk and the pathology-based outcome of malignancy versus benign. Results: In the study cohort of 546 patients, 20.3% (111) underwent preventive surgery. Conservatively, at a 12.8% FPR[1], MIA3G would have stratified approximately 70 patients, a projection of 37% less for surgery. Partitioning by clinical characteristic: (i) symptomatic: In comparison to 27.8% (73/263) of patients referred to surgery, MIA3G projections would have resulted in a 54.8%(33/263) reduction. (ii) asymptomatic: 22.5%(31/138) of patients were referred to surgery; MIA3G projections would have resulted in a 45.2% (17/138) reduction. In the 111 preventive surgeries, pathology confirmed a malignancy rate of 6.3% (7/111). The overall concordance of MIA3G with pathology was 84.68% (94/111) which increased to 91.98% (102/111) in the pre-menopausal (PRE) sub-cohort. The malignant discordancy (MIA3G:FN), all in PRE, comprised of early-stage epithelial: endometreoid, Leiomysarcoma and Sertoli-Leydig cell where the masses were characterized as cystic benign/indeterminate by ultrasound. These findings underscore the power of MIA3G when preventive surgery is considered for patients with ovarian cancer risk. Conclusions: The multivariate index assay MIA3G reduces numbers of preventative surgery for ovarian cancer risk. The high concordance establishes that MIA3G non-invasive surveillance-based clinical management can be effective for the risk assessment of ovarian cancer in patients presented with adnexal mass. Surgical management should be reserved for high probability of malignancy. [1]: DOI 10.3389/fmed.2023.1102437.