Obstetrical & Gynecological Survey · Nov 5, 2026
Comment on “Patient-Centered Approach to Surgical Prevention of Ovarian Cancer: A Nonrandomized Clinical Trial”
By Van Le L
The only evidence-based intervention to decrease the incidence of ovarian cancer for individuals at high risk of ovarian cancer is risk-reducing salpingo-oophorectomy (RRSO). Guidelines recommend that this surgery be performed between the ages of 35 and 50 for high-risk individuals. Though some aspects of surgically induced menopause that result from RRSO can be mitigated with hormone replacement therapy (HRT), not all symptoms can be alleviated, and sexual function is a concern for many individuals . One potential solution to this is to perform an interval salpingectomy, then delayed oophorectomy (ISDO), which involves removing the fallopian tubes initially, then performing oophorectomy later, which is thought to reduce ovarian cancer risk since the origin of cancer is the tube, but maintains ovarian hormonal supply for a while longer. Recent studies have shown that there is strong interest and acceptability for this strategy in high-risk individuals in the United States and the Netherlands. This study was designed to compare sexual function, menopausal symptoms, and other outcomes in individuals at high risk for ovarian cancer undergoing ISDO or RRSO for cancer prevention. This was a prospective, multicenter, 2-group, nonrandomized clinical trial performed at 9 cancer centers in the United States between June 2016 and October 2020. Inclusion criteria were premenopausal or perimenopausal women aged 30 to 50 with a documented P/LP variant in BRCA1 , BRCA2 , MLH1 , MSH2 , MSH6 , PMS2 , EPCAM , BRIP1 , BARD1 , RAD51C , RAD51D , and PALB2 . Exclusion criteria were a history of ovarian, fallopian tube, or peritoneal cancer, current use of tamoxifen or aromatase inhibitors, or elevated cancer antigen or transvaginal ultrasonography findings suggesting cancer. Questionnaires were used to collect data at baseline, 6, 12, and 24 months after surgery. Sexual function was measured via the Female Sexual Function Index, and the primary outcome for the study was the change in sexual function from baseline to 6 months post-surgery. Sexual distress was assessed via the Female Sexual Distress Scale—Revised. RRSO patients were also divided into those who used HRT after surgery and those who did not. Menopausal symptoms were measured using the Menopausal Symptom Checklist (MSC), and secondary outcomes included decisional regret using the Decision Regret Scale, physical and mental quality of life using the Veterans RAND 12-Item Health Surveys, cancer worry as assessed by the Impact of Events Scale, and anxiety and depression as assessed by the Generalized Anxiety Disorder 7-Item and Patient Health Questionnaire-9 tools. Final analysis included 334 patients, with 165 in the RRSO group and 169 in the ISDO group, who completed the 6-month follow-up post-surgery. Mean age was lower in the ISDO group (37.5 vs. 40.9, P <0.001), and those undergoing ISDO were more likely to report a history of risk-reducing mastectomy and less likely to be married or living with a partner. A total of 77.8% of patients without a history of breast cancer in the RRSO group used HRT, and 24.0% of those with a history of breast cancer used HRT. Concurrent hysterectomy was more common in the RRSO group ( P <0.001). Īn all, 76.1% of patients in the RRSO group and 66.0% of patients in the ISDO group were sexually active at baseline, and significantly more patients in the RRSO group experienced clinically meaningful worsening of sexual function at 6 months post-surgery [odds ratio (OR): 2.0, 95% confidence interval (CI): 1.20-3.35, P =0.006]. This difference was also significant at 12 months (OR: 1.69, 95% CI: 1.09-2.63, P =0.01) but was nonsignificant at 24 months. However, when those undergoing RRSO who did not take HRT were excluded, there were no significant differences in clinically significant worsening of sexual function at any time point assessed. Concurrent hysterectomy was not a significant predictor of sexual function. MSC scores worsened significantly more in the RRSO group compared with the ISDO group at 6 and 12 months (mean change: 6.04, 95% CI: 3.90-8.17, P =0.03; mean change: 6.76, 95% CI: 4.63-8.90, P =0.02, respectively), but not at 24 months, with the most common symptoms being hot flashes and vaginal dryness. Similarly to the primary analysis, when the RRSO group was restricted to those using HRT, there were no significant differences in MSC. Physical quality of life was significantly worsened in the RRSO group compared with the ISDO group at 6 months, and this remained true after restricting to those using HRT (mean change: −3.79, 95% CI: −5.94 to 1.64, P <0.001; mean change ∼3.97, 95% CI: −6.64 to -1.29, P =0.003, respectively). No significant differences were shown in mental quality of life, sexual distress, or cancer worry. More patients in the RRSO group reported high decisional regret, but this difference was not significant when restricting to those using HRT. These results indicate that ISDO patients had better sexual function after surgery compared with RRSO, but that taking hormone replacement could improve symptoms. The next step in the comparison of these 2 techniques is a noninferiority study to determine the effectiveness of ISDO at reducing ovarian cancer risk. Future research should also focus on the validation of the safety and efficacy of ISDO as well as on other outcomes that are significant barriers to patient adoption of RRSO. (Summarized from Lu KH, Norquist BM, Chisholm GB, et al. Patient-centered approach to surgical prevention of ovarian cancer: a nonrandomized clinical trial. JAMA Netw Open . 2026;9(7):e2622026. doi:10.1001/jamanetworkopen.2026.22026).