Risks and Benefits of Surgical Preventive Strategies for Ovarian Cancer

Abstract

Ovarian cancer is the deadliest gynecologic cancer and the fifth leading cause of cancer deaths among U.S. women. Due to the lack of effective screening tests, preventive surgeries are a critical component of reducing the burden of ovarian cancer. Surgeries to prevent ovarian cancer are structured around the removal of the ovaries (bilateral oophorectomy) and fallopian tubes (bilateral salpingectomy). However, the long-term risks and benefits of preventive surgeries for ovarian cancer remain poorly understood. The objectives of this dissertation were (1) to examine the uptake of opportunistic salpingectomy (OS) and factors associated with an increased likelihood of OS, (2) to evaluate the prevalence and predictors of occult cancer at the time of OS and bilateral salpingo-oophorectomy (BSO), and (3) to examine the association between BSO and distribution of fat and lean body mass.

For the first study, we utilized inpatient and outpatient claims from 48 million privately insured women between 2010 and 2017. We found that OS for ovarian cancer prevention has rapidly diffused into clinical practice with the speed of adoption bolstered by the release of recommendations from national societies. In 2010, OS accounted for <1% of all sterilization encounters and benign hysterectomies compared to 20% of all sterilization encounters and benign hysterectomies in 2017. The largest increase in OS for sterilization rates occurred in women <45 years, while the largest increase in hysterectomy and OS rates occurred in women 45-55 years. OS rates increased in all U.S. geographic regions, in both rural and urban areas, across all types of health plans, and in women with and without a family history of breast or ovarian cancer.

For the second study, we utilized inpatient and outpatient claims from 538,471 privately insured women undergoing benign gynecologic surgery between 2010 and 2017. The age-adjusted prevalence of occult cancer was 0.053% (95% CI: 0.047-0.059) overall and 0.042% (95% CI: 0.014-0.048) after excluding women with a family history of and genetic susceptibility to breast or ovarian cancer. The prevalence was similar in women undergoing OS for sterilization and hysterectomy and BSO. Independent predictors of an occult cancer diagnosis at surgery included age, family history of and genetic susceptibility to breast or ovarian cancer, surgical indication, and pre-surgical comorbidities. No women with an occult cancer diagnosis developed peritoneal cancer after BSO. In women without an occult cancer diagnosis, 12 developed peritoneal cancer after BSO (age-adjusted incidence: 4.57 per 100,000 women).

For the last study, we used data from a population-based cross-sectional survey of 3,764 women with information on total and regional fat and lean body mass assessed using dual-energy x-ray absorptiometry (DXA) scans. We found that women with a history of BSO were more likely to have increased fat mass and decreased lean mass, particularly in the trunk and arms, compared to women without a history of BSO. The association between BSO and body composition was stronger in women who reported BSO <45 years and women with a normal body mass index at DXA scan.

Overall, the results of this dissertation provide some of the first evidence showing a significant nationwide increase in the performance of OS for ovarian cancer prevention. Given the low prevalence of occult ovarian cancer in average-risk women and uncertainties regarding the efficacy of OS, whether OS for ovarian cancer prevention should be offered to all average-risk women warrants further investigation. In addition, our findings identify a subset of women who may benefit from additional monitoring after BSO. Collectively the results enhance our understanding of the risks and benefits of new and established preventive surgeries for ovarian cancer.