   Summary: Risk-reducing early removal of fallopian tubes followed by removal of ovaries at a later date was acceptable to women at high risk of ovarian cancer due to an inherited mutation in a recent study. This was especially true for women worried about sexual dysfunction associated with surgical menopause. (12/24/20) Relevance: This article is most relevant for Women at high risk of ovarian cancer who are considering undergoing risk-reducing surgery. Printer Friendly Page Read the article that we reviewed This article is relevant for: Women at high risk of ovarian cancer who are considering undergoing risk-reducing surgery. This article is also relevant for:Women under 45Women over 45People with a genetic mutation linked to cancer riskContents At a glance Strengths and limitations What does this mean for me? Questions for your doctor In-depth Clinical trials Questions for your doctor Resources and reference Relevance Rating Details STUDY AT A GLANCE This study is about: Understanding how women feel about surgery to lower the risk for ovarian cancer. Why is this study important? For women at high risk of ovarian cancer, surgery to remove the ovaries and fallopian tubes (risk-reducing salpingo-oophorectomy or RRSO) is the most effective way to prevent ovarian cancer. However, RRSO can have multiple side effects related to surgical menopause. There is growing evidence that many ovarian cancers start in the fallopian tubes. Because of this evidence and the side effects of RRSO, several large clinical trials are looking at a two-step risk-reducing approach: early salpingectomy (removal of the fallopian tubes).delayed oophorectomy (removal of the ovaries) in a separate surgery later. The two-step approach is known as “risk-reducing early salpingectomy followed by delayed oophorectomy (RRESDO). This study is the largest to date looking at patients’ attitudes and experiences with risk-reducing surgery. Study findings: This study was done in the United Kingdom between October 2017 and June 2019. A total of 683 women at high risk of ovarian cancer filled out a 39-item questionnaire. Participants filled out different parts of the questionnaire depending on whether or not they had undergone RRSO. It is important to note that patients in this study did not undergo RRESDO. Differences in side effects between RRSO and RRESDO were not measured. Patients were asked about their opinion of RRESDO and if they had previously undergone RRSO, how they felt about that procedure. Premenopausal women who did not previously have preventative surgery Among premenopausal women at high risk for ovarian cancer who had not yet had preventative surgery:About 55% (145 of 262) thought RRESDO was acceptable.About 70% (181 of 262) thought participating in a study looking at RRESDO was acceptable.Many factors affected acceptability of RRESDO among high-risk women. Those more likely to find RRESDO acceptable compared to RRSO were most concerned about: sexual dysfunctiondelaying hot flashes/night sweatsThose less likely to find RRESDO acceptable compared to RRSO were more concerned about: having two surgeries.not knowing how much RRESDO reduces ovarian cancer risk compared to RRSO.interval monitoring between surgeries.developing an interval ovarian cancer between surgeries.Premenopausal women who had RRSO Among premenopausal women who had RRSO:88% (143/161) were satisfied with having undergone RRSO.9% (15/160) regretted undergoing RRSO.11% (18/160) felt that it did them a lot of harm.Among women who had undergone premenopausal RRSO, 38% (61/159) said they would have considered RRESDO instead.Hormone replacement therapy (HRT) use among premenopausal women who did not have breast cancer and had RRSO was high (74%).HRT use did not affect their satisfaction/regret with RRSOHRT use did reduce vaginal dryness.Postmenopausal women who had RRSO Among postmenopausal women who had RRSO:95% (80/84) were satisfied.1% (1/81) regretted undergoing RRSO.This woman noted that experiencing night sweats, sleep disturbances, sexual dysfunction or urinary incontinence contributed to her regret.5% (4/80) felt it did them a lot of harm.This study shows that the idea of RRESDO is acceptable among high-risk women, particularly those who are concerned about sexual dysfunction. This study also shows higher acceptance than an earlier study that found about 35 percent acceptance of RRESDO. This earlier research was published by FORCE and researchers from MD Anderson Cancer Center (Holman et al., 2014). Greater acceptability of RRESDO may be due to the increased awareness among high-risk women that most ovarian cancer begins in the fallopian tubes. Strengths and Limitations: Strengths This is the largest study to date reporting on RRESDO acceptability and menopausal satisfaction or regret following RRSO. A strength of this study is that all participants were counseled in detail about preventive surgery for ovarian cancer. Limitations Limitations include that most participants in this study were white, had at least a university degree and a relatively high household income, and may not be representative of all patients. These results may differ for minority women or women who are less educated or affluent. Participants in this study did not undergo RRESDO, and differences in outcome were not measured. What does this mean for me? Most women considering RRSO are concerned that it will change their quality of life. RRESDO may be an alternative with less long-term impact on quality of life. Two studies measuring quality of life after these two different surgical approaches (Women Choosing Surgical Prevention or WISP and Early Salpingectomy (Tubectomy) With Delayed Oophorectomy in BRCA1/2 Gene Mutation Carriers or TUBA) will be published in the near future. However, it is a two-stage surgical procedure, and having two operations may also impact quality of life. While salpingectomy is available as a means of birth control (like tubal ligation), it is not standard of care for risk reduction in high-risk women. This is because it is unclear if or how much RRESDO lowers ovarian cancer risk or whether it decreases survival compared to RRSO. Ideally, women considering this surgery should consider enrolling in a clinical trial, where they will be followed closely. Share your thoughts on this XRAYS article by taking our brief survey. Expert Guidelines The National Comprehensive Cancer Network (NCCN) creates guidelines for the management of risk in women at high risk for ovarian cancer.The NCCN recommends risk-reducing salpingo-oophorectomy for women with BRCA1 and BRCA2 mutations. For women with BRCA1 mutations, the surgery is recommended between ages 35 and 40 and upon completion of childbearing. For women with BRCA2 mutations, delaying risk-reducing removal of ovaries and fallopian tubes until ages 40 to 45 is considered “reasonable.” The NCCN suggests that women with an MLH1, MSH2, MSH6, EPCAM (Lynch syndrome), BRIP1, RAD51C or RAD51D mutation consider undergoing risk-reducing surgery between the ages of 45 and 50. The NCCN states that not enough evidence exists to recommend risk-reducing surgery for all women with a PMS2 mutation.Women should discuss the benefits and risks of surgery with their doctors.  In their 2020 update, NCCN specifically commented that salpingectomy alone should not be considered standard of care for risk reduction.Questions for your doctor Is risk-reducing removal of the fallopian tubes followed by delayed removal of the ovaries (RRESDO) an option for me?What can I expect after RRSO?What can I expect after RRESDO?How do the benefits of RRESDO compare to the risks?How would two surgeries with RRESDO impact my quality of life compared to one surgery with RRSO?If I have RRESDO, what type of screening should I consider prior to the second surgery?Do I qualify for any research studies on ovarian cancer risk reduction?I am experiencing menopause effects from my RRSO. Can you refer me to a menopause expert?Open Clinical Trials NCT04251052: A Study to Compare Two Surgical Procedures in Women with BRCA1 Mutations to Assess Reduced Risk of Ovarian Cancer (SOROCk). This study is looking at whether removal of just the fallopian tubes can reduce the risk of ovarian cancer nearly as much as removing both the ovaries and fallopian tubes among women with an inherited BRCA1 mutation. The study will also exam various patient-reported quality of life outcomes.NCT03382574: Pilot Study of Denosumab in BRCA1 or BRCA2 Mutation Carriers Scheduling Risk-Reducing Salpingo-Oophorectomy. This study is looking at the effects of denosumab on ovarian cancer risk markers among premenopausal women with a BRCA1 or BRCA2 mutation, who are scheduled to undergo risk-reducing surgery to remove their ovaries and fallopian tubes. Denosumab is an FDA-approved injectable medication that is used to treat osteoporosis and to prevent fractures in cancer patients with bone metastases.IN-DEPTH REVIEW OF RESEARCH Study background For very high-risk women, risk-reducing salpingo-oophorectomy (RRSO) is the most effective method to reduce ovarian cancer risk. In women with an inherited BRCA or other high-risk ovarian cancer mutation, RRSO significantly reduces ovarian cancer risk. However, RRSO has disadvantages. In premenopausal women, it results in surgical menopause and infertility. Premature surgical menopause has known side effects, including increased risk of heart disease, osteoporosis, cognitive decline and sexual dysfunction. These side effects may be worse for women who are unable or chose not to use hormone replacement therapy. However, nonhormonal interventions may be available to mitigate some of these side effects With increasing evidence that most ovarian cancer begins in the fallopian tubes, a number of clinical trials are currently evaluating risk-reducing early salpingectomy (removal of the fallopian tubes) followed by delayed oophorectomy (removal of the ovaries)—RRESDO—in high-risk women. This two-stage alternative offers some level of risk reduction (the extent is currently unknown) and avoids the consequences of premature menopause. This study provides data from multiple centers in the United Kingdom on women at increased risk of ovarian cancer and the acceptability of RRESDO, the complications following RRSO and satisfaction/regret following RRSO. Researchers of this study wanted to know: How acceptable risk-reducing salpingectomy followed by delayed oophorectomy is among high-risk women. The researchers also looked at surgical menopause satisfaction and regret. Populations looked at in this study: Between October 2017 and June 2019 to total of 773 women at high risk for ovarian cancer were recruited from six clinics in the United Kingdom. Ninety people were excluded because they did not meet eligibility criteria. Study design: A total of 683 women completed a 39-item questionnaire. They were asked about social and economic demographics, surgical procedures, menstrual data, family health information and consequences of premature menopause that influenced their decisions to undergo, delay or decline RRSO. Participants filled out different parts of the questionnaire depending on whether they had undergone RRSO. Study findings: Between October 2017 and June 2019, 773 people completed the questionnaire. Of the remaining 683 participants:49% (337/683) had not undergone RRSO.51% (346/683) had undergone RRSO.Among premenopausal women at high risk for ovarian cancer who did not previously have preventative surgery: 55% (145 of 262) found RRESDO acceptable.20% (53/262) did not find RRESO acceptable.24% (64/262) were unsure if RRESDO was acceptable.When premenopausal women who had not undergone RRSO were asked if they would participate in a research study offering RRESDO: 70% (181/262) said they would consider taking part in a study that offered RRESDO.31% (81/262) said they probably would not participate in an RRESDO study.Premenopausal women concerned with sexual dysfunction were more likely to find RRESDO acceptable.When premenopausal women who already had RRSO were asked whether they would have considered RRESDO instead: 38% (61/159) would have considered RRESDO.62% (98/1590) would not have considered RRESDO.Premenopausal women who experienced sexual dysfunction following RRSO were more likely to find RRESDO acceptable.Among women who had undergone premenopausal RRSO: 89% (143/161) were satisfied with their decision.9% (15/160) of premenopausal and 1% (1/81) of postmenopausal women regretted their decision.These women experienced night sweats, sleep disturbances, sexual dysfunction and urinary incontinence, which led to them to regret their decision to undergo RRSO.Hormone replacement therapy (HRT) use among premenopausal women who did not have breast cancer and had RRSO was high (74%).HRT use did not affect their satisfaction/regret with RRSOHRT use did reduce vaginal dryness.When women who had undergone premenopausal RRSO were asked whether they would have considered undergoing RRESDO instead of RRSO had it been offered: 38% (61/159) said ‘probably/maybe’.62% (98/159) said ‘probably not/definitely’These women were more likely to have experienced hot flashes, osteoporosis or fatigue compared to women who ‘probably/maybe’ would have considered RRESDO.Strengths and Limitations: Strengths This is the largest study to date reporting on RRESDO acceptability and menopausal satisfaction or regret following RRSO. A strength of this study is that all participants were counseled in detail about preventive surgery for ovarian cancer. Limitations Limitations include that most participants in this study were white, had at least a university degree and a relatively high household income, and may not be representative of all patients. These results may differ for minority women or women who are less educated or affluent. Participants in this study did not undergo RRESDO, and differences in outcome were not measured. Context: RRSO has been shown to lower risk of ovarian cancer-related, breast cancer-related and overall mortality in high-risk women. In this study, concerns about sexual dysfunction were identified as significant factors associated with both acceptance of RRESDO and regret after RRSO. The findings of this study are not surprising given concerns high-risk women have about sexual dysfunction. New data from a prospective study supports the validity of these concerns due to the significant decline in sexual function experienced by women who had undergone RRSO. These findings should help direct additional research for high-risk women. While RRESDO and advances in reproductive technology and HRT benefit patients, they have resulted in an increasingly complex set of options for high-risk women. Conclusions: Most women find RRESDO acceptable, particularly if they are concerned about sexual dysfunction. However, it is important to note that the effect of RRESDO on ovarian cancer risk-reduction is unknown. Although most women are satisfied with RRSO, regret is higher for premenopausal women than for postmenopausal women. Some research has shown that these women experience a decrease in sexual functioning. These symptoms are improved by HRT, but not to pre-surgical levels. In this study, HRT following RRSO did not increase satisfaction but did decrease vaginal dryness. Share your thoughts on this XRAYS article by taking our brief survey. Rating Details: Relevance: Medium High This is the largest study on acceptability on RRESDO among premenopausal women at high risk of ovarian cancer.When the results of this study are combined with the upcoming results of similar studies (WISP and TUBA) it is likely that together they will guide clinical care and future research on ovarian cancer risk reduction in women at high risk of ovarian cancer due to an inherited mutation.Scientific Strength: Medium High To date, this is the largest study looking at the acceptability of RRESDO in women at high risk for ovarian cancer.This is a multicenter, cohort questionnaire study looking at acceptability of RRESDO in high-risk women.While the findings of this study may have been influenced by the expert counseling participants received, it also likely reflects the high-risk community’s increased awareness of the role of the fallopian tube in ovarian cancer.Research Timeline: Human Research Currently, in the US, completion of oophorectomy (removal of fallopian tubes and ovaries) is still recommended to reduce ovarian cancer risk in women at high risk. The results of this study as well as the upcoming results of the WISP and TUBA studies may result in a modification of US guidelines for ovarian cancer risk reduction in high risk women. |
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