Risk-Reducing Surgery for Ovarian Cancer

Recruiting at 12 trial locations

Overseen By Roni Wilke, MD

Age: 18+

Sex: Female

Trial Phase: Academic

Sponsor: M.D. Anderson Cancer Center

Disqualifiers: Postmenopausal, Ovarian cancer, Legally incapable, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: Varies based on individual treatment plan

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores different surgical options to reduce ovarian cancer risk in women with certain genetic mutations, such as BRCA1 or BRCA2. Participants will join one of three groups, each undergoing a different surgery: removal of the fallopian tubes (Risk-Reducing Salpingectomy), removal of the ovaries (Risk-Reducing Oophorectomy), or both (Risk-Reducing Salpingo-Oophorectomy). The trial aims to determine if delaying ovary removal while initially removing only the fallopian tubes is as effective as the standard procedure of removing both at once. Women who have not gone through menopause, have specific genetic profiles, and no longer need their fallopian tubes for natural childbearing might be suitable for this trial. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could shape future surgical standards for ovarian cancer prevention.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the treatments in this trial have varying levels of safety based on past studies.

For the Risk-Reducing Oophorectomy, research has examined its effectiveness in lowering ovarian cancer risk. This surgery, which involves removing the ovaries, is generally well-tolerated, though specific safety details are not highlighted in the available data.

The Risk-Reducing Salpingo-Oophorectomy (RRSO) has been extensively studied and is considered safe for many individuals. It can reduce ovarian cancer risk by up to 96% and significantly lowers the overall death rate. These studies suggest that the procedure is both effective and well-tolerated.

The Risk-Reducing Salpingectomy, involving the removal of the fallopian tubes, has been shown to reduce ovarian cancer risk by 42% to 65%. Past studies suggest it is a safe and acceptable option for many women.

Overall, these treatments have been studied for their ability to reduce cancer risk and are generally well-tolerated with a good safety record. For those considering joining the trial, these findings indicate that the treatments are generally safe. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these surgical approaches for reducing the risk of ovarian cancer due to their potential advantages over the current standard treatment, which typically involves the complete removal of both the ovaries and fallopian tubes. The Risk-Reducing Oophorectomy (RRO) focuses specifically on removing the fallopian tubes, which may lower cancer risk while potentially preserving hormonal function longer. The Risk-Reducing Salpingectomy (RRS) offers the option of removing only the fallopian tubes first, with possible delayed removal of the ovaries, which could offer a balance between cancer prevention and maintaining quality of life. The Risk-Reducing Salpingo-Oophorectomy (RRSO) remains a standard option, but by comparing these approaches, researchers aim to evaluate whether less invasive techniques can effectively reduce cancer risk while minimizing impacts on hormonal health and overall well-being.

What evidence suggests that this trial's treatments could be effective for reducing ovarian cancer risk?

Research has shown that a risk-reducing salpingo-oophorectomy (RRSO), one of the procedures studied in this trial, effectively prevents ovarian cancer. This surgery significantly lowers the risk of ovarian cancer and also reduces breast cancer risk in high-risk individuals. Studies indicate that RRSO can lead to a 68% decrease in overall death rates and a 94% decrease in ovarian cancer cases. Another procedure in this trial, the risk-reducing salpingectomy (RRS), has evidence suggesting it lowers the risk of high-grade serous carcinoma, a specific type of ovarian cancer, by 42-65%. These procedures offer promising options for reducing ovarian cancer risk. ^{1 4 6 7 8}

Who Is on the Research Team?

Roni Wilke, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for premenopausal women aged 25-50 with specific genetic mutations (BRCA1, BRCA2, BRIP1, RAD51C/D) who have completed childbearing and have at least one fallopian tube. It's not for those with a history of ovarian cancers or currently in cancer treatment.

Inclusion Criteria

I am within the age range specified for my specific genetic mutation.

Informed consent must be obtained and documented

I have at least one fallopian tube.

Exclusion Criteria

I am currently being treated for cancer.

I have had ovarian, fallopian tube, or peritoneal cancer.

I have had both of my fallopian tubes surgically removed.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo risk-reducing salpingectomy with delayed oophorectomy or risk-reducing salpingo-oophorectomy

Varies based on individual treatment plan

Follow-up

Participants are monitored for safety, ovarian cancer incidence, and other secondary outcomes

5-10 years

Exploratory Analysis

Estimate high grade serous (ovarian) cancer incidence for innovative and standard treatments in BRIP1, RAD51C, and RAD51D gene germline mutation carriers

What Are the Treatments Tested in This Trial?

Interventions

• Risk-Reducing Oophorectomy-RRO
• Risk-Reducing Salpingectomy (RRS)
• Risk-Reducing Salpingo-Oophorectomy-RRSO

Trial Overview The study compares two preventive surgeries for high-risk women: immediate removal of fallopian tubes and ovaries (RRSO) versus just the tubes first then ovaries later (RRS with delayed RRO). The goal is to see if delaying ovary removal affects cancer incidence.

How Is the Trial Designed?

Group I: Risk-Reducing Salpingo-Oophorectomy-RRSO Experimental Treatment 1 Intervention

Can help to lower the risk of ovarian cancer as well as the standard-of-care risk-reducing procedure involving the removal of the fallopian tubes and ovaries (risk-reducing salpingo-oophorectomy-RRSO)

Group II: Risk-Reducing Salpingectomy-RRS Experimental Treatment 1 Intervention

Can help to lower the risk of ovarian cancer with a delayed removal of 1.

Group III: Risk-Reducing Oophorectomy-RRO Experimental Treatment 1 Intervention

Can help to lower the risk of ovarian cancer removing both fallopian tubes.

Risk-Reducing Oophorectomy-RRO is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Risk-Reducing Oophorectomy for:

• Ovarian cancer prevention in high-risk individuals
• Breast cancer prevention in high-risk individuals

Approved in European Union as Risk-Reducing Oophorectomy for:

• Ovarian cancer prevention in high-risk individuals
• Breast cancer prevention in high-risk individuals

Approved in Canada as Risk-Reducing Oophorectomy for:

• Ovarian cancer prevention in high-risk individuals
• Breast cancer prevention in high-risk individuals

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Published Research Related to This Trial

Risk-reducing salpingo-oophorectomy (RRSO) significantly lowers the risk of breast cancer in women with BRCA1/2 mutations, with a hazard ratio of 0.49, indicating nearly a 51% reduction in risk.

RRSO also greatly reduces the risk of ovarian or fallopian tube cancer in BRCA1/2 mutation carriers, with a hazard ratio of 0.21, suggesting a 79% reduction in risk, making it a crucial option for cancer prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Meta-analysis of risk reduction estimates associated with risk-reducing salpingo-oophorectomy in BRCA1 or BRCA2 mutation carriers. Rebbeck, TR., Kauff, ND., Domchek, SM.[2022]

In a study of 580 BRCA1/2 mutation carriers, the uptake of risk-reducing salpingo-oophorectomy (RRSO) was extremely high, with 98.5% of BRCA1 and 97.5% of BRCA2 carriers opting for the surgery, often before the age of 40 or 45, respectively.

The high uptake of RRSO is likely due to effective counseling at the Family Cancer Clinic, highlighting the need for future research to address the long-term health impacts of premature surgical menopause, potentially through improved hormone replacement therapy or alternative strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Very high uptake of risk-reducing salpingo-oophorectomy in BRCA1/2 mutation carriers: A single-center experience. Harmsen, MG., Arts-de Jong, M., Horstik, K., et al.[2022]

In a study of 644 women undergoing risk-reducing salpingo-oophorectomy (RRSO), 2.6% were found to have occult neoplasms, with a higher occurrence in BRCA1 carriers, particularly those aged 45 and older, indicating a significant risk for this group.

The study highlights the importance of serial sectioning during RRSO to detect hidden cancers, as it revealed that 88.2% of the occult neoplasms were located in the fallopian tubes, emphasizing the need for thorough examination in high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pathologic findings and clinical outcomes in women undergoing risk-reducing surgery to prevent ovarian and fallopian tube carcinoma: A large prospective single institution experience. Rush, SK., Swisher, EM., Garcia, RL., et al.[2020]

Laparoendoscopic single-site (LESS) risk-reducing salpingo-oophorectomy (RRSO) is a safe and feasible procedure for BRCA carriers and high-risk women, with no surgical complications reported in a study of 58 patients.

The procedure has favorable outcomes, including a mean operative time of 38.1 minutes and minimal postoperative pain, making it suitable for patients undergoing active cancer treatment, as it allows for a quicker recovery and less disruption to ongoing therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-port risk-reducing salpingo-oophorectomy with and without hysterectomy: surgical outcomes and learning curve analysis. Escobar, PF., Starks, DC., Fader, AN., et al.[2010]

A study involving 60 high-risk women aged 30 to 50 revealed that concerns about surgical menopause and loss of fertility are significant barriers to undergoing risk-reducing bilateral salpingo-oophorectomy (RRBSO), despite the understanding that it reduces ovarian cancer risk.

Participants expressed a strong desire for more information on managing the short- and long-term effects of surgical menopause, highlighting an unmet need for support and education in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exploring factors that impact uptake of risk-reducing bilateral salpingo-oophorectomy (RRBSO) in high-risk women. Hickey, M., Rio, I., Trainer, A., et al.[2021]

Risk-reducing salpingo-oophorectomy (RRSO) is cost-effective for preventing ovarian cancer in premenopausal women with a lifetime risk of 4% or higher, providing a life expectancy gain of 42.7 days at an incremental cost-effectiveness ratio (ICER) of £19,536 per quality-adjusted life-year (QALY).

The analysis suggests that RRSO remains cost-effective even at higher risk thresholds (up to 8.2% without hormone replacement therapy), indicating that current guidelines should be reconsidered to allow more at-risk women access to this preventive surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Specifying the ovarian cancer risk threshold of 'premenopausal risk-reducing salpingo-oophorectomy' for ovarian cancer prevention: a cost-effectiveness analysis. Manchanda, R., Legood, R., Antoniou, AC., et al.[2022]

In a study of 57 premenopausal women at high risk for ovarian cancer, those who underwent risk-reducing bilateral salpingo-oophorectomy (RRSO) experienced a significant decline in perceived cognitive impairment within the first 6 months post-surgery, regardless of hormone therapy use.

While hormone therapy did not significantly impact cognitive scores, it was noted that sleep disruption was common after RRSO and was not alleviated by hormone therapy, indicating a need for further support in managing menopausal symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short-term impact of surgically induced menopause on cognitive function and wellbeing in women at high risk for ovarian cancer following risk-reducing bilateral salpingo-oophorectomy. Chang, H., Kamara, D., Bresee, C., et al.[2021]

A study of 301 Norwegian women who underwent risk-reducing salpingo-oophorectomy (RRSO) found that their quality of life (QoL) and fatigue levels were similar to those of age-matched women from the general population, indicating that RRSO does not negatively impact these aspects of life.

Women who had a cancer diagnosis prior to RRSO reported significantly lower QoL and higher fatigue compared to those without a cancer history, suggesting that the effects of prior cancer may overshadow the benefits of the surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fatigue and quality of life after risk-reducing salpingo-oophorectomy in women at increased risk for hereditary breast-ovarian cancer. Michelsen, TM., Dørum, A., Tropé, CG., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8932494/

Risk-Reducing Bilateral Salpingo-Oophorectomy for ... RRSO decreases the incidence of HGSC and improves mortality, with Cochrane reviews finding a 68% reduction in overall mortality and 94% reduction in OC- ...

2. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2839003

Estimands for Clinical Effectiveness of Risk-Reducing Early ... Risk-reducing salpingo-oophorectomy (RRSO) is the most effective option for preventing OC. RRSO substantially reduces OC risk, along-with all- ...

3. thelancet.com thelancet.com/journals/lanonc/article/PIIS1470-2045(25)00156-1/fulltext

Long-term health outcomes of bilateral salpingo ... BSO was associated with a reduced risk of all-cause mortality for both BRCA1 and BRCA2 pathogenic variant carriers (HR 0·52, 95% CI 0·41–0·64) ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1048891X24021765

Effectiveness of Risk-Reducing Salpingo-Oophorectomy in ... Risk-reducing salpingo-oophorectomy is highly effective in preventing ovarian, fallopian tube, and breast cancers in a high-risk French Canadian population.

5. med.upenn.edu med.upenn.edu/drapkinlab/assets/user-content/documents/pennington-etal-obstet-gynecolg-2025.pdf

Optimization of Timing for Risk-Reducing Salpingectomy ... For individuals with a significantly increased risk of ovarian cancer, risk- reducing bilateral salpingo-oophorectomy is highly effective, but uptake at the ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12441877/

Estimands for Clinical Effectiveness of Risk-Reducing Early ... Our sensitivity analysis also considered a 55% and 60% risk reduction for RRES. For RRSO vs no surgery, we assumed a 96% risk reduction, ...

7. bmjopen.bmj.com bmjopen.bmj.com/content/14/6/e082608

Risk-reducing salpingo-oophorectomy among diverse ... Over 95% (n=159) received the recommendation for age-appropriate rrBSO, and 52% (n=87) underwent rrBSO. Women who completed rrBSO were older in univariable ...

8. gavinpublishers.com gavinpublishers.com/article/view/risk-reducing-salpingo-oophorectomy-in-patients-at--high-risk-of-epithelial-ovarian-and-fallopian-tube-cancer-a-review-article

Risk-Reducing Salpingo-Oophorectomy in Patients at High ... Risk-reducing salpingo-oophorectomy has been linked to a reduction in epithelial ovarian cancer incidence (about 80%), as well as cancer- ...