Surgical Procedures for Reducing Ovarian Cancer Risk

(SOROCk Trial)

Recruiting at 459 trial locations

Age: 18 - 65

Sex: Female

Trial Phase: Academic

Sponsor: NRG Oncology

Must not be taking: Cytotoxic chemotherapy

Disqualifiers: Prior ovarian cancer, Abnormal CA-125, others

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

Compensation: Varies

Number of Visits: 11

Duration: Immediate (surgical procedure)

2262 Participants Needed

Trial Summary

What is the purpose of this trial?

This clinical trial evaluates how well two surgical procedures (bilateral salpingectomy and bilateral salpingo-oophorectomy) work in reducing the risk of ovarian cancer for individuals with BRCA1 mutations. Bilateral salpingectomy involves the surgical removal of fallopian tubes, and bilateral salpingo-oophorectomy involves the surgical removal of both the fallopian tubes and ovaries. This study may help doctors determine if the two surgical procedures are nearly the same for ovarian cancer risk reduction for women with BRCA1 mutations.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are on cytotoxic chemotherapy, you must not have received it within the past 30 days to be eligible.

What data supports the effectiveness of the treatment Bilateral Salpingectomy and related procedures for reducing ovarian cancer risk?

Risk-reducing bilateral salpingo-oophorectomy (RRSO) has been shown to reduce ovarian cancer deaths in high-risk women, particularly those with BRCA1/2 mutations. However, the effectiveness of bilateral salpingectomy alone in reducing ovarian cancer risk remains unclear, though it is being studied for its safety and acceptability. ^{1 2 3 4 5}

Is the surgical procedure for reducing ovarian cancer risk safe?

Studies suggest that procedures like bilateral salpingectomy and salpingo-oophorectomy are generally safe, but they can lead to early menopause and hormone deficiency, which have their own risks. Some women may also develop a rare cancer called primary peritoneal carcinomatosis after the surgery. ^{1 2 3 6 7}

How does the treatment Bilateral Salpingectomy with Oophorectomy differ from other treatments for reducing ovarian cancer risk?

Bilateral Salpingectomy with Oophorectomy is unique because it involves the removal of both fallopian tubes and sometimes the ovaries to reduce ovarian cancer risk, especially in women with genetic predispositions. This approach is different from other treatments as it is often performed opportunistically during other surgeries like hysterectomy or sterilization, and it aims to prevent cancer by removing tissues where cancer often starts. ^{1 5 6 8 9}

Research Team

Kathryn P Pennington

Principal Investigator

NRG Oncology

Eligibility Criteria

This trial is for women aged 35-50 with a BRCA1 mutation, who are considering or have deferred risk-reducing surgery of the fallopian tubes and ovaries. They must be medically fit for surgery, not currently have ovarian cancer, and understand they can't naturally conceive post-surgery.

Inclusion Criteria

I have chosen not to undergo or to delay surgery to remove my ovaries and fallopian tubes despite being at high risk due to BRCA1 mutation.

The patient or a legally authorized representative must provide study-specific informed consent prior to study entry

I am between 35 and 50 years old.

Exclusion Criteria

I've had abnormal pelvic screening results in the last 6 months.

I am not healthy enough for my planned surgery.

An abnormal CA-125 is defined as a level > 50 U/ml in premenopausal individuals if they are not current users of oral contraceptives; an abnormal CA-125 is defined as a level > 40 U/ml for premenopausal individuals who are current users of oral contraceptives. An abnormal CA-125 is defined as a level > 35 U/ml in postmenopausal individuals.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

Pelvic or transvaginal ultrasound and blood sample collection

Treatment

Participants undergo either bilateral salpingectomy or bilateral salpingo-oophorectomy

Immediate (surgical procedure)

1 visit (in-person for surgery)

Follow-up

Participants are monitored for safety, effectiveness, and quality of life post-surgery

Up to 24 months

Follow-up visits at 10-60 days, 6, 12, and 24 months

Long-term follow-up

Annual monitoring for adverse events and cancer development

Up to 20 years

Treatment Details

Interventions

• Bilateral Salpingectomy
• Bilateral Salpingectomy with Oophorectomy

Trial Overview The study compares two surgeries to lower ovarian cancer risk in women with BRCA1 mutations: removal of both fallopian tubes (bilateral salpingectomy) and removal of both tubes and ovaries (salpingo-oophorectomy). It includes quality-of-life assessments and regular ultrasounds.

Participant Groups

Group I: Group I (bilateral salpingectomy) Experimental Treatment 6 Interventions

Patients undergo bilateral salpingectomy. Patients may then undergo oophorectomy after initial surgery. Patients also undergo a pelvic or transvaginal ultrasound during screening and blood sample collection throughout the trial.

Group II: Group II (bilateral salpingo-oophorectomy) Active Control 6 Interventions

Patients undergo bilateral salpingo-oophorectomy. Patients also undergo a pelvic or transvaginal ultrasound during screening and blood sample collection throughout the trial.

Bilateral Salpingectomy is already approved in Canada, United States, European Union for the following indications:

Approved in Canada as Opportunistic Salpingectomy for:

• Prevention of ovarian cancer
• Specifically high-grade serous carcinoma (HGSC)

Approved in United States as Bilateral Salpingectomy for:

• Prevention of ovarian cancer
• Specifically high-grade serous carcinoma (HGSC)

Approved in European Union as Salpingectomy for:

• Prevention of ovarian cancer
• Specifically high-grade serous carcinoma (HGSC)

Who Is Running the Clinical Trial?

NRG Oncology

Lead Sponsor

Trials

242

Recruited

105,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

Bilateral salpingo-oophorectomy significantly reduces the incidence of ovarian cancer by 0.38% over 20 years in women undergoing benign hysterectomy, with a hazard ratio of 0.23, indicating a strong protective effect against developing the disease.

In postmenopausal women (≥50 years), the absolute risk reduction increases to 0.62%, suggesting that this procedure may be particularly beneficial for older women at the time of hysterectomy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ovarian cancer incidence and death in average-risk women undergoing bilateral salpingo-oophorectomy at benign hysterectomy. Cusimano, MC., Ferguson, SE., Moineddin, R., et al.[2022]

In a pilot study involving 43 pre-menopausal BRCA1/2 mutation carriers, those who underwent bilateral salpingectomy with delayed oophorectomy (BS/DO) experienced no surgical complications and reported high satisfaction with their choice of procedure.

Patients who chose BS/DO showed significant reductions in cancer worry and anxiety levels 12 months post-surgery, indicating that this approach may be a psychologically beneficial alternative to immediate risk-reducing salpingo-oophorectomy (RRSO).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bilateral salpingectomy with delayed oophorectomy for ovarian cancer risk reduction: A pilot study in women with BRCA1/2 mutations. Nebgen, DR., Hurteau, J., Holman, LL., et al.[2022]

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]

Opportunistic bilateral salpingectomy (OBS) during vaginal hysterectomy (VH) has a high success rate of 86.8%, regardless of the presence of relative contraindications (RCs) to the vaginal approach, indicating its feasibility as a concurrent procedure.

Factors such as lack of prolapse, obesity, and previous cesarean sections significantly increase the odds of unsuccessful salpingectomy, particularly in patients with multiple RCs, who should be informed about the higher likelihood of failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility and Outcomes of Opportunistic Bilateral Salpingectomy in Patients with Traditional Relative Contraindications to Vaginal Hysterectomy. Chichura, AM., Yao, M., Bretschneider, CE., et al.[2021]

Gynecologic oncologists showed significantly higher adherence to the recommended surgical guidelines for risk-reducing bilateral salpingo-oophorectomy, with 72% performing all 5 steps compared to only 5% of general gynecologists.

Despite the higher surgical compliance among gynecologic oncologists, all cases of occult malignancy (2.70%) were diagnosed in surgeries performed by general gynecologists, highlighting the importance of specialized training in detecting hidden cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adherence to risk-reducing salpingo-oophorectomy guidelines among gynecologic oncologists compared to general gynecologists. Blustein, P., Werner, SR., Uppalapati, P., et al.[2023]

Prophylactic bilateral salpingectomy during laparoscopic hysterectomy does not negatively impact ovarian reserve in premenopausal women, as measured by hormone levels and follicle counts before and after surgery.

This surgical approach may help reduce the risk of ovarian cancer without compromising ovarian function, as no significant differences were found in ovarian reserve markers between women who had the salpingectomy and those who did not.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of prophylactic bilateral salpingectomy on ovarian reserve in patients who underwent laparoscopic hysterectomy. Wang, S., Gu, J.[2023]

In a study of 4128 women who underwent prophylactic bilateral salpingo-oophorectomy (BSO) for non-cancer reasons, only 1 case of primary peritoneal carcinomatosis (PPC) was reported, indicating a low incidence of this cancer type following BSO.

The study also found that BSO is associated with a statistically significant reduction in breast cancer rates among average-risk women, with a Standardized Incidence Ratio (SIR) of 0.71, suggesting that BSO may provide protective benefits against breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Malignancies following bilateral salpingo-oophorectomy (BSO). Gotlieb, WH., Barchana, M., Ben-Baruch, G., et al.[2007]

Bilateral salpingectomy significantly reduces the risk of ovarian cancer compared to traditional sterilization methods, based on a review of 4 high-quality studies.

The procedure does not appear to have a significant long-term impact on ovarian reserve and offers additional benefits like improved contraceptive efficacy, but it also carries risks such as increased surgical time and potential complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risks and Benefits of Salpingectomy at the Time of Sterilization. Castellano, T., Zerden, M., Marsh, L., et al.[2022]

A survey of 225 Obstetrics and Gynecology specialists in Portugal revealed that laparoscopic tubal electrocoagulation is the most common sterilization method, while opportunistic salpingectomy is considered the best option for women seeking permanent contraception, despite being less frequently performed.

Salpingectomy during cesarean sections is seen as a feasible and safe procedure, with 69% of specialists advocating for it as the preferred method, highlighting the need for discussions about its benefits and risks with patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Opportunistic Salpingectomy for Permanent Contraception: A Cross Sectional Study in Portugal]. São Pedro, V., Pires, R., Santos, F., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Ovarian cancer incidence and death in average-risk women undergoing bilateral salpingo-oophorectomy at benign hysterectomy. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Bilateral salpingectomy with delayed oophorectomy for ovarian cancer risk reduction: A pilot study in women with BRCA1/2 mutations. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Exploring factors that impact uptake of risk-reducing bilateral salpingo-oophorectomy (RRBSO) in high-risk women. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Feasibility and Outcomes of Opportunistic Bilateral Salpingectomy in Patients with Traditional Relative Contraindications to Vaginal Hysterectomy. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Adherence to risk-reducing salpingo-oophorectomy guidelines among gynecologic oncologists compared to general gynecologists. [2023]

6. England pubmed.ncbi.nlm.nih.gov

The effect of prophylactic bilateral salpingectomy on ovarian reserve in patients who underwent laparoscopic hysterectomy. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Malignancies following bilateral salpingo-oophorectomy (BSO). [2007]

8. United States pubmed.ncbi.nlm.nih.gov

Risks and Benefits of Salpingectomy at the Time of Sterilization. [2022]

9. Portugal pubmed.ncbi.nlm.nih.gov

[Opportunistic Salpingectomy for Permanent Contraception: A Cross Sectional Study in Portugal]. [2021]