A Bidirectional Cohort Study on Prophylactic Resection Surgery in Populations at Moderate-to-High Risk for Hereditary Ovarian Cancer

April 8, 2026 updated by: Peking University Third Hospital

The goal of this multi-center observational study is to learn about the effectiveness and safety of different prophylactic (preventive) surgical options in women at moderate-to-high genetic risk for hereditary ovarian cancer (HOC).

The main questions it aims to answer are:

Does individualized prophylactic surgery (such as removing fallopian tubes now and delaying ovary removal) effectively reduce the risk of developing ovarian cancer compared to standard care or close monitoring?

How do these different surgical interventions affect a woman's ovarian function and quality of life?

What Participants Will Do:

Participants who are healthy carriers of specific genetic mutations (such as BRCA1/2, RAD51C/D, etc.) will be followed in a bidirectional cohort. Depending on the medical care and surgical path they choose with their doctors (Standard RRSO, Delayed Oophorectomy, or Close Monitoring), researchers will collect their clinical data, surgical pathology results, and follow-up information regarding cancer incidence and quality of life for 3 years.

Study Overview

Status

Recruiting

Conditions

Detailed Description

  1. Study Rationale and Background Epithelial ovarian cancer (OC) remains a significant health burden in China, with high mortality due to the lack of effective early screening methods. Approximately 20% of OC cases are attributed to hereditary factors, primarily germline pathogenic variants in BRCA1/2 and other homologous recombination repair (HRR) genes.

    The traditional standard for risk reduction is Risk-Reducing Salpingo-Oophorectomy (RRSO). However, the "dualistic model" of ovarian carcinogenesis suggests that a significant proportion of high-grade serous carcinomas (HGSC) originate as Serous Tubal Intraepithelial Carcinoma (STIC) in the fallopian tubes. This provides a biological rationale for Prophylactic Salpingectomy with Delayed Oophorectomy (PSDO, also known as RS-DO). This study aims to establish a Chinese bidirectional cohort to evaluate the effectiveness, safety, and impact on quality of life (QoL) of individualized prophylactic surgical strategies.

  2. Study Design and Cohort Construction This is a bidirectional (combined retrospective and prospective) cohort study.

    Retrospective Component: Data will be extracted from clinical records dating back to 2020 for individuals who meet the high-risk genetic criteria and have previously undergone risk-reducing surgery or entered clinical monitoring.

    Prospective Component: Eligible participants will be recruited and followed for a minimum of 5 years. Participants are categorized into three cohorts based on the clinical intervention received:

    RRSO Group: Concomitant removal of fallopian tubes and ovaries.

    RS-DO Group: Initial salpingectomy followed or not followed by delayed oophorectomy (typically at age 45-50 or based on mutation type).

    Close Monitoring Group: For those declining surgery, intensive surveillance via transvaginal ultrasound and serum CA-125/HE4 testing.

  3. Quality Assurance and Registry Procedures

    To ensure the highest data integrity, the following procedures are implemented:

    Centralized Pathology Review: All surgical specimens from prophylactic procedures must undergo the SEE-FIM (Sectioning and Extensively Examining the FIMbria) protocol to detect occult STIC or early invasive carcinoma.

    Data Validation: An Electronic Data Capture (EDC) system is utilized with automated data checks for range, consistency, and logical errors.

    Source Data Verification (SDV): Regular on-site or remote audits will be conducted on 20% of the registry entries to verify accuracy against primary medical records and genetic testing reports.

    Data Dictionary: All variables are predefined in a comprehensive data dictionary. Genetic variants are classified according to the American College of Medical Genetics and Genomics (ACMG) guidelines. Clinical complications are graded using the Clavien-Dindo classification.

  4. Statistical Analysis Plan (SAP)

    Sample Size: Based on the estimated incidence of OC in the Chinese high-risk population, the study aims to enroll approximately 480 participants (160 per arm) to provide sufficient power (80%) for survival analysis.

    Primary Endpoint Analysis: The cumulative incidence of ovarian, fallopian tube, and peritoneal cancer will be estimated using the Kaplan-Meier method. Differences between intervention groups will be compared using the Log-rank test and Cox Proportional Hazards Models, adjusting for age, parity, and specific mutation types (e.g., BRCA1 vs. BRCA2 vs. RAD51C/D).

    Secondary Endpoint Analysis: Changes in menopausal symptoms and sexual function scores (GCS, SF-36, FSFI) will be analyzed using Repeated Measures ANOVA (RM-ANOVA) or ANCOVA to adjust for baseline differences and hormone replacement therapy (HRT) use.

    Missing Data: A multiple imputation approach will be used for missing covariates, while sensitivity analysis will be performed to assess the impact of loss to follow-up.

  5. Standard Operating Procedures (SOPs)

The registry operates under standardized protocols for:

Standardized pre-test and post-test genetic counseling.

Uniform surgical techniques for salpingectomy and oophorectomy.

Standardized follow-up intervals (every 6-12 months).

Adverse event reporting and management of unexpected pathological findings (STIC).

Study Type

Observational

Enrollment (Estimated)

480

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Associate Chief Physician/Associate Consultant, Doctor
  • Phone Number: 18610689868
  • Email: yuanli@bjmu.edu.cn

Study Locations

  • China
    • Beijing Municipality
      • Beijing, Beijing Municipality, China, 100191
        • Recruiting
        • Peking University Third Hospital
        • Contact:
          • Associate Chief Physician/Associate Consultant, Doctor
          • Phone Number: 18610689868
          • Email: yuanli@bjmu.edu.cn

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

This study targets Chinese women at moderate-to-high genetic risk for hereditary ovarian cancer (HOC). The population includes documented carriers of pathogenic or likely pathogenic (P/LP) germline mutations in high-risk susceptibility genes, primarily BRCA1 and BRCA2, as well as other HRR-related genes such as RAD51C, RAD51D, BRIP1, and PALB2. The population encompasses both premenopausal and postmenopausal women seeking individualized risk-management strategies.

Description

Inclusion Criteria:

  • Gender: Female. Age: 18 years or older at the time of enrollment.Genetic Risk: Documented carriers of pathogenic or likely pathogenic germline mutations in high-risk ovarian cancer susceptibility genes (including BRCA1, BRCA2, RAD51C, RAD51D, BRIP1, PALB2). Data Availability: Willing to provide informed consent and allow access to clinical records, genetic testing reports, and follow-up data (bidirectional cohort). Psychosocial Status: Ability to complete quality of life and psychological assessment scales (e.g., GCS, SF-36, FSFI).

Exclusion Criteria:

  • Prior Malignancy: History of ovarian, fallopian tube, or primary peritoneal cancer prior to the baseline intervention. Synchronous Malignancy: Diagnosis of any other advanced-stage malignancy. Inability to Follow-up: Significant psychological, social, or geographical factors that would prevent regular long-term follow-up (3 years). Previous Extensive Pelvic Surgery: History of extensive pelvic surgery that precludes the feasibility of laparoscopic prophylactic salpingectomy or oophorectomy.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Label 1: Standard RRSO Group. Label 2: Individualized RS-DO Group. Label 3: Close Monitoring Group
Description of Label 1: Participants undergoing concurrent bilateral salpingo-oophorectomy per guidelines. Description of Label 2: Participants undergoing salpingectomy with delayed oophorectomy to preserve hormones.Description of Label 3: Participants declining surgery and choosing regular ultrasound and CA-125 surveillance.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of Ovarian Cancer
Time Frame: From the date of enrollment/surgery up to 15 years.
The primary efficacy endpoint is the development of histologically confirmed epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer among high-risk mutation carriers in different intervention groups.
From the date of enrollment/surgery up to 15 years.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of Breast Cancer
Time Frame: From the date of enrollment up to 15 years.
Occurrence of new-onset breast cancer during the follow-up period, particularly for BRCA1/2 mutation carriers.
From the date of enrollment up to 15 years.
Incidence of Serous Tubal Intraepithelial Carcinoma (STIC)
Time Frame: At the time of prophylactic surgery (approx. 1 day)
Frequency of STIC or occult invasive carcinoma detected in the surgical specimens of the fallopian tubes, examined using the standardized SEE-FIM pathological protocol.
At the time of prophylactic surgery (approx. 1 day)
Comprehensive Assessment of Quality of Life and Menopausal Symptoms
Time Frame: Baseline, 1 month, 6 months and 1 year post-enrollment.
A multi-dimensional evaluation of the participants' physical and endocrine-related health status using Greene Climacteric Scale (GCS), SF-36 Health Survey and other scales.
Baseline, 1 month, 6 months and 1 year post-enrollment.
Evaluation of Psychological Distress
Time Frame: Baseline, 1 month, 6 months and 1 year post-enrollment.
An assessment of the psychosocial impact of prophylactic surgery and cancer-related anxiety using Cancer Worry Scale (CWS), Female Sexual Distress Scale (FSDS) and other scales.
Baseline, 1 month, 6 months and 1 year post-enrollment.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Peking University Third Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 30, 2025

Primary Completion (Estimated)

September 30, 2026

Study Completion (Estimated)

September 30, 2035

Study Registration Dates

First Submitted

April 8, 2026

First Submitted That Met QC Criteria

April 8, 2026

First Posted (Actual)

April 15, 2026

Study Record Updates

Last Update Posted (Actual)

April 15, 2026

Last Update Submitted That Met QC Criteria

April 8, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • M20250883

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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