Rapid Review Quiz: Ovarian Cancer Screening and Prevention
Risk-reducing salpingo-oophorectomy remains the cornerstone of prevention for high-risk patients, while oral contraceptives offer a risk-reducing effect in the general population. Additionally, genetic counseling has become an essential step in identifying at-risk individuals who may benefit from tailored interventions.
How much do you know about recent developments in ovarian cancer screening and prevention? Test your knowledge with this updated review.
Despite significant research efforts, no screening strategy has yet demonstrated a mortality benefit in average-risk female patients. As noted in the National Comprehensive Cancer Network (NCCN) guidelines, landmark clinical trials — including the PLCO (Prostate, Lung, Colorectal, and Ovarian) cancer screening trial — failed to show a survival benefit from annual CA-125 testing or transvaginal ultrasound alone or in combination. The risk of ovarian cancer algorithm (ROCA) — which evaluates CA-125 trends over time — did improve early-stage detection rates but did not ultimately reduce mortality. As a result, current guidelines from the United States Preventive Services Task Force and other expert bodies, including the NCCN, recommend against routine screening for ovarian cancer in asymptomatic, average-risk females. Instead, attention has shifted toward identifying and managing high-risk individuals through genetic counseling and risk-reducing strategies. Routine screening in the general population is considered ineffective and may result in harms from false-positive tests and unnecessary surgical interventions.
Learn more about the workup for ovarian cancer.
Risk-reducing salpingo-oophorectomy (RRSO) remains the most effective strategy for preventing ovarian and fallopian tube cancer in individuals with BRCA1 or BRCA2 mutations. Guidelines recommend RRSO typically between ages 35 and 45, depending on the specific mutation and family history. This surgery significantly lowers the risk of high-grade serous carcinoma, the most common and aggressive subtype. Studies have shown that RRSO can reduce ovarian cancer risk significantly also confer a survival benefit, particularly in BRCA1 carriers. While oral contraceptives also reduce risk, they do not offer the same degree of protection as surgical removal of at-risk tissue. Annual pelvic exams and imaging have not demonstrated efficacy in early detection or mortality reduction in this population. Patients considering RRSO should be counseled about surgical menopause and may require hormone therapy depending on age and symptom burden. The procedure is essential in the preventive care of high-risk individuals.
Learn more more about ovarian cancer deterrence and prevention.
Emerging evidence over the past decade suggests that the fallopian tube epithelium — not the ovary — is the origin of many high-grade serous ovarian carcinomas. As a result, the practice of opportunistic salpingectomy — removing the fallopian tubes during hysterectomy or tubal sterilization procedures — has gained traction as a preventive strategy, even in females at average risk. Major gynecologic societies now endorse this practice as a safe and effective risk-reducing option during pelvic surgery for benign indications. The rationale is grounded in the theory of serous tubal intraepithelial carcinoma as a precursor lesion to high-grade serous cancer. Unlike endometrial cancer, whose origin lies in the uterine lining, salpingectomy directly targets the tissue where most serous carcinomas are thought to begin.
Learn more about ovarian cancer and surgical considerations.
Current guidelines recommend genetic counseling and consideration of BRCA and multigene panel testing in females with a personal or strong family history of breast, ovarian, fallopian tube, or peritoneal cancer. Identifying carriers of pathogenic variants enables implementation of life-saving risk-reducing strategies, including salpingo-oophorectomy or enhanced surveillance. Importantly, such testing is also offered to individuals with male relatives who have had breast cancer, early-onset cancers, or known mutations in cancer susceptibility genes. Genetic testing should ideally be preceded by counseling to interpret results accurately and discuss implications for family members. Patients with unrelated gynecologic conditions like endometriosis or abnormal uterine bleeding, and those without relevant family history, are not routinely offered genetic testing unless other risk factors emerge. Early identification of mutation carriers is essential for tailored management, timely preventive interventions, and cascade testing of at-risk relatives.
Learn more about risk assessment and genetic counseling in ovarian cancer.
Multiple large observational studies and meta-analyses have consistently demonstrated a protective effect of combined oral contraceptives (COCs) against ovarian cancer. The reduction in risk is observed with long-term use, typically over 5 years, and persists for decades after discontinuation. The proposed mechanism involves suppression of ovulation, thereby reducing the repetitive trauma and repair cycles to the ovarian epithelium, which may underlie carcinogenesis. The protective effect spans multiple histologic subtypes, including high-grade serous, endometrioid, and clear cell carcinomas. While other agents such as NSAIDs have been evaluated, their protective role is less well established and not considered standard for chemoprevention. Aromatase inhibitors and bisphosphonates are not used for ovarian cancer prevention. As with any medication, the decision to use oral contraceptives must consider individual risk profiles, including thromboembolic and cardiovascular risks, and be guided by patient preferences and shared decision-making.
Learn more about ovarian cancer and the impact of oral contraceptives.
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Maurie Markman, MD Malignant ovarian neoplasms are a significant cause of cancer mortality in women.[1] Important risk factors include age, family history of breast or ovarian cancer (OC), personal history of breast cancer, endometriosis, and pelvic inflammatory disease.[2] Maurie Markman, MD, is president of medicine & science at City of Hope, and he talked to Medscape about the clinical implications of familial and genetic risk in OC. What is the importance of genetics in OC? We know a lot about OC genetics compared to when I started in this area. This is a fascinating part of medical history from over 50 years ago when nobody talked about OC. Patients would tell you that a family member — their mother, sister, or grandmother — had died of something that involved the stomach area. Historically, however, if you went back, there was no way of knowing if it was OC or gastric cancer because gastric cancer was extremely common. Additionally, there was nothing you could do about genetic risk at the time, nor much appreciation of how substantial this risk really is. The cumulative OC risk to age 80 years for women with BRCA1 is 36%-53% and 11%-25% for BRCA2 carriers.[3] What do we know about familial and genetic risk in OC? All patients diagnosed with OC should receive germline genetic testing. This is a decade-old recommendation from the National Comprehensive Cancer Network, American Society of Clinical Oncology,[4] Society of Gynecologic Oncology,[5] and European Society for Medical Oncology[6] and it still isn't done. This recommendation is based not only on the increased risk for OC in patients with genetic mutations, including BRCA1 , BRCA2 , MLH1 , MSH2 , or MSH6 (the Lynch syndrome genes), but also due to its implications to patient management and risk-reduction strategies. There is evidence showing that most eligible patients are not offered genetic testing, and the main factors associated with this noncompliance are older age, ethnicity, and insurance coverage.[7] This is a real problem. All healthcare providers, not just gynecologic oncologists, should be aware of the importance of germline genetic testing. Can you tell us more about the implications of genetic testing to patient management? The first implication is to the patient diagnosed with OC. BRCA1 and BRCA2 are tumor-suppressor genes involved in DNA repair, and their loss may cause cancer or change its course. BRCA1/BRCA2 mutation is recognized as a genetic marker for targeted therapy. There is overwhelming evidence that poly(ADP-ribose) polymerase (PARP) inhibitors have incredible impact on overall survival in OC as first-line, second-line, or later maintenance therapy in patients with platinum-sensitive relapsed tumors.[8,9] The impact on survival is enormous. This is not a treatment decision up for debate, and you won't know which patient will benefit from PARP inhibitors unless you carry out genetic testing. Beyond patient management, what is the impact of germline genetic testing? Germline testing helps determine a person's genetic predisposition to OC which is different from somatic testing of cancerous cells.[10] The impact extends to the patient's family and their support system. Family members, both male and female, could be at risk for genetic discrimination, including problems with life and health insurance, relationships, and even employment based on cancer risk. Genetic counselors are fundamental to guide patients and healthcare providers to understand the risks associated with pathogenic mutations and to decide on risk-reduction options. Today, genetic testing is strongly recommended because there are risk-reduction strategies that outweigh these negative risks I just mentioned.[4,5,6] When should genetic testing be offered to family members? Personal circumstances and preferences, such as family planning and reproductive options, should guide discussions about screening recommendations. Genetic testing is recommended to individuals with significant family history of OC and those from populations with high pathologic variant carrier frequencies, including Ashkenazi Jews, for example.[4,5,6] For asymptomatic women without a known high-risk hereditary cancer syndrome, the US Preventive Services Task Force recommends no screening for OC. What are the strategies for risk reduction? The most effective approach to prevent ovarian and fallopian tube cancers is risk-reducing bilateral salpingo-oophorectomy.[11] Typically, it is recommended to patients with pathologic variants in BRCA1/2, BRIP1, RAD51C, RAD51D , or MLH1, MSH2 , and MSH6 . Surgery can reduce the risk for gynecologic tumors by 80%-90% and decrease the all-cause mortality by 77%. The timing of surgery is also influenced by the patient's age, desire for pregnancy, family history, and the consequences of premature menopause. Can you tell us more about ongoing clinical trials about OC that could change clinical practice? I can mention two different approaches that could change clinical practice: bilateral salpingectomy for OC prevention and antibody-drug conjugates (ADCs) for the treatment of patients with poor survival prospects. Based on a theory that most OCs originate in the fimbriated end of the fallopian tube and then spread to the ovary, the hypothesis is that surgical resection of the fallopian tubes in women with increased risk may prevent the development of epithelial OC and avoid premature menopause.[12] We still need to know more about surgery eligibility and long-term survival outcomes. Very interesting. What are ADCs? ADCs are targeted therapies consisting of monoclonal antibodies capable of delivering cytotoxic drugs, the payload, directly to the tumor site while reducing systemic exposure and toxicity. Ideally, the payload should be released in the intracellular space.[13] Currently, there are many clinical trials trying to identify suitable targets and clinically effective therapies that could increase overall survivor in patients with OC.[14]
