Average Risk Of Ovarian Cancer Research Articles

Incidental Serous Tubal Intraepithelial Carcinoma Finding in a Nepalese Patient Undergoing Opportunistic Salpingectomy and the Discovery of a BRCA1 Pathogenic Variant

BACKGROUND: Serous tubal intraepithelial carcinoma lesions are the precursor to high-grade serous ovarian carcinomas, which have the highest mortality rate among gynecologic malignancies. In women diagnosed with high-grade serous ovarian carcinoma, 20% of the carcinomas are found to be secondary to hereditary causes, with the majority being associated with germline pathogenic variants in BRCA1 and BRCA2 genes. Patients with a pathogenic variant are at high risk for developing high-grade serous ovarian carcinoma, so it is recommended that they undergo risk-reducing salpingo-oophorectomy in their 30s–40s. Opportunistic salpingectomy is the only ovarian cancer prevention method available for patients at average risk. Although serous tubal intraepithelial carcinoma lesions are rare in women at average risk, studies quote incidental serous tubal intraepithelial carcinoma lesion findings in 1–7% of patients undergoing opportunistic salpingectomy. CASE: A 38-year-old woman, gravida 2 para 2, of Nepalese ethnicity had an incidental finding of a serous tubal intraepithelial carcinoma lesion at the time of opportunistic salpingectomy for permanent sterilization at cesarean delivery. The serous tubal intraepithelial carcinoma lesion was found with representative sampling of the fallopian tubes because the patient was considered to be at average risk for ovarian cancer. This method is much less sensitive than the Sectioning and Extensively Examining the Fimbriated End (SEE-FIM) protocol, which is used with women known to be at high risk. This ultimately led to discovery of a BRCA1 mutation in the patient. CONCLUSION: The SEE-FIM protocol is used to identify serous tubal intraepithelial carcinoma lesions, but it is not routinely used on fallopian tubes of patients at average risk. Using the SEE-FIM protocol would lead to fewer missed serous tubal intraepithelial carcinoma lesions, but it is unclear how much extra cost and effort would be required to implement this protocol. There are knowledge gaps when it comes to understudied populations and hereditary breast and ovarian cancer gene prevalence. Studies show that current BRCA prediction models underestimate hereditary breast and ovarian cancer gene prevalence in Asian populations. Diagnosing serous tubal intraepithelial carcinoma lesions in understudied populations could lead to the discovery of a hereditary breast and ovarian cancer pathogenic variant that the patient may not have discovered until after a cancer diagnosis. Identification of a serous tubal intraepithelial carcinoma in a patient at average risk should lead to a referral for genetic counseling and screening.

Association of Premenopausal Bilateral Oophorectomy With Parkinsonism and Parkinson Disease

The association of premenopausal bilateral oophorectomy with parkinsonism and Parkinson disease (PD) remains controversial. To assess whether women who underwent premenopausal bilateral oophorectomy were at increased risk of parkinsonism and PD and whether the associations varied by age at oophorectomy and by receipt of estrogen replacement therapy. This cohort study used data from a combination of 2 independent cohort studies, the Mayo Clinic Cohort Study of Oophorectomy and Aging 1 and 2, which were based on the Rochester Epidemiology Project medical records-linkage system. A population-based sample of 5499 women from Olmsted County, Minnesota, were included; of those, 2750 women underwent bilateral oophorectomy for a benign indication before spontaneous menopause between January 1, 1950, and December 31, 2007 (oophorectomy cohort), and 2749 age-matched women who did not undergo bilateral oophorectomy were randomly sampled from the general population (reference cohort). Data were analyzed from March 1 to April 30, 2022. The date of oophorectomy was considered the index date for both groups. Medical record documentation of bilateral oophorectomy abstracted from a medical records-linkage system (Rochester Epidemiology Project). Incidence and risk of parkinsonism or PD, with diagnoses confirmed by in-person examination or medical record review. Among 5499 participants (median [IQR] age, 45.0 [40.0-48.0] years; 5312 [96.6%] White), 2750 women (2679 White [97.4%]) underwent bilateral oophorectomy at a median age of 45.0 years (IQR, 40.0-48.0 years), and 2749 women (2633 White [95.8%]) with a median age of 45.0 years (IQR, 40.0-48.0 years) at the index date were included in the reference cohort. Bilateral oophorectomy was associated with an increased risk of parkinsonism overall (hazard ratio [HR], 1.59; 95% CI, 1.02-2.46) and in women younger than 43 years at oophorectomy (HR, 7.67; 95% CI, 1.77-33.27). There was a pattern of increasing risk with younger age at the time of oophorectomy using 4 age strata (≥50 years: HR, 1.43 [95% CI, 0.50-4.15]; 46-49 years: HR, 1.55 [95% CI, 0.79-3.07]; 40-45 years: HR, 1.36 [95% CI, 0.64-2.89]; <40 years: HR, 8.82 [95% CI, 1.08-72.00]; P = .02 for trend). The number needed to harm was 53 women overall and 27 women younger than 43 years at the time of oophorectomy. Bilateral oophorectomy was also associated with an increased risk of PD in women younger than 43 years at oophorectomy (HR, 5.00; 95% CI, 1.10-22.70), with a number needed to harm of 48 women. Among women who underwent oophorectomy at 45 years and younger, the risk was lower in women who received estrogen after the procedure and through age 50 years compared with women who did not. For parkinsonism, the HRs were 1.72 (95% CI, 0.54-5.53) vs 2.05 (95% CI, 0.80-5.23); for PD, the HRs were 1.53 (95% CI, 0.29-8.23) vs 2.75 (95% CI, 0.84-9.04). However, the differences were not significant. In this study, premenopausal women who underwent bilateral oophorectomy before age 43 years had an increased risk of parkinsonism and PD compared with women who did not undergo bilateral oophorectomy. These findings suggest that a reduction in the practice of prophylactic bilateral oophorectomy in premenopausal women at average risk of ovarian cancer may have substantial benefit for reducing the risk of parkinsonism and PD.

Ovarian Function in Patients Who Underwent Opportunistic Bilateral Salpingectomy during Hysterectomy

Objective(s): To provide additional data and to inform all women at average risk of ovarina cancer, undergoing a benign gynecological laparoscopic procedure about the Pro’s and the Con’s of opportunistic bilateral salpingectomy (OBS). Mechanism: Risk reducing salpingo-oophorectomy to prevent epithelial ovarian cancer (EOC) is associated with decreased quality of life and increased overall mortality. OBS has emerged as a primary prevention of ovarian cancer through a paradigm shift in which fallopian tubes are often the cause of ovarian cancer rather than the ovaries themselves. Findings in Brief: Causal relationship of salpingectomy and reduced risk of ovarian cancer has not been proven yet. There are several population-based studies that showed bilateral salpingectomy reduced risk of EOC by 42–67%, but there also is a study that suggest increased risk of ovarian cancer after salpingectomy. As for risk of surgical complications, several cohort studies have demonstrated that there was no increase in rates of hospital readmission, blood transfusion, day of hospital stay. However, recent meta-analysis stated that there were insufficient data to assess any difference in both intraoperative and postoperative complication rates. The procedure of salpingectomy can disrupt blood supply to the ovary. Data of reproductive outcome after assisted reproductive technologies such as in vitro fertilization and embryo transfer (IVF-ET) are conflicting. Some studies suggest that salpingectomy did not compromise the outcome of IVF-ET, but other studies found that salpingectomy may lead to decreased ovarian reserve after salpingectomy. For patients who do not wish fertility, data on the effect of OBS during hysterectomy suggest that changes in serum ovarian reserve markers were not different between OBS group and control group. Conclusions: Bilateral salpingectomy should be considered at the time of abdominal or pelvic for women at average risk of ovarian cancer. However, physicians should discuss the protective benefit of bilateral salpingectomy against ovarian cancer and controversial data on ovarian reserve.

Ovarian Cancer Detection in Average-Risk Women: Classic- versus Nonclassic-appearing Adnexal Lesions at US.

Background Several US risk stratification schemas for assessing adnexal lesions exist. These multiple-subcategory systems may be more multifaceted than necessary for isolated adnexal lesions in average-risk women. Purpose To explore whether a US-based classification scheme of classic versus nonclassic appearance can be used to help appropriately triage women at average risk of ovarian cancer without compromising diagnostic performance. Materials and Methods This retrospective multicenter study included isolated ovarian lesions identified at pelvic US performed between January 2011 and June 2014, reviewed between September 2019 and September 2020. Lesions were considered isolated in the absence of ascites or peritoneal implants. Lesions were classified as classic or nonclassic based on sonographic appearance. Classic lesions included simple cysts, hemorrhagic cysts, endometriomas, and dermoids. Otherwise, lesions were considered nonclassic. Outcomes based on histopathologic results or clinical or imaging follow-up were recorded. Diagnostic performance and frequency of malignancy were calculated. Frequency of malignancy between age groups was compared using the χ2 test, and Poisson regression was used to explore relationships between imaging features and malignancy. Results A total of 970 isolated lesions in 878 women (mean age, 42 years ± 14 [SD]) were included. The malignancy rate for classic lesions was less than 1%. Of 970 lesions, 53 (6%) were malignant. The malignancy rate for nonclassic lesions was 32% (33 of 103) when blood flow was present and 8% (16 of 194) without blood flow (P < .001). For women older than 60 years, the malignancy rate was 50% (10 of 20 lesions) when blood flow was present and 13% (five of 38) without blood flow (P = .004). The sensitivity, specificity, positive predictive value, and negative predictive value of the classic-versus-nonclassic schema was 93% (49 of 53 lesions), 73% (669 of 917 lesions), 17% (49 of 297 lesions), and 99% (669 of 673 lesions), respectively, for detection of malignancy. Conclusion Using a US classification schema of classic- or nonclassic-appearing adnexal lesions resulted in high sensitivity and specificity in the diagnosis of malignancy in ovarian cancer. The highest risk of cancer was in isolated nonclassic lesions with blood flow in women older than 60 years. © RSNA, 2022 See also the editorial by Baumgarten in this issue.

Benign-appearing Incidental Adnexal Cysts at US, CT, and MRI: Putting the ACR, O-RADS, and SRU Guidelines All Together

Adnexal cysts are a common incidental finding at US, CT, and MRI but have historically caused a diagnostic dilemma for determining when to follow up and how to manage them. Characteristic imaging features of simple adnexal cysts include a simple fluid collection with smooth walls and no solid or vascular components. Day-to-day practice guidelines were recently updated to reflect the overwhelming evidence that incidental cystic adnexal masses are almost always benign. Three major consensus articles on adnexal cystic masses were published between 2019 and 2020: the Society of Radiologists in Ultrasound (SRU) consensus update on adnexal cysts, the Ovarian-Adnexal Reporting and Data System (O-RADS) US consensus guideline, and the American College of Radiology (ACR) white paper on the management for incidental adnexal findings at CT and MRI. All three standardize reporting terminology, are based on evidence-based data and institutional practice patterns, and apply to nonpregnant women of average risk for ovarian cancer. While there are small differences in follow-up recommendations based on size thresholds, the goal of each is the same-to limit unnecessary imaging follow-up and, by doing so, save the patient time, money, and anxiety. For the diagnostic radiologist to use these guidelines, it is essential that the entire mass is visualized well. Without adequate visualization, further characterization of the mass may be necessary. To put it all together, the SRU consensus guideline and ACR white paper are easily applied in day-to-day practice for masses that are O-RADS 2 and below. An invited commentary by Patel is available online.The online slide presentation from the RSNA Annual Meeting is available for this article.©RSNA, 2022.

Risk of de novo cancer after premenopausal bilateral oophorectomy

Hysterectomy is one of the most frequent gynecologic surgeries in the United States. Women undergoing hysterectomy are commonly offered bilateral oophorectomy for ovarian and breast cancer prevention. Although bilateral oophorectomy may dramatically reduce the risk of gynecologic cancers, some studies suggested that bilateral oophorectomy may be associated with an increased risk of other types of cancer, such as lung cancer and colorectal cancer. However, the results are conflicting. To study the association between bilateral oophorectomy and the risk of subsequent cancer of any type. This population-based cohort study included all premenopausal women who underwent bilateral oophorectomy for a nonmalignant indication before the age of 50, between January 1, 1988 and December 31, 2007 in Olmsted County, Minnesota, and a random sample of age-matched (±1 year) referent women who did not undergo bilateral oophorectomy. Women with cancer before oophorectomy (or index date) or within 6 months after the index date were excluded. Time-to-event analyses were performed to assess the risk of de novo cancer. Cancer diagnosis and type were confirmed using medical record review. Over a median follow-up of 18 years, the risk of any cancer did not significantly differ between the 1562 women who underwent bilateral oophorectomy before natural menopause and the 1610 referent women (adjusted hazard ratio, 0.82; 95% confidence interval, 0.66-1.03). However, women who underwent bilateral oophorectomy had a decreased risk of gynecologic cancers (adjusted hazard ratio, 0.15; 95% confidence interval, 0.06-0.34) but not of nongynecologic cancers (adjusted hazard ratio, 0.99; 95% confidence interval, 0.78-1.26). In particular, the risk of breast cancer, gastrointestinal cancer, and lung cancer did not differ between these 2 cohorts. Use of estrogen therapy through the age of 50 years in women who underwent bilateral oophorectomy did not modify the results. Women who underwent bilateral oophorectomy before menopause have a reduced risk of gynecologic cancer but not of other types of cancer including breast cancer. Women at average risk of ovarian cancer should not consider bilateral oophorectomy for the prevention of breast cancer or other nongynecologic cancers.

Cost Analysis of Bilateral Salpingectomy Pathology for Women of Average Risk of Ovarian Cancer

Bilateral salpingectomy has gained traction as a preferred form of surgical sterilization over tubal ligation due to the potential reduction in the risk of ovarian cancer. This paper argues it is safe and economical for the physician performing the salpingectomy in patients with an average risk of ovarian cancer to use clinical judgement in deciding whether the specimen should undergo gross and histologic examination. Implementing this new strategy could help decrease medical expenditures concerning surgical pathology by an estimated $10,075,980. Reducing costs and unnecessary strain on healthcare resources will improve the efficiency of medical systems and the quality of care they provide. Keywords: Cost-effectiveness; Health economics; Gynecologic pathology; Surgical pathology; Bilateral salpingectomy; Sterilization; Ovarian cancer; Serous tubal intraepithelial carcinoma

Trends in opportunistic salpingectomy following vaginal delivery

<h3>Objectives:</h3> The fallopian tube has been implicated as the site of origin in up to 70% of ovarian carcinomas. In November 2013, the Society of Gynecologic Oncology (SGO) advised that women of average risk for ovarian cancer undergo opportunistic salpingectomy at the time of abdominal or pelvic surgery, such as hysterectomy or tubal sterilization, to reduce the risk of ovarian cancer. Opportunistic salpingectomy has previously been incorporated into various surgical procedures including cesarean section, however a paucity of data exists regarding salpingectomy following vaginal deliveries. Our objective was to assess the uptake of opportunistic salpingectomy as a form of postpartum sterilization after vaginal delivery following the 2013 release of the SGO clinical practice statement. <h3>Methods:</h3> We performed an IRB-approved, retrospective cohort study of all postpartum tubal sterilization procedures performed during delivery admissions between January 2009 and December 2019. All patients undergoing tubal sterilization within 48 hours of vaginal delivery were included. We collected patient demographics, medical history, peripartum and perioperative data. The primary outcome was proportion of sterilization procedures completed as salpingectomies before and after January 1st, 2014. Secondary outcomes included estimated blood loss (EBL), perioperative complications and readmission within 6 weeks postpartum. We used Pearson's c2 test, Fisher's exact and Student's t-test to compare the time periods. We analyzed trends using the Cochran-Mantel-Haenszel test. <h3>Results:</h3> A total of 317 postpartum sterilization procedures were performed during the study period. 113 salpingectomies were performed during or after 2014 (<i>p</i>-value < 0.001). Patient demographics before and after January 1st, 2014 did not significantly differ. In 2014, 5.9% of sterilization procedures were completed as salpingectomies. By 2019, salpingectomies comprised 80% of postpartum sterilization procedures (Figure 1, p-value for trend < 0.001). Prior to 2014, the majority of tubal sterilizations occurred with placement of occlusive Filshie Clips (53.7%). Their use decreased to 0% by 2016 (p-value for trend < 0.001). There were no differences in EBL, postoperative complications or readmission during the time periods studied. Patients undergoing tubal sterilization prior to 2014 were more likely to be prescribed opioids at discharge compared to after (OR 0.37, 95% CI [0.20-0.70]). <h3>Conclusions:</h3> Postpartum opportunistic salpingectomy rates following vaginal deliveries increased significantly from 2014 to 2019 after the release of the SGO recommendations to consider salpingectomy as an ovarian cancer prevention strategy. This trend in postpartum salpingectomy occurred without an observed increase in complications or readmissions. Opportunistic salpingectomy should be considered a safe and feasible means of potential ovarian cancer risk reduction for patients who undergo vaginal deliveries and desire immediate postpartum sterilization.

Tubal ligation does not impact age of natural menopause

This study aimed to determine the effect of tubal ligation (TL) on age at natural menopause, as a marker of long-term ovarian function. We utilized three pre-existing population-based cohorts for this cross-sectional study. Data from each cohort was analyzed separately. The cohorts included a referent cohort of women from the Rochester Epidemiology Project (REP, Cohort 1), and participants in the Mayo Clinic Biobank (Cohort 2) or the Mayo Mammography Health Study (Cohort 3). The cohorts for this project were restricted to women who never smoked and had reached natural menopause, without prior hysterectomy or oophorectomy. All cohorts included women from Olmsted County, MN and Cohorts 2 and 3 also included women from six surrounding counties. The following variables were self-reported on a questionnaire by participants in Cohorts 2 and 3: race, age of menarche, age of menopause, history of hysterectomy or oophorectomy, number of pregnancies and live births, tobacco use, and ever use of hormonal contraception. These variables were manually abstracted in Cohort 1, along with the type of TL and age at TL. For Cohorts 2 and 3, history of TL was obtained from a separate institutional form administered to all patients prior to an outpatient clinic visit at the Mayo Clinic and supplemented with procedure information from the resources of the REP. The primary outcome, age at natural menopause, was compared between the two groups (those with and those without a history of TL before natural menopause) using a two-sample t-test. 555 women from Cohort 1, 1,816 women from Cohort 2, and 1,540 women from Cohort 3 met inclusion criteria. Baseline characteristics did not differ between cohorts. The rate of TL was the same in all cohorts: 26.0%, 25.5%, and 25.0%, respectively. Women who underwent TL were more likely to have had at least one pregnancy and to have used hormonal contraception compared to women who did not have a TL. In Cohort 1, the women with prior TL reached menopause an average of 0.6 years later (mean (SD) 50.7 (3.7) vs. 50.1 (3.5) years, p=0.08), whereas in Cohort 2 the women with prior TL reached menopause an average of 0.3 years earlier (49.6 (4.7) vs. 49.9 (4.5) years, p=0.20). The average age of menopause was the same in Cohort 3 (50.0 (4.4) vs. 50.0 (4.2) years, p= 0.80). The type of TL (Cohort 1 only) had no effect on the age of menopause. TL did not impact the age at which women underwent natural menopause in any of the 3 large cohorts included in this study, which suggests that TL does not impart negative long-term effects on ovarian function. Salpingectomy for permanent contraception and opportunistic salpingectomy at the time of benign hysterectomy have emerged as potential cancer risk reduction strategies in women at average risk for ovarian cancer. The impact of these procedures on ovarian function requires further study.

Abstract DPOC-004: MAGENTA: MAking GENetic Testing more Accessible

Abstract The standard paradigm for cancer susceptibility genetic testing has been for patients to 1) be identified by their provider as being at high risk due to extensive family history or another diagnosis (e.g., breast cancer for ovarian risk testing), and 2) attend in–person pre and post– genetic test sessions with a genetic counselor to prepare for testing and learn about the results. This arrangement places boundaries around the types of women willing to spend this time and effort receiving testing, as providers are required to act as gatekeepers to the testing process. More open methods of accessing genetic testing and providing support need to be evaluated. We propose to deliver personal, risk–based genetic testing and results to women from the general public using the Internet. Internet–based services offer several advantages over either in–person or telephone interventions. First, information can be accessed by participants and providers on their own schedules, at any location with internet access, and can be consumed at the pace and style that is best for individual tastes and styles. If necessary, information and support can be re–reviewed if the patient does not remember the initial counseling session. Second, delivery of information through the internet can be performed in a more efficient and cost–effective manner, reserving the limited in–person genetic counseling for individuals who need it the most, while providing support to the general public about basic medical and risk–based information. Recruitment via social media outlets can directly link potential participants to the Internet systems that screen for eligibility and provide testing support. Finally, Internet delivery can bring genetic testing to the patient in their home, eliminating a major barrier to testing (multiple visits to the provider) The main objective of MAGENTA is to test the effects of on–line genetic education versus telephone genetic counseling on cancer distress and other psychological outcomes. We will recruit women using social media and other eHealth methods to participate in a randomized trial of ovarian cancer counseling and testing that is conducted online and using the telephone. We will conduct a (2x2 factorial design) randomized trial to test online versus telephone pre– and post–test genetic counseling for ovarian cancer risk among women at higher than average risk for ovarian cancer. We expect to enroll 3000 women through our media contacts to participate in MAGENTA. For genetic risk assessment, we will evaluate and provide feedback on 19 breast and ovarian cancer (OC) genes that have a clear relationship to cancer risk in collaboration with Color Genomics. Variants include ATM, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, EPCAM, MSH2, MSH6, MLH1, NBN, PALB2, PMS2, PTEN, RAD51C, RAD51D, TP53, and STK1. We will follow women for main psychological outcomes at 3 months post testing and longer for other outcomes. Citation Format: Swisher E., Lu K., Bowen DJ, Gavin K. MAGENTA: MAking GENetic Testing more Accessible [abstract]. In: Proceedings of the 11th Biennial Ovarian Cancer Research Symposium; Sep 12-13, 2016; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(11 Suppl):Abstract nr DPOC-004.

Opportunistic Salpingectomy as an Ovarian Cancer Primary Prevention Strategy.

Ovarian cancer is the most lethal form of all gynecologic malignancies. The presenting clinical symptoms of ovarian cancer are very vague and often appear late in the course of disease. Hence, most patients are diagnosed at later stages. At present, there is no effective screening of ovarian cancer. Primary prevention could be considered a strategy to decrease the mortality from ovarian cancer, not only in women at high risk but also in those at low risk. Most "ovarian cancers," and more specifically the high-grade serous carcinoma (HGSC) subtype of ovarian cancer, actually could originate in the fallopian tube. Women who have known BRCA1 or BRCA2 germline mutations should be counseled regarding bilateral salpingo-oophorectomy, immediately after completion of childbearing, as the best strategy for reducing their risk of developing ovarian cancer. If the patient is reluctant, they should be counseled regarding risk-reducing salpingectomy when childbearing is complete followed by oophorectomy in the future. For women at average risk of ovarian cancer, risk-reducing salpingectomy should also be discussed and considered with patients at the time of any abdominal or pelvic surgery, hysterectomy or tubal ligation.

Tips and Tricks for Performing Salpingectomy at the Time of Laparoscopic Hysterectomy

Study ObjectiveTo demonstrate various techniques to perform salpingectomy efficiently at the time of laparoscopic hysterectomy. DesignStep-by-step explanation of the techniques by video with narration (educational video) (Canadian Task Force Classification III). InterventionSalpingectomy at the time of laparoscopic hysterectomy. Measurements and Main ResultsOvarian cancer is the deadliest gynecologic malignancy and has no effective screening strategies for average-risk women. After recognizing that the origin site for pelvic serous carcinomas may be the fallopian tube, the Society of Gynecologic Oncology published a practice statement in November 2013 addressing the role of salpingectomy at the time of hysterectomy or other pelvic surgery in average-risk women. (https://www.sgo.org/clinical-practice/guidelines/sgo-clinical-practice-statement-salpingectomy-for-ovarian-cancer-prevention). They now recommend that these women consider opportunistic salpingectomy to reduce their risk of fallopian tube and ovarian cancers. Various techniques allow the surgeon to complete the salpingectomy in a highly efficient manner. ConclusionSalpingectomy at the time of laparoscopic hysterectomy or other pelvic surgery should be considered in women at average risk of ovarian cancer. Salpingectomy can be performed either before or after control of the uterine blood supply. The surgical approach must also consider the coexisting pelvic pathology. Efficient dissection occurs if the surgeon maximizes exposure to the fallopian tube, optimizes presentation of the tissue to the working instrument, and provides gentle yet constant traction with accompanying countertraction. The fallopian tube specimen should be removed immediately to prevent its loss in the pelvis.

Society of Gynecologic Oncology Recommendations for the Prevention of Ovarian Cancer

Early detection of epithelial ovarian carcinoma through screening and symptom detection has failed to reduce mortality from this lethal malignancy. The only available strategy likely to reduce mortality from this cancer is prevention. This review summarizes evidence that implementation of several prevention strategies can substantially reduce mortality from ovarian cancer. Potential strategies recommended by the Society of Gynecologic Society that can reduce the risk of ovarian cancer are discussed. Recommendations are based on analysis of the current literature. • A key aim of preventive strategies is to identify and treat women at hereditary increased risk of ovarian cancer. • There has been increasing evidence in the past decade that most type 2 serous ovarian cancers arise from neoplastic progression of epithelial cells in the fallopian tube. With the current assumption that the fallopian tubes are the potential source of high-grade serous cancer in women with and without known genetic mutations, many gynecologic surgeons believe that risk reduction in both women at high risk or average risk may be achieved by opportunistic salpingectomy. • Salpingectomy should be considered for average-risk women undergoing hysterectomy, elective pelvic surgery, and sterilization techniques at the completion of childbearing. Salpingectomy can also be considered at the completion of childbearing in women at increased genetic risk of ovarian cancer who refuse to have salpingo-oophorectomy. • Oral contraceptives reduce the risk of both types 1 and 2 ovarian cancer and are considered safe for carriers of the BRCA1 and BRCA2 mutation. These drugs are also effective for reducing risk in women with an average risk of ovarian cancer. • Another prevention strategy, tubal ligation, has been associated with a reduction in ovarian cancer in both high-risk women as well as the general population. • The most proven method for preventing ovarian cancer in women with a deleterious BRCA1 or BRCA2 mutation is risk-reducing salpingo-oophorectomy (RRSO). Following RRSO, a 70% to 85% reduction in ovarian cancer has been reported. • Women at inherited increased risk of ovarian cancer or who have this cancer should be offered genetic counseling to assess their risk. Individualized genetic counseling is followed by elective genetic testing, which should include BRCA1 and BRCA2. Despite clear evidence of benefit from counseling, about 50% of women with ovarian cancer seen at academic centers and 80% in a community setting are not referred for genetic counseling. • The majority of high-grade serous cancers have precursor lesions in the fallopian tube, and salpingectomy is presumed to reduce the incidence of type 2 ovarian cancer. However, there are no data showing a reduction in ovarian cancer risk with opportunistic salpingectomy among either women at inherited risk or those at average risk.

Round Ligament Technique and Use of a Vessel-sealing Device to Facilitate Complete Salpingectomy at the Time of Vaginal Hysterectomy.

Prophylactic salpingectomy at the time of hysterectomy has been recommended for women at average risk for ovarian cancer. Vaginal hysterectomy is considered the preferred approach to a benign hysterectomy, and adnexectomy should not be considered a contraindication to this approach. This paper with accompanying video describes and demonstrates the round ligament technique and use of a vessel-sealing device to facilitate removal of the entire fallopian tube at the time of vaginal hysterectomy.

Costs and Benefits of Opportunistic Salpingectomy as an Ovarian Cancer Prevention Strategy

Evidence accumulated over the past decade suggests that the majority of ovarian cancers arise in the fallopian tube and not the ovary. This led to the recommendation that opportunistic salpingectomy be offered as an elective concurrent procedure for premenopausal women at average risk of ovarian cancer who undergo either hysterectomy for benign gynecologic conditions or surgical sterilization. It has been estimated that opportunistic salpingectomy could reduce the ovarian cancer risk by 20% to 40% over the next 20 years. There are few hard data, however, on the long-term risks and benefits associated with this procedure. Because a clinical trial is not feasible, a population-based cohort study is essential to establish the long-term risks, benefits, and cost-effectiveness of opportunistic salpingectomy. Such a cohort study would take many years to yield results; more timely data on the likely costs and benefits of this strategy could be obtained from a decision analytic model. The aim of this study was to conduct a cost-effectiveness analysis of opportunistic salpingectomy as an ovarian cancer prevention strategy in the general population. A Markov Monte Carlo simulation model was used to estimate the costs and benefits of opportunistic salpingectomy in a hypothetical cohort of premenopausal Canadian women undergoing hysterectomy for benign gynecologic conditions or surgical sterilization as permanent contraception. Three strategies were compared: hysterectomy alone, hysterectomy with salpingectomy, and hysterectomy with bilateral salpingo-oophorectomy (BSO). The main outcome measure was the incremental cost-effectiveness ratio. Effectiveness was calculated in terms of average years of life expectancy gain. Multiple sensitivity analyses accounted for uncertainty around various parameters, including treatment costs, age at surgery, and estimates of risk reduction attributable to salpingectomy. The number of ovarian cancer cases associated with each strategy was estimated in the simulation model. The model predicted that salpingectomy with hysterectomy would be less costly ($11,044 ± $1.56) and more effective (21.12 ± 0.02 years) than either hysterectomy alone ($11,207 ± $29.81, 21.10 ± 0.03 years) or BSO ($12,627 ± $13.11, 20.94 ± 0.03 years), respectively. The model also predicted that salpingectomy for sterilization would be marginally more costly than tubal ligation ($9720 ± $3.74 vs $9339 ± $26.74) but more effective (22.45 ± 0.02 vs 22.43 ± 0.02 years of life expectancy), with an incremental cost-effectiveness ratio of $27,278 per year of life gained. Results were stable over a wide range of treatment costs and estimates of risk reduction. In the Monte Carlo simulation model, salpingectomy reduced the risk of ovarian cancer by 38.1% (95% confidence interval, 36.5%–41.3%) compared with hysterectomy alone and 29.2% (95% confidence interval, 28.0%–31.4%) compared with tubal ligation. This analytic model shows that opportunistic salpingectomy with hysterectomy for benign conditions has the potential to decrease ovarian cancer risk at acceptable cost and that salpingectomy is a cost-effective alternative to use of tubal ligation for sterilization. These findings suggest that prophylactic salpingectomy should be considered in all women undergoing these procedures.

Cognitive and affective influences on perceived risk of ovarian cancer.

Studies suggest that both affective and cognitive processes are involved in the perception of vulnerability to cancer and that affect has an early influence in this assessment of risk. We constructed a path model based on a conceptual framework of heuristic reasoning (affect, resemblance, and availability) coupled with cognitive processes involved in developing personal models of cancer causation. From an eligible cohort of 16 700 women in a managed care organization, we randomly selected 2524 women at high, elevated, and average risk of ovarian cancer and administered a questionnaire to test our model (response rate 76.3%). Path analysis delineated the relationships between personal and cognitive characteristics (number of relatives with cancer, age, ideas about cancer causation, perceived resemblance to an affected friend or relative, and ovarian cancer knowledge) and emotional constructs (closeness to an affected relative or friend, time spent processing the cancer experience, and cancer worry) on perceived risk of ovarian cancer. Our final model fit the data well (root mean square error of approximation (RMSEA) = 0.028, comparative fit index (CFI) = 0.99, normed fit index (NFI) = 0.98). This final model (1) demonstrated the nature and direction of relationships between cognitive characteristics and perceived risk; (2) showed that time spent processing the cancer experience was associated with cancer worry; and (3) showed that cancer worry moderately influenced perceived risk. Our results highlight the important role that family cancer experience has on cancer worry and shows how cancer experience translates into personal risk perceptions. This understanding informs the discordance between medical or objective risk assessment and personal risk assessment. Published in 2014. This article is a U.S. Government work and is in the public domain in the USA.

Obstetrician-gynecologists’ opinions on elective bilateral oophorectomy at the time of hysterectomy in the United States

This study aims to assess obstetrician-gynecologists' opinions on elective bilateral oophorectomy (BO) at the time of hysterectomy in the United States and to describe factors that influence their views. In April 2012, an anonymous survey was mailed twice to practicing obstetrician-gynecologists, randomly selected from a list produced by the American Medical Association, in an effort to assess their opinions regarding elective BO at the time of hysterectomy. The effects of gynecologists' various characteristics on their opinions were also evaluated. Of 1,002 mailed surveys, 443 (44%) were returned completed. Of the respondents, 59% were male and 79% were white. The largest age group was 51 to 55 years (20%), and the mean time since completion of residency was 23 years. In women with an average risk of ovarian cancer, the proportions of physicians who favored elective BO were as follows: women younger than 51 years, 32%; women aged 51 to 65 years, 62%; women older than 65 years, 6%. These recommendations were not influenced by the physicians' age, sex, training, or geographic region. If a hysterectomy candidate was younger than 51 years and had a personal history of breast or ovarian cancer and a family history of ovarian cancer, these proportions were increased to 77% and 64%, respectively. Other factors that influenced the respondents' recommendations were the women's personal history of cardiovascular disease (21%), osteoporosis (23%), and sexual dysfunction (23%). One third of obstetrician-gynecologists continue to recommend elective BO for hysterectomy candidates younger than 51 years. The majority recommend elective BO for women aged 51 to 65 years. Their demographic characteristics do not influence their opinions.

A 2‐stage ovarian cancer screening strategy using the Risk of Ovarian Cancer Algorithm (ROCA) identifies early‐stage incident cancers and demonstrates high positive predictive value

A 2-stage ovarian cancer screening strategy was evaluated that incorporates change of carbohydrate antigen 125 (CA125) levels over time and age to estimate risk of ovarian cancer. Women with high-risk scores were referred for transvaginal ultrasound (TVS). A single-arm, prospective study of postmenopausal women was conducted. Participants underwent an annual CA125 blood test. Based on the Risk of Ovarian Cancer Algorithm (ROCA) result, women were triaged to next annual CA125 test (low risk), repeat CA125 test in 3 months (intermediate risk), or TVS and referral to a gynecologic oncologist (high risk). A total of 4051 women participated over 11 years. The average annual rate of referral to a CA125 test in 3 months was 5.8%, and the average annual referral rate to TVS and review by a gynecologic oncologist was 0.9%. Ten women underwent surgery on the basis of TVS, with 4 invasive ovarian cancers (1 with stage IA disease, 2 with stage IC disease, and 1 with stage IIB disease), 2 ovarian tumors of low malignant potential (both stage IA), 1 endometrial cancer (stage I), and 3 benign ovarian tumors, providing a positive predictive value of 40% (95% confidence interval = 12.2%, 73.8%) for detecting invasive ovarian cancer. The specificity was 99.9% (95% confidence interval = 99.7%, 100%). All 4 women with invasive ovarian cancer were enrolled in the study for at least 3 years with low-risk annual CA125 test values prior to rising CA125 levels. ROCA followed by TVS demonstrated excellent specificity and positive predictive value in a population of US women at average risk for ovarian cancer.

Reported referral for genetic counseling or BRCA 1/2 testing among United States physicians

Genetic counseling and testing is recommended for women at high but not average risk of ovarian cancer. National estimates of physician adherence to genetic counseling and testing recommendations are lacking. Using a vignette-based study, we surveyed 3200 United States family physicians, general internists, and obstetrician/gynecologists and received 1878 (62%) responses. The questionnaire included an annual examination vignette asking about genetic counseling and testing. The vignette varied patient age, race, insurance status, and ovarian cancer risk. Estimates of physician adherence to genetic counseling and testing recommendations were weighted to the United States primary care physician population. Multivariable logistic regression identified independent patient and physician predictors of adherence. For average-risk women, 71% of physicians self-reported adhering to recommendations against genetic counseling or testing. In multivariable modeling, predictors of adherence against referral/testing included black versus white race (relative risk [RR], 1.16; 95% confidence interval [CI], 1.03-1.31), Medicaid versus private insurance (RR, 1.15; 95% CI, 1.02-1.29), and rural versus urban location. Among high-risk women, 41% of physicians self-reported adhering to recommendations to refer for genetic counseling or testing. Predictors of adherence for referral/testing were younger patient age [35 vs 51 years [RR, 1.78; 95% CI, 1.41-2.24]), physician sex (female vs male [RR, 1.30; 95% CI, 1.07-1.64]), and obstetrician/gynecologist versus family medicine specialty (RR, 1.64; 95% CI, 1.31-2.05). For both average-risk and high-risk women, physician-estimated ovarian cancer risk was the most powerful predictor of recommendation adherence. Physicians reported that they would refer many average-risk women and would not refer many high-risk women for genetic counseling/testing. Intervention efforts, including promotion of accurate risk assessment, are needed.

ACR Appropriateness Criteria© Ovarian Cancer Screening

The majority of women with ovarian cancer have advanced stage disease at the time of diagnosis and a poor 5 year survival rate. Hence, screening has been investigated in the hopes of improving survival by diagnosing ovarian cancer at an earlier stage. Most screening methods thus far have included ultrasound and/or serum tumor markers. However, low prevalence of the disease, high false positive rate of current screening methods, and the probable rapid growth of most ovarian carcinomas from no defined precursor lesion, all contribute to difficulty in screening for ovarian cancer. While screening may be able to detect ovarian cancer at an earlier stage, adequate data is presently lacking on whether screening improves survival. The results of ongoing large clinical trials will be available in a few years and should provide critical information regarding the usefulness of screening. Pending results of those large clinical trials, screening is not currently recommended for women at average risk for ovarian cancer. Screening is most likely to be performed in women with an increased familial risk of ovarian cancer, but patients should be aware that even with this risk factor, there is currently insufficient evidence to know if screening is effective. New screening methods, including new or multiple serum markers and proteomics, are also being investigated.