Care after premenopausal risk-reducing salpingo-oophorectomy in high-risk women: Scoping review and international consensus recommendations.

Women at high inherited risk of ovarian cancer are offered risk-reducing salpingo-oophorectomy (RRSO) from age 35 to 45 years. Although potentially life-saving, RRSO may induce symptoms that negatively affect quality of life and impair long-term health. Clinical care following RRSO is often suboptimal. This scoping review describes how RRSO affects short- and long-term health and provides evidence-based international consensus recommendations for care from preoperative counselling to long-term disease prevention. This includes the efficacy and safety of hormonal and non-hormonal treatments for vasomotor symptoms, sleep disturbance and sexual dysfunction and effective approaches to prevent bone and cardiovascular disease.

Factors influencing genetic counseling and testing for hereditary breast and ovarian cancer syndrome in a large US health care system.

Investigate whether disparities and other factors influence referral to genetic counseling and testing for hereditary breast and ovarian cancer syndrome (HBOC) in a large health care system. Examination of clinical, demographic, and socioeconomic factors from electronic health records associated with genetic referral and testing within 12 months after a new cancer diagnosed between August 1, 2013 and December 31, 2018. For patients meeting institutional criteria for HBOC testing, 60.6% were referred for genetic counseling, 88% of whom underwent germline testing; at least one pathogenic variant was found in 15.3%. Referral rates for patients with breast (69%) or ovarian cancer (65.7%) were much higher than for metastatic prostate (11.1%, p < 0.0001) or pancreatic cancer (22.3%, p < 0.0001); referral criteria were implemented more recently for the latter two cancers. Younger age, family history, and chemotherapy were associated with referral. Higher Elixhauser comorbidity score and prior cancer were associated with non-referral. No other factors were associated with genetic referral for all eligible cancers combined, although differences were seen in specific cancers. Race was a significant factor only for breast cancer, with fewer Asians than Whites referred. Health disparities in referral to genetics for HBOC cancers are mitigated in a comprehensive integrated health care system.

Management of ovarian and breast cancer risk in non-BRCA HBOC pathogenic variant carriers in a large California health care system.

PURPOSE: To describe breast and ovarian cancer risk reduction strategies in the clinical management of women who test positive for non-BRCA hereditary breast and ovarian cancer (HBOC) pathogenic variants compared to those who test positive for pathogenic BRCA variants or have negative germline panel testing. METHODS: Examination of imaging and preventive surgeries in women undergoing HBOC genetic testing from 1/1/2015 to 12/31/2018, with follow up to 03/31/2020 in Kaiser Permanente Northern California. RESULTS: A total of 13,271 tests which included HBOC genes were identified. Rate of bilateral salpingo-oophorectomy after genetic testing were similar for BRCA and the non-BRCA moderate risk ovarian pathogenic variants (PVs) (47.4% vs 54%, p = 0.25). Rates were lower for low risk or unknownrisk non-BRCA PVs (12.8%, p < 0.001, 5.3% (p < 0.001). Rates of surveillance for ovarian cancer with ultrasound and CA 125 in the first year was 63.3% and 64.7% for BRCA PV, 37.5% and 27.1%, for non-BRCA moderate risk PVs and 13.7% and 4.6%, for low-risk PVs. Bilateral mastectomy rates were 19.7% for BRCA PV, 10.1% (p = 0.028) for non-BRCA breast high risk PVs, for moderate risk PVs 7.7% (p < 0.001) and for unknown risk 0.4% (p < 0.001). MRI surveillance rates in the first year similarly were 47.4% for non-BRCA BRCA PV, 43% for breast high risk PV, 39.4% for moderate risk and 4.9% for unknown risk PV. CONCLUSION: Surgical and surveillance strategies are underutilized for HBOC PV, however there is concordance of uptake of preventive strategies with specific risk associated with non-BRCA PVs.

Ovarian cancer surveillance in the clinical follow up of women with known BRCA1 or BRCA2 pathogenic variants in a large health care system.

OBJECTIVE: To assess CA 125 and transvaginal ultrasound surveillance in women with BRCA1 or BRCA2 pathogenic variants in a pragmatic clinical setting with>1 year follow up. METHODS: Retrospective cohort study in a large integrated health care system of women identified from 1/1/2003 to 12/31/2017 with a BRCA1 or BRCA2 pathogenic variant with at least one intact ovary. Demographic and clinical data were collected from date of genetic testing until oophorectomy, an ovarian cancer diagnosis, or 7/1/2019. Primary outcome was frequency and findings of CA 125 tests and ultrasounds performed; secondary outcome was epithelial ovarian cancers diagnosed. RESULTS: There were 1418 women, age ≥ 30 years with a BRCA1 or BRCA2 pathogenic variant with at least one intact ovary. Of the total of 1683 ultrasounds and 2437 CA 125 tests done, 1022 ultrasounds and 1709 CA 125 tests were performed for surveillance in 771 women followed >1 year. Of these women 241 (31%) women had no surveillance, and 530 (69%) women underwent any surveillance. Only 108 (20%) underwent regular surveillance. The number who underwent regular surveillance declined each year. Twenty-one women underwent surveillance indicated surgery with only 2 ovarian cancers found by surveillance. CONCLUSIONS: Many women with BRCA1 or BRCA2 pathogenic variants undergo ultrasound and CA 125 surveillance testing but abnormal surveillance testing led to diagnosis of ovarian cancer in only two cases. These findings question the use of CA 125 and ultrasound surveillance in the clinical setting for ovarian cancer detection in women with BRCA1 or BRCA2 pathogenic variants.

Cytological sampling of fallopian tubes using a hysteroscopic catheter: A multi-center study.

OBJECTIVE: To assess the feasibility of a novel hysteroscopic catheter to collect fallopian tube cytologic samples and to correlate cytologic findings with histopathology. METHODS: This was a prospective, multicenter, single-arm pilot study. Women undergoing salpingo-oophorectomy for a pelvic mass suspicious for malignancy or for prevention of cancer for BRCA mutation carriers were recruited from 3 gynecologic oncology centers (October 2016-August 2017). Cytologic samples were collected from the fallopian tube using a novel FDA-cleared hysteroscopic catheter and evaluated by a pathologist blinded to surgical or pathologic findings. The correlation between cytologic results and final surgical pathology was assessed. RESULTS: Of the 50 patients enrolled, 42 were eligible. Hysteroscopies were completed in 40 patients with 78 fallopian tubes, of which 65 ostia (83%) were identified. Of these, 61 (72%) were successfully catheterized resulting in 44 (68%) cytology samples adequate for further evaluation: 5 were classified as positive (3 neoplastic and 2 malignant) and 39 as negative (34 benign and 5 reactive/atypical). A comparison of cytology results with fallopian tube histopathology showed a concordance rate of 95% (42/44). Of the two samples with discordant results, both had positive cytology but negative tubal pathology, and both were stage I ovarian cancers with malignant ovary histology. CONCLUSIONS: Deployment of the device yielded an evaluable cytologic sample in 68% of cases with a high rate of concordance with histopathology. Further evaluation of the device's ability to detect malignancy in high risk populations is warranted.

Feasibility, patient compliance and acceptability of ovarian cancer surveillance using two serum biomarkers and Risk of Ovarian Cancer Algorithm compared to standard ultrasound and CA 125 among women with BRCA mutations.

OBJECTIVE: We assessed the feasibility, patient acceptability of and compliance of a new surveillance strategy for ovarian cancer surveillance in women with BRCA mutations, based on assessments of serum CA125 and HE4 every 4 months (Risk of Ovarian Cancer Algorithm (ROCA) arm), compared to Standard of Care (SOC) surveillance with CA125 blood tests and pelvic ultrasounds every 6 months. METHODS: Women were recruited 6/13/16-9/11/17 from an integrated health care system in California for this non-randomized prospective cohort study. Women were invited to participate in a novel serum biomarker surveillance strategy using ROCA or they could opt to be in the standard of care control arm with ultrasound and CA 125 every 6 months. Outcomes assessed included compliance, self-reported distress using the Impact of Event Scale (IES) and cancer anxiety using the Cancer Worry Scale. RESULTS: There were 159 women in the ROCA arm and 43 in the SOC arm. Overall, compliance was higher in the ROCA arm (83.2%) than in SOC (51.9%), p < 0.0001. Based on the IES, ROCA arm women reported less feelings about intrusion and avoidance at 12 months compared to baseline; the difference approached significance for intrusion (7.6% vs 4.1% severe, p = 0.057) and was statistically significant for avoidance (20.8% vs 9.9% severe, p = 0.034). CONCLUSIONS: This pilot demonstrated that compliance was high with blood tests performed every four months for ovarian cancer surveillance. Moreover, ROCA women had lower stress scores over time than SOC women. Given the lack of clinical utility and poor compliance shown with traditional ultrasound and CA125 tests, further investigation is warranted of longitudinal biomarker surveillance for early detection of ovarian cancer.

Development of a longitudinal two-biomarker algorithm for early detection of ovarian cancer in women with BRCA mutations.

OBJECTIVE: To develop a longitudinal algorithm combining two biomarkers, CA125 and HE4, for early detection of ovarian cancer in women with BRCA mutations. METHODS: Women with BRCA mutations and intact ovaries were invited to participate in a novel ovarian cancer early detection prospective study. The Risk of Ovarian Cancer Algorithm (ROCA) identifying significant increases above each woman's baseline in serum CA125 and HE4 was performed every four months; abnormal risks triggered a subsequent ultrasound. The study first used a risk algorithm for only CA125, a second algorithm was developed for HE4 and finally a risk algorithm combining the two biomarkers was implemented. The ROCA strategy was compared to Standard of Care (SOC) surveillance strategy. RESULTS: A total of 149 women enrolled in the ROCA arm while 43 women enrolled in the SOC arm. Abnormal scores were found in 24% of ROCA CA125 tests, 16% if ROCA CA125 or the novel ROCA HE4 were used independently and reduced to 8% using the new two-marker ROCA, significantly lower than the 15% of abnormal tests seen in the SOC arm (p = 0.042). The average false positive rate among women without ovarian cancer for two-marker ROCA for referral to ultrasound was 6.6% (specificity 93.4%), and for the two-marker ROCA plus ultrasound for referral to surgical consultation was 1.7% (specificity 98.3%). CONCLUSION: A newly developed two-marker ROCA administered every 4 months had lower call-back rates than SOC surveillance. Having established high specificity, the two-marker ROCA score deserves further evaluation for sensitivity in a larger trial.

Comparison of two Lynch screening strategies in endometrial cancer in a California health system.

OBJECTIVE: Compare detection of Lynch syndrome in endometrial cancer between regions of a health care system with different screening strategies. METHODS: A retrospective study of endometrial cancer (EC) cases from 2 regions of an integrated health care system (Kaiser Permanente Northern (KPNC) and Southern (KPSC) California). Within KPNC, immunohistochemistry tumor screening (IHC) was physician ordered and risk-based; within KPSC, IHC was universal and automated. Clinical risk factors associated with abnormal IHC and Lynch Syndrome (LS) were identified. RESULTS: During the study, there were 2045 endometrial cancers: 1399 in the physician-order group and 646 in the universal testing group. In the physician-order group: among women < age 60, 34% underwent IHC; 9.6% were abnormal, and 3% were possible LS after methylation testing; among women ≥60, 11% underwent IHC, 3% were abnormal and <1% were possible LS. In the universal group, 87% of women age <60 had IHC, 19.4% were abnormal, and 6% were possible LS; Among women age ≥60, 82% underwent IHC, 26% were abnormal, and 2% were possible LS. There were no differences in LS cases between the physician-order group and the universal group in either age strata (<60: 3% vs. 3.6%, p=0.62; ≥60: <1% vs. 1%, p=0.63) Factors associated with LS were younger age (odds ratio (OR) 0.11, 95% confidence interval (CI) 0.04-0.29) and lower body mass index (BMI), (OR 0.38 95% CI 0.18-0.80). CONCLUSIONS: Universal IHC screening did not result in increased LS detection in EC.

Streamlining genetic testing for women with ovarian cancer in a Northern California health care system.

OBJECTIVE: Referral to Genetics for pre-testing counseling may be inefficient for women with ovarian cancer. This study assesses feasibility of gynecologic oncologists directly offering genetic testing. METHODS: A prospective pilot study was conducted at two gynecologic oncology hubs in an integrated healthcare system from May 1 to November 6, 2019. Gynecologic oncologists offered multigene panel testing to women with newly diagnosed ovarian cancer, followed by selective genetic counseling. Outcomes were compared between study participants and women from other hubs in the health system. RESULTS: Of ovarian cancer patients at study sites, 40 participated and all underwent genetic testing. Of 101 patients diagnosed at other sites, 85% were referred to genetics (p = .0061 compared to pilot participants) and 67% completed testing (p < .0001). The time from diagnosis to blood draw and notification of result was 18.5 and 34 days for the pilot group compared to 25.5 and 53 days at other sites. Panel testing detected 9 (22.5%) and 7 (10.3%, p = .08) pathogenic mutations in each group, respectively. Patients and providers were highly satisfied with the streamlined process. CONCLUSION: Genetic testing performed at the gynecologic oncology point of care for patients with ovarian cancer is feasible, increases uptake of testing, and improves time to results.

Sexual function, menopausal symptoms, depression and cancer worry in women with BRCA mutations.

OBJECTIVES: Assess sexual function, menopausal symptoms, and depression in women with BRCA mutations associated with oophorectomy and menopause status. METHODS: Women age 40 and older with BRCA mutations completed a questionnaire with validated measures of sexual activity, menopausal symptoms, depression, and cancer worry. These measures were compared between those with intact ovaries and those who had undergone pre- or post-menopausal risk-reducing salpingo-oophorectomy (RRSO). RESULTS: Of the 244 women, 21 had intact ovaries and 223 had undergone RRSO. Women with intact ovaries had less menopausal symptoms (Menopausal Symptom Checklist (MSCL) score 14 versus 23, P = .01) but more cancer worry than women who had undergone RRSO (median Cancer Worry Scale (CWS) score 5 versus 4, P < .0001) with no significant difference in sexual activity or function. Compared with women with postmenopausal RRSO, women with premenopausal RRSO were more likely to be sexually active (56.3% versus 42.0%, P =.04) but had similar sexual functioning, including frequency, pleasure and discomfort. Women with premenopausal RRSO were also more likely to report menopausal symptoms (MSCL score 26 versus 19, P = .04) and depression (PHQ-8 score 4 versus 2, P < .001). Factors associated with sexual activity included younger age, lower BMI, living with a partner, and lower depression scores. Higher current depression score was associated with history of depression and more menopausal symptoms. CONCLUSIONS: Risk-reducing surgery decreases cancer risk and worry in women with BRCA mutations. Among women undergoing oophorectomy, factors such as age and history of depression were related to reduced sexual activity and increased depression, but menopausal status was not related.

Clinical characteristics and outcomes in elderly women with BRCA1 and BRCA2 mutations.

OBJECTIVE: Describe clinical characteristics and risk reducing strategies utilized among women with a BRCA mutation who lived to age 75 and above. METHODS: A retrospective study of women with BRCA mutations identified from 1995 to 2015 in a California health care system. From a database of 1189 women, 69 participants were identified who lived to age 75 or older. Demographic and clinical characteristics were recorded, as well as cancer history and risk-reducing strategies utilized. Descriptive and bivariate analyses were used to analyze the cohort. RESULTS: The median age of the cohort at study entry was 78 (IQR: 76-84) and the median age at time of genetic testing was 73 (IQR 68-79). Fifty (72%) women had a prior history of breast cancer and 27 (39%) had a history of ovarian cancer. Three of 19 (16%) women with no history of breast cancer elected to undergo a risk-reducing mastectomy (RRM) after their positive genetic test. Among 30 women with ovaries still in place, 14 (47%) underwent a risk-reducing salpingo-oophorectomy (RRSO); six were age 70 or older at the time of surgery. Four (6%) women in the cohort developed BRCA-related cancer after testing, one developed breast cancer and three developed pancreatic cancer. CONCLUSIONS: Most women with BRCA mutations surviving beyond age 75 received their genetic test result at an older age and had a history of BRCA-related cancer. Women continued surveillance and risk reducing surgeries at an older age. Pancreatic cancer was the most common new cancer diagnosed in older BRCA mutation carriers.

Risk of cardiovascular disease in women with BRCA1 and BRCA2 mutations.

OBJECTIVE: Estimate the prevalence of cardiovascular disease risk factors and endpoints in women with BRCA mutations. METHODS: Women, age 40 and older, with BRCA mutations identified in Kaiser Permanente Northern California completed a questionnaire and underwent a lipid and fasting glucose panel. Bivariable analysis of clinical and demographic factors was performed. The Atherosclerotic Cardiovascular Disease (ASCVD) calculator was used to predict 10-year risk of a cardiovascular event. RESULTS: Of the 233 women, 19 women had intact ovaries (median age 56.0) and 214 had undergone risk-reducing salpingo-oophorectomy (RRSO). Among the 108 women with RRSO under age 50 (median age 51.0), compared to the 106 women who had RRSO at or over age 50 (median age 63.5) 6.5% vs 10.4% reported diabetes (p = 0.30), 23.2% versus 28.3% had elevated fasting blood glucose (p = 0.39), 21.3% versus 34.0% reported hypertension (p = 0.04) with median systolic blood pressure of 118 mmHg versus 125.5 mmHg (p < 0.009), 25% versus 32% reported hyperlipidemia (p = 0.40), and 42% versus 49% had any abnormal lipid test (p = 0.28). An elevated 10-year ASCVD risk of over 10% was seen in 6.1% versus 24.8% respectively (p = 0.0001). CONCLUSION: Women who underwent RRSO at age of 50 and over, had higher ASCVD 10-year risk than women who underwent RRSO at younger ages most likely owing to older age at study entry. The ASCVD risks for women with BRCA mutation who had RRSO did not suggest increased risk associated with being a BRCA mutation carrier.

Bone loss in women with BRCA1 and BRCA2 mutations.

OBJECTIVE: Estimate the prevalence and identify risk factors for bone loss in women with BRCA mutations. METHODS: Women, age 40 and older, with BRCA mutations identified from the Breast Cancer Surveillance database at Kaiser Permanente Northern California were invited to participate and undergo a dual-energy x-ray absorptiometry scan to assess for bone loss (osteopenia or osteoporosis). Multivariable logistic regression analysis was performed to assess clinical factors associated with bone loss. RESULTS: Of the 238 women in the final cohort, 20 women had intact ovaries (median age 54.5years) and 218 had undergone risk reducing salpingo-oophorectomy (RRSO) (median age 57). The prevalence of bone loss was 55% in the no RRSO group and 72.5% in the RRSO group (P=0.10). In multivariable analysis, only higher body mass index (OR 0.6 per 5kg/m2, 95% CI: 0.4-0.7) and nonwhite race compared to white (OR 0.5, 95% CI: 0.2-0.9) were protective for bone loss while older age (OR 1.5 per 10years, 95% CI: 1.1-2.1) and selective estrogen receptor modulator use (3.1, 95% CI: 1.2-10.1) were associated with increased odds of bone loss. Among women with RRSO, bone loss was more frequent in women who had postmenopausal (n=106) compared to women who had premenopausal RRSO (n=112), (82.1% and 63.4% respectively, P=0.002). In multivariable analysis, only BMI was protective of bone loss (OR 0.5, 95%, CI: 0.4-0.7) but neither age nor menopausal status at RRSO were associated with bone loss. CONCLUSION: Bone loss is common in women with BRCA mutations who undergo RRSO.

Impact of body mass index on ovarian cancer survival varies by stage.

BACKGROUND: Research on the effect of body mass index (BMI) on ovarian cancer survival is inconsistent, but previous studies did not consider the possible impact of ascites, bowel obstruction, or cachexia, which commonly occur in late-stage disease. METHODS: We evaluated the association of BMI, before and around the time of diagnosis, with overall and disease-specific survival in a cohort study of primary invasive epithelial ovarian cancers diagnosed from 2000 to 2013 in Kaiser Permanente Northern California (KPNC) (n=1184). Deaths were identified through December 2014, with a median follow-up of 37 months. Proportional hazards regression was used to estimate overall and ovarian cancer-specific mortality, accounting for prognostic variables including age at diagnosis, race, stage, grade, histology, comorbidities, treatment, post-treatment CA125 levels, ascites, and bowel obstruction. RESULTS: There was no evidence of an association between BMI and overall or ovarian cancer-specific survival. However, we found strong effect modification by stage (Pinteraction<0.01). Compared with normal prediagnosis BMI (18.5-24.9 kg m-2), for women who were obese before diagnosis (BMI⩾35 kg m-2) ovarian cancer-specific survival was lower among those diagnosed at stages I/II (hazard ratio (HR): 3.40; 95% confidence interval (CI): 1.16-9.99), but increased among those diagnosed with stage IV disease (HR: 0.58; 95% CI: 0.35-0.96). Associations were attenuated after excluding those diagnosed with cachexia (n=82) and further adjustment for ascites and bowel obstruction, with no evidence of effect modification by these factors. CONCLUSIONS: Associations of obesity with ovarian cancer survival may differ by stage, with decreased survival among those with localised disease and increased survival among those with late-stage disease. Stage-specific effects of obesity on survival suggest a tailored approach to improve prognosis may be appropriate.

Does Surgical Teaching Take Time? Resident Participation in Minimally Invasive Hysterectomy for Endometrial Cancer.

STUDY OBJECTIVE: To determine the association between resident involvement and operative time for minimally invasive surgery (MIS) for endometrial cancer. DESIGN: A retrospective cohort study (Canadian Task Force classification II-2). SETTING: An integrated health care system in Northern California. PATIENTS: A total of 1433 women who underwent MIS for endometrial cancer and endometrial intraepithelial neoplasia from January 2009 to January 2014. INTERVENTIONS: Resident participation in 430 of 688 laparoscopic cases (62%) and 341 of 745 robotic cases (46%). MEASUREMENTS AND MAIN RESULTS: The primary outcome was the impact of resident involvement on surgical time. When residents were involved in laparoscopic and robotic surgery, there was an increase of 61 minutes (median operative time, 186 vs 125 minutes; p < .001) and 31 minutes (median operative time, 165 vs 134 minutes; p < .001), respectively. Resident participation was associated with increased operative times in all levels of surgical complexity from hysterectomy alone to hysterectomy with pelvic and para-aortic lymph node dissection. Resident participation was also associated with increased major intraoperative complications (3.4% vs 1.8%, p = .02) as well as major postoperative complications (6.4% vs 3.8%, p = .003). CONCLUSION: The presence of a resident was associated with a 32% increase in operative time for minimally invasive cases in gynecologic oncology for endometrial cancer. Because of the retrospective nature, we cannot infer causality of operative outcomes because residents were also involved in more high-risk patients and complex cases. For health care systems using surgical metrics, there may be a need to allocate more time for resident involvement.

Venous thromboembolism following minimally invasive surgery among women with endometrial cancer.

OBJECTIVE: To determine the rate of venous thromboembolism (VTE) among women undergoing minimally invasive surgery (MIS) for endometrial cancer. METHODS: Women undergoing robotic or laparoscopic hysterectomy for endometrial carcinoma or complex hyperplasia with atypia were identified between January 2009 and 2014 in a community based health care system. Patient data including age, race, cancer stage, grade, procedure type, length of hospital stay, use of prophylaxis, and diagnosis of VTE were collected retrospectively. The primary outcome was the rate of VTE within 30days following surgery. Fischer's exact tests were performed to evaluate factors associated with VTE. RESULTS: During the study period, 1433 patients underwent MIS for endometrial cancer, with 20 excluded due to known thrombophilia, VTE history, or long-term anticoagulation. A total of 1413 patients were included (739 robotic and 674 laparoscopic cases). All women received mechanical prophylaxis per hospital policy and 61% had additional pharmacologic prophylaxis. The rate of VTE was 0.35% (5/1413), which did not differ among those who received pharmacologic compared to mechanical prophylaxis (0.23% [2/865] versus 0.55% [3/548] respectively, p=0.38). No factors were associated with increased risk of VTE due to the low event rate. CONCLUSION: VTE in patients undergoing MIS for endometrial cancer was very low irrespective of the mode of prophylaxis received in this large cohort. National guidelines for VTE prophylaxis need to differentiate the low risk associated with MIS surgery from the risk associated with laparotomy for endometrial cancer. We recommend mechanical prophylaxis is sufficient for these women undergoing MIS.

Classification of Postoperative Complications in Robotic-assisted Compared With Laparoscopic Hysterectomy for Endometrial Cancer.

STUDY OBJECTIVE: To compare intraoperative and postoperative surgical complications and outcomes between robotic-assisted and laparoscopic surgical management of endometrial cancer using a standardized classification system. DESIGN: A retrospective cohort study (Canadian Task Force classification II-2). SETTING: An integrated health care system in Northern California. PATIENTS: One thousand four hundred thirty-three women with a diagnosis of complex atypical hyperplasia and endometrial cancer managed by minimally invasive hysterectomy and surgical staging from January 2009 to January 2014. INTERVENTIONS: Seven hundred forty-five robotic-assisted and 688 laparoscopic hysterectomies were evaluated. MEASUREMENTS AND MAIN RESULTS: The primary outcome was intraoperative and postoperative complications within 30 days. All complications were categorized using the Clavien-Dindo classification system. Secondary outcomes included total operative time, estimated blood loss, transfusion rates, length of stay, conversion to laparotomy, and number of pelvic and para-aortic lymph nodes retrieved. The modality of hysterectomy was not associated with either overall intraoperative complications or major postoperative complications (p > .1). However, there were significantly fewer minor postoperative complications with robotic surgery (16.6% vs 25.6%, p < .01). Statistically significant differences were also noted in the following outcomes: decreased median operative time, length of stay, estimated blood loss, conversion to laparotomy, and median number of lymph nodes retrieved in the robotic group when compared with the laparoscopic group. CONCLUSION: There was no difference in the rate of major complication between robotic and laparoscopic surgery using the Clavien-Dindo system of categorizing surgical complications; however, there were clinically significant differences favoring the robotic approach, including a lower rate of minor complications and conversion rate to laparotomy.

Society of Gynecologic Oncology recommendations for the prevention of ovarian cancer.

Mortality from ovarian cancer may be dramatically reduced with the implementation of attainable prevention strategies. The new understanding of the cells of origin and the molecular etiology of ovarian cancer warrants a strong recommendation to the public and health care providers. This document discusses potential prevention strategies, which include 1) oral contraceptive use, 2) tubal sterilization, 3) risk-reducing salpingo-oophorectomy in women at high hereditary risk of breast and ovarian cancer, 4) genetic counseling and testing for women with ovarian cancer and other high-risk families, and 5) salpingectomy after childbearing is complete (at the time of elective pelvic surgeries, at the time of hysterectomy, and as an alternative to tubal ligation). The Society of Gynecologic Oncology has determined that recent scientific breakthroughs warrant a new summary of the progress toward the prevention of ovarian cancer. This review is intended to emphasize the importance of the fallopian tubes as a potential source of high-grade serous cancer in women with and without known genetic mutations in addition to the use of oral contraceptive pills to reduce the risk of ovarian cancer.

Osteoporosis risk and management in BRCA1 and BRCA2 carriers who undergo risk-reducing salpingo-oophorectomy.

OBJECTIVE: Characterize current management of osteoporosis risk in BRCA carriers following risk-reducing salpingo-oophorectomy (RRSO). METHODS: Women with a BRCA1 or BRCA2 mutation who underwent RRSO were identified from a community-based health system in Northern California from 1995 to 2012. Retrospective chart review using the electronic medical record was performed. The primary outcome was the number of women who had a dual-energy X-ray absorptiometry scan post-RRSO. Secondary outcomes included new diagnoses of osteopenia, osteoporosis, and fracture. Information on the following risk factors was also recorded: calcium and vitamin D use, history of breast cancer, chemotherapy, use of aromatase inhibitors, and use of hormone replacement therapy. RESULTS: Two hundred and twenty five women tested positive for a BRCA1 or BRCA2 mutation and underwent RRSO. Median follow-up was 41 months from testing. Ninety-nine (44.0%) had at least one DXA scan following testing. The median time from RRSO to a diagnosis of bone disease was 29 months (range 1-170). Seventy-two percent had only one DXA scan (range 1-7) following testing. Thirty-two percent had normal results, 55.6% had osteopenia and 12.1% had osteoporosis. Four percent of women had an atraumatic fracture after surgery. Age, breast cancer history, prior chemotherapy, and tamoxifen or aromatase inhibitor (AI) use were not associated with having osteoporosis or osteopenia. CONCLUSIONS: Women with BRCA mutations who undergo RRSO have many risk factors for bone loss. The majority of these women are not being screened for bone loss. A clear guideline for screening needs to be established to improve detection of post-RRSO bone disease.

Society of Gynecologic Oncology statement on risk assessment for inherited gynecologic cancer predispositions.

Women with germline mutations in the cancer susceptibility genes, BRCA1 or BRCA2, associated with Hereditary Breast & Ovarian Cancer syndrome, have up to an 85% lifetime risk of breast cancer and up to a 46% lifetime risk of ovarian, tubal, and peritoneal cancers. Similarly, women with mutations in the DNA mismatch repair genes, MLH1, MSH2, MSH6, or PMS2, associated with the Lynch/Hereditary Non-Polyposis Colorectal Cancer (HNPCC) syndrome, have up to a 40-60% lifetime risk of both endometrial and colorectal cancers as well as a 9-12% lifetime risk of ovarian cancer. Mutations in other genes including TP53, PTEN, and STK11 are responsible for hereditary syndromes associated with gynecologic, breast, and other cancers. Evaluation of the likelihood of a patient having one of these gynecologic cancer predisposition syndromes enables physicians to provide individualized assessments of cancer risk, as well as the opportunity to provide tailored screening and prevention strategies such as surveillance, chemoprevention, and prophylactic surgery that may reduce the morbidity and mortality associated with these syndromes. Evaluation for the presence of a hereditary cancer syndrome is a process that includes assessment of clinical and tumor characteristics, education and counseling conducted by a provider with expertise in cancer genetics, and may include genetic testing after appropriate consent is obtained. This commentary provides guidance on identification of patients who may benefit from assessment for the presence of a hereditary breast and/or gynecologic cancer syndrome.