Cost-Effectiveness of Gene-Specific Prevention Strategies for Ovarian and Breast Cancer.

Importance: Pathogenic variants (PVs) in BRCA1, BRCA2, PALB2, RAD51C, RAD51D, and BRIP1 cancer susceptibility genes (CSGs) confer an increased ovarian cancer (OC) risk, with BRCA1, BRCA2, PALB2, RAD51C, and RAD51D PVs also conferring an elevated breast cancer (BC) risk. Risk-reducing surgery, medical prevention, and BC surveillance offer the opportunity to prevent cancers and deaths, but their cost-effectiveness for individual CSGs remains poorly addressed. Objective: To estimate the cost-effectiveness of prevention strategies for OC and BC among individuals carrying PVs in the previously listed CSGs. Design, Setting, and Participants: In this economic evaluation, a decision-analytic Markov model evaluated the cost-effectiveness of risk-reducing salpingo-oophorectomy (RRSO) and, where relevant, risk-reducing mastectomy (RRM) compared with nonsurgical interventions (including BC surveillance and medical prevention for increased BC risk) from December 1, 2022, to August 31, 2023. The analysis took a UK payer perspective with a lifetime horizon. The simulated cohort consisted of women aged 30 years who carried BRCA1, BRCA2, PALB2, RAD51C, RAD51D, or BRIP1 PVs. Appropriate sensitivity and scenario analyses were performed. Exposures: CSG-specific interventions, including RRSO at age 35 to 50 years with or without BC surveillance and medical prevention (ie, tamoxifen or anastrozole) from age 30 or 40 years, RRM at age 30 to 40 years, both RRSO and RRM, BC surveillance and medical prevention, or no intervention. Main Outcomes and Measures: The incremental cost-effectiveness ratio (ICER) was calculated as incremental cost per quality-adjusted life-year (QALY) gained. OC and BC cases and deaths were estimated. Results: In the simulated cohort of women aged 30 years with no cancer, undergoing both RRSO and RRM was most cost-effective for individuals carrying BRCA1 (RRM at age 30 years; RRSO at age 35 years), BRCA2 (RRM at age 35 years; RRSO at age 40 years), and PALB2 (RRM at age 40 years; RRSO at age 45 years) PVs. The corresponding ICERs were -£1942/QALY (-$2680/QALY), -£89/QALY (-$123/QALY), and £2381/QALY ($3286/QALY), respectively. RRSO at age 45 years was cost-effective for RAD51C, RAD51D, and BRIP1 PV carriers compared with nonsurgical strategies. The corresponding ICERs were £962/QALY ($1328/QALY), £771/QALY ($1064/QALY), and £2355/QALY ($3250/QALY), respectively. The most cost-effective preventive strategy per 1000 PV carriers could prevent 923 OC and BC cases and 302 deaths among those carrying BRCA1; 686 OC and BC cases and 170 deaths for BRCA2; 464 OC and BC cases and 130 deaths for PALB2; 102 OC cases and 64 deaths for RAD51C; 118 OC cases and 76 deaths for RAD51D; and 55 OC cases and 37 deaths for BRIP1. Probabilistic sensitivity analysis indicated both RRSO and RRM were most cost-effective in 96.5%, 89.2%, and 84.8% of simulations for BRCA1, BRCA2, and PALB2 PVs, respectively, while RRSO was cost-effective in approximately 100% of simulations for RAD51C, RAD51D, and BRIP1 PVs. Conclusions and Relevance: In this cost-effectiveness study, RRSO with or without RRM at varying optimal ages was cost-effective compared with nonsurgical strategies for individuals who carried BRCA1, BRCA2, PALB2, RAD51C, RAD51D, or BRIP1 PVs. These findings support personalizing risk-reducing surgery and guideline recommendations for individual CSG-specific OC and BC risk management.

Bilateral salpingo-oophorectomy at the time of benign hysterectomy among females with disabilities: a population-based cross-sectional study.

BACKGROUND: Up to 40% of patients aged ≤55 years undergo concomitant bilateral salpingo-oophorectomy at the time of benign hysterectomy, with practice variation in bilateral salpingo-oophorectomy occurring along the lines of patient health and social factors. Disability is common in premenopausal women and is an important determinant of reproductive health more broadly; however, studies on bilateral salpingo-oophorectomy rates among women with disabilities are lacking. OBJECTIVE: This study aimed to examine whether the use of concomitant bilateral salpingo-oophorectomy at the time of benign hysterectomy differs by preexisting disability status in adult females aged ≤55 years. STUDY DESIGN: This population-based cross-sectional study used data from the 2016-2019 US National Inpatient Sample. Females undergoing inpatient hysterectomy for a benign gynecologic indication (n=74,315) were classified as having physical (6.1%), sensory (0.1%), intellectual or developmental (0.2%), or multiple (0.2%) disabilities and compared with those without a disability. Logistic regression was used to estimate risk ratios for differences in bilateral salpingo-oophorectomy rates by disability status, adjusted for patient and clinical factors. Models were stratified by potentially avoidable or potentially appropriate bilateral salpingo-oophorectomy based on the presence of clinical indications for ovarian removal and by age group. RESULTS: Bilateral salpingo-oophorectomy at the time of benign hysterectomy occurred in 26.0% of females without a disability, with rates clearly elevated in those with a physical (33.2%; adjusted risk ratio, 1.10; 95% confidence interval, 1.05-1.14) or intellectual or developmental (31.1%; adjusted risk ratio, 1.32; 95% confidence interval, 1.02-1.64) disability, possibly elevated in those with multiple disabilities (38.2%; adjusted risk ratio, 1.20; 95% confidence interval, 0.94-1.45), and similar in those with a sensory disability (31.2%; adjusted risk ratio, 0.98; 95% confidence interval, 0.83-1.13). The results were similar but with lower statistical precision for potentially avoidable and potentially appropriate bilateral salpingo-oophorectomy, which occurred in 9.1% and 17.0% of females without a disability, respectively. The largest differences in bilateral salpingo-oophorectomy rates among women with any disability were observed in the perimenopausal 45- to 49-year age group. CONCLUSION: Females with disabilities experienced elevated concomitant bilateral salpingo-oophorectomy rates at the time of benign hysterectomy, particularly those with an intellectual or developmental disability and those of perimenopausal age, although some estimates were imprecise. Equity-focused physician training in surgical counseling and research into the epidemiology and experiences of gynecologic conditions among females with a disability may be beneficial.

Salpingo-oophorectomy or surveillance for ovarian endometrioma in asymptomatic premenopausal women: a cost-effectiveness analysis.

BACKGROUND: The lifetime risk of ovarian cancer is 1.9% among women with endometriosis compared with 1.3% among the general population. When an asymptomatic endometrioma is incidentally discovered on imaging, gynecologists must weigh the procedural complications and the potential for subsequent surgical menopause against future ovarian pathology or cancer. OBJECTIVE: We aimed to determine if performing unilateral salpingo-oophorectomy is a more cost-effective strategy for the prevention of death than surveillance for asymptomatic endometriomas. STUDY DESIGN: We created a cost-effectiveness model using TreeAge Pro (TreeAge Software Inc; Williamstown, MA) with a lifetime horizon. Our hypothetical cohort included premenopausal patients with 2 ovaries who did not desire fertility. Those diagnosed with asymptomatic endometrioma underwent either unilateral salpingo-oophorectomy or surveillance (ultrasound 6-12 weeks after diagnosis, then annually). Our primary effectiveness outcome was mortality, including death from ovarian cancer or surgery and all-cause mortality related to surgical menopause (± hormone replacement therapy) if the contralateral ovary is removed. We modeled the probabilities of surgical complications, occult malignancy, development of contralateral adnexal pathology, surgical menopause, use of hormone replacement therapy, and development of ovarian cancer. The costs included surgical procedures, complications, ultrasound surveillance, hormone therapy, and treatment of ovarian cancer, with information gathered from Medicare reimbursement data and published literature. Cost-effectiveness was determined using the incremental cost-effectiveness ratio of Δ costs / Δ deaths with a willingness-to-pay threshold of $11.6 million as the value of a statistical life. Multiple 1-way sensitivity analyses were performed to evaluate model robustness. RESULTS: Our model demonstrated that unilateral salpingo-oophorectomy is associated with improved outcomes compared with surveillance, with fewer deaths (0.28% vs 1.50%) and fewer cases of ovarian cancer (0.42% vs 2.96%). However, it costs more than sonographic surveillance at $6403.43 vs $5381.39 per case of incidental endometrioma. The incremental cost-effectiveness ratio showed that unilateral salpingo-oophorectomy costs $83,773.77 per death prevented and $40,237.80 per case of ovarian cancer prevented. As both values were well below the willingness-to-pay threshold, unilateral salpingo-oophorectomy is cost-effective and is the preferred strategy. If unilateral salpingo-oophorectomy were chosen over surveillance for premenopausal patients with incidental endometriomas, 1 diagnosis of ovarian cancer would be prevented in every 40 patients and 1 death averted in every 82 patients. We performed 1-way sensitivity analyses for all input variables and determined that there were no reasonable inputs that would alter our conclusions. CONCLUSION: Unilateral salpingo-oophorectomy is cost-effective and is the preferred strategy compared with surveillance for the management of incidental endometrioma in a premenopausal patient not desiring fertility. It incurs fewer deaths and fewer cases of ovarian cancer with costs below the national willingness-to-pay thresholds.

A Revised Markov Model Evaluating Oophorectomy at the Time of Hysterectomy for Benign Indication: Age 65 Years Revisited.

OBJECTIVE: To perform an updated Markov modeling to assess the optimal age for bilateral salpingo-oophorectomy (BSO) at the time of hysterectomy for benign indication. METHODS: We performed a literature review that assessed hazard ratios (HRs) for mortality by disease, age, hysterectomy with or without BSO, and estrogen therapy use. Base mortality rates were derived from national vital statistics data. A Markov model from reported HRs predicted the proportion of the population staying alive to age 80 years by 1-year and 5-year age groups at time of surgery, from age 45 to 55 years. Those younger than age 50 years were modeled as either taking postoperative estrogen or not; those 50 and older were modeled as not receiving estrogen. Computations were performed with R 3.5.1, using Bayesian integration for HR uncertainty. RESULTS: Performing salpingo-oophorectomy before age 50 years for those not taking estrogen yields a lower survival proportion to age 80 years than hysterectomy alone before age 50 years (52.8% [Bayesian CI 40.7-59.7] vs 63.5% [Bayesian CI 62.2-64.9]). At or after age 50 years, there were similar proportions of those living to age 80 years with hysterectomy alone (66.4%, Bayesian CI 65.0-67.6) compared with concurrent salpingo-oophorectomy (66.9%, Bayesian CI 64.4-69.0). Importantly, those taking estrogen when salpingo-oophorectomy was performed before age 50 years had similar proportions of cardiovascular disease, stroke, and people living to age 80 years as those undergoing hysterectomy alone or those undergoing hysterectomy and salpingo-oophorectomy at age 50 years and older. CONCLUSION: This updated Markov model argues for the consideration of concurrent salpingo-oophorectomy for patients who are undergoing hysterectomy at age 50 and older and suggests that initiating estrogen in those who need salpingo-oophorectomy before age 50 years mitigates increased mortality risk.

Cost-effectiveness Analysis of Genotype-Specific Surveillance and Preventive Strategies for Gynecologic Cancers Among Women With Lynch Syndrome.

Importance: With the expansion of multigene testing for cancer susceptibility, Lynch syndrome (LS) has become more readily identified among women. The condition is caused by germline pathogenic variants in DNA mismatch repair genes (ie, MLH1, MSH2, MSH6, and PMS2) and is associated with high but variable risks of endometrial and ovarian cancers based on genotype. However, current guidelines on preventive strategies are not specific to genotypes. Objective: To assess the cost-effectiveness of genotype-specific surveillance and preventive strategies for LS-associated gynecologic cancers, including a novel, risk-reducing surgical approach associated with decreased early surgically induced menopause. Design, Setting, and Participants: This economic evaluation developed a cohort-level Markov simulation model of the natural history of LS-associated gynecologic cancer for each gene, among women from ages 25 to 75 years or until death from a health care perspective. Age was varied at hysterectomy and bilateral salpingo-oophorectomy (hyst-BSO) and at surveillance initiation, and a 2-stage surgical approach (ie, hysterectomy and salpingectomy at age 40 years and delayed oophorectomy at age 50 years [hyst-BS]) was included. Extensive 1-way and probabilistic sensitivity analyses were performed. Interventions: Hyst-BSO at ages 35 years, 40 years, or 50 years with or without annual surveillance beginning at age 30 years or 35 years or hyst-BS at age 40 years with oophorectomy delayed until age 50 years. Main Outcomes and Measures: Incremental cost-effectiveness ratio (ICER) between management strategies within an efficiency frontier. Results: For women with MLH1 and MSH6 variants, the optimal strategy was the 2-stage approach, with respective ICERs of $33 269 and $20 008 compared with hyst-BSO at age 40 years. Despite being cost-effective, the 2-stage approach was associated with increased cancer incidence and mortality compared with hyst-BSO at age 40 years for individuals with MLH1 variants (incidence: 7.76% vs 3.84%; mortality: 5.74% vs 2.55%) and those with MSH6 variants (incidence: 7.24% vs 4.52%; mortality: 5.22% vs 2.97%). Hyst-BSO at age 40 years was optimal for individuals with MSH2 variants, with an ICER of $5180 compared with hyst-BSO at age 35 years, and was associated with 4.42% cancer incidence and 2.97% cancer mortality. For individuals with PMS2 variants, hyst-BSO at age 50 years was optimal and all other strategies were dominated; hyst-BSO at age 50 years was associated with an estimated cancer incidence of 0.68% and cancer mortality of 0.29%. Conclusions and Relevance: These findings suggest that gene-specific preventive strategies for gynecologic cancers in LS may be warranted and support hyst-BSO at age 40 years for individuals with MSH2 variants. For individuals with MLH1 and MSH6 variants, these findings suggest that a novel 2-stage surgical approach with delayed oophorectomy may be an alternative to hyst-BSO at age 40 years to avoid early menopause, and for individuals with PMS2 variants, the findings suggest that hyst-BSO may be delayed until age 50 years.

Uptake of cancer risk management strategies among women who undergo cascade genetic testing for breast cancer susceptibility genes.

BACKGROUND: Uptake of cancer risk management based on inherited predispositions, which encompasses bilateral mastectomy (BLM), bilateral salpingo-oophorectomy (BSO), and intensified screening, is the primary motivation for cascade testing for hereditary breast and ovarian cancer (HBOC). However, long-term outcome data for cascade testers are lacking. METHODS: Medical records were abstracted for all unaffected women with pathogenic variants in HBOC genes from 2 cancer hospitals (2013-2019) with at least 1 year of follow-up to compare the uptake of surgery and screening between cascade and noncascade testers. RESULTS: Cascade testers (79.8%) were younger than noncascade testers (mean age, 37.6 vs 43.5 years; P = .002). Among women aged ≥40 years, 43% underwent BLM, and 71.6% underwent BSO, with no significant difference in uptake between cascade and noncascade testers. The mean time to BSO among cascade testers was shorter among women aged ≥40 years versus those aged <40 years (11.8 vs 31.9 months; P = .04); no such difference was observed among noncascade testers. Mammography and breast magnetic resonance imaging rates were low in the recorded 6 years for both groups after genetic counseling. CONCLUSIONS: Management uptake among cascade testers is high with rates comparable to those for unaffected BRCA-positive women. A large proportion of women act on cascade test results, and this represents a novel report of utilization of cancer management strategies.

Practice variation in bilateral salpingo-oophorectomy at benign abdominal hysterectomy: a population-based study.

BACKGROUND: Bilateral salpingo-oophorectomy at benign hysterectomy is not recommended in premenopausal women who are in the premenopausal stage because of its potential associations with increased all-cause mortality and cardiovascular disease; however, contemporary practice patterns are unknown. OBJECTIVE: This study aimed to quantify between-surgeon variation in bilateral salpingo-oophorectomy and identify surgeon and patient characteristics associated with bilateral salpingo-oophorectomy to evaluate current quality of care and identify targets for knowledge translation and future research. STUDY DESIGN: We conducted a population-based retrospective cross-sectional study of adult women (≥20 years) undergoing benign abdominal hysterectomy from 2014 to 2018 in Ontario, Canada. Hierarchical multivariable logistic regression models, stratified by age group (<45, 45-54, ≥55 years), were used to model between-surgeon variation after multivariable adjustment for patient and surgeon characteristics. Cases of bilateral salpingo-oophorectomy were classified as potentially appropriate or potentially avoidable based on the presence or absence of diagnostic indications. RESULTS: Of 44,549 eligible women, 17,797 (39.9%) underwent concurrent bilateral salpingo-oophorectomy, and 26,752 (60.1%) did not. In all three age strata, the individual surgeon providing care was one of the strongest factors influencing whether patients received bilateral salpingo-oophorectomy (median odds ratio, 2.00-2.53). Surgeons accounted for more than 22% of the residual observed variation in bilateral salpingo-oophorectomy in women aged 45-54 years compared with 16% and 14% of the residual observed variation in bilateral salpingo-oophorectomy in women aged <45 and ≥55 years, respectively. Non-gynecologic patient factors, such as obesity (odds ratio, 1.33; 95% confidence interval, 1.17-1.52; P<.001) and residing in low-income regions (odds ratio, 1.34; 95% confidence interval, 1.16-1.55; P<.001), were also associated with bilateral salpingo-oophorectomy. Approximately 40% of patients who underwent bilateral salpingo-oophorectomy had no indication for the procedure in their discharge records. CONCLUSION: Marked between-surgeon variation in bilateral salpingo-oophorectomy rates, even after adjusting for patient case mix, suggests ongoing uncertainty in practice. Stronger evidence-based guidelines on the risks and benefits of salpingo-oophorectomy as women age are needed, particularly focusing on perimenopausal women.

Concomitant Bilateral Salpingo-Oophorectomy at Hysterectomy: Differences by Race and Menopausal Status in the Veterans Affairs Health Care System, 2007-2014.

Background: Hysterectomy can be performed with concomitant bilateral salpingo-oophorectomy (BSO) to treat symptomatic pathology of the ovary (e.g., endometriosis) or to prevent ovarian cancer. Our objective was to examine the relationship between race and concomitant BSO by menopausal status in the Veterans Affairs (VA) health care system. Methods: This is a longitudinal study utilizing VA administrative data to identify hysterectomies provided or paid for by VA (i.e., source of care) between 2007 and 2014. We defined BSO as removal of both ovaries and fallopian tubes at the time of hysterectomy, identified by International Classification of Diseases-Ninth Revision codes. Covariates included demographic (e.g., ethnicity) and gynecological diagnoses (e.g., endometriosis). We used generalized linear models with a log-link and binomial distribution to estimate associations of race with BSO by menopausal status and source of care. Results: We identified 6,785 Veterans with hysterectomies, including 2,320 with concomitant BSO. Overall, Black Veterans were more likely to be single, obese, and undergo abdominal hysterectomy. After adjustment, premenopausal Black Veterans had a 41% lower odds of BSO than their White counterparts (odds ratio [OR]: 0.59, 95% confidence interval [CI]: 0.51-0.68). Stratifying on source of care, these results remained unchanged (provided: OR: 0.61, 95% CI: 0.52-0.72; paid: OR: 0.58, 95% CI: 0.48-0.71). There was insufficient evidence of an association among postmenopausal Veterans. Conclusions: Premenopausal Black Veterans are less likely to undergo BSO even after adjustment for salient characteristics. Our findings may have implications for equitable gynecological care for Veterans. Additional research is needed to better understand the role of differential preferences or cancer risk in these racial differences.

Management of high, moderate, and low penetrance ovarian cancer susceptibility mutations: an assessment of current risk reduction practices.

OBJECTIVE: Limited information exists regarding risk reduction strategies for women with moderate and low penetrance ovarian cancer susceptibility mutations. We sought to assess current risk reduction practice patterns for carriers of these mutations through a survey of members of the Society of Gynecologic Oncology. METHODS: Society of Gynecologic Oncology members were emailed a survey consisting of two vignettes: (1) a 35-year-old premenopausal woman; (2) a 55-year-old postmenopausal woman with comorbidities. Each vignette contained sub-scenarios in which the patient had either a BRCA1 (relative risk (RR)=30-60), RAD51C (RR=5.0), or ATM (RR=1.5-2.0) mutation. Respondents were queried about their preferred management approach. Summary statistics were performed to describe results of the survey. We used χ2 testing for statistical analyses, comparing results according to mutation type and demographic information. RESULTS: A total of 193 (15%) of 1284 Society of Gynecologic Oncology members responded. For the premenopausal woman, 99%, 80%, and 40% would perform a risk reducing salpingo-oophorectomy prior to menopause in the setting of a BRCA1, RAD51C, and ATM mutation, respectively. For the postmenopausal woman, 98%, 85%, and 42% would proceed with risk reducing salpingo-oophorectomy in the setting of a BRCA1, RAD51C, and ATM mutation, respectively. Response distribution for carriers of RAD51C and ATM mutations were different from BRCA1 in both vignettes (p<0.001). CONCLUSIONS: Respondents were more likely to perform risk reducing salpingo-oophorectomy, in the setting of a BRCA1, RAD51C, and ATM mutation, earlier and more frequently in the setting of a BRCA1 mutation. However, there was a lack of consensus about management of the moderate and low penetrance mutations, suggesting that more data regarding age specific risks and appropriate risk reduction strategies for these alterations are needed.

Precision prophylaxis: Identifying the optimal timing for risk-reducing salpingo-oophorectomy based on type of BRCA1 and BRCA2 cluster region mutations.

OBJECTIVES: Current risk-reducing salpingo-oophorectomy (RRSO) guidelines for individuals with BRCA1/2 mutations do not account for risk variability due to BRCA1/2 cluster region mutations that are associated with varying risks for the development of breast and ovarian cancer. We assessed whether current recommendations are appropriate for individual patients considering mutation-specific risks. METHODS: Using a hypothetical cohort of patients with BRCA1/2 mutations, we constructed Markov models allowing for the estimation of mean life expectancy based upon BRCA1/2 mutation, the presence of a cluster region mutation (Ovarian Cancer Cluster Region (OCCR), Breast Cancer Cluster Region (BCCR), or non-BCCR/OCCR), age at time of BRCA1/2 diagnosis (20-65), and age at time of RRSO (21-80). RESULTS: For all BRCA1/2 mutation types, the optimal strategy was to undergo RRSO as early as possible. For BRCA1/2 carriers who delayed RRSO or who were identified with a mutation later in life, the OCCR mutation tended to be associated with lower life expectancy estimates than the BCCR and non-BCCR/OCCR mutations. Minimal delays in RRSO (i.e., neighboring 5-year intervals) were associated with minor losses in life expectancy. Variables associated with greatest impact on life expectancy included ovarian cancer risk after RRSO, breast cancer mortality rate, non-cancer mortality associated with RRSO, and breast cancer stage distribution. CONCLUSIONS: BRCA1/2 cluster regions may provide more precise estimates of life expectancy in counselling and shared decision-making. The most appropriate timing for RRSO is a complex decision and must be individualized for each patient.

Risk-reducing Bilateral Salpingo-oophorectomy: Assessing the Incidence of Occult Ovarian Cancer and Surgeon Adherence to Recommended Practices.

STUDY OBJECTIVE: This study aimed to determine the incidence of ovarian cancer diagnosed at the time of risk-reducing bilateral salpingo-oophorectomy in a large cohort of patients with a BRCA mutation. In addition, we aimed to determine the adherence to the recommended practices for performing a risk-reducing bilateral salpingo-oophorectomy as described by the American College of Obstetricians and Gynecologists and the Society of Gynecologic Oncology. We sought to determine if adherence differed by the type of training (i.e., gynecologic oncologists vs benign gynecologists). DESIGN: Descriptive, retrospective analysis. SETTING: Academic medical center. PATIENTS: Two hundred sixty-nine patients with a known BRCA mutation. INTERVENTIONS: Prophylactic risk-reducing bilateral salpingo-oophorectomy performed either by a gynecologic oncologist or a benign gynecologist between July 2007 and September 2018. MEASUREMENTS AND MAIN RESULTS: Among 269 patients who underwent risk-reducing bilateral salpingo-oophorectomies, 220 procedures were performed by gynecologic oncologists, and 49 were performed by benign gynecologists. Washings were not performed in 5% of the procedures performed by gynecologic oncologists and 37% of the procedures performed by benign gynecologists (p <.001). Complete serial sectioning of the adnexa was not performed in 12% of the procedures performed by oncologists, and 13% of the procedures performed by benign gynecologists (p = .714). There were 8 cases (2.9%) of tubal or ovarian cancer diagnosed within this cohort. Of these cases, only 3 (1.1%) were diagnosed at the time of surgery and met the criteria for conversion to a staging procedure. CONCLUSION: Because the incidence of ovarian cancer diagnosis at the time of risk-reducing bilateral salpingo-oophorectomy is low and is often not diagnosed at the time of surgery owing to the presence of only microscopic disease, it may not be necessary for gynecologic oncologists to exclusively perform these procedures. However, this study also revealed that when this procedure is performed by benign gynecologic surgeons, some of the recommended practices are not routinely followed. If general gynecologic surgeons are to routinely perform risk-reducing bilateral salpingo-oophorectomies, it is important to promote better adherence to these practices.

Implementation of a sentinel lymph node mapping algorithm for endometrial cancer: surgical outcomes and hospital charges.

INTRODUCTION: The purpose of this study was to compare operative times, surgical outcomes, resource utilization, and hospital charges before and after the implementation of a sentinel lymph node (SLN) mapping algorithm in endometrial cancer. METHODS: All patients with clinical stage I endometrial cancer were identified pre- (2012) and post- (2017) implementation of the SLN algorithm. Clinical data were summarized and compared between groups. Total hospital charges incurred on the day of surgery were extracted from the hospital financial system for each patient and all charges were adjusted to 2017 US dollars. RESULTS: A total of 203 patients were included: 71 patients in 2012 and 130 patients in 2017. There was no difference in median age, body mass index, or stage. In 2012, 35/71 patients (49.3%) underwent a lymphadenectomy. In 2017, SLN mapping was attempted in 120/130 patients (92.3%) and at least one SLN was identified in 110/120 (91.7%). Median estimated blood loss was similar between groups (100 mL vs 75 mL, p=0.081). There was a significant decrease in both median operative time (210 vs 171 min, p=0.007) and utilization of intraoperative frozen section (63.4% vs 14.6%, p<0.0001). No significant differences were noted in intraoperative (p=1.00) or 30 day postoperative complication rates (p=0.30). The median total hospital charges decreased by 2.73% in 2017 as compared with 2012 (p=0.96). DISCUSSION: Implementation of an SLN mapping algorithm for high- and low-risk endometrial cancer resulted in a decrease in both operative time and intraoperative frozen section utilization with no change in surgical morbidity. While hospital charges did not significantly change, further studies are warranted to assess the true cost of SLN mapping.

Cost effectiveness of bilateral risk-reducing mastectomy and salpingo-oophorectomy.

BACKGROUND: Growing demand for risk-reducing surgery in individuals with inherited susceptibility to cancer leads to the question whether these procedures are cost effective for the executing hospitals. This study compared the clinical costs for bilateral risk-reducing mastectomy (BRRM) with and without different types of reconstruction, risk-reducing salpingo-oophorectomy (RRSO), and their combinations with corresponding reimbursements in the statutory health-care system in Germany. PATIENTS AND METHODS: Real total costs of care for BRRM with and without reconstruction, RRSO, and their combinations were calculated as the sum of all personnel and technical costs. These costs calculated in a German University hospital were compared with the sum of all reimbursements in the German DRG-based health-care system. RESULTS: While sole RRSO, BRRM without reconstruction, and BRRM with secondary DIEP (deep inferior epigastric perforator)-reconstruction still result in a small benefit, we even found shortfalls for the hospital with all other prophylactic operations under consideration. The calculated deficits were especially high for BRRM with implant-based breast reconstruction and for combined operations when the risk reduction is achieved with a minimum of separate operations. CONCLUSIONS: Risk-reducing surgery in BRCA-mutation carriers is frequently not cost-covering for the executing hospitals in the German health-care system. Thus, appropriate concepts are required to ensure a nationwide care.

A Microsimulation Model for Evaluating the Effectiveness of Cancer Risk Management for BRCA Pathogenic Variant Carriers: miBRovaCAre.

OBJECTIVES: To develop a validated model for evaluating the real-world effectiveness of long-term clinical management strategies for women with germline BRCA1 or BRCA2 pathogenic variants. METHODS: A microsimulation model was developed that included a BRCA-specific natural history for breast and ovarian cancer, a clinical framework for carrier follow-up, and cancer risk management strategies (breast screening, risk-reducing mastectomy, and bilateral salpingo-oophorectomy). Adherence rates and outcomes for breast screening and risk-reducing surgery were obtained from BRCA carriers seen through a familial cancer service in Melbourne, Australia. The model was assessed for internal and external validity. The model was used to compare women perfectly adhering to screening recommendations versus actual adherence of the clinical cohort. RESULTS: The model accurately predicted cancer incidence, pathology, and mortality. Using actual adherence for breast screening resulted in additional breast cancer deaths (per 1000 women: BRCA1, 2.7; BRCA2, 1.6) compared with perfect screening adherence. This decreased average life expectancy by 0.30 life-years for BRCA1 and 0.07 life-years for BRCA2. When carriers had access to risk-reducing mastectomy, the benefit from improved screening adherence was not significant. CONCLUSIONS: The developed model is a good descriptor of BRCA carriers' lifetime trajectory and its modification by use of risk management strategies alone or in combination. Evaluations of breast screening in BRCA carriers may overestimate the benefits of screening programs unless adherence is considered. By incorporating real-world clinical practice and patient behavior, this model can assist in developing clinical services and improving clinical outcomes for carriers.

Impact of different adjuvant radiotherapy modalities on women with early-stage intermediate- to high-risk endometrial cancer.

OBJECTIVE: Vaginal brachytherapy was recommended for patients with intermediate-risk endometrial cancer, however, optimal radiotherapy modalities for intermediate-high- or high-risk patients remains controversial. Previous studies have mainly focused on survival outcomes and have seldom taken cost issues into consideration, especially for high-risk patients. The purpose of this study is to compare the survival outcomes and costs associated with two adjuvant radiotherapy modalities in the management of patients with early-stage, intermediate- to high-risk endometrial cancer. METHODS: According to ESMO-ESCO-ESTRO criteria, 238 patients with stage I/II, intermediate- to high-risk endometrial cancer who underwent radiotherapy from January 2003 to December 2015 at our institution were reviewed. The vaginal brachytherapy group and external beam radiation therapy combined with the vaginal brachytherapy group were propensity score-matched at a 1:1 ratio. The Kaplan-Meier method and Cox proportional hazards regression model were used. RESULTS: A total of 361 patients met our inclusion criteria, the median age of the patients was 58 years (range, 28-85). All were diagnosed with stage I-II endometrial cancer (324 with stage I and 37 with stage II; 350 with endometrioid adenocarcinoma; and 10 with mucinous carcinoma). The median follow-up time was 60.5 months (range, 3-177). Among 119 matched pairs, no significant differences were found in overall (10.9% vs 8.4%, P=0.51), locoregional (4.2% vs 1.7%, P=0.45), or distant recurrence rates (6.7% vs 6.7%, P=1.0) between the two groups. There were also no differences in the 5-year overall (94.8% vs 93.9%, P=0.78) or progression-free survival (90.0% vs 84.4%, P=0.23) between the two groups. The rates of acute and late toxicity were significantly higher in the external beam radiation therapy combined with vaginal brachytherapy vs the vaginal brachytherapy group (all P<0.05), except for the acute hematological toxicity rate (17.6% vs 9.2%, P=0.06). External beam radiation therapy combined with vaginal brachytherapy had a higher median cost ($2759 vs $937, P<0.001) and longer median radiotherapy duration (41 days vs 17 days, P<0.001) than vaginal brachytherapy. CONCLUSION: Vaginal brachytherapy was associated with similar local control and long-term survival outcomes relative to the combination of external beam radiotherapy and vaginal brachytherapy and it also minimizes radiation-related complications, reduces medical costs, and shortens radiotherapy duration. Vaginal brachytherapy may be the optimal radiation modality for patients with early-stage endometrial cancer at intermediate to high risk.

Economic modeling of risk-adapted screen-and-treat strategies in women at high risk for breast or ovarian cancer.

BACKGROUND: The 'German Consortium for Hereditary Breast and Ovarian Cancer' (GC-HBOC) offers women with a family history of breast and ovarian cancer genetic counseling. The aim of this modeling study was to evaluate the cost-effectiveness of genetic testing for BRCA 1/2 in women with a high familial risk followed by different preventive interventions (intensified surveillance, risk-reducing bilateral mastectomy, risk-reducing bilateral salpingo-oophorectomy, or both mastectomy and salpingo-oophorectomy) compared to no genetic test. METHODS: A Markov model with a lifelong time horizon was developed for a cohort of 35-year-old women with a BRCA 1/2 mutation probability of ≥ 10%. The perspective of the German statutory health insurance (SHI) was adopted. The model included the health states 'well' (women with increased risk), 'breast cancer without metastases', 'breast cancer with metastases', 'ovarian cancer', 'death', and two post (non-metastatic) breast or ovarian cancer states. Outcomes were costs, quality of life years gained (QALYs) and life years gained (LYG). Important data used for the model were obtained from 4380 women enrolled in the GC-HBOC. RESULTS: Compared with the no test strategy, genetic testing with subsequent surgical and non-surgical treatment options provided to women with deleterious BRCA 1 or 2 mutations resulted in additional costs of €7256 and additional QALYs of 0,43 (incremental cost-effectiveness ratio of €17,027 per QALY; cost per LYG: €22,318). The results were robust in deterministic and probabilistic sensitivity analyses. CONCLUSION: The provision of genetic testing to high-risk women with a BRCA1 and two mutation probability of ≥ 10% based on the individual family cancer history appears to be a cost-effective option for the SHI.

Different Patterns of Risk Reducing Decisions in Affected or Unaffected BRCA Pathogenic Variant Carriers.

PURPOSE: The purpose of this study was to investigate decision patterns to reduce the risks of BRCArelated breast and gynecologic cancers in carriers of BRCA pathogenic variants. We found a change in risk-reducing (RR) management patterns after December 2012, when the National Health Insurance System (NHIS) of Korea began to pay for BRCA testing and riskreducing salpingo-oophorectomy (RRSO) in pathogenic-variant carriers. MATERIALS AND METHODS: The study group consisted of 992 patients, including 705 with breast cancer (BC), 23 with ovarian cancer (OC), 10 with both, and 254 relatives of high-risk patients who underwent BRCA testing at the National Cancer Center of Korea from January 2008 to December 2016.We analyzed patterns of and factors in RR management. RESULTS: Of the 992 patients, 220 (22.2%) were carriers of BRCA pathogenic variants. About 92.3% (203/220) had a family history of BC and/or OC,which significantly differed between BRCA1 and BRCA2 carriers (p < 0.001). All 41 male carriers chose surveillance. Of the 179 female carriers, 59 of the 83 carriers (71.1%) with BC and the 39 of 79 unaffected carriers (49.4%) underwent RR management. None of the carriers affected with OC underwent RR management. Of the management types, RRSO had the highest rate (42.5%) of patient choice. The rate of RR surgery was significantly higher after 2013 than before 2013 (46.3% [74/160] vs. 31.6% [6/19], p < 0.001). CONCLUSION: RRSO was the preferred management for carriers of BRCA pathogenic variants. The most important factors in treatment choice were NHIS reimbursement and/or the severity of illness.

[Cost-effectiveness of risk-reducing salpingo-oophorectomy in cases of BRCA1 gene mutation in Colombia]. / Costo efectividad de la cirugía reductora de riesgo en trompas y ovarios en casos con mutación del gen BRCAI en Colombia.

OBJECTIVE: To assess the usefulness of risk reduction salpingo-oophorectomy in cases with mutation of the BRCA1 gene in Colombia. MATERIAL AND METHODS: Cost-effectiveness analysis in which three processes are incorporated: a. Patients with screening tests for breast and ovarian cancer. b. Risk reduction surgery in the fallopian tubes and ovaries c. Reductive surgery in the fallopian tubes and ovaries with bilateral mastectomy. The outcome is evaluated as the gain in years of survival. RESULTS: The cohort with risk reduction surgery in the fallopian tubes and ovaries and bilateral mastectomy is the one with the highest gain with 13 years, while the risk reduction surgery in the fallopian tubes and ovaries gain 4.95 years with respect to the follow-up group. CONCLUSIONS: The three options evaluated are acceptable, but of them the one with the greatest gain in survival is the combination of risk-reducing surgery in the fallopian tubes and ovaries with bilateral mastectomy.

OBJETIVO: Evaluar la utilidad de la cirugía reductora de riesgo en trompas y ovarios en casos con mutación del gen BRCA1 en Colombia. MATERIAL Y MÉTODOS: Análisis de costo-efectividad en el que se incorporan tres procesos: a. Pacientes con pruebas de tamización para cáncer de mama y ovario. b. cirugía reductora de riesgo en trompas y ovarios c. cirugía reductora de riesgo en trompas y ovarios con mastectomía bilateral. Se evalúa como desenlace la ganancia en años de supervivencia. RESULTADOS: La cohorte con cirugía reductora de riesgo en trompas y ovarios y mastectomía bilateral es la de mayor ganancia con 13 años mientras que la cirugía reductora de riesgo en trompas y ovarios gana 4,95 años con respecto al grupo de seguimiento. CONCLUSIONES: Las tres opciones evaluadas son aceptables, pero de ellas la de mayor ganancia en la supervivencia es la combinación de cirugía reductora de riesgo en trompas y ovarios con mastectomía bilateral.

Long-term quality of life after comprehensive surgical staging of high-risk endometrial cancer - results from the RASHEC trial.

PURPOSE: The health-related quality of life (HRQoL) outcomes after comprehensive surgical staging including infrarenal paraaortic lymphadenectomy in women with high-risk endometrial cancer (EC) are unknown. Our aim was to investigate the long-term HRQoL between robot-assisted laparoscopic surgery (RALS) and laparotomy (LT). PATIENTS AND METHODS: A total of 120 women with high-risk stage I-II EC were randomised to RALS or LT for hysterectomy, bilateral salpingoophorectomy, pelvic and infrarenal paraaortic lymphadenectomy in the previously reported Robot-Assisted Surgery for High-Risk Endometrial Cancer trial. The HRQoL was measured with the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-30) and its supplementary questionnaire module for endometrial cancer (QLQ-EN24) questionnaire. Women were assessed before and 12 months after surgery. In addition, the EuroQol Eq5D non-disease specific questionnaire was used for descriptive analysis. RESULTS: There was no difference in the functional scales (including global health status) in the intention to treat analysis, though LT conferred a small clinically important difference (CID) over RALS in 'cognitive functioning' albeit not statistically significant -6 (95% CI-14 to 0, p = .06). LT conferred a significantly better outcome for the 'nausea and vomiting' item though it did not reach a CID, 4 (95% CI 1 to 7, p = .01). In the EORTC-QLQ/QLQ-EN24, no significant differences were observed. Eq5D-3L questionnaire demonstrated a higher proportion of women reporting any extent of mobility impairment 12 months after surgery in the LT arm (p = .03). CONCLUSION: Overall, laparotomy and robot-assisted surgery conferred similar HRQoL 12 months after comprehensive staging for high-risk EC.

Hysterectomy with Bilateral Salpingo-Oophorectomy in Female-to-Male Gender Affirmation Surgery: Comparison of Two Methods.

INTRODUCTION: The optimal route for hysterectomy with bilateral salpingo-oophorectomy in female-to-male gender affirmation surgery is still under debate, due to the quite limited and inconsistent published data. The aim of this study is to present and compare the results of vaginal and laparoscopic hysterectomy as part of gender affirmation surgery in female-to-male transsexuals. MATERIALS AND METHODS: Between 2012 and 2017, 124 female-to-male transsexuals, aged 18-43 years (mean age: 28.5), underwent hysterectomy with bilateral salpingo-oophorectomy, followed by colpocleisis and gender affirmation surgery. Transvaginal and laparoscopic hysterectomy were performed in 92 and 32 patients, respectively. Standard outcome measures (types and rates of complications, operative time, blood loss, and postoperative hospital stay) were used to compare the two groups of patients. RESULTS: The mean follow-up was 41 months (ranged from 6 to 65 months). The duration of transvaginal approach was significantly shorter (51 minutes compared to 76 minutes, p < 0.001). The total complication rates (less than 3%), reoperation rates (0%), blood loss, and postoperative hospital stays (4.3 days compared to 4.5 days) showed no statistical difference. CONCLUSIONS: Both approaches are safe, with minimal complications. However, we prefer transvaginal hysterectomy due to its shorter operative time, cost-effectiveness, and simpler continuation with one-stage female-to-male gender affirmation surgery.