Trends in uterine cancer incidence in the United States: The contribution of age, period and cohort effects.

OBJECTIVE: In the U.S., uterine cancer incidence is rising, with racial and ethnic minorities experiencing the largest increases. We performed age-period-cohort analyses using novel methods to examine the contribution of age at diagnosis (age), year of diagnosis (period), and birth cohort (cohort), to trends in uterine cancer incidence. METHODS: We used uterine cancer incidence data from the Surveillance, Epidemiology, and End Result (SEER) 12 database (1992-2019), and performed hysterectomy-correction. We generated hexamaps to visualize age, period, and cohort effects, and used mutual information to estimate the percent contribution of age, period, and cohort effects, individually and combined, on uterine cancer incidence, overall and by race and ethnicity and histology. RESULTS: Hexamaps showed an increase in uterine cancer in later time periods, and a cohort effect around 1933 showing a lower incidence compared with earlier and later cohorts. Age, period, and cohort effects combined contributed 86.6% (95% CI: 86.4%, 86.9%) to the incidence. Age effects had the greatest contribution (65.1%, 95% CI: 64.3%, 65.9), followed by cohort (20.7%, 95% CI: 20.1%, 21.3%) and period (14.2%, 95% CI: 13.7%, 14.8%) effects. Hexamaps showed higher incidence in recent years for non-Hispanic Blacks and non-endometrioid tumors. CONCLUSIONS: Age effects had the largest contribution to uterine cancer incidence, followed by cohort and period effects overall and across racial and ethnic groups and histologies. IMPACT: These findings can inform uterine cancer modeling studies on the effects of interventions that target risk factors which may vary across age, period, or cohort.

Weight-loss therapy in patients with obesity with endometrial intraepithelial neoplasia and uterine cancer.

OBJECTIVE: Although obesity is an important risk factor for endometrial intraepithelial neoplasia (EIN) and uterine cancer, little is known about the trends in use of weight-loss therapy for patients with obesity with EIN and uterine cancer. We examined the use of weight-loss therapy among patients with obesity with EIN and uterine cancer. METHODS: The Merative MarketScan Database was used to identify patients aged 18-70 years who were obese and diagnosed with EIN or uterine cancer. The primary treatment for EIN or uterine cancer was categorized as either primary hysterectomy or hormonal therapy. Nutrition counseling, bariatric surgeries, and weight-management medications were identified as weight-loss therapy. We analyzed trends in the use of any weight-loss therapies with Cochran-Armitage tests. A multivariable logistic regression model was developed to examine factors associated with weight-loss therapy use. RESULTS: Overall, 15,374 patients were identified, including 5561 (36.2%) patients with EIN and obesity, and 9813 (63.8%) patients with uterine cancer and obesity. Weight-loss therapy was utilized within 1 year after diagnosis in 480 (8.6%) patients with EIN and in 802 (8.2%) patients with uterine cancer. Use of any weight-loss therapy after diagnosis of EIN increased from 4.1% in 2009 to 12.6% in 2020 (P < .001), and the use of any weight-loss therapy after diagnosis of uterine cancer increased from 4.9% in 2009 to 11.4% in 2020 (P < .001). In a multivariable regression model, younger age and patients with high comorbidity score were associated with a higher likelihood of using any weight-loss therapy. CONCLUSIONS: Use of weight-loss therapy has increased, however there is still a significant underuse of this adjunctive therapy in patients with obesity with EIN or uterine cancer.

Menopausal hormone therapy use and risk of ovarian cancer by race: the ovarian cancer in women of African ancestry consortium.

BACKGROUND: Most studies examining post-menopausal menopausal hormone therapy (MHT) use and ovarian cancer risk have focused on White women and few have included Black women. METHODS: We evaluated MHT use and ovarian cancer risk in Black (n = 800 cases, 1783 controls) and White women (n = 2710 cases, 8556 controls), using data from the Ovarian Cancer in Women of African Ancestry consortium. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association of MHT use with ovarian cancer risk, examining histotype, MHT type and duration of use. RESULTS: Long-term MHT use, ≥10 years, was associated with an increased ovarian cancer risk for White women (OR = 1.38, 95%CI: 1.22-1.57) and the association was consistent for Black women (OR = 1.20, 95%CI: 0.81-1.78, pinteraction = 0.4). For White women, the associations between long-term unopposed estrogen or estrogen plus progesterone use and ovarian cancer risk were similar; the increased risk associated with long-term MHT use was confined to high-grade serous and endometroid tumors. Based on smaller numbers for Black women, the increased ovarian cancer risk associated with long-term MHT use was apparent for unopposed estrogen use and was predominately confined to other epithelial histotypes. CONCLUSION: The association between long-term MHT use and ovarian cancer risk was consistent for Black and White women.

Model-Projected Cost-Effectiveness of Adult Hearing Screening in the USA.

BACKGROUND: While 60% of older adults have hearing loss (HL), the majority have never had their hearing tested. OBJECTIVE: We sought to estimate long-term clinical and economic effects of alternative adult hearing screening schedules in the USA. DESIGN: Model-based cost-effectiveness analysis simulating Current Detection (CD) and linkage of persons with HL to hearing healthcare, compared to alternative screening schedules varying by age at first screen (45 to 75 years) and screening frequency (every 1 or 5 years). Simulated persons experience yearly age- and sex-specific probabilities of acquiring HL, and subsequent hearing aid uptake (0.5-8%/year) and discontinuation (13-4%). Quality-adjusted life-years (QALYs) were estimated according to hearing level and treatment status. Costs from a health system perspective include screening ($30-120; 2020 USD), HL diagnosis ($300), and hearing aid devices ($3690 year 1, $910/subsequent year). Data sources were published estimates from NHANES and clinical trials of adult hearing screening. PARTICIPANTS: Forty-year-old persons in US primary care across their lifetime. INTERVENTION: Alternative screening schedules that increase baseline probabilities of hearing aid uptake (base-case 1.62-fold; range 1.05-2.25-fold). MAIN MEASURES: Lifetime undiscounted and discounted (3%/year) costs and QALYs and incremental cost-effectiveness ratios (ICERs). KEY RESULTS: CD resulted in 1.20 average person-years of hearing aid use compared to 1.27-1.68 with the screening schedules. Lifetime total per-person undiscounted costs were $3300 for CD and ranged from $3630 for 5-yearly screening beginning at age 75 to $6490 for yearly screening beginning at age 45. In cost-effectiveness analysis, yearly screening beginning at ages 75, 65, and 55 years had ICERs of $39,100/QALY, $48,900/QALY, and $96,900/QALY, respectively. Results were most sensitive to variations in hearing aid utility benefit and screening effectiveness. LIMITATION: Input uncertainty around screening effectiveness. CONCLUSIONS: We project that yearly hearing screening beginning at age 55+ is cost-effective by US standards.

Maternal morbidity and mortality among patients with cancer at time of delivery.

BACKGROUND: Individuals with cancer during pregnancy are a medically complex patient population that is anticipated to grow. A better understanding of this population and patterns of risk at time of delivery would offer an opportunity for providers to mitigate maternal morbidity. OBJECTIVE: This study aimed to estimate the prevalence in the United States of concurrent cancer diagnoses at time of delivery by cancer type and associated maternal morbidity and mortality. STUDY DESIGN: Using the National Inpatient Sample, we identified delivery-associated hospitalizations between 2007 and 2018. Concurrent cancer diagnoses were classified using the Clinical Classifications Software. Main outcomes included severe maternal morbidity, as defined by the Centers for Disease Control and Prevention indicators, and mortality during delivery hospitalization. We calculated adjusted rates for cancer diagnosis at time of delivery and adjusted odds ratios of severe maternal morbidity and maternal death during hospitalization using survey-weighted multivariable logistic regression models. RESULTS: In this sample of 9,418,761 delivery-associated hospitalizations, 63 per 100,000 deliveries had a concurrent cancer diagnosis (95% confidence interval, 60-66; national weighted estimate, 46,654,042). The most common cancer types were breast cancer (8.4 per 100,000 deliveries), leukemia (8.4 per 100,000 deliveries), Hodgkin lymphoma (7.4 per 100,000 deliveries), non-Hodgkin lymphoma (5.4 per 100,000 deliveries), and thyroid cancer (4.0 per 100,000 deliveries). Patients with cancer were at significantly higher risk for any severe maternal morbidity (adjusted odds ratio, 5.25; 95% confidence interval, 4.73-5.83) and maternal death (adjusted odds ratio, 67.5; 95% confidence interval, 45.1-101.4). Risks of hysterectomy (adjusted odds ratio, 16.92; 95% confidence interval, 13.96-20.52), acute respiratory distress (adjusted odds ratio, 12.76; 95% confidence interval, 9.92-16.42), sepsis (adjusted odds ratio, 11.91; 95% confidence interval, 8.68-16.32), and embolism (adjusted odds ratio, 11.12; 95% confidence interval, 6.94-17.82) were particularly heightened among patients with cancer. Patients with leukemia, specifically, had the highest risk of adverse maternal outcomes (adjusted rate, 113 per 1000 deliveries; 95% confidence interval, 91-135 per 1000) when evaluating risk by cancer type. CONCLUSION: Patients with cancer are at markedly increased risk of maternal morbidity and all-cause mortality during delivery-associated hospitalization. Risk is distributed unevenly within this population, with certain cancer types carrying unique risks for specific morbidity events.

Long-term health-related quality of life and symptom severity following hysterectomy, myomectomy, or uterine artery embolization for the treatment of symptomatic uterine fibroids.

BACKGROUND: Few studies have directly compared different surgical procedures for uterine fibroids with respect to long-term health-related quality of life outcomes and symptom improvement. OBJECTIVE: We examined differences in change from baseline to 1-, 2-, and 3-year follow-up in health-related quality of life and symptom severity among patients who underwent abdominal myomectomy, laparoscopic or robotic myomectomy, abdominal hysterectomy, laparoscopic or robotic hysterectomy, or uterine artery embolization. STUDY DESIGN: The COMPARE-UF registry is a multiinstitutional prospective observational cohort study of women undergoing treatment for uterine fibroids. A subset of 1384 women aged 31 to 45 years who underwent either abdominal myomectomy (n=237), laparoscopic myomectomy (n=272), abdominal hysterectomy (n=177), laparoscopic hysterectomy (n=522), or uterine artery embolization (n=176) were included in this analysis. We obtained demographics, fibroid history, and symptoms by questionnaires at enrollment and at 1, 2, and 3 years posttreatment. We used the UFS-QoL (Uterine Fibroid Symptom and Quality of Life) questionnaire to ascertain symptom severity and health-related quality of life scores among participants. To account for potential baseline differences across treatment groups, a propensity score model was used to derive overlap weights and compare total health-related quality of life and symptom severity scores after enrollment with a repeated measures model. For this health-related quality of life tool, a specific minimal clinically important difference has not been determined, but on the basis of previous research, a difference of 10 points was considered as a reasonable estimate. Use of this difference was agreed upon by the Steering Committee at the time when the analysis was planned. RESULTS: At baseline, women undergoing hysterectomy and uterine artery embolization reported the lowest health-related quality of life scores and highest symptom severity scores compared with those undergoing abdominal myomectomy or laparoscopic myomectomy (P<.001). Those undergoing hysterectomy and uterine artery embolization reported the longest duration of fibroid symptoms with a mean of 6.3 years (standard deviation, 6.7; P<.001). The most common fibroid symptoms were menorrhagia (75.3%), bulk symptoms (74.2%), and bloating (73.2%). More than half (54.9%) of participants reported anemia, and 9.4% women reported a history of blood transfusion. Across all modalities, total health-related quality of life and symptom severity score markedly improved from baseline to 1-year with the largest improvement in the laparoscopic hysterectomy group (Uterine Fibroids Symptom and Quality of Life: delta= [+] 49.2; symptom severity: delta= [-] 51.3). Those undergoing abdominal myomectomy, laparoscopic myomectomy, and uterine artery embolization also demonstrated significant improvement in health-related quality of life (delta= [+]43.9, [+]32.9, [+]40.7, respectively) and symptom severity (delta= [-]41.4, [-] 31.5, [-] 38.5, respectively) at 1 year, and the improvement persisted from baseline for uterine-sparing procedures during second (Uterine Fibroids Symptom and Quality of Life: delta= [+]40.7, [+]37.4, [+]39.3 SS: delta= [-] 38.5, [-] 32.0, [-] 37.7 and third year (Uterine Fibroids Symptom and Quality of Life: delta= [+] 40.9, [+]39.9, [+]41.1 and SS: delta= [-] 33.9, [-]36.5, [-] 33.0, respectively), posttreatment intervals, however with a trend toward decline in degree of improvement from years 1 and 2. Differences from baseline were greatest for hysterectomy; however, this may reflect the relative importance of bleeding in the Uterine Fibroids Symptom and Quality of Life, rather than clinically meaningful symptom recurrence among women undergoing uterus-sparing treatments. CONCLUSION: All treatment modalities were associated with significant improvements in health-related quality of life and symptom severity reduction 1-year posttreatment. However, abdominal myomectomy, laparoscopic myomectomy and uterine artery embolization indicated a gradual decline in symptom improvement and health-related quality of life by third year after the procedure.

Geographic variation in the rate and route of hysterectomy for benign disease in the USA: A retrospective cross-sectional study.

OBJECTIVES: To describe population rate of hysterectomy for benign disease in the USA, including geographic variation across states and Hospital Service Areas (HSAs; areas defined by common patient flows to healthcare facilities). DESIGN: Cross-sectional study. SETTING: Four US states including 322 HSAs. POPULATION: A total of 316 052 cases of hysterectomy from 2012 to 2016. METHODS: We compiled annual hysterectomy cases, merged female populations, and adjusted for reported rates of previous hysterectomy. We assessed small-area variation and created multi-level Poisson regression models. MAIN OUTCOME MEASURES: Prior-hysterectomy-adjusted population rates of hysterectomy for benign disease. RESULTS: The annual population rate of hysterectomy for benign disease was 49 per 10 000 hysterectomy-eligible residents, declining slightly over time, mostly among reproductive-age populations. Rates peaked among residents ages 40-49 years, and declined with increasing age, apart from an increase with universal coverage at age 65 years. We found large differences in age-standardised population rates of hysterectomy across states (range 42.2-69.0), and HSAs (range: overall 12.9-106.3; 25th-75th percentile 44.0-64.9). Among the non-elderly population, those with government-sponsored insurance had greater variation than those with private insurance (coefficient of variation 0.61 versus 0.32). Proportions of minimally invasive procedures were similar across states (71.0-74.8%) but varied greatly across HSAs (27-96%). In regression models, HSA population characteristics explained 31.8% of observed variation in annual rates. Higher local proportions of government-sponsored insurance and non-White race were associated with lower population rates. CONCLUSIONS: We found substantial variation in rate and route of hysterectomy for benign disease in the USA. Local population characteristics explained less than one-third of observed variation.

Cost-effectiveness of agents used for evaluation of ureteral patency during intraoperative cystoscopy in gynecologic and urogynecologic surgery.

BACKGROUND: Intraoperative evaluation of ureteral patency is often performed in gynecologic and urogynecologic surgery. Many agents are used to help assess the patency, each with its own associated cost, ease of use, and adverse reactions. Some agents, such as dextrose, are used as an instillation fluid to create a viscosity difference and aid the visualization of a ureteral jet. Others, such as oral phenazopyridine or the intravenous use of sodium fluorescein and indigo carmine, cause a color change of the urine to directly aid the visualization of ureteral jets. Recently, numerous studies have examined the efficacy and surgeon satisfaction of these agents. The studies have also emphasized certain options as associated with a lower cost. However, there have not been any cost studies comparing these agents. OBJECTIVE: To compare the cost-effectiveness of the following 4 agents that are commonly used in assessing ureteral patency intraoperatively: oral phenazopyridine, dextrose instillation, intravenous sodium fluorescein, and intravenous indigo carmine. STUDY DESIGN: We constructed a decision-analytic model to compare cystoscopy using oral phenazopyridine, dextrose instillation, intravenous sodium fluorescein, and intravenous indigo carmine. Failure to see efflux resulted in work-ups for ureteral obstruction. The probabilities were obtained from published studies, and the probability of successfully seeing efflux ranged from 0.92 with oral phenazopyridine to 0.99 with intravenous indigo carmine. The costs of the agents, adverse effects, and ureteral obstruction work-ups were obtained from the University of North Carolina at Chapel Hill Department of Pharmacy, the Healthcare Cost and Utilization Project 2016 database and the FAIR Health Consumer database. The cost of a ureteral obstruction work-up used in our model ranged from $9755 for intraoperative evaluation with retrograde pyelograms and stents to $29,034 for hospitalization. Our primary outcome was the incremental cost-effectiveness ratio per unnecessary work-up for ureteral obstruction avoided. Sensitivity analyses were performed to identify the key uncertainties. RESULTS: Oral phenazopyridine, followed by an intravenous agent if needed, had a mean cost of $110 per patient. Dextrose averaged $151 more per patient, with only a slight improvement in avoiding unnecessary ureteral obstruction work-ups and a higher cost associated with adverse reactions (incremental cost-effectiveness ratio, $62,000). Intravenous agents cost approximately $1000 more per patient and were less effective at preventing unnecessary work-ups. Sensitivity analyses did not identify any thresholds that would significantly change the outcomes. CONCLUSION: Our model suggests that oral phenazopyridine and dextrose instillation are the least expensive and the most effective agents to aid in the visualization of ureteral patency during intraoperative cystoscopy, although dextrose is associated with higher costs owing to a higher rate of adverse reactions (primarily urinary tract infections). Intravenous sodium fluorescein and indigo carmine are historically popular first-choice agents. However, they were found to be more expensive and less effective as primary agents in our model and should likely be reserved for use as secondary agents in the event that the visualization of ureteral jets is unclear with the initial use of phenazopyridine or dextrose.

Surveillance for gestational trophoblastic neoplasia following molar pregnancy: a cost-effectiveness analysis.

BACKGROUND: Historically, published guidelines for care after molar pregnancy recommended monitoring human chorionic gonadotropin levels for the development of gestational trophoblastic neoplasia until normal and then for 6 months after the first normal human chorionic gonadotropin. However, there are little data underlying such recommendations, and recent evidence has demonstrated that gestational trophoblastic neoplasia diagnosis after human chorionic gonadotropin normalization is rare. OBJECTIVE: We sought to estimate the cost-effectiveness of alternative strategies for surveillance for gestational trophoblastic neoplasia after human chorionic gonadotropin normalization after complete and partial molar pregnancy. STUDY DESIGN: A Markov-based cost-effectiveness model, using monthly cycles and terminating after 36 months/cycles, was constructed to compare alternative strategies for asymptomatic human chorionic gonadotropin surveillance after the first normal (none; monthly testing for 1, 3, 6, and 12 months; or every 3-month testing for 3, 6, and 12 months) for both complete and partial molar pregnancy. The risk of reduced surveillance was modeled by increasing the probability of high-risk disease at diagnosis. Probabilities, costs, and utilities were estimated from peer-reviewed literature, with all cost data applicable to the United States and adjusted to 2020 US dollars. The primary outcome was cost per quality-adjusted life year ($/quality-adjusted life year) with a $100,000/quality-adjusted life year willingness-to-pay threshold. RESULTS: Under base-case assumptions, we found no further surveillance after the first normal human chorionic gonadotropin to be the dominant strategy from both the healthcare system and societal perspectives, for both complete and partial molar pregnancy. After complete mole, this strategy had the lowest average cost (healthcare system, $144 vs maximum $283; societal, $152 vs maximum $443) and highest effectiveness (2.711 vs minimum 2.682 quality-adjusted life years). This strategy led to a slightly higher rate of death from gestational trophoblastic neoplasia (0.013% vs minimum 0.009%), although with high costs per gestational trophoblastic neoplasia death avoided (range, $214,000 to >$4 million). Societal perspective costs of lost wages had a greater impact on frequent surveillance costs than rare gestational trophoblastic neoplasia treatment costs, and no further surveillance was more favorable from this perspective in otherwise identical analyses. No further surveillance remained dominant or preferred with incremental cost-effectiveness ratio of <$100,000 in all analyses for partial mole, and most sensitivity analyses for complete mole. Under the assumption of no disutility from surveillance, surveillance strategies were more effective (by quality-adjusted life year) than no further surveillance, and a single human chorionic gonadotropin test at 3 months was found to be cost-effective after complete mole with incremental cost-effectiveness ratio of $53,261 from the healthcare perspective, but not from the societal perspective (incremental cost-effectiveness ratio, $288,783). CONCLUSION: Largely owing to the rare incidence of gestational trophoblastic neoplasia after human chorionic gonadotropin normalization after molar pregnancy, prolonged surveillance is not cost-effective under most assumptions. It would be reasonable to reduce, and potentially eliminate, current recommendations for surveillance after human chorionic gonadotropin normalization after molar pregnancy, particularly among partial moles. With any reduction in surveillance, patients should be counseled on symptoms of gestational trophoblastic neoplasia and established in routine gynecologic care.

Protocol for implementation of an evidence based parentally administered intervention for preterm infants.

BACKGROUND: Multi-sensory behavioral interventions for preterm infants have the potential to accelerate feeding, growth, and optimize developmental trajectories and increase parents' interactive engagement with their infants. However, few neonatal intensive care units (NICUs) provide evidence-based standardized early behavioral interventions as routine care. Lack of implementation is a major gap between research and clinical practice. H-HOPE, is a standardized behavioral intervention with an infant- directed component (Massage+) and a parent-directed component (four participatory guidance sessions that focus on preterm infants' behaviors and appropriate responses). H-HOPE has well documented efficacy. The purpose of this implementation study is to establish H-HOPE as the standard of care in 5 NICUs. METHODS: The study employs a Type 3 Hybrid design to simultaneously examine the implementation process and effectiveness in five NICUs. To stagger implementation across the clinical sites, we use an incomplete stepped wedge design. The five participating NICUs were purposively selected to represent different acuity levels, number of beds, locations and populations served. Our implementation strategy integrates our experience conducting H-HOPE and a well-established implementation model, the Consolidated Framework for Implementation Research (CFIR). The CFIR identifies influences (facilitators and barriers) that affect successful implementation within five domains: intervention characteristics, outer setting (the hospital and external events and stakeholders), inner setting (NICU), implementers' individual characteristics, and the implementation process. NICUs will use the CFIR process, which includes three phases: Planning and Engaging, Executing, and Reflecting and Evaluating. Because sustaining is a critical goal of implementation, we modify the CFIR implementation process by adding a final phase of Sustaining. DISCUSSION: This study builds on the CFIR, adding Sustaining H-HOPE to observe what happens when sites begin to maintain implementation without outside support, and extends its use to the NICU acute care setting. Our mixed methods analysis systematically identifies key facilitators and barriers of implementation success and effectiveness across the five domains of the CFIR. Long term benefits have not yet been studied but may include substantial health and developmental outcomes for infants, more optimal parent-child relationships, reduced stress and costs for families, and substantial indirect societal benefits including reduced health care and special education costs. TRIAL REGISTRATION: ClinicalTrials.gov registration number NCT04555590 , Registered on 8/19/2020.

Cost-effectiveness analysis comparing "PARP inhibitors-for-all" to the biomarker-directed use of PARP inhibitor maintenance therapy for newly diagnosed advanced stage ovarian cancer.

OBJECTIVES: Clinical trials evaluating universal PARP inhibitor (PARPi) frontline maintenance therapy for advanced stage ovarian cancer have reported progression-free survival (PFS) benefit. It is unclear whether PARPi maintenance therapy will universally enhance value (clinical benefits relative to cost of delivery). We compared a "PARPi-for-all" to a biomarker-directed frontline maintenance therapy approach as a value-based care strategy. METHODS: The cost of two frontline PARPi maintenance strategies, PARPi-for-all and biomarker-directed maintenance, was compared using modified Markov decision models simulating the study designs of the PRIMA, VELIA, and, PAOLA-1 trials. Outcomes of interest included overall costs and incremental cost-effectiveness ratios (ICERs) reported in US dollars per quality adjusted progression-free life-year (QA-PFY) gained. RESULTS: PARPi-for-all was more costly and provided greater PFS benefit than a biomarker-directed strategy for each trial. The mean cost per patient for the PARPi-for-all strategy was $166,269, $286,715, and $366,506 for the PRIMA, VELIA, and PAOLA-1 models, respectively. For the biomarker-directed strategy, the mean cost per patient was $98,188, $167,334, and $260,671 for the PRIMA, VELIA, and PAOLA-1 models. ICERs of PARPi-for-all compared to biomarker-directed maintenance were: $593,250/QA-PFY (PRIMA), $1,512,495/QA-PFY (VELIA), and $3,347,915/QA-PFY (PAOLA-1). At current drug pricing, there is no PFS improvement in a biomarker negative cohort that would make PARPi-for-all cost-effective compared to biomarker-directed maintenance. CONCLUSIONS: This study highlights the high costs of universal PARPi maintenance treatment, compared with a biomarker-directed PARPi strategy. Maintenance therapy in the front-line setting should be reserved for those with germline or somatic HRD mutations until the cost of therapy is significantly reduced.

Addressing heterogenous outcomes in uterine fibroid research: a call to action.

Uterine fibroid tumors are the most common benign pelvic tumors in women, with complications that include heavy menstrual bleeding, pelvic pain, reproductive complications, and bulk-related symptoms. Although the majority of uterine fibroid tumors are asymptomatic, those women who experience symptoms can experience substantial burdens on quality of life and daily functioning. Comparative effectiveness reviews of available medical, surgical, and radiologic treatments have found that a lack of high-quality data to inform treatment decisions is, in part, due to the use of heterogeneous outcomes and instruments in clinical studies. With multiple new interventions emerging, this call-to-action encourages the development and use of a core outcome set that will capture the most relevant, patient-important outcomes in late-phase and after-marketing therapeutic trials for uterine fibroid tumors. The core outcome set should be developed by a diverse, multistakeholder group comprised of key healthcare decision-makers. Development and uptake of a core outcome set ensures that a consistent, collaboratively vetted set of outcomes will be accessible across different studies and promotes transparency for innovators who seek to anticipate the evidence needs of patients, providers, payers, regulators, and other stakeholders.

Short-term quality of life after myomectomy for uterine fibroids from the COMPARE-UF Fibroid Registry.

BACKGROUND: Uterine fibroids may decrease quality of life in a significant proportion of affected women. Myomectomy offers a uterine-sparing treatment option for patients with uterine fibroids that can be performed abdominally, laparoscopically (with or without robotic assistance), and hysteroscopically. Quality of life information using validated measures for different myomectomy routes, especially hysteroscopic myomectomy, is limited. OBJECTIVE: To compare women's perception of their short-term health-related quality of life measures and reported time to return to usual activities and return to work for different routes of myomectomy. MATERIALS AND METHODS: Comparing Options for Management: Patient-centered Results for Uterine Fibroids (COMPARE-UF) is a prospective nationwide fibroid registry that enrolled premenopausal women seeking treatment for uterine fibroids at 8 clinical sites. For this analysis, we included women undergoing hysteroscopic, abdominal, or laparoscopic myomectomy who completed the postprocedure questionnaire scheduled between 6 and 12 weeks after surgery. Health-related quality of life outcomes, such as pain, anxiety, and return to usual activitie, were assessed for each route. The hysteroscopic myomectomy group had large differences in demographics, fibroid number, and uterine size compared to the other groups; thus, a direct comparison of quality of life measures was performed only for abdominal and laparoscopic approaches after propensity weighting. Propensity weighting was done using 24 variables that included demographics, quality of life baseline measures, and fibroid and uterine measurements. RESULTS: A total of 1206 women from 8 COMPARE-UF sites underwent myomectomy (338 hysteroscopic, 519 laparoscopic, and 349 abdominal). All women had substantial improvement in short-term health-related quality of life and symptom severity scores, which was not different among groups. Average symptom severity scores decreased about 30 points in each group. Return to usual activities averaged 0 days (interquartile range, 0-14 days) for hysteroscopic myomectomy, 21 days (interquartile range, 14-28 days) for laparoscopic myomectomy, and 28 days (interquartile range, 14-35 days) for abdominal myomectomy. After propensity adjustment, quality of life outcomes in the laparoscopic and abdominal myomectomy groups were similar except for more anxiety in the laparoscopic myomectomy group and slightly more pain in the abdominal myomectomy group. After propensity weighting, return to usual activities favored laparoscopic compared to abdominal procedures; median time was the same at 21 days, but the highest quartile of women in the abdominal group needed an additional week of recovery (interquartile range,14.0-28.0 for laparoscopic versus 14.0-35.0 for abdominal, P < .01). Time to return to work was also longer in the abdominal arm (median, 22 days; interquartile range, 14-40 days, versus median, 42; interquartile range, 27-56). CONCLUSION: Women who underwent myomectomy had substantial improvement in health-related quality of life, regardless of route of myomectomy. After propensity weighting, abdominal myomectomy was associated with a nearly 2-week longer time to return to work than laparoscopic myomectomy.

Estimating the number of potential family members eligible for BRCA1 and BRCA2 mutation testing in a "Traceback" approach.

U.S. guidelines recommend BRCA1/2 mutation testing for women diagnosed with high-grade ovarian cancer (HGOC) to increase recognition of carriers, but most remain unidentified and at risk. Accordingly, an approach termed "Traceback" has been proposed in which probands are retrospectively identified by testing archived pathology specimens, and family members are traced to provide genetic counseling and testing. We used population-based data to estimate the number of family members who might be contacted through such a program. We used incidence data from the Surveillance, Epidemiology, and End Results (SEER) Program to estimate the number of women diagnosed with HGOC from 2005 to 2016, and census data to estimate the number of spouses, offspring, and siblings (both sexes). Using overall survival for HGOC from SEER and all-cause mortality rates from the Centers for Diseases Control and Prevention, we estimated the number of patients, spouses, offspring, and siblings of HGOC cases living in 2017. Due to the high mortality rate of HGOC, consent from living probands may be possible in only 42% of the cases; consent to test pathology specimens would need to be sought from next of kin for the remainder. In 2017, an estimated 406,919 living next of kin (spouses, siblings, offspring) would be available for potential consent. Testing archived ovarian cancer pathology specimens may enable the identification of BRCA1/2 mutation carriers, but consent from next of kin would be required in in 58% of cases. Although Traceback offers the possibility of identifying unaffected BRCA1/2 mutation carriers, pilot feasibility studies that include assessment of methods to secure consent are needed.

Perspectives on the Costs of Cancer Care: A Survey of the American Society of Breast Surgeons.

BACKGROUND: Cancer treatment costs are not routinely addressed in shared decisions for breast cancer surgery. Thus, we sought to characterize cost awareness and communication among surgeons treating breast cancer. METHODS: We conducted a self-administered, confidential electronic survey among members of the American Society of Breast Surgeons from 1 July to 15 September 2018. Questions were based on previously published or validated survey items, and assessed surgeon demographics, cost sensitivity, and communication. Descriptive summaries and cross-tabulations with Chi-square statistics were used, with exact tests where warranted, to assess findings. RESULTS: Of those surveyed (N = 2293), 598 (25%) responded. Surgeons reported that 'risk of recurrence' (70%), 'appearance of the breast' (50%), and 'risks of surgery' (47%) were the most influential on patients' decisions for breast cancer surgery; 6% cited out-of-pocket costs as significant. Over half (53%) of the surgeons agreed that doctors should consider patient costs when choosing cancer treatment, yet the majority of surgeons (58%) reported 'infrequently' (43%) or 'never' (15%) considering patient costs in medical recommendations. The overwhelming majority (87%) of surgeons believed that patients should have access to the costs of their treatment before making medical decisions. Surgeons treating a higher percentage of Medicaid or uninsured patients were more likely to consistently consider costs (p < 0.001). Participants reported that insufficient knowledge or resources (61%), a perceived inability to help with costs (24%), and inadequate time (22%) impeded cost discussions. Notably, 20% of participants believed that discussing costs might impact the quality of care patients receive. CONCLUSIONS: Cost transparency remains rare, however in shared decisions for breast cancer surgery, improved cost awareness by surgeons has the potential to reduce financial hardship.

American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology screening guidelines for the prevention and early detection of cervical cancer.

An update to the American Cancer Society (ACS) guideline regarding screening for the early detection of cervical precancerous lesions and cancer is presented. The guidelines are based on a systematic evidence review, contributions from 6 working groups, and a recent symposium cosponsored by the ACS, the American Society for Colposcopy and Cervical Pathology, and the American Society for Clinical Pathology, which was attended by 25 organizations. The new screening recommendations address age-appropriate screening strategies, including the use of cytology and high-risk human papillomavirus (HPV) testing, follow-up (eg, the management of screen positives and screening intervals for screen negatives) of women after screening, the age at which to exit screening, future considerations regarding HPV testing alone as a primary screening approach, and screening strategies for women vaccinated against HPV16 and HPV18 infections.

Simulation model of the relationship between cesarean section rates and labor duration.

Cesarean delivery is the most common major abdominal surgery in many parts of the world, and it accounts for nearly one-third of births in the United States. For a patient who requires a C-section, allowing prolonged labor is not recommended because of the increased risk of infection. However, for a patient who is capable of a successful vaginal delivery, performing an unnecessary C-section can have a substantial adverse impact on the patient's future health. We develop two stochastic simulation models of the delivery process for women in labor; and our objectives are (i) to represent the natural progression of labor and thereby gain insights concerning the duration of labor as it depends on the dilation state for induced, augmented, and spontaneous labors; and (ii) to evaluate the Friedman curve and other labor-progression rules, including their impact on the C-section rate and on the rates of maternal and fetal complications. To use a shifted lognormal distribution for modeling the duration of labor in each dilation state and for each type of labor, we formulate a percentile-matching procedure that requires three estimated quantiles of each distribution as reported in the literature. Based on results generated by both simulation models, we concluded that for singleton births by nulliparous women with no prior complications, labor duration longer than two hours (i.e., the time limit for labor arrest based on the Friedman curve) should be allowed in each dilation state; furthermore, the allowed labor duration should be a function of dilation state.

Induction of Labor versus Scheduled Cesarean in Morbidly Obese Women: A Cost-Effectiveness Analysis.

OBJECTIVE: To assess the costs, complication rates, and harm-benefit tradeoffs of induction of labor (IOL) compared to scheduled cesarean delivery (CD) in women with class III obesity. STUDY DESIGN: We conducted a cost analysis of IOL versus scheduled CD in nulliparous morbidly obese women. Primary outcomes were surgical site infection (SSI), chorioamnionitis, venous thromboembolism, blood transfusion, and readmission. Model outcomes were mean cost of each strategy, cost per complication avoided, and complication tradeoffs. We assessed the costs, complication rates, and harm-benefit tradeoffs of IOL compared with scheduled CD in women with class III obesity. RESULTS: A total of 110 patients underwent scheduled CD and 114 underwent IOL, of whom 61 (54%) delivered via cesarean. The group delivering vaginally experienced fewer complications. SSI occurred in 0% in the vaginal delivery group, 13% following scheduled cesarean, and 16% following induction then cesarean. In the decision model, the mean cost of induction was $13,349 compared with $14,575 for scheduled CD. Scheduled CD costs $9,699 per case of chorioamnionitis avoided, resulted in 18 cases of chorioamnionitis avoided per additional SSI and 3 cases of chorioamnionitis avoided per additional hospital readmission. In sensitivity analysis, IOL is cost saving compared with scheduled CD unless the cesarean rate following induction exceeds 70%. CONCLUSION: In morbidly obese women, induction of labor remains cost-saving until the rate of cesarean following induction exceeds 70%.

The Comparing Options for Management: PAtient-centered REsults for Uterine Fibroids (COMPARE-UF) registry: rationale and design.

BACKGROUND: Uterine fibroids are common in premenopausal women, yet comparative effectiveness research on uterine fibroid treatments is rare. OBJECTIVE: The purpose of this study was to design and establish a uterine fibroid registry based in the United States to provide comparative effectiveness data regarding uterine fibroid treatment. STUDY DESIGN: We report here the design and initial recruitment for the Comparing Options for Management: Patient-centered REsults for Uterine Fibroids (COMPARE-UF) registry (Clinicaltrials.gov, NCT02260752), funded by the Agency for Healthcare Research and Quality in collaboration with the Patient-Centered Outcomes Research Institute. COMPARE-UF was designed to help answer critical questions about treatment options for women with symptomatic uterine fibroids. Women who undergo a procedure for uterine fibroids (hysterectomy, myomectomy [abdominal, hysteroscopic, vaginal, and laparoscopic/robotic], endometrial ablation, radiofrequency fibroid ablation, uterine artery embolization, magnetic resonance-guided focused ultrasound, or progestin-releasing intrauterine device insertion) at 1 of the COMPARE-UF sites are invited to participate in a prospective registry with 3 years follow up for postprocedural outcomes. Enrolled participants provide annual follow-up evaluation through an online portal or through traditional phone contact. A central data abstraction center provides information obtained from imaging, operative or procedural notes, and pathology reports. Women with uterine fibroids and other stakeholders are a key part of the COMPARE-UF registry and participate at all points from study design to dissemination of results. RESULTS: We built a network of 9 clinical sites across the United States with expertise in the care of women with uterine fibroids to capture geographic, racial, ethnic, and procedural diversity. Of the initial 2031 women who were enrolled in COMPARE-UF, 42% are self-identified as black or African American, and 40% are ≤40 years old, with 16% of participants <35 years old. Women who undergo myomectomy comprise the largest treatment group at 46% of all procedures, with laparoscopic or robotic myomectomy comprising the largest subset of myomectomies at 19% of all procedures. Hysterectomy is the second most common treatment within the registry at 38%. CONCLUSION: In response to priorities that were identified by our patient stakeholders, the initial aims within COMPARE-UF will address how different procedures that are used to treat uterine fibroids compare in terms of long-lasting symptom relief, potential for recurrence, medical complications, improvement in quality of life and sexual function, age at menopause, and fertility and pregnancy outcomes. COMPARE-UF will generate evidence on the comparative effectiveness of different procedural options for uterine fibroids and help patients and their caregivers make informed decisions that best meet an individual patient's short- and long-term preferences. Building on this infrastructure, the COMPARE-UF team of investigators and stakeholders, including patients, collaborate to identify future priorities for expanding the registry, such as assessing the efficacy of medical therapies for uterine fibroids. COMPARE-UF results will be disseminated directly to patients, providers, and other stakeholders by traditional academic pathways and by innovative methods that include a variety of social media platforms. Given demographic differences among women who undergo different uterine fibroid treatments, the assessment of comparative effectiveness for this disease through clinical trials will remain difficult. Therefore, this registry provides optimized evidence to help patients and their providers better understand the pros and cons of different treatment options so that they can make more informed decisions.

Cost Effectiveness of Risk-Reducing Mastectomy versus Surveillance in BRCA Mutation Carriers with a History of Ovarian Cancer.

BACKGROUND: The appropriate management of breast cancer risk in BRCA mutation carriers following ovarian cancer diagnosis remains unclear. We sought to determine the survival benefit and cost effectiveness of risk-reducing mastectomy (RRM) among women with BRCA1/2 mutations following stage II-IV ovarian cancer. DESIGN: We constructed a decision model from a third-party payer perspective to compare annual screening with magnetic resonance imaging (MRI) and mammography to annual screening followed by RRM with reconstruction following ovarian cancer diagnosis. Survival, overall costs, and cost effectiveness were determined by decade at diagnosis using 2015 US dollars. All inputs were obtained from the literature and public databases. Monte Carlo probabilistic sensitivity analysis was performed with a $100,000 willingness-to-pay threshold. RESULTS: The incremental cost-effectiveness ratio (ICER) per year of life saved (YLS) for RRM increased with age and BRCA2 mutation status, with greater survival benefit demonstrated in younger patients with BRCA1 mutations. RRM delayed 5 years in 40-year-old BRCA1 mutation carriers was associated with 5 months of life gained (ICER $72,739/YLS), and in 60-year-old BRCA2 mutation carriers was associated with 0.8 months of life gained (ICER $334,906/YLS). In all scenarios, $/YLS and mastectomies per breast cancer prevented were lowest with RRM performed 5-10 years after ovarian cancer diagnosis. CONCLUSION: For most BRCA1/2 mutation carriers following ovarian cancer diagnosis, RRM performed within 5 years is not cost effective when compared with breast cancer screening. Imaging surveillance should be advocated during the first several years after ovarian cancer diagnosis, after which point the benefits of RRM can be considered based on patient age and BRCA mutation status.