Cost-effectiveness of lenvatinib plus pembrolizumab versus chemotherapy for recurrent mismatch repair-proficient endometrial cancer after platinum-based therapy.

OBJECTIVE: The recent Study 309-KEYNOTE-775 showed improved survival for lenvatinib plus pembrolizumab compared to chemotherapy in patients with recurrent endometrial cancer. We created a decision model to compare the cost-effectiveness of lenvatinib plus pembrolizumab in patients with recurrent mismatch repair-proficient (pMMR) endometrial cancer who had progressed after first-line chemotherapy. METHODS: A Markov model was created to simulate the clinical trajectory of 10,000 patients with recurrent pMMR endometrial cancer. The initial decision point in the model was treatment with ether lenvatinib plus pembrolizumab or chemotherapy (doxorubicin or dose-dense paclitaxel). Model probabilities, utility values and costs were derived with assumptions drawn from published literature. A cycle length of 3 months and a time horizon of 2 years was used. The effectiveness was calculated in terms of average quality adjusted life years (QALYs) gained. The primary outcome was incremental cost-effectiveness ratios (ICERs), expressed in 2020 US dollars/QALYs. One-way, two-way and probabilistic sensitivity analyses were performed. RESULTS: Chemotherapy was the least costly strategy at $66,693 followed by lenvatinib plus pembrolizumab ($193,590). Lenvatinib plus pembrolizumab resulted in more patients being alive at 2 years (lenvatinib plus pembrolizumab: 367, chemotherapy: 109). Chemotherapy was cost-effective compared with lenvatinib plus pembrolizumab (ICER: $164,493/QALYs). Lenvatinib plus pembrolizumab became cost-effective when its cost was reduced by $1553 per month (7.8% reduction). CONCLUSION: For patients with recurrent pMMR endometrial cancer Lenvatinib plus pembrolizumab is associated with greater survival but is more costly than chemotherapy. The cost of lenvatinib and pembrolizumab would have to be reduced by approximately 7% to be considered cost-effective.

Hospital Volume and Quality of Care for Emergency Gynecologic Care.

OBJECTIVE: To evaluate the association between hospital volume and the quality of gynecologic emergency care for tubal ectopic pregnancies, ovarian torsion, and pelvic inflammatory disease (PID). METHODS: In this cross-sectional analysis, we analyzed patients who presented for emergency care for tubal ectopic pregnancies, ovarian torsion, and PID using the Premier Healthcare Database from 2006 to 2020. We measured the following outcomes: methotrexate use for ectopic pregnancy, ovarian cystectomy for torsion, and guideline-based antibiotic use for PID. For each condition, we measured outlier hospitals that performed the above interventions at below the 10th percentile. Multivariable logistic regression models were used to analyze associations between outlier care and hospital factors such as annualized mean case volume, urban or rural location, teaching status, bed capacity, and geographic region, as well as hospital-level patient population factors, including age, insurance status, and race. RESULTS: A total of 602 hospitals treated patients with tubal ectopic pregnancies, of which 21.9% were outliers, with no cases managed with methotrexate. Of 512 hospitals treating patients with ovarian torsion, 17.4% were outliers, with no cases managed with cystectomy. Of 929 hospitals that treated patients with PID, 9.9% were deemed outliers with low rates of guideline-adherent antibiotic administration. Low-volume hospitals were more likely to be outliers with low rates of use of methotrexate for ectopic pregnancy (6.7% of high-volume hospitals vs 49.7% of low-volume hospitals were outliers; adjusted odds ratio [aOR] 0.13, 95% CI, 0.05-0.31 for high-volume hospitals) and cystectomy for torsion (34.9% of low-volume vs 2.4% of high-volume hospitals were outliers; aOR 0.05, 95% CI, 0.01-0.18 for high-volume hospitals). There was no association between hospital volume and lower rates of guideline-based antibiotic use for PID. CONCLUSION: Higher hospital volume is associated with use of conservative, fertility-preserving treatment of emergency gynecologic conditions, including ectopic pregnancy and ovarian torsion.

Ambient particulate matter air pollution exposure and ovarian cancer incidence in the USA: An ecological study.

OBJECTIVE: To investigate associations between air particulate matter of ≤2.5 µm in diameter (PM2.5 ) and ovarian cancer. DESIGN: County-level ecological study. SETTING: Surveillance, epidemiology, and end results from a collection of state-level cancer registries across 744 counties. Data from the Environmental Protection Agency's network for PM2.5 monitoring was used to calculate trailing 5- and 10-year PM2.5 county-level values. County-level data on demographic characteristics were obtained from the American Community Survey. POPULATION: A total of 98 751 patients with histologically confirmed ovarian cancer as a primary malignancy from 2000 to 2016. METHODS: Generalised linear regression models were developed to estimate the association between PM2.5 and PM10 levels, over 5- and 10-year periods of exposure, and ovarian cancer risk, after accounting for county-level covariates. MAIN OUTCOME MEASURES: Risk ratios for associations between ovarian cancer (both overall and specifically epithelial ovarian cancer) and PM2.5 levels. RESULTS: For the 744 counties included, the average PM2.5 level from 1990 through 2018 was 11.75 µg/m3 (SD = 3.7) and the average PM10 level was 22.7 µg/m3 (SD = 5.7). After adjusting for county-level covariates, the overall annualised ovarian cancer incidence was significantly associated with increases in 5-year PM2.5 (RR = 1.11 per 10 units (µg/m3 ) increase, 95% CI 1.06-1.16). Similarly, when the analysis was limited to epithelial cell tumours and adjusted for county-level covariates there was a significant association with trailing 5-year PM2.5 exposure models (RR = 1.12 per 10 units increase, 95% CI 1.08-1.17). Likewise, 10-year PM2.5 exposure was associated with ovarian cancer overall and with epithelial ovarian cancer. CONCLUSIONS: Higher county-level ambient PM2.5 levels are associated with 5- and 10-year incidences of ovarian cancer, as measurable in an ecological study.

Estrogen replacement therapy and non-hormonal medication use among patients with uterine cancer.

OBJECTIVE: As the prognosis for endometrial cancer is excellent, management of the effects of estrogen deprivation has an important influence on quality of life. We examined the trends in the use of estrogen replacement therapy (ERT) and non-hormonal medications among patients with uterine cancer following surgery. METHODS: The MarketScan Database was used to identify patients 18-49 years who underwent hysterectomy plus oophorectomy and those aged 50-75 years who underwent hysterectomy between 2008 and 2020. ERT and non-hormonal treatments of menopause were identified preoperatively and postoperatively. After propensity score balancing, difference-in-differences (DID) analyses were performed to compare the pre-and-postoperative changes in ERT and non-hormonal medication use between groups. The trends in postoperative use of ERT were assessed and tested using Cochran-Armitage trend tests. RESULTS: A total of 19,700 patients with uterine cancer and 185,150 controls were identified. Overall, postoperative ERT use decreased for both age groups and for patients with and without uterine cancer. The DID in ERT use between those with uterine cancer and those with benign pathology after hysterectomy was -37.1% (95% CI, -40.5 to -33.6%) for patients 18-49 years of age and - 10.4% (95% CI, -10.9 to -9.9%) for those 50-75 years. The DID for non-hormonal medication use between those with uterine cancer and those with benign pathology after hysterectomy was 11.2% (95% CI, 7.8 to 14.7%) for younger patients and 3.4% (95% CI, 2.9 to 4.0%) for those 50-75 years. The postoperative new ERT use has been declining over time in patients with uterine cancer in those 18-49 years of age (P = .02) and those 50-75 years of age (P < .001). CONCLUSIONS: The use of ERT is uncommon and has declined over time in patients with uterine cancer. Conversely, non-hormonal medications are more commonly used among patients with uterine cancer.

Systemic Progestins and Progestin-Releasing Intrauterine Device Therapy for Premenopausal Patients With Endometrial Intraepithelial Neoplasia.

OBJECTIVE: To estimate trends in use and outcomes of progestin therapy for premenopausal patients with endometrial intraepithelial neoplasia. METHODS: The MarketScan Database was used to identify patients aged 18-50 years with endometrial intraepithelial neoplasia from 2008 to 2020. Primary treatment was classified as hysterectomy or progestin-based therapy. Within the progestin group, treatment was classified as systemic therapy or progestin-releasing intrauterine device (IUD). The trends in use of progestins and the pattern of progestin use were examined. A multivariable logistic regression model was fit to examine the association between baseline characteristics and the use of progestins. The cumulative incidence of hysterectomy, uterine cancer, and pregnancy since initiation of progestin therapy was analyzed. RESULTS: A total of 3,947 patients were identified. Hysterectomy was performed in 2,149 (54.4%); progestins were used in 1,798 (45.6%). Use of progestins increased from 44.2% in 2008 to 63.4% in 2020 ( P =.002). Among the progestin users, 1,530 (85.1%) were treated with systemic progestin, and 268 (14.9%) were treated with progestin-releasing IUD. Among progestin users, use of IUD increased from 7.7% in 2008 to 35.6% in 2020 ( P <.001). Hysterectomy was ultimately performed in 36.0% (95% CI 32.8-39.3%) of those who received systemic progestins compared with 22.9% (95% CI 16.5-30.0%) of those treated with progestin-releasing IUD ( P <.001). Subsequent uterine cancer was documented in 10.5% (95% CI 7.6-13.8%) of those who received systemic progestins compared with 8.2% (95% CI 3.1-16.6%) of those treated with progestin-releasing IUD ( P =.24). Venous thromboembolic complications occurred in 27 (1.5%) of those treated with progestins; the venous thromboembolism (VTE) rate was similar for oral progestins and progestin-releasing IUD. CONCLUSION: The rate of conservative treatment with progestins in premenopausal individuals with endometrial intraepithelial neoplasia has increased over time, and among progestin users, progestin-releasing IUD use is increasing. Progestin-releasing IUD use may be associated with a lower rate of hysterectomy and a similar rate of VTE compared with oral progestin therapy.

Clear Cell Ovarian Carcinoma With C1 Lateral Mass Metastasis and Pathologic Fracture: A Case Report.

Osseous metastasis (OM) in ovarian cancer (OC) are rare, with an incidence ranging from 0.8% to 2.6%, and are associated with poor prognosis. The available literature on their management and associated complications is scarce. We report a case of International Federation of Gynecology and Obstetrics (FIGO) stage IVB clear cell epithelial OC (EOC) who presented with neck pain. Imaging revealed multiple cervical spine metastases with left vertebral artery encasement and concurrent C1 lateral mass compression fracture, without neurological deficit, requiring occiput to C2 posterior instrumentation and fusion. Early OM may be associated with shorter overall survival, and survival after OM diagnosis is on the order of months. Management of OM should include a multidisciplinary team and may require surgical stabilization in addition to systemic chemotherapy, local radiotherapy, and osteoclast inhibitors.

Heterogeneity of outcomes of endometrial cancer patients included in prospective clinical trials.

OBJECTIVE: To assess heterogeneity in five-year overall survival of patients with endometrial cancer using a large retrospective database with cohorts defined by recent prospective clinical trials. METHODS: The National Cancer Database was used to identify patients with endometrial cancer who underwent hysterectomy from 2004 to 2016. The reported inclusion criteria for GOG-249, PORTEC-3, and GOG-258 were used to define the respective cohorts. Five-year overall survival for each cohort was stratified by tumor characteristics and adjuvant therapy regimens. RESULTS: A total of 89,133 patients were identified who would have fulfilled the entry criteria to GOG-249, PORTEC-3, or GOG-258. When stratified by tumor characteristics, irrespective of adjuvant therapy, five-year overall survival ranged from 59.9%-81.7% for patients meeting GOG-249 inclusion criteria, 40.2%-81.8% for patients meeting PORTEC-3 inclusion criteria, and 17.5%-75.0% for those meeting GOG-258 inclusion criteria. Analysis of subgroups by adjuvant therapy regimen revealed significant improvement in five-year overall survival for chemoradiotherapy compared to chemotherapy or radiotherapy alone for endometroid stage III and stage IVA disease and for some stages of serous and clear cell histology. CONCLUSIONS: Recent prospective trials of adjuvant therapy for endometrial cancer have included heterogeneous cohorts of patients based on five-year overall survival rates when the populations are stratified by tumor characteristics. The variation in expected five-year overall survival for subsets of patients may result in underpowered studies or misleading results.

Dostarlimab for recurrent mismatch repair-deficient endometrial cancer: A cost-effectiveness study.

OBJECTIVE: Patients with recurrent endometrial cancer treated with carboplatin and paclitaxel whose disease progresses have few effective treatment options. Based on promising clinical trial data, the anti-programmed cell death 1 (anti-PD-1) antibody dostarlimab was recently granted accelerated approval for endometrial cancer by the US Food and Drug Administration. We developed a decision model to examine the cost-effectiveness of dostarlimab for patients with progressive/recurrent deficient mismatch repair (dMMR) endometrial cancer whose disease has progressed with first-line chemotherapy. DESIGN: Cost-effectiveness study. POPULATION: Hypothetical cohort of 6000 women with progressive/recurrent dMMR endometrial cancer. METHODS: The initial decision point in the Markov model was treatment with dostarlimab, pembrolizumab or pegylated liposomal doxorubicin (PLD). Model probabilities, and cost and utility values were derived with assumptions drawn from published literature. Effectiveness was estimated as average quality-adjusted life years (QALYs) gained. One-way, two-way and probabilistic sensitivity analyses were performed to vary the assumptions across a range of plausible values. MAIN OUTCOME MEASURES: The primary outcome was the incremental cost-effectiveness ratio (ICER). RESULTS: Pegylated liposomal doxorubicin (PLD) was the least costly strategy, at $55,732, followed by dostarlimab ($151,533) and pembrolizumab ($154,597). Based on a willingness-to-pay threshold of $100,000/QALY, PLD was cost-effective compared with dostarlimab, with an ICER of $331,913 per QALY gained for dostarlimab, whereas pembrolizumab was ruled out by extended dominance (less effective, more costly), compared with dostarlimab. In one-way sensitivity analyses, dostarlimab was cost-effective when its cost was reduced to $4905 (52% reduction). These results were robust in a variety of sensitivity analyses. CONCLUSIONS: Dostarlimab is associated with greater survival compared with other treatments for women with recurrent dMMR endometrial cancer. Although the agent is substantially more costly, dostarlimab became cost-effective when its cost was reduced to $5489 per cycle.

Temporal Trends in Cervical Cancer Screening Practices and Associated Downstream Abnormalities and Procedures Among Women With Insurance in the United States.

OBJECTIVE: To examine temporal trends in cervical cancer screening practices and associated downstream abnormalities and procedures. METHODS: Women aged 18-64 years with commercial insurance or Medicaid insurance from 2008 to 2019 were identified using the IBM MarketScan databases. The annual rates of screening overall and by type of test (cytology, co-testing, or primary human papillomavirus testing) were examined. Downstream abnormal cytologic and histologic test results, colposcopies, and excisional procedures were examined, and rates were reported for the population of eligible patients with continuous insurance and for those who underwent screening. Changes over time in testing and outcomes were compared using χ2 tests and Spearman's correlation. RESULTS: From 2008 to 2019, the annual screening prevalence decreased from 42.6% to 29.4% in women with commercial insurance (P<.001) and from 27.9% to 12.4% among women with Medicaid insurance (P<.001). In the cohort of women with commercial insurance, cytology usage decreased from 79.4% to 38.9% and co-testing increased from 20.1% to 59.6% (P<.001). Per 1,000 women screened, the rate of abnormal histologic and cytologic test results rose from 96 to 119 (P<.001) and colposcopies rose from 33 to 42 (P<.001); excisional procedures remained relatively constant. Per 1,000 eligible women, the rate of abnormal histologic and cytologic test results decreased from 41 to 35 (P<.001), colposcopies declined from 14 to 12, and excisional procedures decreased from 3 to 2. CONCLUSION: Human papillomavirus testing has been rapidly incorporated into cervical cancer screening and is associated with an increasing trend of downstream abnormalities and procedures among screened women but a declining trend at the population level.

Utilization and outcomes of adjuvant therapy for stage II and III uterine leiomyosarcoma.

OBJECTIVES: The optimal adjuvant therapy for uterine leiomyosarcoma (uLMS) remains uncertain. We analyzed the utilization of adjuvant chemotherapy and radiation therapy for stage II and III uLMS and explored the association between use of adjuvant therapy and survival. METHODS: Patients with stage II or III uLMS treated from 2004 to 2016 and recorded in the National Cancer Database were identified. Multivariable regression models were fit to estimate predictors of use of either adjuvant radiation therapy or chemotherapy. To analyze the impact of chemotherapy on all-cause mortality, an inverse probability of treatment weighted (IPTW) propensity score method was used to account for measured confounders, and the receipt of radiation therapy was adjusted in the outcome model. The process was repeated to analyze the impact of radiation therapy on all-cause mortality by using an IPTW propensity score method and adjusting for the receipt of adjuvant chemotherapy. RESULTS: A total of 890 patients were identified. Adjuvant chemotherapy use increased from 62.2% in 2010 to 70.4% in 2016, whereas radiation usage decreased from 26.7% in 2010 to 10.4% in 2016. Patients with stage III (vs. stage II) disease were less likely to receive radiation therapy. After propensity score weighting, chemotherapy was associated with a 30% decreased risk of all-cause mortality in stage III patients (HR 0.70, 95% CI 0.45-0.98) but had no effect on mortality for stage II patients (HR 0.93, 95% CI 0.70-1.20). Radiation therapy was associated with a 26% decreased risk of mortality for stage II tumors (HR 0.74; 95% CI, 0.53-0.99) and a 57% decrease in mortality for stage III disease (HR 0.43, 95% CI 0.18-0.99). CONCLUSIONS: Among women with stage II-III uLMS, use of chemotherapy is increasing while use of radiation therapy is decreasing. Radiation therapy is associated with improved survival in both stage II and III disease, while there was no association between use of adjuvant chemotherapy and survival in stage II patients.

Prophylactic endovascular internal iliac balloon placement during cesarean hysterectomy for placenta accreta spectrum.

BACKGROUND: The utility of prophylactic endovascular internal iliac balloon placement in the surgical management of placenta accreta spectrum is debated. OBJECTIVE: In this study, we review outcomes of surgical management of placenta accreta spectrum with and without prophylactic endovascular internal iliac balloon catheter use at a single institution. STUDY DESIGN: This is a retrospective cohort study of consecutive viable singleton pregnancies with a confirmed pathologic diagnosis of placenta accreta spectrum undergoing scheduled delivery from October 2018 through November 2020. In the T1 period (October 2018-August 2019), prophylactic endovascular internal iliac balloon catheters were placed in the operating room before the start of surgery. Balloons were inflated after neonatal delivery and deflated after hysterectomy completion. In the T2 period (September 2019-November 2020), endovascular catheters were not used. In both time periods, all surgeries were performed by a dedicated multidisciplinary team using a standardized surgical approach. The outcomes compared included the estimated blood loss, anesthesia duration, operating room time, surgical duration, and a composite of surgical complications. Comparisons were made using the Wilcoxon rank-sum test and the Fisher exact test. RESULTS: A total of 30 patients were included in the study (T1=10; T2=20). The proportion of patients with placenta increta or percreta was 80% in both groups, as defined by surgical pathology. The median estimated blood loss was 875 mL in T1 and 1000 mL in T2 (P=.84). The proportion of patients requiring any packed red blood cell transfusion was 60% in T1 and 40% in T2 (P=.44). The proportion of patients requiring >4 units of packed red blood cells was 20% in T1 and 5% in T2 (P=.25). Surgical complications were observed in 1 patient in each group. Median operative anesthesia duration was 497 minutes in T1 and 296 minutes in T2 (P<.001). Median duration of operating room time was 498 minutes in T1 and 205 minutes in T2 (P<.001). Median surgical duration was 227 minutes in T1 and 182 minutes in T2 (P<.05). The median duration of time for prophylactic balloon catheter placement was 74 minutes (range, 46-109 minutes). The median postoperative length of stay was similar in both groups (6 days in T1 and 5.5 days in T2; P=.36). CONCLUSION: The use of prophylactic endovascular internal iliac balloon catheters was not associated with decreased blood loss, packed red blood cell transfusion, or surgical complications. Catheter use was associated with increased duration of anesthesia, operating room time, and surgical time.

Pathologic characteristics, patterns of care, and outcomes of Asian-Americans and Pacific islanders with uterine cancer.

OBJECTIVES: To compare the patterns of care and outcomes of Asian-Americans/Pacific Islanders (AAPI) to non-Hispanic White (NHW) women with uterine cancer, and examine differences across Asian country of origin. METHODS: National Cancer Database was used to identify AAPI and NHW women with uterine cancer diagnosed from 2004 to 2017. Marginal multivariable log-linear regression models and Cox proportional-hazards models were developed to estimate differences in quality-of-care and all-cause mortality between AAPI and NHW women and across AAPI ethnic groups. RESULTS: We identified 13,454 AAPI and 354,693 NHW women. Compared to NHW women, AAPI patients were younger at diagnosis (median age 57 vs. 62 years), had fewer comorbidities, more often had serous or sarcoma histologic subtypes and stage III/IV cancer. AAPI women had a slightly higher rate of receiving pelvic lymphadenectomy for deeply invasive or high-grade tumors (77.6% vs. 74.3%), and a lower rate of undergoing minimally invasive surgery (70.4% vs. 74.8%) for stage I-IIIC tumors. Among patients undergoing hysterectomy, AAPI women had a lower mortality compared with NHW women for cancer stage I/II/III, and a 28% reduction for type I (grade 1 or 2 endometrioid cancers) disease (aHR = 0.72; 95% CI, 0.64-0.81). Among AAPI subgroups, Pacific Islanders had the worst survival across different cancer stage and disease type. CONCLUSION: AAPI women are diagnosed with uterine cancer at a younger age and have more aggressive histologic subtypes and advanced stage than their White counterparts. They have a similar level of quality-of-care as NHW women, and an improved survival for early stage and type I disease.

Uptake and outcomes of sentinel lymph node mapping in women undergoing minimally invasive surgery for endometrial cancer.

OBJECTIVE: To examine the patterns and outcomes of sentinel lymph node (SLN) assessment in women with endometrial cancer. DESIGN: Retrospective cohort study. SETTING: United States inpatient and outpatient hospital services. POPULATION: Women with endometrial cancer who underwent a laparoscopic or robotic-assisted hysterectomy. METHODS: The Perspective Database from 2012 to 2018 was used. Performance of lymph node dissection was classified as SLN mapping, lymph node dissection or no nodal evaluation. Adjusted regression models were developed to examine the association between SLN mapping and morbidity and cost. MAIN OUTCOME MEASURES: Utilisation rates, morbidity and cost of both lymph node dissection and SLN mapping. RESULTS: Among 45 381 patients, SLN mapping was performed for 7768 patients (17.1%), lymph node dissection was performed for 23 214 patients (51.2%) and no lymphatic evaluation was performed for 14 399 patients (31.7%). SLN mapping increased from 1.8% in 2012 to 35.3% in 2018, whereas the rate of lymph node dissection decreased from 63.5% to 39.1% (p < 0.001). Among women who underwent nodal evaluation, residence in the west, White race and use of robotic-assisted hysterectomy were associated with SLN mapping (p < 0.05 for all). The complication rate was 5.9% for SLN mapping, compared with 7.3% in those that underwent lymph node dissection (aRR 0.85, 95% CI 0.77-0.95). The median hospital costs for women who underwent SLN mapping ($10 479) and lymph node dissection ($10 747) were higher than for those who did not undergo nodal assessment ($9149) (p < 0.001). CONCLUSIONS: The performance of SLN mapping is increasing for endometrial cancer. Compared with lymph node dissection, SLN mapping is associated with lower morbidity. SLN mapping significantly increases the costs compared with hysterectomy alone. TWEETABLE ABSTRACT: SLN mapping is increasing rapidly for endometrial cancer and is associated with decreased perioperative morbidity.

Long-term outcomes of vaginal hysterectomy for endometrial cancer.

BACKGROUND: Total vaginal hysterectomy (TVH) has been proposed as an alternative to laparoscopic (TLH) and abdominal hysterectomy (TAH), particularly for women with medical comorbidities. We examined the use and long-term outcomes of vaginal hysterectomy for women with early-stage endometrial cancer. METHODS: The Surveillance, Epidemiology, and End Results-Medicare database was used to identify women with stage I-II endometrial cancer treated with primary hysterectomy from 2000 to 2015. Multivariable regression models were developed to examine clinical, demographic, and pathologic factors associated with performance of TVH. The association between route of hysterectomy and cancer-specific and overall survival was examined using multivariable Cox proportional hazards models. RESULTS: A total of 19,212 patients including 837 (4.6%) who underwent TVH were identified. Performance of TVH declined from 4.5% in 2000 to 2.2% in 2015 (P < 0.0001). Compared to patients 65-69 years of age, patients 75-79 years old (aRR = 1.46; 95% CI, 1.19-1.79) and those >80 years old (aRR = 1.60; 95% CI, 1.30-1.97) were more likely to undergo TVH. Women with high grade tumors were less likely to undergo TVH. Five-year overall and cancer specific survivals were similar for TAH, TLH, and TVH. In multivariable models, there was no association between TVH and either cancer-specific survival (HR = 0.89; 95% CI, 0.65-1.22) compared to laparoscopic hysterectomy. CONCLUSION: Use of TVH for stage I and II endometrial cancer has decreased in the U.S. Chronologic age is the greatest predictor of performance of TVH. Performance of TVH does not negatively impact survival for women with early-stage endometrial cancer.

Patterns of cervical cancer screening among Medicaid beneficiaries.

OBJECTIVE: Cervical cancer screening guidelines have evolved over time with the incorporation of human papillomavirus (HPV) testing along with cytology. Current screening guidelines recommend cytological screening every 3 years or HPV testing with or without cytology every 5 years in women age 30-65 years. We examined the use of cervical cancer screening among average-risk Medicaid beneficiaries. DESIGN: Retrospective cohort study. POPULATION: Women age 30-64 years at average risk for cervical cancer who underwent cervical cancer screening with cytology, co-testing or primary HPV testing from 2013 to 2016. METHODS: The IBM Watson Health Multi-State Medicaid MarketScan Database was used. Subsequent screening rates within 3 years of the index test were examined. MAIN OUTCOME MEASURE: The rate of repeat cervical cancer screening was analysed using a cumulative incidence function. RESULTS: A total of 265 083 patients were identified. Overall, 43.1% (n = 114 312) had index co-testing, 55.2% (n = 146 309) had cytology and 1.7% (n = 4462) had primary HPV testing. The cumulative incidence of early, repeat cervical cancer screening was 3.9% at 12 months, 22.7% at 24 months and 33.3% at 36 months. During the period from 12 to 24 months after follow up, 20.9% of women underwent repeat screening while 19.4% underwent repeat screening 24-36 months after the index test. Among women who did not undergo repeat cervical cancer screening, a yearly gynaecological examination was performed in only 16 627 (10.7%) during year 2 and in 11 116 (8.8%) during year 3. CONCLUSION: Among average-risk Medicaid beneficiaries, cervical cancer screening is frequently overused. Women who do not undergo cervical cancer screening are unlikely to undergo routine gynaecological examination. TWEETABLE ABSTRACT: Among average-risk Medicaid beneficiaries, cervical cancer screening is frequently overused.

Adoption of minimally invasive surgery after neoadjuvant chemotherapy in women with metastatic uterine cancer.

OBJECTIVE: Utilization of neoadjuvant chemotherapy (NACT) for advanced stage uterine cancer is increasing. We analyzed the use and outcomes of open versus minimally invasive surgery (MIS) for women with stage IV uterine cancer who received NACT and underwent IDS. METHODS: The National Cancer Database was used to identify women with stage IV uterine cancer diagnosed from 2010 to 2017 and treated with NACT. Among women who underwent IDS, overall survival (OS) was compared between those who underwent laparotomy vs a minimally invasive approach. To account for imbalances in confounders, a propensity score analysis using inverse probability of treatment weighting (IPTW) was performed. RESULTS: A total of 1618 women were identified. Minimally invasive IDS was performed in 31.1% and increased from 16.2% in 2010 to 40.4% in 2017 (P < 0.001). More recent year of diagnosis and performance of surgery at a comprehensive cancer center were associated with increased use of MIS (P < 0.05). Women with serous and clear cell tumors, and carcinosarcomas (compared to endometrioid tumors), as well as Medicaid coverage (compared to commercial insurance) were less likely to undergo an MIS approach (P < 0.05). The median OS was 28 months (95% CI 23.7-30.7) and 24.3 months (95% CI 22.3-26.1) for MIS and laparotomy, respectively. After propensity score balancing, there was no association between the use of MIS and survival (HR = 0.90, 95% CI 0.71-1.14). CONCLUSIONS: Among women with stage IV uterine cancer treated with NACT performance of minimally invasive debulking surgery is increasing. Compared to laparotomy, MIS does not appear to negatively impact survival.

Trends in the Use of Minimally Invasive Adnexal Surgery in the United States.

OBJECTIVE: To examine the utilization of minimally invasive adnexal surgery, including ovarian cystectomy and oophorectomy, among women with benign gynecologic diseases and compare the associated morbidity and mortality of minimally invasive and open surgery. METHODS: Women with benign ovarian pathology who underwent an ovarian cystectomy or oophorectomy from 2016 through 2018 in the Nationwide Ambulatory Surgery Sample and Nationwide Inpatient Sample databases were included. Patients with a diagnosis of gynecologic malignancy or concurrent hysterectomy were excluded. Population-level weighted estimates were developed, and perioperative morbidity, mortality, and hospital charges were examined based on surgical approach for each procedure. RESULTS: The cohort included 351,207 women who underwent oophorectomy and 220,893 women who underwent cystectomy, when weighted representing 547,836 and 328,408 patients, respectively, nationwide. A minimally invasive surgical approach was used in 294,190 (89.6%) patients who underwent ovarian cystectomy, and in 478,402 (87.3%) of patients who underwent oophorectomy. Use of minimally invasive surgery for cystectomy increased from 88.7% in 2016 to 91.0% in 2018, and the rate of minimally invasive surgery for oophorectomy increased from 85.8% to 88.7% over the same time period (P<.001 for both). The complication rates for ovarian cystectomy were 2.7% for minimally invasive surgery and 8.8% for laparotomy (P<.001); for oophorectomy the complication rate was 3.1% for minimally invasive surgery and 22.9% for laparotomy (P<.001). CONCLUSION: Minimally invasive surgery is used in the majority of women who are undergoing oophorectomy and ovarian cystectomy for benign indications. Compared with laparotomy, minimally invasive surgery is associated with fewer complications.

Intraoperative Rupture of the Ovarian Capsule in Early-Stage Ovarian Cancer: A Meta-analysis.

OBJECTIVE: To examine the effects of intraoperative ovarian capsule rupture on progression-free survival and overall survival in women who are undergoing surgery for early-stage ovarian cancer. DATA SOURCES: MEDLINE using PubMed, EMBASE (Elsevier), ClinicalTrials.gov, and Scopus (Elsevier) were searched from inception until August 11, 2020. METHODS OF STUDY SELECTION: High-quality studies reporting survival outcomes comparing ovarian capsule rupture to no capsule rupture among patients with early-stage epithelial ovarian cancer who underwent surgical management were abstracted. Study quality was assessed with the Newcastle-Ottawa Scale, and studies with scores of at least 7 points were included. TABULATION, INTEGRATION, AND RESULTS: The data were extracted independently by multiple observers. Random-effects models were used to pool associations and to analyze the association between ovarian capsule rupture and oncologic outcomes. Seventeen studies met all the criteria for inclusion in the meta-analysis. Twelve thousand seven hundred fifty-six (62.6%) patients did not have capsule rupture and had disease confined to the ovary on final pathology; 5,532 (33.7%) patients had intraoperative capsule rupture of an otherwise early-stage ovarian cancer. Patients with intraoperative capsule rupture had worse progression-free survival (hazard ratio [HR] 1.92, 95% CI 1.34-2.76, P<.001), with moderate heterogeneity (I2=41%, P=.07) when compared with those without capsule rupture. Pooled results from these studies showed a worse overall survival (HR 1.48, 95% CI 1.15-1.91, P=.003), with moderate heterogeneity (I2=53%, P=.02) when compared with patients without intraoperative capsule rupture. This remained significant in a series of sensitivity analyses. CONCLUSION: This systematic review and meta-analysis of high-quality observational studies shows that intraoperative ovarian capsule rupture results in decreased progression-free survival and overall survival in women with early-stage ovarian cancer who are undergoing initial surgical management. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42021216561.

Disparities in Access to High-Volume Surgeons Within High-Volume Hospitals for Hysterectomy.

OBJECTIVE: To examine access to high-volume surgeons in comparison with low-volume surgeons who perform hysterectomies within high-volume hospitals and to compare perioperative morbidity and mortality between high-volume and low-volume surgeons within these centers. METHODS: Women who underwent hysterectomy in New York State between 2000 and 2014 at a high-volume (top quartile by volume) hospital were included. Surgeons were classified into quartiles based on average annual hysterectomy volume. Multivariable models were used to determine characteristics associated with treatment by a low-volume surgeon in comparison with a high-volume surgeon and to estimate the association between physician volume, and morbidity and mortality. RESULTS: A total of 300,586 patients cared for by 5,505 surgeons at 59 hospitals were identified. Women treated by low-volume surgeons, in comparison with high-volume surgeons, were more often Black (19.4% vs 14.3%; adjusted odds ratio [aOR] 1.26; 95% CI 1.09-1.46) and had Medicare insurance (20.6% vs 14.5%; aOR 1.22; 95% CI 1.04-1.42). Low-volume surgeons were more likely to perform both emergent-urgent procedures (26.1% vs 6.4%; aOR 3.91; 95% CI 3.26-4.69) and abdominal hysterectomy, compared with minimally invasive hysterectomy (77.8% vs 54.7%; aOR 1.91; 95% CI 1.62-2.24). Compared with patients cared for by high-volume surgeons, those operated on by low-volume surgeons had increased risk of a complication (31.0% vs 10.3%; adjusted risk ratios [aRR] 1.84; 95% CI 1.71-1.98) and mortality (2.2% vs 0.2%; aRR 3.04; 95% CI 2.20-4.21). In sensitivity analyses, differences in morbidity and mortality remained for emergent-urgent procedures, elective operations, cancer surgery, and noncancer procedures. CONCLUSION: Socioeconomic disparities remain in access to high-volume surgeons within high-volume hospitals for hysterectomy. Patients who undergo hysterectomy at a high-volume hospital by a low-volume surgeon are at substantially greater risk for perioperative morbidity and mortality.

Association of New Perioperative Benzodiazepine Use With Persistent Benzodiazepine Use.

Importance: Increased use of benzodiazepines has resulted in increasing rates of misuse and adverse effects associated with these drugs. Little is known about the initial exposure and source of benzodiazepines among those who use them persistently. Objective: To examine the frequency of use and persistent use of benzodiazepines among patients undergoing major and minor surgical procedures. Design, Setting, and Participants: This cohort study included 2 509 599 adult patients who underwent 1 of 11 common surgical procedures in the United States from 2009 to 2017 and were recorded in the MarketScan database. The rates of perioperative and persistent benzodiazepine use were examined in benzodiazepine-naive patients. Data analysis was conducted from July to November 2020. Main Outcomes and Measures: Receipt of a perioperative benzodiazepine prescription and persistent use (ie, fill of a second prescription 90-180 days after surgery) among those who received a benzodiazepine perioperatively. Results: Among 2 509 599 included patients, the mean (SD) age was 54.4 (15.3) years, and 1 596 137 (63.6%) were women. Perioperative benzodiazepine use was noted in 63 931 patients (2.6%). The median (interquartile range) benzodiazepine supply was 10 (5-23) days. Among benzodiazepine-naive patients prescribed a perioperative benzodiazepine, the rate of persistent benzodiazepine use was 19.5% (95% CI, 19.2%-19.8%). During the 90 to 180-day period after surgery, 7013 of 12 468 patients (56.2%) received 1 prescription for benzodiazepines while 5455 (43.8%) received 2 or more prescriptions. Among patients prescribed a benzodiazepine, persistent use was more common in Medicaid recipients (vs patients with commercial insurance: adjusted rate ratio [aRR], 1.29; 95% CI, 1.03-1.62), patients 70 years or older (vs those aged 40-49 years: aRR, 1.14; 95% CI, 1.05-1.23), in women (vs men: aRR, 1.10; 95% CI, 1.06-1.15), in patients with more medical comorbidities (eg, Elixhauser comorbidity score ≥3 vs 0: aRR, 1.11; 95% CI, 1.04-1.19), and in those with diagnoses of anxiety, depression, insomnia or substance use disorder (eg, with vs without anxiety: aRR, 1.43; 95% CI, 1.37-1.50). Conclusions and Relevance: In this study, a relatively small percentage of surgical patients were prescribed benzodiazepines in the perioperative period; however, 1 in 5 of these patients went on to persistent benzodiazepine use.