Faculty Bibliography

OBJECTIVE:To explore trends of ovarian conservation (OCN) over time in young women with early stage leiomyosarcoma (LMS) and examine the association between OCN and survival. METHODS:Patients under the age of 50 who were diagnosed with stage I LMS who underwent hysterectomy with and without oophorectomy between 2010 and 2016 were identified in the National Cancer Database (NCDB). Performance of oophorectomy vs. OCN was determined using surgery codes. Trends of OCN were reported. Multivariable regression models were fit to estimate predictors of OCN. An inverse probability of treatment weighted propensity score method was used to examine the association between all-cause mortality and OCN. RESULTS:Overall, 225 patients (28%) underwent OCN. Rates of OCN decreased from 41.2% (2010) to 14.3% (2016); this finding was consistent across age groups: <35, 35-39, 40-44, and 45-49 years. Race, insurance, and stage did not affect performance of OCN. Women with poorly differentiated tumors were less likely to undergo OCN compared to well-differentiated tumors (aRR 0.59; 95% CI 0.40-0.86). After propensity score weighting, there was no association between OCN and mortality (HR 1.19, 95% CI 0.80-1.77). Five-year survival for the OCN group was 67.1% (95% CI 59.8-75.2%) compared to 72.2% for the oophorectomy group (95% CI 67.2-77.5%). CONCLUSIONS:OCN for early stage LMS in premenopausal women has decreased over time. There was no association between OCN and mortality among women with stage I LMS. OCN should be considered in premenopausal women with stage I LMS given the health benefits.

OBJECTIVE:To examine the utilization, morbidity, and cost of sentinel lymph node mapping in women undergoing hysterectomy for complex atypical endometrial hyperplasia. METHODS:Women with complex atypical endometrial hyperplasia who underwent hysterectomy from 2012 to 2018 in the Perspective database were examined. Perioperative morbidity, mortality, and cost were examined based on performance of sentinel lymph node mapping, lymph node dissection or no nodal evaluation. RESULTS:Among 10,266 women, sentinel lymph node mapping was performed in 620 (6.0%), lymph node dissection in 538 (5.2%), and no lymphatic evaluation in 9,108 (88.7%). Use of sentinel lymph node mapping increased from 0.8% in 2012 to 14.0% in 2018, and the rate of lymph node dissection rose from 5.7% to 6.4% (P<.001). In an adjusted model, residence in the western United States, treatment by high-volume hospitals and use of robotic-assisted hysterectomy were associated with sentinel lymph node mapping (P<.05 for all). The complication rates were similar between the three groups. The median cost for sentinel lymph node mapping ($9,673) and lymph node dissection ($9,754) were higher than in those who did not undergo nodal assessment ($8,435) (P<.001). CONCLUSION:Performance of sentinel lymph node mapping is increasing rapidly for women with complex atypical endometrial hyperplasia but is not associated with increased perioperative morbidity or mortality.

IMPORTANCE:While cervical cancer screening with cytologic and human papillomavirus (HPV) testing has reduced mortality from cervical cancer, overuse of these tests is associated with downstream psychological and medical consequences, as well as significant costs. Guidelines now recommend less frequent testing, although adherence to these recommendations is uncertain. OBJECTIVE:To determine the frequency of overuse of cervical cancer screening tests. DESIGN, SETTING, AND PARTICIPANTS:This cohort study included 2 299 177 women aged 30 to 65 years recorded in the MarketScan database who underwent cervical cancer screening with cervical cytologic testing, cotesting, or primary HPV testing in 2013 through 2014. Women were followed-up for 3 years, and use of repeat testing during this period was noted. Clinical and demographic characteristics associated with overuse of screening and the association between screening and performance of routine gynecologic examinations were recorded. Data were analyzed from June 15 to September 15, 2020. MAIN OUTCOMES AND MEASURES:Cumulative performance of overuse of cervical cancer screening with repeat cytologic or HPV testing within 36 months of the index screening test. RESULTS:A total of 2 299 177 women with a median (interquartile range) age of 47 (39-54) years were identified. Initial cervical cancer screening consisted of cytologic testing alone in 1 286 179 women (55.9%), cotesting in 991 583 women (43.1%) and HPV testing in 21 415 women (0.9%). The cumulative incidence of repeat cervical cancer screening was 17.7% (95% CI, 17.6%-17.7%) at 12 months, 51.1% (95% CI, 51.0%-51.2%) at 24 months and 65.8% (65.7%-65.8%) at 36 months. Repeat screening was less common in older women (32 198 women [60.2%] aged 60-64 years vs 194 665 women [67.8%] aged 30-39 years; P < .001), women with medical comorbidities (125 197 women [64.1%] with ≥2 comorbidities vs 423 012 women [64.7%] with no comorbidities; P < .001), women screened in 2014 (176 734 women [53.4%] in 2014 vs 555 767 women [69.4%] in 2013; P < .001), and those screened with cotesting (277 032 women [56.9%] for cotesting vs 450 438 [71.2%] for cytologic testing; P < .001). In contrast, overuse of testing was more common in the Northeastern US (143 916 women [68.1%] in the Northeast vs 81 552 women [51.6%] in the West; P < .001), in women with more frequent outpatient visits (238 510 women [71.1%] with ≥6 visits vs 279 412 [58.7%] with ≤2 visits; P < .001). Women with a sexually transmitted infection after their index testing were also more likely to undergo repeat testing (adjusted odds ratio, 1.42 [95% CI, 1.21-1.68]). Women who did not undergo repeat screening were significantly less likely to undergo a gynecological exam after the index screening test: during year 2 of follow-up, 657 749 women (96.7%) who underwent repeating screening had a gynecological examination compared with 203 566 women (26.2%) who did not undergo a gynecological examination. CONCLUSIONS AND RELEVANCE:These findings suggest that among commercially insured women with average risk, cervical cancer screening tests were frequently overused.

OBJECTIVE:A systematic review was performed to examine the outcomes of simple hysterectomy for women with low-risk, early-stage cervical cancer. DATA SOURCES:MEDLINE, Embase, Web of Science, and ClinicalTrials.gov were searched from inception until November 4, 2020. STUDY ELIGIBILITY CRITERIA:Original research reporting recurrence or survival outcomes among women with early-stage cervical cancer (defined as stage IA2 to IB1 disease) who were treated with simple hysterectomy. METHODS:Data regarding study characteristics, tumor characteristics, other treatment modalities, adjuvant therapy, recurrence, and survival outcomes were analyzed. Studies that reported both simple hysterectomy and radical hysterectomy outcomes were compared in a subgroup analysis. Summary statistics were reported and eligible studies were further analyzed to determine an estimated hazard ratio comparing simple hysterectomy with radical hysterectomy. RESULTS:A total of 21 studies were included, of which 3 were randomized control trials, 14 retrospective studies, 2 prospective studies, and 2 population-level data sets. The cohort included 2662 women who underwent simple hysterectomy, of which 36.1% had stage IA2 disease and 61.0% stage IB1 disease. Most cases (96.8%) involved tumors of ≤2 cm in size, and 15.4% of cases were lymphovascular space invasion positive. Approximately 71.8% of women who underwent simple hysterectomy had a lymph node assessment, and 30.7% of women underwent adjuvant chemotherapy or radiation. The most common complications described were lymphedema (24%), lymphocysts (22%), and urinary incontinence (18.5%). The total death rate for studies that reported deaths was 5.5%. By stage, there was a 2.7% mortality rate among IA2 disease and a 7.3% mortality rate among IB1 disease. Of note, 18 studies reported outcomes for both simple and radical hysterectomy, with a 4.5% death rate in the radical hysterectomy group and a 5.8% death rate in the simple hysterectomy group. Estimated and reported hazard ratio demonstrated no significant association for mortality between radical and nonradical surgeries for IA2 disease but potentially increased risk of mortality among IB1 disease. All studies had a moderate to high risk of bias, including the 3 randomized control trials. Level of evidence was limited to III to IV. CONCLUSION:The use of less radical surgery for women with stage IA2 and small volume IB1 cervical cancers appears favorable. However, there is concern that simple hysterectomy in women with stage IB1 tumors may adversely impact survival. Overall, the quality of studies available is modest, limiting the conclusions that can be drawn from the available literature.

BACKGROUND:Women with newly diagnosed cervical cancer are often treated with extensive, multimodal therapies that may include a combination of surgery, radiation, and chemotherapy. Little is known about the cost of treatment or how these costs are passed on to the patients. OBJECTIVE:The objectives of this study were to examine the cost of care during the first year after a diagnosis of cervical cancer, to estimate the sources of the costs, and to explore the out-of-pocket costs. STUDY DESIGN:We performed a study of women with commercial insurance who received a new diagnosis of cervical cancer, and whose cases were recorded in the MarketScan database from 2008 to 2016. Patients were categorized based on the primary treatment received being either surgery (hysterectomy with or without adjuvant radiation or chemotherapy) or radiation. The inflation-adjusted medical expenditures for a 12-month period beginning on the date of the first treatment were estimated. The payments were divided into the expenditures of inpatient care, outpatient care (including chemotherapy), and outpatient pharmacy costs. The out-of-pocket costs incurred by the patients in the form of copayments, coinsurance, and deductibles were estimated. RESULTS:A total of 4495 patients, including 3014 (67%) who underwent surgery and 1481 (33%) who primarily underwent radiotherapy, were identified. The median total expenditure per patient during the first year after the diagnosis was $56,250 (interquartile range, $25,767-$107,532). The median total expenditure for patients with surgery as the primary treatment was $37,222 (interquartile range, $20,957-$75,555). The median total expenditure for patients treated primarily with radiotherapy was $101,266 (interquartile range, $63,155-$160,760). For patients treated primarily with surgery, inpatient services accounted for $15,145 (interquartile range, $0-$26,898), outpatient services accounted for $18,430 (interquartile range, $5354-$48,047), and outpatient pharmacy costs accounted for $628 (interquartile range, $141-$1847). The median cost for those women who did not require adjuvant therapy was $26,164 compared with $89,760 for women treated with adjuvant radiation. The median out-of-pocket costs for the cohort was $2253 (interquartile range, $1137-$3990) or 3.9% of the total costs. CONCLUSION:The cost of care for women with newly diagnosed cervical cancer is substantial. Overall, patients are responsible for approximately 3.9% of the costs in the form of out-of-pocket expenditures.

OBJECTIVE:To synthesize evidence from studies investigating survival outcomes for patients with ovarian cancer undergoing minimally invasive surgery (traditional or robotic laparoscopy) compared with those for patients with ovarian cancer undergoing laparotomy. DATA SOURCES:We searched Ovid MEDLINE and Embase (from inception to December 2019). METHODS OF STUDY SELECTION:Observational cohort studies and randomized controlled trials that compared risk of recurrence or death between women undergoing minimally invasive and open procedures for staging (10), interval cytoreduction (4), secondary cytoreduction (2), and evaluation of resectability (1) were included. TABULATION, INTEGRATION, AND RESULTS:Data on the number of participants, number of deaths and recurrences, and results of analyses of overall or progression-free survival were abstracted for all studies. A random-effects meta-analysis was used to pool the results of studies comparing minimally invasive staging and open staging. The surgical approach (minimally invasive versus open) was not significantly associated with hazard of death or recurrence (pooled hazard ratio 0.92; 95% confidence interval, 0.61-1.38) or all-cause mortality (pooled hazard ratio 0.96; 95% confidence interval, 0.49-1.89). One randomized trial demonstrated that diagnostic laparoscopy could triage patients to neoadjuvant chemotherapy and avoid suboptimal primary surgery, without affecting recurrence-free or overall survival. Most studies included in this review were observational and at high risk for bias, and few studies accounted for potential confounding. CONCLUSION:Although existing studies do not demonstrate deleterious survival effects associated with minimally invasive surgery for ovarian cancer, these data must be viewed with caution given the significant methodologic shortcomings in the existing literature.

OBJECTIVE:To evaluate the perioperative morbidity and mortality of patients with COVID-19 who undergo urgent and emergent surgery. SUMMARY BACKGROUND DATA:Although COVID-19 infection is usually associated with mild disease, it can lead to severe respiratory complications. Little is known about the perioperative outcomes of patients with COVID-19. METHODS:We examined patients who underwent urgent and emergent surgery at 2 hospitals in New York City from March 17 to April 15, 2020. Elective surgical procedures were cancelled throughout and routine, laboratory based COVID-19 screening was instituted on April 1. Mortality, complications, and admission to the intensive care unit were compared between patients with COVID-19 detected perioperatively and controls. RESULTS:Among 468 subjects, 36 (7.7%) had confirmed COVID-19. Among those with COVID-19, 55.6% were detected preoperatively and 44.4% postoperatively. Before the routine preoperative COVID-19 laboratory screening, 7.7% of cases were diagnosed preoperatively compared to 65.2% after institution of screening (P = 0.0008). The perioperative mortality rate was 16.7% in those with COVID-19 compared to 1.4% in COVID-19 negative subjects [aRR = 9.29; 95% confidence interval (CI), 5.68-15.21]. Serious complications were identified in 58.3% of COVID-19 subjects versus 6.0% of controls (aRR = 7.02; 95%CI, 4.96-9.92). Cardiac arrest, sepsis/shock, respiratory failure, pneumonia, acute respiratory distress syndrome, and acute kidney injury were more common in those with COVID-19. The intensive care unit admission rate was 36.1% in those with COVID-19 compared to 16.4% of controls (aRR = 1.34; 95%CI, 0.86-2.09). CONCLUSIONS:COVID-19 is associated with an increased risk for serious perioperative morbidity and mortality. A substantial number of patients with COVID-19 are not identified until after surgery.

IMPORTANCE:Although primary debulking surgery (PDS) is often considered the criterion standard for treatment of stage IV endometrial cancer, PDS is associated with significant morbidity and poor survival. Neoadjuvant chemotherapy (NACT) has been proposed as an alternative treatment strategy. OBJECTIVE:To determine the use of and outcomes associated with NACT for women with stage IV endometrial cancer. DESIGN, SETTING, AND PARTICIPANTS:This cohort study used the National Cancer Database to identify women with stage IV endometrial cancer treated from January 1, 2010, to December 31, 2015. The cohort was limited to women aged 70 years or younger with minimal comorbidity (comorbidity score = 0). Women were stratified based on receipt of NACT or PDS. A propensity score analysis with inverse probability weighting was performed to balance the clinical characteristics of the groups. Survival was examined using flexible parametric Royston-Parmer models to account for time-varying hazards associated with use of NACT. An intention-to-treat (ITT) analysis was performed, as was a per-protocol (PP) analysis that included only women who received treatment with both chemotherapy and surgery (in either sequence). Data were analyzed from March 15, 2018, to July 20, 2018. MAIN OUTCOMES AND MEASURES:Use of NACT and overall survival. RESULTS:Of a total of 4890 women (median age, 60 years [interquartile range, 54-65 years]) with stage IV endometrial cancer, NACT was used in 952 women (19.5%). Use of NACT increased from 106 of 661 women (16.0%; 95% CI, 13.2%-18.8%) in 2010 to 224 of 938 women (23.9%; 95% CI, 21.2%-26.6%) in 2015 (P < .001). In a multivariate model, more recent year of diagnosis (risk ratio [RR], 1.42; 95% CI, 1.21-1.79 for 2015 vs 2010), stage IVB disease (RR, 1.31; 95% CI, 1.03-1.67 for stage IVB vs IVA), and serous histology (RR, 1.38; 95% CI, 1.13-1.69 for serous vs endometrioid histology) were associated with use of NACT. In a propensity score-balanced cohort, use of NACT displayed a time-varying association with survival. In the ITT analysis, use of NACT was associated with decreased mortality for the first 3 months after diagnosis (hazard ratio [HR] at 2 months, 0.81; 95% CI, 0.66-0.99). After 4 months, the survival curves crossed, and receipt of NACT was associated with increased mortality (HR at 6 months, 1.23; 95% CI, 1.09-1.39). In the PP analysis, use of NACT was associated with decreased mortality for the first 8 months after diagnosis (HR at 6 months, 0.79; 95% CI, 0.63-0.98). After 9 months, the survival curves crossed, and receipt of NACT was associated with increased mortality (HR at 12 months, 1.22; 95% CI, 1.04-1.43). CONCLUSIONS AND RELEVANCE:The results of this cohort study suggest that women treated with PDS are at increased risk of early death but have a more favorable long-term prognosis. In contrast, results suggest that women treated with NACT, particularly if they ultimately undergo surgery, may have superior survival in the short term. Based on these findings, NACT may be appropriate for select patients with advanced uterine serous carcinoma.

OBJECTIVE:We used a novel machine learning algorithm to develop a precision prognostication system for endometrial cancer. METHODS:The Ensemble Algorithm for Clustering Cancer Data (EACCD) unsupervised machine learning algorithm was applied to women with endometrioid endometrial cancer in the Surveillance, Epidemiology, and End Results database from 2004 to 2015. The prognostic system was created based on TNM stage, grade, and age. The concordance (C-index) was used to cut dendrograms and create prognostic groups. Kaplan-Meier cancer-specific survival was employed to visualize the survival function of EACCD-based prognostic groups and AJCC groups. RESULTS:A total of 46,773 women were identified. Using the machine learning algorithm with TNM stage, grade, and three age groups, eleven prognostic groups were generated with a C-index of 0.8380. The five-year survival rates for the eleven groups ranged from 37.9-99.8%. To simplify the classification system further, using visual inspection of the data we created a modified EACCD grouping, and combined the top six survival groups into three new prognostic groups. The new five-year survival rates for these eight modified prognostic groups included: 99.1% for group 1, 96.5% for group 2, 92.2% for group 3, 84.8% for group 4, 72.7% for group 5, 61.1% for group 6, 52.6% for group 7, and 37.9% for group 8. The C-index for the modified eight prognostic groups was 0.8313. CONCLUSION:This novel machine learning algorithm demonstrates improved prognostic prediction for patients with endometrial cancer. Using machine learning for endometrial cancer allows for the integration of multiple factors to develop a precision prognostication system.

OBJECTIVE:The optimal adjuvant therapy for stage III endometrial cancer is unknown. Studies have suggested that combination therapy with chemotherapy and radiation is associated with improved survival. We examined early and late-term toxicities associated with chemotherapy (CT), external beam radiotherapy (RT), or combination chemoradiotherapy for stage III uterine cancer. METHODS:The SEER-Medicare database was used to identify women age ≥ 65 years with stage III uterine cancer who received adjuvant CT, RT, or chemoradiotherapy from 2000 to 2015. The associations between therapy and early and late-term toxicities identified with billing claims, hospitalizations and emergency department visits were examined using multivariable regression models. RESULTS:A total of 2185 patients were identified including 574 (26.3%) who received CT, 636 (29.1%) who received RT, and 975 (44.6%) who received chemoradiotherapy. The proportion of patients receiving chemoradiotherapy or CT increased over time. During the first 6 and 12 months of adjuvant therapy, RT was associated with a lower risk of early-term toxicity compared to chemoradiotherapy (aRR = 0.59, 95%CI 0.49-0.70 and aRR = 0.76, 95%CI 0.67-0.86, respectively) while CT shared a similar risk of early toxicities as chemoradiotherapy. CT and RT shared a similar risk of late-term toxicities compared to chemoradiotherapy. CT and RT alone were associated with a higher hazard for overall mortality than chemoradiotherapy (aHR = 1.27, 95% CI 1.10-1.47 and aHR = 1.25, 95% CI 1.08-1.44, respectively). CONCLUSION:Chemoradiotherapy is associated with lower mortality compared to single modality therapy and has a similar risk of early and late term toxicities compared to CT, though higher risk of early toxicities compared to RT.