Fertility-sparing surgery vs standard surgery for early-stage cervical cancer: difference in 5-year life expectancy by tumor size.

BACKGROUND: Cervical cancer incidence among premenopausal women is rising, and fertility-sparing surgery serves as an important option for this young population. There is a lack of evidence on what tumor size cutoff should be used to define candidacy for fertility-sparing surgery. OBJECTIVE: We sought to describe how the association between fertility-sparing surgery (compared with standard surgery) and life expectancy varies by tumor size among patients with cervical cancers measuring ≤4 cm in largest diameter. Our secondary objective was to quantify the probability of undergoing adjuvant radiotherapy among patients who underwent fertility-sparing surgery as a function of tumor size. STUDY DESIGN: We identified patients in the National Cancer Database aged ≤45 years, diagnosed with stage I cervical cancer with tumors ≤4 cm between 2006 and 2018, who received no preoperative radiation or chemotherapy, and who underwent either fertility-sparing surgery (cone or trachelectomy, either simple or radical) or standard surgery (simple or radical hysterectomy) as their primary treatment. Propensity-score matching was performed to compare patients who underwent fertility-sparing surgery with those who underwent standard surgery. A flexible parametric model was employed to quantify the difference in life expectancy within 5 years of diagnosis (restricted mean survival time) based on tumor size among patients who underwent fertility-sparing and those who underwent standard surgery. In addition, among those who underwent fertility-sparing surgery, a logistic regression model was used to explore the relationship between tumor size and the probability of receiving adjuvant radiation. RESULTS: A total of 11,946 patients met the inclusion criteria of whom 904 (7.6%) underwent fertility-sparing surgery. After propensity-score matching, 897 patients who underwent fertility-sparing surgery were matched 1:1 with those who underwent standard surgery. Although the 5-year life expectancy was similar among patients who had fertility sparing surgery and those who had standard surgery regardless of tumor sizes, the estimates of life-expectancy differences associated with fertility-sparing surgery were more precise among patients with smaller tumors (1-cm tumor: restricted mean survival time difference, -0.10 months; 95% confidence interval, -0.67 to 0.47) than among those with larger tumors (4-cm tumor: restricted mean survival time difference, -0.11 months; 95% confidence interval, -3.79 to 3.57). The probability of receiving adjuvant radiation increased with tumor size, ranging from 5.6% (95% confidence interval, 3.9-7.9) for a 1-cm tumor to 37% (95% confidence interval, 24.3-51.8) for a 4-cm tumor. CONCLUSION: Within 5 years of diagnosis, young patients with stage I cancers measuring ≤4 cm had similar survival outcomes after either fertility-sparing surgery or standard surgery. However, because few patients with tumors >2 cm underwent fertility-sparing surgery, a clinically important survival difference could not be excluded in this population.

Adjuvant external beam radiotherapy combined with brachytherapy for intermediate-risk cervical cancer.

OBJECTIVE: Patients with intermediate-risk cervical cancer receive external beam radiotherapy (EBRT) as adjuvant treatment. It is commonly administered with brachytherapy without proven benefits. Therefore, we evaluated the frequency of brachytherapy use, the doses for EBRT administered alone or with brachytherapy, and the overall survival impact of brachytherapy in patients with intermediate-risk, early-stage cervical cancer. METHODS: This retrospective cohort study was performed using data collected from the National Cancer Database. Patients diagnosed with cervical cancer from 2004 to 2019 who underwent a radical hysterectomy and lymph node staging and had disease limited to the cervix but with tumors larger than 4 cm or ranging from 2 to 4 cm with lymphovascular space invasion (LVSI) were included. Patients with distant metastasis or parametrial involvement were excluded. Patients who underwent EBRT alone were compared with those who also received brachytherapy after 2:1 propensity score matching. RESULTS: In total, 1174 patients met the inclusion criteria, and 26.7% of them received brachytherapy. After 2:1 propensity score matching, we included 620 patients in the EBRT group and 312 in the combination treatment group. Patients who received brachytherapy had higher equivalent doses than those only receiving EBRT. Overall survival did not differ between the two groups (hazard ratio (HR) 0.88 (95% confidence interval (CI), 0.62 to 1.23]; p=0.45). After stratification according to tumor histology, LVSI, and surgical approach, brachytherapy was not associated with improved overall survival. However, in patients who did not receive concomitant chemotherapy, the overall survival rate for those receiving EBRT and brachytherapy was significantly higher than that for those receiving EBRT alone (HR, 0.48 (95% CI, 0.27 to 0.86]; p=0.011). CONCLUSION: About one-fourth of the study patients received brachytherapy and EBRT. The variability in the doses and radiotherapy techniques used highlights treatment heterogeneity. Overall survival did not differ for EBRT with and without brachytherapy. However, overall survival was longer for patients who received brachytherapy but did not receive concomitant chemotherapy.

Delivery of hereditary cancer genetics services to patients newly diagnosed with ovarian and endometrial cancers at three gynecologic oncology clinics in the USA, Brazil, and Mexico.

OBJECTIVE: Three gynecologic oncology clinics located in the USA, Brazil, and Mexico collaborated to evaluate their delivery of hereditary cancer genetics services. This descriptive retrospective review study aimed to establish baseline rates and timeliness of guideline-recommended genetics service delivery to patients with ovarian, fallopian tube, primary peritoneal (ovarian), and endometrial cancers at each clinic. METHODS: Patients who were newly diagnosed with ovarian and endometrial cancers between September 1, 2018 and December 31, 2020 were identified from the medical records of the clinics. Genetics service delivery metrics included the rates of mismatch repair deficiency tumor testing for patients with endometrial cancer (microsatellite instability/immunohistochemistry, MSI/IHC), referral to genetics services for patients with ovarian cancer, completed genetics consultations, and germline genetic testing for patients with ovarian and endometrial cancers. Timeliness was calculated as the average number of days between diagnosis and the relevant delivery metric. Descriptive statistics were used to analyze data. RESULTS: In total, 1195 patients (596 with ovarian cancer, 599 with endometrial cancer) were included in the analysis, and rates of genetics service delivery varied by clinic. For patients with ovarian cancer, referral rates ranged by clinic from 32.6% to 89.5%; 30.4-65.1% of patients completed genetics consultation and 32.6-68.7% completed genetic testing. The timeliness to genetic testing for patients with ovarian cancer ranged by clinic from 107 to 595 days. A smaller proportion of patients with endometrial cancer completed MSI/IHC testing (10.0-69.2%), with the average time to MSI/IHC ranging from 15 to 282 days. Rates of genetics consultation among patients with endometrial cancer ranged by clinic from 10.8% to 26.0% and 12.5-16.6% completed genetic testing. CONCLUSIONS: All clinics successfully established baseline rates and timeliness of delivering hereditary cancer genetics services to patients with ovarian and endometrial cancers. Lower rates of delivering genetics services to patients with endometrial cancer warrant additional research and quality improvement efforts.

Recurrence After Biopsy-Confirmed Cervical High-Grade Intraepithelial Lesion Followed by Negative Conization: A Systematic Review and Meta-analysis.

ABSTRACT: The aim of the study is to assess the recurrence rate (as cervical intraepithelial neoplasia 2+ [CIN2+]) in patients who had a confirmed high-grade squamous intraepithelial lesion (CIN2-3) in a cervical biopsy specimen followed by a negative conization specimen. MATERIALS AND METHODS: A systematic literature review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. Ovid/MEDLINE, Ovid/Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched from inception until January 2023. The study protocol was registered in PROSPERO (ID number CRD42023393951). The search identified 3,089 articles; 1,530 were removed as duplicates, and 1,559 titles and abstracts were assessed for inclusion. The full text of 26 studies was assessed for eligibility, and finally, 12 studies with 1,036 patients were included. All included studies were retrospective cohort studies. A proportion meta-analysis was performed. RESULTS: For patients with negative conization specimens, the recurrence rate as CIN2+ during follow-up was 6% (95% CI, 1.8%-12.1%; I2 = 49.2; p < .0001, 215 patients and 4 studies) in the proportion meta-analysis, ranging from 0.3% to 13.0% for the individual studies. For patients with ≤CIN1 conization specimens, the recurrence rate as CIN2+ during follow-up was 3.6% (95% CI, 1.2%-7%; I2 = 75.1; p < .0001, 991 patients and 10 studies) in the proportion meta-analysis and ranged from 0.6% to 13.0% for the individual studies. CONCLUSIONS: The recurrence rate as CIN2+ for patients with a confirmed high-grade intraepithelial lesion on a cervical biopsy followed by a negative conization specimen is 6%. In patients with negative and CIN1 conization specimens, the recurrence rate is 3.6%.

All-cause and cancer-specific mortality after fertility-sparing surgery for stage IA and IC epithelial ovarian cancer.

OBJECTIVE: To compare all-cause and cancer-specific mortality between women who underwent fertility-sparing surgery (FSS) versus standard surgery for stage IA and IC epithelial ovarian cancer. METHODS: Reproductive aged patients (18-45) with stage IA or IC epithelial ovarian cancer diagnosed between 2000 and 2015 were identified in the California Cancer Registry. FSS was defined as retention of the contralateral ovary and the uterus, and standard surgery included at least removal of both ovaries and the uterus. The primary outcome was all-cause mortality and the secondary outcome was cancer-specific mortality. Inverse probability of treatment weighting (IPTW) was used to create two groups balanced on covariates of interest. The Kaplan-Meier method and Cox proportional hazards analysis were used to model survival outcomes. RESULTS: Among 1119 women who met inclusion criteria, 390 (34.9%) underwent FSS. IPTW yielded a balanced cohort of 394 women who underwent FSS and 723 women who underwent standard surgery. Among patients who underwent FSS, there were 45 deaths corresponding to an 85.4% (95% confidence interval [CI] 0.79-0.92) 10-year all-cause survival probability, compared to 81 deaths and 86.4% 10-year all-cause survival probability (95% CI 0.83-0.90) among patients who underwent standard surgery. FSS was not associated with increased all-cause mortality (HR 1.04, 95% CI 0.72-1.49) or cancer-specific mortality (HR 1.50, 95%CI 0.97-2.31). CONCLUSIONS: Among reproductive-aged patients with early-stage epithelial ovarian cancer fertility-sparing surgery was not associated with an increased risk of death compared to standard surgery.

Minimally invasive interval debulking surgery for advanced ovarian cancer after neoadjuvant chemotherapy.

OBJECTIVE: Assess outcomes of interval debulking surgery (IDS) after neoadjuvant chemotherapy via minimally invasive surgery (MIS) compared with laparotomy in patients with advanced epithelial ovarian cancer. METHODS: Patients diagnosed with stage IIIC or IV epithelial ovarian cancer between 2013 and 2018 who received neoadjuvant chemotherapy and IDS were identified in the National Cancer Database. Primary outcome was overall survival. Secondary outcomes were 5-year survival, 30- and 90-day postoperative mortality, extent of surgery, residual disease, hospitalization duration, surgical conversions, and unplanned readmissions. Propensity score matching was used to compare MIS and laparotomy for IDS. Association of treatment approach with overall survival was assessed using Kaplan-Meier method and Cox regression. Sensitivity analysis was conducted for effect of unmeasured confounders. RESULTS: A total of 7897 patients met inclusion criteria; 2021 (25.6%) underwent MIS. Percentage undergoing MIS increased from 20.3%-29.0% over the study period. After propensity score matching, median overall survival was 46.7 months in the MIS group versus 41.0 months in the laparotomy group [hazard ratio (HR) 0.86 (95%CI 0.79-0.94)]. Five-year survival probability was higher in MIS versus laparotomy (38.3% vs 34.8%, p < 0.01). There was lower 30- and 90-day mortality (0.3% vs 0.7% [p = 0.04] and 1.4% vs 2.5% [p = 0.01], respectively), shorter length of stay (median 3 vs 5 days, p < 0.01), lower residual disease (23.9% vs 26.7%, p < 0.01), and lower additional cytoreductive procedures (59.3% vs 70.8%, p < 0.01) in MIS compared to laparotomy, with similar rates of unplanned readmission (2.7% vs 3.1%, p = 0.39). CONCLUSIONS: Patients who undergo IDS by MIS have similar overall survival and decreased morbidity compared with laparotomy.

Systematic mapping review of guidelines for BRCA1/2 genetic testing globally: investigating geographic and regional disparities in health equity for women and families at risk for hereditary ovarian cancer.

OBJECTIVE: Identification of persons at risk for hereditary syndromes through genetic testing prior to cancer diagnosis may proactively reduce the cancer burden morbidity and mortality. Using a framework of health equity, this study characterizes the global landscape of publication and reference to BRCA1/2 genetic testing guidelines (GTG). METHODS: This study used a systematic literature search supplemented by an International Gynecologic Cancer Society (IGCS) informal survey and cross referenced with Myriad Genetics records, to identify published GTG, their country of origin, and countries referencing them. RESULTS: Of 1011 identified publications, 166 met the inclusion criteria, from which 46 unique guidelines were identified, published by 18 countries and two regions (Europe and the UK). Authorship from the USA accounted for 63% of publications on GTG. Systematic mapping reviews revealed 34 countries with published and/or referenced guidelines, the IGCS survey revealed 22 additional countries, and coordination with Myriad Genetics revealed additional information for two countries and primary information for one country. Of the 57 countries evaluated, 33% published their own guidelines and reference guidelines from another country/region, 5% published their own guidelines without referencing another country/region, and 61% only referenced a guideline from another country/region. No data were available for 138 of 195 countries, disproportionately from Africa, the Middle East, Eastern Europe, and Southeast Asia. CONCLUSIONS: Global geographic disparities in the publication and referencing of GTG exist, with a large emphasis on North American and European guidelines in the published literature. These disparities highlight a need for uniform BRCA GTG to improve global health equity.

What happens in the long term: Uptake of cancer surveillance and prevention strategies among at-risk relatives with pathogenic variants detected via cascade testing.

BACKGROUND: Cascade genetic testing for hereditary cancer syndromes offers affected relatives the opportunity to pursue cancer screening and risk-reducing surgery and thus reduces morbidity and mortality. The purpose of this study was to measure the long-term utilization of targeted cancer prevention and quality of life among at-risk relatives offered clinician-facilitated cascade genetic testing. METHODS: In a pilot study, at-risk relatives of patients with a hereditary cancer syndrome were contacted directly by the clinical team and offered telephone genetic counseling and genetic testing via an at-home, mailed saliva kit. Two-year follow-up results evaluating the use of targeted cancer prevention strategies and the quality of life for enrolled relatives were reported. Quality-of-life was measured with validated surveys, and scores were compared to the time of initial contact by the Wilcoxon signed-rank test. RESULTS: Ninety-five at-risk relatives were enrolled in the initial pilot study, and 72 (76%) participated in the 2-year follow-up; 57 of these (79%) had completed genetic testing. Twenty-five of those 57 relatives (44%) were found to harbor an inherited pathogenic variant. Guideline-based cancer surveillance was recommended to 18 relatives; 13 (72%) completed at least one recommended screening, and six (33%) completed all recommended screenings. Risk-reducing surgery was recommended to 10 relatives; four (40%) completed a total of eight procedures. Quality-of-life surveys demonstrated low levels of anxiety, depression, distress, and uncertainty. CONCLUSIONS: The 2-year follow-up of the original pilot study revealed that clinician-facilitated cascade testing resulted in genetically targeted cancer screening and prevention with preserved quality of life. These results, to be confirmed by larger randomized controlled trials, suggest that medical systems should consider supporting clinician-facilitated cascade testing programs.

Interventions to improve delivery of cancer genetics services in the United States: A scoping review.

PURPOSE: Interventions that decrease barriers and improve clinical processes can increase patient access to guideline-recommended cancer genetics services. We sought to identify and describe interventions to improve patient receipt of guideline-recommended cancer genetics services in the United States. METHODS: We performed a comprehensive search in Ovid MEDLINE and Embase, Scopus, and Web of Science from January 1, 2000 to February 12, 2020. Eligible articles reported interventions to improve the identification, referral, genetic counseling (GC), and genetic testing (GT) of patients in the United States. We independently screened titles and abstracts and reviewed full-text articles. Data were synthesized by grouping articles by clinical process. RESULTS: Of 44 included articles, 17 targeted identification of eligible patients, 14 targeted referral, 15 targeted GC, and 16 targeted GT. Patient identification interventions included universal tumor testing and screening of medical/family history. Referral interventions included medical record system adaptations, standardizing processes, and provider notifications. GC interventions included supplemental patient education, integrated GC within oncology clinics, appointment coordination, and alternative service delivery models. One article directly targeted the GT process by implementing provider-coordinated testing. CONCLUSION: This scoping review identified and described interventions to improve US patients' access to and receipt of guideline-recommended cancer genetics services.

Peritoneal carcinomatosis after minimally invasive surgery versus open radical hysterectomy: systematic review and meta-analysis.

OBJECTIVE: To assess the incidence of peritoneal carcinomatosis in patients undergoing minimally invasive or open radical hysterectomy for cervical cancer. METHODS: The MEDLINE (accessed through Ovid), Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Clinical Trials, and Scopus databases were searched for articles published from inception up to April 2022. Articles published in English were considered. The included studies reported on patients with International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IA-IIA squamous cell carcinoma, adenocarcinoma, and/or adenosquamous carcinoma of the cervix who underwent primary surgery. Studies had to report at least one case of peritoneal carcinomatosis as a recurrence pattern, and only studies comparing recurrence after minimally invasive surgery versus open surgery were considered. Variables of interest were manually extracted into a standardized electronic database. This study was registered in PROSPERO (CRD42022325068). RESULTS: The initial search identified 518 articles. After the removal of the duplicate entries from the initial search, two authors independently reviewed the titles and abstracts of the remaining 453 articles. Finally, 78 articles were selected for full-text evaluation; 22 articles (a total of 7626 patients) were included in the analysis-one randomized controlled trial and 21 observational retrospective studies. The most common histology was squamous cell carcinoma in 60.9%, and the tumor size was <4 cm in 92.8% of patients. Peritoneal carcinomatosis pattern represented 22.2% of recurrences in the minimally invasive surgery approach versus 8.8% in open surgery, accounting for 15.5% of all recurrences. The meta-analysis of observational studies revealed a statistically significant higher risk of peritoneal carcinomatosis after minimally invasive surgery (OR 1.90, 95% CI 1.32 to 2.74, p<0.05). CONCLUSION: Minimally invasive surgery is associated with a statistically significant higher risk of peritoneal carcinomatosis after radical hysterectomy for cervical cancer compared with open surgery.

Employment disruption among women with gynecologic cancers.

BACKGROUND: Adverse employment outcomes pose significant challenges for cancer patients, though data patients with gynecologic cancers are sparse. We evaluated the decrease in employment among patients in the year following the diagnosis of a gynecologic cancer compared with population-based controls. METHODS: Patients aged 18 to 63 years old, who were diagnosed with cervical, ovarian, endometrial, or vulvar cancer between January 2009 and December 2017, were identified in Truven MarketScan, an insurance claims database of commercially insured patients in the USA. Patients working full- or part-time at diagnosis were matched to population-based controls in a 1:4 ratio via propensity score. Multivariable Cox proportional hazards models were used to evaluate the risk of employment disruption in patients versus controls. RESULTS: We identified 7446 women with gynecologic cancers (191 vulvar, 941 cervical, 1839 ovarian, and 4475 endometrial). Although most continued working following diagnosis, 1579 (21.2%) changed from full- or part-time employment to long-term disability, retirement, or work cessation. In an adjusted model, older age, the presence of comorbidities, and treatment with surgery plus adjuvant therapy versus surgery alone were associated with an increased risk of employment disruption (p<0.0003, p=0.01, and p<0.0001, respectively) among patients with gynecologic cancer. In the propensity-matched cohort, patients with gynecologic cancers had over a threefold increased risk of employment disruption relative to controls (HR 3.67, 95% CI 3.44 to 3.95). CONCLUSION: Approximately 21% of patients with gynecologic cancer experienced a decrease in employment in the year after diagnosis. These patients had over a threefold increased risk of employment disruption compared with controls.

Association between time to diagnosis, time to treatment, and ovarian cancer survival in the United States.

OBJECTIVE: Evaluate the association between time to diagnosis and treatment of advanced ovarian cancer with overall and ovarian cancer specific mortality using a retrospective cross sectional study of a population based cancer registry database. METHODS: The Surveillance, Epidemiology, and End Results-Medicare database was searched from 1992 to 2015 for women aged ≥66 years with epithelial ovarian cancer and abdominal/pelvic pain, bloating, difficulty eating, or urinary symptoms within 1 year of cancer diagnosis. Time from presentation to diagnosis and treatment were evaluated as outcomes and covariables. Cox regression models and adjusted Kaplan-Meier curves evaluated 5 year overall and cancer-specific survival. RESULTS: Among 13 872 women, better survival was associated with longer time from presentation to diagnosis (overall survival hazard ratio (HR) 0.95, 95% confidence interval (CI) 0.94 to 0.95; cancer specific survival HR 0.95, 95% CI 0.94 to 0.96) and diagnosis to treatment (overall survival HR 0.94, 95% CI 0.92 to 0.96; cancer specific survival HR 0.93, 95% CI 0.91 to 0.96). There was longer time from presentation to diagnosis in Hispanic women (relative risk (RR) 1.21, 95% CI 1.12 to 1.32) and from diagnosis to treatment in non-Hispanic black women (RR 1.36, 95% CI 1.21 to 1.54), with lower likelihood of survival at 5 years after adjustment for time to diagnosis and treatment among non-Hispanic black women (HR 1.15, 95% CI 1.05 to 1.26) compared with non-Hispanic white women. Gynecologic oncology visit was associated with improved overall (p<0.001) and cancer specific (p<0.001) survival despite a longer time from presentation to treatment (p<0.001). CONCLUSION: Longer time to diagnosis and treatment were associated with improved survival, suggesting that tumor specific features are more important prognostic factors than the time interval of workup and treatment. Significant sociodemographic disparities indicate social determinants of health influencing workup and care. Gynecologic oncologist visits were associated with improved survival, highlighting the importance of appropriate referral for suspected ovarian cancer.

Fertility preservation in women with early-stage gynecologic cancer: optimizing oncologic and reproductive outcomes.

Almost all standard therapies for gynecologic cancer, including surgical intervention, gonadotoxic chemotherapy, and radiation therapy, threaten a woman's childbearing potential. Preservation of fertility should be discussed with premenopausal women with early-stage gynecologic cancer shortly after diagnosis and, for women who desire to preserve fertility, during treatment planning. Many authors have investigated both oncologic and reproductive outcomes following fertility-sparing therapy, and there is ongoing development of assisted reproduction techniques available to cancer patients and survivors. Women with early-stage (IA1-IB1) cervical cancer may be candidates for fertility-sparing cervical conization, simple trachelectomy, or radical trachelectomy. In women with stage I epithelial ovarian cancer, fertility-sparing surgery appears safe overall, although controversy remains in patients with high-risk features (eg, high pathologic grade, clear cell histology, or stage IC disease). In women with low-grade, early-stage endometrial cancer, hormonal therapy has emerged as a viable option. Criteria for patient selection for fertility-sparing therapy are not well defined, thus patients and providers must carefully discuss potential risks and benefits. In general, in carefully selected patients, survival outcomes do not appear to differ significantly between radical and fertility-sparing approaches. Women who undergo fertility-sparing therapies may experience a number of fertility and obstetric complications. Preconception counseling with high-risk obstetric specialists is important to optimize health before a woman attempts to conceive. Identifying appropriate candidates for fertility-sparing treatments, assessing fertility potential, and helping women conceive after cancer treatment is best accomplished through multidisciplinary collaboration between gynecologic oncologists and fertility specialists.

Facilitated cascade testing (FaCT): a randomized controlled trial.

BACKGROUND: Identifying mutation-carrying relatives of patients with hereditary cancer syndromes via cascade testing is an underused first step in primary cancer prevention. A feasibility study of facilitated genetic testing of at-risk relatives of patients with a known pathogenic mutation demonstrated encouraging uptake of cascade testing. PRIMARY OBJECTIVE: Our primary objective is to compare the proportion of genetic testing of identified first-degree relatives of probands with a confirmed BRCA1/2 mutation randomized to a facilitated cascade testing strategy versus standard of care, proband-mediated, information sharing. STUDY HYPOTHESIS: We hypothesize that facilitated cascade testing will drive significantly higher uptake of genetic testing than the standard of care. TRIAL DESIGN: The FaCT (Facilitated Cascade Testing) trial is a prospective multi-institutional randomized study comparing the efficacy of a multicomponent facilitated cascade testing intervention with the standard of care. Patients with a known BRCA1/2 mutation (probands) cared for at participating sites will be randomized. Probands randomized to the standard of care group will be instructed to share a family letter with their first-degree relatives and encourage them to complete genetic testing. First-degree relatives of probands randomized to the intervention arm will receive engagement strategies with a patient navigator, an educational video, and accessible genetic testing services. MAJOR INCLUSION/EXCLUSION CRITERIA: Adult participants who are first-degree relatives of a patient with a BRCA1/2 mutation and have not had prior genetic testing will be included. PRIMARY ENDPOINT: Analyses will assess the proportion of first-degree relatives identified by the proband who complete genetic testing by 6 months in the intervention arm versus the control arm. SAMPLE SIZE: One hundred and fifty probands with a BRCA1/2 mutation will be randomized. Each proband is expected to provide an average of 3 relatives, for an expected 450 participants. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: January 2024. TRIAL REGISTRATION: NCT04613440.

Correlation of surgeon radiology assessment with laparoscopic disease site scoring in patients with advanced ovarian cancer.

BACKGROUND: Radiographic triage measures in patients with new advanced ovarian cancer have yielded inconsistent results. OBJECTIVE: To determine the correlation between surgeon radiology assessment and laparoscopic scoring by disease sites in patients with newly diagnosed advanced stage ovarian cancer. METHODS: Fourteen gynecologic oncology surgeons from a single institution performed a blinded review of pre-operative contrast-enhanced CT imaging from patients with advanced stage ovarian cancer. Each of the patients had also undergone laparoscopic scoring assessment, between April 2013 and December 2017, to determine primary resectability using the validated Fagotti scoring method, and assigned a predictive index value score. Surgeons were asked to provide expected predictive index value scores based on their blinded review of the antecedent CT imaging. Linear mixed models were conducted to calculate the correlation between radiologic and laparoscopic score for surgeons individually, and as a group. Once the model was fit, the inter-class correlation and 95% CI were calculated. RESULTS: Radiology review was performed on 20 patients with advanced stage ovarian cancer who underwent laparoscopic scoring assessment. Surgeon faculty rank included assistant professor (n=5), associate professor (p=4), and professor (n=5). The kappa inter-rater agreement was -0.017 (95% CI -0.023 to -0.005), indicating low inter-rater agreement between radiology review and actual laparoscopic score. The inter-class correlation in this model was 0.06 (0.02-0.21), indicating that surgeons do not score the same across all the images. When using a clinical cut-off point for the predictive index value of 8, the probability of agreement between radiology and actual laparoscopic score was 0.56 (95% CI 0.49 to 0.73). Examination of disease site sub-scales showed that the probability of agreement was as follows: peritoneum 0.57 (95% CI 0.51 to 0.62), diaphragm 0.54 (95% CI 0.48 to 0.60), mesentery 0.51 (95% CI 0.45 to 0.57), omentum 0.61 (95% CI 0.55 to 0.67), bowel 0.54 (95% CI 0.44 to 0.64), stomach 0.71 (95% CI 0.65 to 0.76), and liver 0.36 (95% CI 0.31 to 0.42). The number of laparoscopic scoring cases, tumor reductive surgery cases, or faculty rank was not significantly associated with overall or sub-scale agreement. CONCLUSIONS: Surgeon radiology review did not correlate highly with actual laparoscopic scoring assessment findings in patients with advanced stage ovarian cancer. Our study highlights the limited accuracy of surgeon radiographic assessment to determine resectability.

Oncological outcomes of laparoscopic radical hysterectomy versus radical abdominal hysterectomy in patients with early-stage cervical cancer: a multicenter analysis.

INTRODUCTION: Recent evidence has shown adverse oncological outcomes when minimally invasive surgery is used in early-stage cervical cancer. The objective of this study was to compare disease-free survival in patients that had undergone radical hysterectomy and pelvic lymphadenectomy, either by laparoscopy or laparotomy. METHODS: We performed a multicenter, retrospective cohort study of patients with cervical cancer stage IA1 with lymph-vascular invasion, IA2, and IB1 (FIGO 2009 classification), between January 1, 2006 to December 31, 2017, at seven cancer centers from six countries. We included squamous, adenocarcinoma, and adenosquamous histologies. We used an inverse probability of treatment weighting based on propensity score to construct a weighted cohort of women, including predictor variables selected a priori with the possibility of confounding the relationship between the surgical approach and survival. We estimated the HR for all-cause mortality after radical hysterectomy with weighted Cox proportional hazard models. RESULTS: A total of 1379 patients were included in the final analysis, with 681 (49.4%) operated by laparoscopy and 698 (50.6%) by laparotomy. There were no differences regarding the surgical approach in the rates of positive vaginal margins, deep stromal invasion, and lymphovascular space invasion. Median follow-up was 52.1 months (range, 0.8-201.2) in the laparoscopic group and 52.6 months (range, 0.4-166.6) in the laparotomy group. Women who underwent laparoscopic radical hysterectomy had a lower rate of disease-free survival compared with the laparotomy group (4-year rate, 88.7% vs 93.0%; HR for recurrence or death from cervical cancer 1.64; 95% CI 1.09-2.46; P=0.02). In sensitivity analyzes, after adjustment for adjuvant treatment, radical hysterectomy by laparoscopy compared with laparotomy was associated with increased hazards of recurrence or death from cervical cancer (HR 1.7; 95% CI 1.13 to 2.57; P=0.01) and death for any cause (HR 2.14; 95% CI 1.05-4.37; P=0.03). CONCLUSION: In this retrospective multicenter study, laparoscopy was associated with worse disease-free survival, compared to laparotomy.

Laparoscopic cytoreduction After Neoadjuvant ChEmotherapy (LANCE).

BACKGROUND: Observational studies have supported the practice of offering minimally invasive interval debulking surgery after neoadjuvant chemotherapy for well-selected patients with advanced epithelial ovarian cancer. However, there are no prospective randomized data comparing the oncologic efficacy of minimally invasive and open interval debulking surgery in epithelial ovarian cancer. PRIMARY OBJECTIVE: The primary objective of this study is to examine whether minimally invasive surgery is non-inferior to laparotomy in terms of disease-free survival in women with advanced stage epithelial ovarian cancer that responded to three or four cycles of neoadjuvant chemotherapy. STUDY HYPOTHESIS: We hypothesize that in patients who had a complete or partial response to neoadjuvant chemotherapy, minimally invasive interval debulking surgery is not inferior to laparotomy. TRIAL DESIGN: The Laparoscopic cytoreduction After Neoadjuvant ChEmotherapy (LANCE) trial is an international, prospective, randomized, multicenter, non-inferiority phase III trial to compare minimally invasive surgery vs laparotomy in women with advanced stage high-grade epithelial ovarian cancer that had a complete or partial response to three or four cycles of neoadjuvant chemotherapy and normalization of CA-125. The first 100 participants will be enrolled into a pilot lead-in to determine feasibility. The study will be considered feasible and will continue to Phase III under the following conditions: the accrual rate reaches at least 80% of the target rate after all pilot sites are open; the crossover rate in the minimally invasive group is less than 25%; and the difference of complete gross resection between the minimally invasive and open group is less than 20%. If the study is determined to be feasible, all remaining participants will be enrolled into the Phase III stage. MAJOR INCLUSION/EXCLUSION CRITERIA: Patients with stage IIIC or IV high-grade epithelial ovarian, primary peritoneal or fallopian tube carcinoma who had a complete or partial response to three or four cycles of neoadjuvant chemotherapy based on imaging and normalization of CA-125 will be enrolled. Patients with evidence of tumor not amenable to minimally invasive resection on pre-operative imaging will be excluded. PRIMARY ENDPOINT: The primary endpoint is non-inferiority of disease-free survival in minimally invasive vs laparotomic interval debulking surgery. SAMPLE SIZE: To demonstrate non-inferiority with a margin of 33% in the hazard ratio (HR=1.33), 549 patients will be randomized.

National trends in bowel and upper abdominal procedures in ovarian cancer surgery.

OBJECTIVES: In the United States, trends in the initial treatment approach for ovarian cancer reflect a shift in paradigm toward the increased use of neoadjuvant chemotherapy and interval cytoreductive surgery. The aim of this study was to evaluate the trends in surgical cytoreductive procedures in ovarian cancer patients who underwent either primary or interval cytoreductive surgery. METHODS: This retrospective, population-based study examined patients with stage III/IV ovarian cancer diagnosed between January 2000 and December 2013 identified using SEER-Medicare. Small or large bowel resection, ostomy creation, and upper abdominal procedures were identified using relevant billing codes and compared over time. A 1:1 primary and interval cytoreductive propensity matched cohort was created using demographic and clinical variables. 30-day complications and the use of acute care services were compared. RESULTS: A total of 5417 women were identified. 34% underwent bowel resections, 16% ostomy creation, and 8% upper abdominal procedures. There was an increase in bowel resections and upper abdominal procedures from 2000 to 2013 in patients who underwent primary cytoreductive surgery. Compared with patients who received primary cytoreduction, patients who underwent interval cytoreductive surgery were less likely to undergo bowel resection (OR=0.50; 95% CI [0.41, 0.61]) or ostomy creation (OR=0.48; 95% CI [0.42, 0.56]). Upper abdominal procedures did not differ between groups. For patients who underwent primary cytoreductive surgery, these procedures were associated with intensive care unit stay (4.6% vs <2%, P<0.01). In both primary and interval cytoreductive surgery patients, the receipt of bowel and upper abdominal procedures was associated with multiple 30-day postoperative complications and higher rates of readmission and emergency room visits. CONCLUSIONS: The performance of upper abdominal procedures in ovarian cancer patients increased from 2000 to 2013. Interval cytoreductive surgery was associated with decreased likelihood of bowel surgery. In matched primary and interval cytoreductive surgery cohorts, the receipt of these procedures were associated with the increased likelihood of postoperative complications and use of acute care services.

Body mass index and attitudes towards health behaviors among women with endometrial cancer before and after treatment.

INTRODUCTION: Some experts have argued that obesity-related malignancies such as endometrial cancer are a "teachable moment" that lead to meaningful changes in health behaviors. It is unclear if endometrial cancer survivors lose weight following treatment. Our goal with this investigation was to evaluate post-treatment changes in body mass index (BMI) and attitudes towards health behaviors in endometrial cancer survivors. METHODS: Incident endometrial cancer cases undergoing surgery between 2009-2015 were identified in the Marketscan Commercial database and linked with BMI data and health behavior questionnaires from the Marketscan Health Risk Assessment database. Patients were excluded for insufficient BMI data. Standard statistical methods, including the two-sample Wilcoxon rank sum test, χ2 test, and McNemar's test, were used. RESULTS: 655 patients with a median age of 54 (IQR 49-58) were identified and analyzed. Median duration of follow-up was 595 days (IQR 360-1091). Mean pre- and post-treatment BMI was 35.5 kg/m2 (median 35.0; IQR 27.0-42.3) and 35.6 kg/m2 (median 34.3; IQR 28.0-42.0), respectively. Median BMI change in the entire cohort was 0 kg/m2 (IQR -1.0 to 2.0). Weight gain (n=302; 46.1%) or no change in weight (n=106; 16.2%) was seen in most patients. Among the 302 patients who gained weight, the mean pre-treatment BMI was 34.0 kg/m2 and mean increase was 2.8 kg/m2 (median 2.0; IQR 1.0-3.4). Among the 247 cases who lost weight, the mean pre-treatment BMI was 38.6 kg/m2 and mean decrease was 3.2 kg/m2 (median 2.0; IQR 1.0-4.0). No pre- to post-treatment differences were observed in health behavior questionnaires regarding intention to better manage their diet, exercise more, or lose weight. DISCUSSION: Most endometrial cancer survivors gain weight or maintain the same weight following treatment. No post-treatment changes in attitudes regarding weight-related behaviors were observed. The systematic delivery of evidence-based weight loss interventions should be a priority for survivors of endometrial cancer.

Total and out-of-pocket costs of different primary management strategies in ovarian cancer.

BACKGROUND: Communicating healthcare costs to patients is an important component of delivering high-quality value-based care, yet cost data are lacking. This is especially relevant for ovarian cancer, where no clinical consensus on optimal first-line treatment exists. OBJECTIVE: The objective of this study was to generate cost estimates of different primary management strategies in ovarian cancer. STUDY DESIGN: All women who underwent treatment for ovarian cancer from 2006-2015 were identified from the MarketScan database (n=12,761) in this observational cohort study. Total and out-of-pocket costs were calculated with the use of all claims within 8 months from initial treatment and normalized to 2017 US dollars. The generalized linear model method was used to assess cost by strategy. RESULTS: Among patients who underwent neoadjuvant chemotherapy and those who underwent primary debulking, mean adjusted total costs were $113,660 and $107,153 (P<.001) and mean out-of-pocket costs were $2519 and $2977 (P<.001), respectively. Total costs for patients who had intravenous standard, intravenous dose-dense, and intraperitoneal/intravenous chemotherapy were $105,047, $115,099, and $121,761 (P<.001); and out-of-pocket costs were $2838, $3405, and $2888 (P<.001), respectively. Total costs for regimens that included bevacizumab were higher than those without it ($171,468 vs $104,482; P<.001); out-of-pocket costs were $3127 vs $2898 (P<.001). Among patients who did not receive bevacizumab, 25% paid ≥$3875, and 10% paid ≥$6265. For patients who received bevacizumab, 25% paid ≥$4480, and 10% paid ≥$6635. Among patients enrolled in high-deductible health plans, median out-of-pocket costs were $4196, with 25% paying ≥$6680 and 10% paying ≥$9751. CONCLUSION: Costs vary across different treatment strategies, and patients bear a significant out-of-pocket burden, especially those enrolled in high-deductible health plans.