BACKGROUND:Metastatic cancer patients receiving systemic chemotherapy face increased risks for venous thromboembolism (VTE). Benefit has been shown for prophylactic anticoagulants in risk-stratified populations. Ovarian cancer (OC) is commonly advanced at diagnosis and treated with chemotherapy. Despite high VTE rates among OC patients, predictors of risk in this population are not well studied, and information on the benefit of oral anticoagulants is lacking. OBJECTIVE:A quality improvement (QI) intervention to improve appropriate anticoagulation in risk-selected OC patients receiving first-line chemotherapy was implemented, prospectively assessing VTE risk reduction. METHODS:Patients receiving first-line chemotherapy for OC at Sheba Medical Center 2020-2025 were included. A QI program (launched 07/2023) included staff education, EMR-incorporated Khorana scoring, integrated apixaban prescriptions and targeted chemo-suite questionnaires. Data was extracted from the EMR using MDClone® software with Natural Language Processing to identify VTE events in imaging reports. Descriptive statistics were used to compare patients treated before and after program implementation. Predictors of VTE were evaluated with logistic regression. RESULTS:Patient characteristics were comparable before and after program implementation. VTE rates were high at 16.9% before, and 12.5% following roll-out. No increase in bleeding events or blood products consumption was appreciated. Program implementation was found to be a significant protective factor on multivariable analysis, adjusting for other risk factors (aOR = 0.39 (0.17-0.81), p = 0.015). CONCLUSION:The implementation of an oral anticoagulation QI program successfully decreased VTE events during first-line chemotherapy for OC with no appreciable increase in risk. Future work will focus on improved risk stratification and selection for thromboprophylaxis.

OBJECTIVE:Pre-operative imaging has the potential to improve selection of surgical candidates in early-stage cervical cancer, but limited evidence exists on its association with post-operative adjuvant treatment. This study investigated the role of imaging in candidate selection for radical surgery and its association with the need for adjuvant treatment in early-stage cervical cancer. METHODS:Retrospective analysis was performed using the Canadian Cervical Cancer Collaborative (4C) database of surgical cases from 11 tertiary centers between 2007 and 2017. All patients with squamous, adenocarcinoma, or adenosquamous histology, staged IAI to IIIC per the International Federation of Gynecology and Obstetrics 2018 system, who underwent primary surgical treatment with radical hysterectomy or trachelectomy were included. Groups were defined as no pre-operative imaging, computed tomography (CT) only, magnetic resonance imaging (MRI) with or without CT ("MRI"), or positron emission tomography (PET) with or without MRI or CT ("PET"). Regression analyses estimated associations of pre-operative imaging with adjuvant treatment, recurrence, and death. RESULTS:A total of 1103 patients were analyzed. PET use increased over the study period. Imaging modality was not associated with odds of lymph node spread (p =.16). Pre-operative PET was associated with decreased odds of adjuvant therapy compared with CT only (adjusted odds ratio 0.35; 95% confidence interval 0.18 to 0.66, p <.001) after controlling for other factors including site and year of surgery, age, surgical approach, and histology. No associations between imaging modality and recurrence-free survival or overall survival were observed. CONCLUSIONS:PET use before radical surgery for early-stage cervical cancer was associated with decreased odds of adjuvant treatment but no significant difference in oncologic outcomes. Future studies may refine our understanding of the predictive performance of multi-modal imaging for adjuvant treatment and prognosis.

OBJECTIVE:To compare the survival of women with high grade endometrial cancer between asymptomatic and women presenting bleeding symptoms. DESIGN:An Israel Gynecologic Oncology Group multi-center retrospective cohort study. METHODS:The study included women who underwent surgery for high-grade endometrial cancer. We compared outcomes between women presenting with postmenopausal bleeding and asymptomatic women diagnosed with high-grade endometrial cancer. Recurrence-free, disease-specific and overall survival were assessed using the Kaplan Meier method and compared using the log-rank test. Risk factors for recurrence and death were evaluated using Cox regression analysis; the primary exposure variable assessed was the presence of postmenopausal bleeding. RESULTS:Of the 584 women with high-grade histology, 498 (85.3 %) presented with postmenopausal bleeding and 86 (14.7 %) were asymptomatic. The median follow-up was 52 months (12-120 months). There was no difference in recurrence-free survival between women diagnosed with postmenopausal bleeding and asymptomatic women (70.1 % vs.64.6 % at 5 years, p = 0.35, respectively). There were no significant differences in disease-specific survival (66.3 % vs. 64.2 % at 5 years, p = 0.83) or in overall survival (56.4 % vs. 58 % at five years, p = 0.55) between study groups. The multivariate Cox regression analysis did not reveal any significant association between postmenopausal bleeding and survival. CONCLUSION:In this study, the diagnosis of high-grade endometrial cancer in asymptomatic women was not associated with earlier disease stage at diagnosis. In women with incidental ultrasonographic findings of a thickened endometrium or polyp, routine invasive evaluation may be unnecessary.

LBA5504 Background: Prior results from ENGOT-cx11/GOG-3047/KEYNOTE-A18 (NCT04221945) showed that pembro + CCRT and then continued after CCRT provided statistically significant and clinically meaningful improvements in OS and PFS vs CCRT alone in pts with newly diagnosed, previously untreated, high-risk LACC. We present the final analysis (FA) results from this study. Methods: Eligible pts with newly diagnosed, previously untreated, high-risk LACC (FIGO 2014 stage IB2-IIB with node-positive disease or stage III-IVA regardless of lymph node status) were randomized 1:1 to 5 cycles of pembro 200 mg or placebo (pbo) Q3W + CCRT, then 15 cycles of pembro 400 mg or pbo Q6W. The CCRT regimen included 5 cycles (with optional 6th dose) of cisplatin 40 mg/m 2 Q1W + EBRT then brachytherapy. Pts were stratified by planned EBRT type (intensity-modulated radiotherapy [IMRT] or volumetric-modulated arc therapy [VMAT] vs non-IMRT or non-VMAT), stage at screening (stage IB2-IIB vs III-IVA) and planned total radiotherapy dose (<70 Gy vs ≥70 Gy equivalent dose). Primary endpoints are PFS per RECIST version 1.1 by investigator and OS. Results: 1060 pts were randomized to pembro + CCRT (n=529) or pbo + CCRT (n=531). At the protocol-specified FA (Jan 7, 2025, data cutoff), median follow-up was 41.9 mo (range, 24.8-55.0). 86 pts had received post-progression immunotherapy; of those, 64 had received pembro. Pembro + CCRT continued to show clinically meaningful improvements in OS and PFS vs pbo + CCRT (Table). The benefit of pembro + CCRT was generally consistent in prespecified subgroups, including pts with stage IB2-IIB node-positive disease (OS HR=0.92 [95% CI, 0.62-1.38]; PFS HR=0.84 [95% CI, 0.63-1.14]). The grade ≥3 TRAE incidence was 69.5% in the pembro + CCRT group and 61.5% in the pbo + CCRT group. Conclusion: With an additional 12 mo median follow-up, pembro + CCRT continued to show clinically meaningful improvements in OS and PFS vs pbo + CCRT in pts with high-risk LACC and had a manageable safety profile. These data are consistent with the prior interim analysis and provide further support for pembro + CCRT as the new standard of care for this population. Clinical trial information: NCT04221945 . Summary of PFS and OS in ENGOT-cx11/GOG-3047/KEYNOTE-A18. Final Analysis 07JAN25 Interim Analysis 2 08JAN24 Interim Analysis 1 09JAN23 Pembro + CCRT Pbo + CCRT Pembro + CCRT Pbo + CCRT Pembro + CCRT Pbo + CCRT OS, median (95% CI) NR (NR-NR) NR (NR-NR) NR (NR-NR) NR (NR-NR) NR (NR-NR) NR (NR-NR) 36-mo OS 81.8% 74.4% 82.6% 74.8% NR (NR-NR) NR (NR-NR) HR (95% CI) 0.73 (0.57-0.94) 0.67 (0.50-0.90); P =0.0040 0.73 (0.49-1.07); P =0.0541 PFS, median (95% CI) 47.6 (47.6-NR) 47.5 (41.0-NR) NR (NR-NR) NR (32.0-NR) NR (NR-NR) NR (NR-NR) 24-mo PFS 70.6% 59.7% 70.6% 58.6% 67.8% 57.3% HR (95% CI) 0.72 (0.59-0.87) 0.68 (0.56-0.84) 0.70 (0.55-0.89); P =0.0020 NR=not reached.

Objective The key presenting symptom of endometrial cancer is abnormal uterine bleeding, most commonly postmenopausal bleeding (PMB), which facilitates early-stage diagnosis. This study aimed to investigate factors influencing delayed medical consultation for PMB, and particularly its association with social determinants. Methods This is a retrospective study that included endometrial cancer patients receiving care in a gynecologic oncology department of a tertiary medical center who presented with PMB. Demographic and oncologic data was collected from the electronic medical charts. Israeli bureau of statistics data was used to assess community socioeconomic index, based on address. Women seeking consultation more than 1 month after experiencing PMB were compared to those seeking earlier care. Results Two hundred ninety-five women were included in the study. One hundred seventy-three sought care after less than 1 month of PMB (early presenters) and 122 sought care after more prolonged PMB (late presenters). Late presenters were more likely to be socioeconomically marginalized (odds ratio [OR], 1.8; P = 0.018), higher body mass index (OR, 1.040; P = 0.022), and greater parity (OR, 1.170; P = 0.032). Socioeconomic marginalized patients experienced a 7-day longer delay from diagnosis to surgery compared to their privileged counterparts (59 vs 52 d, P = 0.022). Conclusions Among women with endometrial cancer, longer duration of PMB before first seeking medical consultation is associated with socioeconomic marginalization. This highlights the need for targeted interventions to minimize delays in diagnosis and treatment initiation among patients from marginalized communities.

INTRODUCTION:Chemo-immunotherapy (IO) is the preferred first-line treatment for stage IVB or recurrent cervical cancer. However, limited data exist on the efficacy and safety of using IO-alone as a de-escalation strategy. We report outcomes from a case series of selected patients treated with IO-alone and review the feasibility of de-escalating first-line treatment. METHODS:The authors conducted a literature review using Google Scholar and PubMed to identify reports using IO-alone as a de-escalation strategy across malignancies published between 1999 and December 2024 and also reviewed a cervical cancer database from a tertiary academic to identify patients with stage IVB or recurrent disease treated with IO-alone. The authors used the Kaplan-Meier method to estimate progression-free survival (PFS) and overall survival (OS). RESULTS:Among 582 patients treated between 2015 and 2021, 18 met the inclusion criteria. The median age was 43 years (range 28-84); 67% had squamous cell carcinoma, 11% adenocarcinoma, and 80% expressed PD-L1. CPS scores were <1 in 20%, 1--10 in 33%, and >10 in 47%. Most patients had oligo-metastatic disease (83%). Treatment with IO-alone began a median of 7 months after platinum-based chemotherapy. Indications included prior adjuvant (44%) or neoadjuvant (22%) chemotherapy, clinical trial participation (11%), or patient preference (22%). Median PFS and OS were 27 months and 82 months, respectively. CONCLUSIONS:These findings support the need for clinical trials evaluating IO-alone as a first-line treatment option for de-escalation in stage IVB or recurrent cervical cancer. Biomarker development is needed to better identify candidates for personalized therapy.

Objectives Preoperative imaging has the potential to improve optimal selection of surgical candidates in early-stage cervical cancer, but limited evidence exists on its association with postoperative adjuvant treatment. This study investigated the role of imaging in candidate selection for radical surgery to limit adjuvant treatment for early-stage cervical cancer. Methods Retrospective analysis was performed using the Canadian Cervical Cancer Collaborative (4C) database of surgical cases from 11 tertiary centers between 2007–2017. All patients with squamous, adenocarcinoma, or adenosquamous histologies stages IAI-IIIC (FIGO 2018) undergoing primary surgical treatment with radical hysterectomy or trachelectomy were included. Groups included no preoperative imaging, CT only, MRI±CT (“MRI”), or PET±MRI±CT (“PET”). Regression analyses estimated associations of preoperative imaging with adjuvant treatment, recurrence, and death. Results A total of 1103 patients were analyzed. PET use increased over the study period. Imaging modality was not associated with odds of lymph node spread (p=0.16). Preoperative PET was associated with decreased odds of adjuvant therapy compared to CT only (aOR 0.35, 95% CI 0.18, 0.66, p<0.001) controlling for other factors including site and year of surgery, age, surgical approach, and histology. No associations between imaging modality, and recurrence-free survival or overall survival were observed. Conclusion PET use before radical surgery for early-stage cervical cancer was associated with decreased odds of adjuvant treatment but no significant difference in oncological outcomes. Future studies may refine our understanding of the predictive performance of multimodal imaging on adjuvant treatment and prognosis.

Objective: Abdominal Radical hysterectomy (ARH) with pelvic lymph node assessment is considered the standard treatment for early-stage cervical cancer. Accepted routes have previously included laparoscopic or robotic approaches (LRH). Laparoscopy-assisted vaginal or vaginal radical hysterectomy (LVRH) are performed in some centers. The objective of this study is to compare surgical and oncological outcomes of LVRH, to laparoscopic and abdominal approaches. Design patients setting: A retrospective multicenter analysis of consecutive cervical cancer cases who underwent a radical hysterectomy between 2007 and 2017 in eleven regional cancer centers across Canada. Measurements: A comparison of patients stratified by surgical technique was undertaken. T-test, Wilcoxon rank-sum and chi-square were used to compare patient characteristics. Log-rank tests and Cox proportional hazards models were employed to compare recurrence and survival across surgical groups. Main results: A total of 1071 patients with cervical cancer stage IA1 with lymphovascular invasion to stage IIIC (FIGO 2018) <4 cm were identified. Postoperative complication rate was lowest for women undergoing LVRH (9.1 %, vs 18.3 % and 22.1 % for minimally invasive and open respectively). During follow up, 114 women recurred, and 70 women died. 5-year recurrence-free survival was 85.4 % for LRH, 89.4 % for ARH and 92.2 % for LVRH. LVRH was not found to be associated with a higher risk of recurrence or death than ARH on multivariable analysis (aHR for recurrence 0.62, CI 0.21-1.77; aHR for death 0.63, CI 0.14-2.77) Conclusion: In this retrospective study, vaginal or laparoscopy-assisted vaginal radical hysterectomy for cervical cancer was associated with favorable perioperative and oncological outcomes.

Background Pembrolizumab has shown efficacy in persistent, recurrent, or metastatic cervical cancer. The effect of chemoradiotherapy might be enhanced by immunotherapy. In this phase 3 trial, we assessed the efficacy and safety of adding pembrolizumab to chemoradiotherapy in locally advanced cervical cancer. Methods In this randomised, double-blind, placebo-controlled, phase 3 ENGOT-cx11/GOG-3047/KEYNOTE-A18 clinical trial, adults (age ≥18 years) at 176 medical centres in 30 countries with newly diagnosed, high-risk, locally advanced cervical cancer were randomly assigned (1:1) using an interactive voice-response system with integrated web response to receive 5 cycles of pembrolizumab (200 mg) or placebo every 3 weeks plus chemoradiotherapy, followed by 15 cycles of pembrolizumab (400 mg) or placebo every 6 weeks. Randomisation was stratified by planned external beam radiotherapy type (intensity-modulated radiotherapy or volumetric-modulated arc therapy vs non-intensity-modulated radiotherapy or non-volumetric-modulated arc therapy), cervical cancer stage at screening (International Federation of Gynecology and Obstetrics 2014 stage IB2–IIB node positive vs stage III–IVA), and planned total radiotherapy (external beam radiotherapy plus brachytherapy) dose (<70 Gy vs ≥70 Gy equivalent dose in 2 Gy fractions). Primary endpoints were progression-free survival per Response Evaluation Criteria in Solid Tumours version 1.1—by investigator or by histopathologic confirmation of suspected disease progression—and overall survival. Primary analysis was conducted in the intention-to-treat population, which included all randomly allocated participants. Safety was assessed in the as-treated population, which included all randomly allocated patients who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, NCT04221945, and is closed to new participants. Findings Between June 9, 2020, and Dec 15, 2022, 1060 participants were randomly assigned to treatment, with 529 assigned to the pembrolizumab–chemoradiotherapy group and 531 to the placebo–chemoradiotherapy group. At data cutoff (Jan 9, 2023), median follow-up was 17·9 months (IQR 11·3–22·3) in both treatment groups. Median progression-free survival was not reached in either group; rates at 24 months were 68% in the pembrolizumab–chemoradiotherapy group versus 57% in the placebo–chemoradiotherapy group. The hazard ratio (HR) for disease progression or death was 0·70 (95% CI 0·55–0·89, p=0·0020), meeting the protocol-specified primary objective. Overall survival at 24 months was 87% in the pembrolizumab–chemoradiotherapy group and 81% in the placebo–chemoradiotherapy group (information fraction 42·9%). The HR for death was 0·73 (0·49–1·07); these data have not crossed the boundary of statistical significance. Grade 3 or higher adverse event rates were 75% in the pembrolizumab–chemoradiotherapy group and 69% in the placebo–chemoradiotherapy group. Interpretation Pembrolizumab plus chemoradiotherapy significantly improved progression-free survival in patients with newly diagnosed, high-risk, locally advanced cervical cancer. Funding Merck Sharp & Dohme, a subsidiary of Merck & Co (MSD).

Introduction: We sought to assess the uptake of minimally invasive hysterectomy among patients with endometrial and cervical cancer in Ontario, Canada, and assess the equity of access to minimally invasive surgery (MIS) by evaluating associations with patient, disease, institutional, and provider factors. Methods: This is a retrospective population-based cohort study of hysterectomy for endometrial and cervical cancer in Ontario (2000-2017). Surgical approach, clinicopathologic, sociodemographic, institutional, and provider factors were identified through administrative databases. Fisher's exact, chi(2), Wilcoxon rank sum, logistic regression, and Cox proportional hazards modeling were used to explore factors associated with MIS. Results: A total of 27 652 patients were included. In total, 6199/24 264 (26%) endometrial and 842/3388 (25%) cervical cancer patients received MIS. The proportion of MIS to open surgeries increased from <0.1% in 2000 to over 55% in 2017 (odds ratio [OR] = 1.31, confidence interval [CI] = 1.28-1.34). Low-income quintile, rurality, low hospital volume, nonacademic hospital, nongynecologic oncology surgeon, and earlier year of surgeon graduation were associated with reduced odds of MIS (OR < 1). Conclusions: The uptake of MIS hysterectomy increased steadily over the time period. Receipt of MIS is dependent upon multiple social determinants, provider variables, and systems factors. These disparities raise concern for health equity in Ontario and have significant implications for health systems planning and resource allocation.

Objective:To compare survival measures of women with Stage I high-grade endometrial cancer who underwent either hysteroscopy or a non-hysteroscopic procedure as a diagnostic procedure. Study design:298 patients with stage I high grade endometrial cancer who underwent surgery between 2002 and 2014. Patients were divided into two groups: hysteroscopy and non-hysteroscopy (curettage or office endometrial biopsy). Clinical, pathological, and survival measures were compared between the groups. High grade histology included endometroid grade -3, uterine serous papillary carcinoma, clear cell carcinoma, and carcinosarcoma. Results:There were 71 patients in the hysteroscopy group and 227 patients in the non-hysteroscopy group. The median follow-up was 52 months (range 12-120 months). There were no differences between the groups in the 5year recurrence-free survival (73.9 % vs. 79.7 %; p = 0.65), disease-specific survival (79.3 % vs. 83.6 %; p = 0.87), and overall survival (65.7 % vs. 80.3 %; p = 0.35). Conclusion:Hysteroscopic diagnosis in women with early-stage and high-grade endometrial cancer does not adversely affect the survival outcomes.

Purpose ENGOT-cx11/GOG-3047/KEYNOTE-A18 (NCT04221945) evaluated pembro + CCRT in patients (pts) with high-risk LACC. Materials and Methods Pts with previously untreated, high-risk LACC (FIGO 2014 stage IB2‒IIB with node-positive disease or stage III‒IVA) were randomized 1:1 to receive 5 cycles of pembro 200 mg or placebo (pbo) Q3W + CCRT then 15 cycles of pembro 400 mg or pbo Q6W. CCRT was 5 cycles (optional 6th dose) of cisplatin 40 mg/m2 QW + EBRT then brachytherapy. Primary endpoints were PFS per RECIST v1.1 by investigator or histopathologic confirmation and OS. Results 1060 pts were randomized to pembro + CCRT (n = 529) or pbo + CCRT (n = 531). At IA1 (data cutoff: Jan 9, 2023), median follow-up was 17.9 mo. Pts received a median of 11 cycles of pembro or pbo and 5 cycles of cisplatin in both arms. Most pts completed radiation treatment (pembro + CCRT, 97.9%; pbo + CCRT, 98.3%); overall median treatment duration was 52 d in both arms. Table 1 summarizes the CCRT treatment. Pembro + CCRT improved PFS vs pbo + CCRT (HR 0.70 [95% CI 0.55‒0.89]; P = 0.0020). Median PFS was not reached in either arm. PFS benefit was generally consistent across prespecified subgroups. With only 103 events (42.9% maturity), pembro + CCRT had a favorable trend in OS (HR 0.73 [95% CI 0.49‒1.07]). Treatment-related AEs (TRAEs) were less common in the pembro monotherapy phase (72.7%) vs pembro + CCRT combination therapy phase (94.5%); results in the pbo arm were 60.0% vs 95.7%. Safety profiles were consistent with the known profiles of pembro monotherapy and chemoradiotherapy. Conclusions Pembro + CCRT showed a statistically significant and clinically meaningful improvement in PFS and a favorable trend in OS vs pbo + CCRT in pts with high-risk LACC. Pembro + CCRT had manageable safety, with most TRAEs occurring during the combination phase of therapy. Pembro + CCRT has potential as a new standard of care for this high-risk population.