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ObjectivesThe Ovarian Cancer Comorbidity Index (OCCI) is an age-specific index developed and previously found to be more predictive of overall and cancer-specific survival than the Charlson Comorbidity Index (CCI). The objective was to perform secondary validation of the OCCI in a US population.MethodsA cohort of ovarian cancer patients undergoing primary or interval cytoreductive surgery from January 2005 to January 2012 was identified in SEER-Medicare. OCCI scores were calculated with the regression coefficients determined from the original developmental cohort for five comorbidities. Cox regression analyses were used to calculate associations between the OCCI risk groups and 5-year overall survival and 5-year cancer-specific survival in comparison to the CCI.ResultsA total of 5052 patients were included. Median age was 74 (range 66–82) years. 47% (n=2375) had stage III and 24% (n=1197) had stage IV disease at diagnosis. 67% had a serous histology subtype (n=3403). All patients were categorized as moderate (48.4%) or high risk (51.6%). The prevalence of the five predictive comorbidities were: coronary artery disease 3.7%, hypertension 67.5%, chronic obstructive pulmonary disease 16.7%, diabetes 21.8%, and dementia 1.2%. Controlling for histology, grade, and age-stratification, worse overall survival was associated with both a higher OCCI (hazard ratio (HR) 1.57; 95% confidence interval (CI) 1.46 to 1.69) and CCI (HR 1.96; 95% CI 1.66 to 2.32). Cancer-specific survival was associated with the OCCI (HR 1.33; 95% CI 1.22 to 1.44) but was not associated with the CCI (HR 1.15; 95% CI 0.93 to 1.43).ConclusionsThis internationally developed comorbidity score for ovarian cancer patients is predictive for both overall and cancer-specific survival in a US population. CCI was not predictive for cancer-specific survival. This score may have research applications when utilizing large administrative datasets.

Drug development is paramount to improve outcomes in patients with gynecologic cancers. A randomized clinical trial should measure whether a clinically relevant improvement is detected with the new intervention compared with the standard of care, using reproductible and appropriate endpoints. Clinically meaningful improvements in overall survival and/or quality of life (QoL) are the gold standards to measure benefit of new therapeutic strategies. Alternative endpoints, such as progression-free survival, provide an earlier measure of the effect of the new therapeutic drug, and are not confounded by the effect of subsequent lines of therapy. Yet, its surrogacy with improved overall survival or QoL is unclear in gynecologic malignancies. Of relevance to studies assessing maintenance strategies are other time-to-event endpoints, such as progression-free survival two and time to second subsequent treatment, which provide valuable information on the disease control in the longer term. Translational and biomarker studies are increasingly being incorporated into gynecologic oncology clinical trials, as they may allow understanding of the biology of the disease, resistance mechanisms, and enable a better selection of patients who might benefit from the new therapeutic strategy. Globally, the endpoint selection of a clinical trial will differ according to the type of study, population, disease setting, and type of therapeutic strategy. This review provides an overview of primary and secondary endpoint selection of relevance for gynecologic oncology clinical trials.

BackgroundPositron emission tomography/computed tomography (PET/CT) fails to detect approximately 25% of aortic lymph node metastasis in patients with PET/CT stage IIIC1 cervical cancer. Surgical staging could lead to treatment modification and to improved para-aortic and distant control.Primary Objective(s)To demonstrate if chemoradiation with tailored external beam radiation field based on surgical staging and pathologic examination of the para-aortic lymph node is associated with improved 3-year disease-free survival compared with patients staged with PET/CT staging only.Study HypothesisSurgical staging followed by tailored chemoradiation will improve disease-free survival while avoiding unnecessary prophylactic extended-field chemoradiation in patients with International Federation of Gynecology and Obstetrics (FIGO) stage IIIC1 cervical cancer.Trial DesignThis is an international multicenter, randomized, phase III study. Eligible patients will be randomized 1:1 between PET/CT staging followed by chemoradiation (control arm), or surgical staging followed by tailored chemo-radiation (experimental arm). Randomization will be stratified by tumor stage according to TNM classification, center, and adjuvant treatment.Major Inclusion/Exclusion CriteriaMain inclusion criteria are histologically proven PET/CT FIGO stage IIIC1 cervical cancer. Main exclusion criteria include unequivocal positive common iliac or para-aortic lymph node at pre-therapeutic imaging PET/CT.Primary Endpoint(s)The primary endpoint is disease-free survival defined as the time from randomization until first relapse (local, regional, or distant), or death from any cause.Sample Size510 eligible patientsEstimated Dates for Completing Accrual and Presenting ResultsThe estimated date for completing accrual will be Q2 2027. The estimated date for presenting results will be Q4 2030.Trial Registration NumberNCT05581121.

ObjectiveAltmetric Attention Score (AAS) is an alternative metric for estimating the impact of academic publications. We studied the association of using podcasting to highlight publications about gynecological cancer with AAS and citation scores.MethodsArticles that were featured in theInternational Journal of Gynecological Cancer(IJGC) podcast series January 2019 to September 2022 were matched 1:1 to control articles by the journal in which the article was published, study topic and design, single/multicenter data, and year of publication. Podcast articles were compared with matched-controls by citation metrics and altmetric scores.ResultsA total of 99 podcasted articles published in 16 journals were matched. Median AAS was significantly higher in the podcast group than the matched-control group (22 (14–42) vs 5 (1–17), pConclusionWhen compared with matched-controls, podcasting an article is associated with a higher AAS but is not associated with generating a high (≥12) number of citations per year. When compared with all articles published in the same journal during the same study period, articles that were featured in a podcast had higher median citations per year.

Introduction We aimed to identify clinical, pathologic, and treatment factors that are predictive of response and survival in patients with cervical cancer referred to phase I clinical trials. Methods Patients with cervical cancer who received at least one dose of a phase I investigational agent at our institution between 2014 and 2022 were included. The log-rank test was used to analyze differences in progression-free survival (PFS) and overall survival (OS), and multivariable regression analysis was performed. Results We included 65 patients with a median age of 41 years (range, 20–74), 3 prior therapies (range, 1–7), and 67.7% squamous carcinoma. The rate of distant metastasis at trial entry was 84.6%. The most common molecular alterations included PIK3CA (46.5%), PD-L1+ (46.2%), EPH (30.0%), and CREBBP (23.1%); 23.1% had received a prior checkpoint inhibitor. Phase I trials were for immunotherapy (58.5%) or targeted therapy (41.5%). The rate of biomarker matching was 21.5%. For all patients, median PFS was 3.6 months (95% CI, 2.0–5.2) and OS was 9.3 months (95% CI, 7.0–10.6). Factors at study entry associated with worse survival were presence of bone metastasis (PFS 1.6 vs 4.4 months: hazard ratio [HR], 2.8; p = 0.001; OS 3.8 vs 10.0 months: HR, 3.9; p < 0.0001) and absolute lymphocyte count below 1000/μL (PFS 1.8 vs 5.2 months: HR, 2.9; p = 0.0004; OS 7.0 vs 10.6 months: HR, 3.2; p = 0.0009). Factors associated only with worse OS were absolute neutrophil count above 4700/μL, hemoglobin below 10.5 g/dL, and smoking status. Grade 3+ treatment-related adverse events were seen in 16.9% of cases. Conclusion Bone metastasis and absolute lymphocyte count below normal range at phase I study entry portend poor survival in patients with recurrent or metastatic cervical cancer.

BackgroundThe Global Gynecological Oncology Surgical Outcomes Collaborative (GO SOAR) has developed a network of gynecological oncology surgeons, surgical departments, and other interested parties that have the long-term ability to collaborate on outcome studies. Presented is the protocol for the GO SOAR2 study.Primary ObjectivesTo compare survival following interval and delayed cytoreductive surgery, between delayed cytoreductive surgery and no surgery (chemotherapy alone); and international variations in access to cytoreductive surgery for women with stage III–IV epithelial ovarian cancer.Study HypothesesThere is no difference in survival following interval and delayed cytoreductive surgery; there is poorer survival with no surgery compared with delayed cytoreductive surgery; and there are international disparities in prevalent practice and access to cytoreductive surgery in women with stage III–IV epithelial ovarian cancer.Trial DesignInternational, multicenter, mixed-methods cohort study. Participating centers, will review medical charts/electronic records of patients who had been consecutively diagnosed with stage III–IV ovarian cancer between January 1, 2006 and December 31, 2021. Qualitative interviews will be conducted to identify factors determining international variations in prevalent practice and access to cytoreductive surgery.Major Inclusion/Exclusion CriteriaInclusion criteria include women with stage III–IV epithelial ovarian cancer, undergoing interval (after 3–4 cycles of chemotherapy) or delayed (≥5 cycles of chemotherapy) cytoreductive surgeries or no cytoreductive surgery (≥5 cycles of chemotherapy alone).Primary EndpointsOverall survival (defined from date of diagnosis to date of death); progression-free survival (defined from date of diagnosis to date of first recurrence); facilitator/barriers to prevalent practice and access to cytoreductive surgery.Sample SizeIn order to determine whether there is a difference in survival following interval and delayed cytoreductive surgery and no surgery, data will be abstracted from 1000 patients.Estimated Dates for Completing Accrual and Presenting ResultsIt is estimated that recruitment will be completed by 2023, and results published by 2024.Trial RegistrationNCT05523804

ObjectivesTo evaluate compliance with an Enhanced Recovery After Surgery (ERAS) protocol for open gynecologic surgery at a tertiary center and the relationship between levels of compliance and peri-operative outcomes.MethodsThis retrospective cohort study was conducted between November 2014 and December 2020. Two groups were defined based on compliance level (ResultsA total of 1879 patients were included. Overall compliance over the period of 6 years was 74% (95% CI 71.9% to 78.2%). Mean overall compliance increased from 69.7% to 75.8% between P1 and P3. Compliance with ERAS ≥80% was associated with lower Clavien–Dindo complication rates (grades III (OR 0.55; 95% CI 0.33 to 0.93) and V (OR 0.08, 95% CI 0.01 to 0.60)), 30-day re-admission rates (OR 0.61; 95% CI 0.43 to 0.88), and length of stay (OR 0.59; 95% CI 0.47 to 0.75). No difference in opioid consumption was seen. Pre-operatively, there was increased adherence to counseling by 50% (p=0.01), optimization by 21% (p=0.02), and carbohydrate loading by 74% (p=0.02). Intra-operatively, compliance with use of short-acting anesthetics increased by 37% (p=0.01) and avoidance of abdominal drainage increased by 7% (p=0.04). Use of goal-directed fluid therapy decreased by 16% (p=0.04). Post-operatively, there was increased compliance with avoiding salt and water overload (8%, p=0.02) and multimodal analgesia (5%, p=0.02).ConclusionsOver the time period of the study, overall compliance increased from 69.7% to 75.8%. Compliance (≥80%) with ERAS is associated with lower complication rates, fewer 30-day re-admissions, and shorter length of stay without impacting re-operation rates and post-operative opioid use.

ObjectivesTo evaluate whether the timing of postoperative urinary catheter removal is associated with voiding dysfunction after radical hysterectomy for early cervical cancer within contemporary surgical practice.MethodsWe performed an institutional retrospective cohort study of patients who underwent Piver type II-III open or minimally invasive radical hysterectomy for early-stage cervical cancer (International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IA1 with lymphovascular invasion to stage IIA) between January 2006 and December 2019. We compared voiding dysfunction (inability to spontaneously void with a post-void residual ResultsAmong 234 patients, 86 (36.8%) underwent open surgery and 112 (47.9%) used enhanced recovery after surgery (ERAS) pathways. 29 (12.4%) patients had urinary catheter removal between 1–5 days postoperatively (group 1), 141 (60.3%) between 6–10 days (group 2), and 64 (27.3%) between 11–15 days (group 3). The overall rate of voiding dysfunction was 11.5%, with no difference between group 1 (17.2%), group 2 (11.3%), and group 3 (9.4%) (p=0.54). Group 1 had a significantly shorter time from surgery to spontaneous voiding (4 days, IQR 3–5 days) compared with group 2 (8 days, IQR 7–10 days) and group 3 (13 days, IQR 11–15 days) (pConclusionThere was no difference in voiding dysfunction or postoperative genitourinary complications based on timing of urinary catheter removal after radical hysterectomy. Early catheter removal should be considered in this population.

ObjectiveCurrent gaps in knowledge limit clinicians from fully implementing patient-reported outcomes in routine post-operative care.MethodsThis prospective study assessed symptoms via the gynecologic module of the MD Anderson Symptom Inventory (MDASI-PeriOp-GYN) in patients who underwent open laparotomy.ResultsAt discharge, patient-reported moderate to severe (≥4 on a 0–10 scale) abdominal bloating or abdominal cramping, combined with length of stay of ≥4 days, were found to be associated with a higher risk of 30-day post-operative grade II–IV complications by the Clavien-Dindo system (all p values ConclusionThis study defined the clinically meaningful symptoms that related to the risk of developing important complications after discharge from major open gynecological surgery.These findings support the integration of assessment of patient-reported outcomes into patient-centered post-operative care.

Endometrial carcinosarcoma is a rare and aggressive high-grade endometrial carcinoma with secondary sarcomatous trans-differentiation (conversion theory). The clinical presentation and diagnostic work-up roughly align with those of the more common endometrioid counterpart, although endometrial carcinosarcoma is more frequently diagnosed at an advanced stage. Endometrial carcinosarcoma is not a single entity but encompasses different histological subtypes, depending on the type of carcinomatous and sarcomatous elements. The majority of endometrial carcinosarcomas are characterized by p53 abnormalities. The proportion ofPOLEand microsatellite instablity-high (MSI-H) is directly related to the epithelial component, being approximately 25% and 3% in endometrioid and non-endometrioid components.The management of non-metastatic disease is based on a multimodal approach with optimal surgery followed by (concomitant or sequential) chemotherapy and radiotherapy, even for early stages. Palliative chemotherapy is recommended in the metastatic or recurrent setting, with carboplatin/paclitaxel doublet being the first-line regimen. Although the introduction of immunotherapy plus/minus a tyrosine kinase inhibitor shifted the paradigm of treatment of patients with recurrent endometrial cancer, patients with endometrial carcinosarcoma were excluded from most studies evaluating single-agent immunotherapy or the combination. However, the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) approved the use of pembrolizumab and lenvatinib in endometrial cancer (all histotypes) after progression on chemotherapy and single-agent immunotherapy in MSI-H cancers. In the era of precision medicine, emerging knowledge on molecular endometrial carcinosarcoma is opening new promising therapeutic options for more personalized treatment. The present review outlines state-of-the-art knowledge and future directions for patients with endometrial carcinosarcoma.

OBJECTIVE: To determine the incidence of postoperative AKI after open gynecologic surgery within ERAS, compare AKI in pre-ERAS and ERAS cohorts, and identify factors associated with AKI. METHODS: We compared postoperative AKI in patients who underwent open gynecologic surgery at one institution before and after ERAS implementation. AKI was defined as acute risk, injury, or failure by RIFLE criteria. Pre-ERAS and ERAS cohorts were matched using propensity score analysis in a 1:1 fashion using the nearest neighbor technique. Chi-squared, Fisher’s Exact, and Wilcoxon rank-sum tests were used. RESULTS: Among 1334 ERAS and 191 pre-ERAS patients, postoperative AKI incidence was higher in the ERAS cohort (13.1% vs 5.8%, p=.004). In 166 matched pairs, ERAS patients had higher incidence (16.9% vs 5.4%, p5 minutes (41.7% vs 30.7%, p

The Society of Gynecologic Oncology (SGO) 2022 Annual Meeting was held between 18-21 March in Phoenix, Arizona. Multiple scientific plenary sessions covered key research concepts that included novel therapeutics, precision oncology, clinical trials, cancer care delivery, diversity, equity and inclusion, surgical trials and translational research. In the present report presentations that may impact clinical care are summarized.

BackgroundVulvar cancer is a rare disease and despite broad adoption of sentinel lymph node mapping to assess groin metastases, inguino-femoral lymph node dissection still plays a role in the management of this disease. Inguino-femoral lymph node dissection is associated with high morbidity, and limited research exists to guide the best surgical approach.ObjectiveTo determine international practice patterns in key aspects of the inguino-femoral lymph node dissection technique and provide data to guide future research.MethodsA survey addressing six key domains of practice patterns in performing inguino-femoral lymph node dissection was distributed internationally to gynecologic oncology surgeons between April and October 2020. The survey was distributed using the British Gynecological Cancer Society, the Society of Gynecologic Oncology, authors' direct links, the UK Audit and Research in Gynecology Oncology group, and Twitter.ResultsA total of 259 responses were received from 18 countries. The majority (236/259, 91.1%) of respondents reported performing a modified oblique incision, routinely dissecting the superficial and deep inguino-femoral lymph nodes (137/185, 74.1%) with sparing of the saphenous vein (227/258, 88%). Most respondents did not routinely use compression dressings/underwear (169/252 (67.1%), used prophylactic antibiotics at the time of surgery only (167/257, 65%), and closed the skin with sutures (192 74.4%). Also, a drain is placed at the time of surgery by 243/259 (93.8%) surgeons, with most practitioners (144/243, 59.3%) waiting for drainage to be less than 30–50 mL in 24 hours before removal; most respondents (66.3%) routinely discharge patients with drain(s) in situ.ConclusionOur study showed that most surgeons perform a modified oblique incision, dissect the superficial and deep inguino-femoral lymph nodes, and spare the saphenous vein when performing groin lymphadenectomy. This survey has demonstrated significant variability in inguino-femoral lymph node dissection in cases of vulvar cancer among gynecologic oncology surgeons internationally.

ObjectiveTo evaluate whether a citation advantage exists for open access (OA) publications in gynecologic oncology.MethodA cross-sectional study of research and review articles published in theInternational Journal of Gynecological Cancer(IJGC) and inGynecologic Oncologyduring 1980–2022. Bibliometric measures were compared between OA publications and non-OA publications. The role of authors in low/middle-income countries was assessed. We analyzed article characteristics associated with a high citations per year (CPY) score.ResultsOverall, 18 515 articles were included, of which 2398 (13.0%) articles were published OA. The rate of OA has increased since 2007. During 2018–2022, the average proportion of articles published OA was 34.0% (range 28.5%–41.4%). OA articles had higher CPY (median (IQR), 3.0 (1.5–5.3) vs 1.3 (0.6–2.7), pIJGC– r(23)=0.90, pGynecologic Oncology– r(23)=0.89, pConclusionOA articles have a higher CPY, with a strong positive correlation between OA proportion and impact factor. OA publishing has increased since 2007, but articles written by authors in low/middle-income countries are under-represented among OA publications.

ObjectiveThe objective of this systematic review was to assess the oncologic outcomes of patients with International Federation of Gynecology and Obstetrics (FIGO) 2018 stage IVB cervical cancer receiving definitive pelvic radiotherapy compared with systemic chemotherapy (with or without palliative pelvic radiotherapy).MethodsThis study was registered in PROSPERO (registration number CRD42022333433). A systematic literature review was conducted following the MOOSE checklist. MEDLINE (through Ovid), Embase, and Cochrane Central Register of Controlled Trials were searched from inception until August 2022. The inclusion criteria were patients with metastatic FIGO 2018 stage IVB cervical cancer, a histologic subtype of squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma that received definitive pelvic radiotherapy (≥45 Gy) as part of management compared with systemic chemotherapy with or without palliative (30 Gy) pelvic radiotherapy. Randomized controlled trials and observational studies with two arms of comparison were considered.ResultsThe search identified 4653 articles; 26 studies were considered potentially eligible after removing duplicates, and 8 met the selection criteria. In total, 2424 patients were included. There were 1357 and 1067 patients in the definitive radiotherapy and chemotherapy groups, respectively. All included studies were retrospective cohort studies, and two were database population studies. The median overall survival reported in seven studies for the definitive radiotherapy arm versus systemic chemotherapy groups were 63.7 months versus 18.4 months (pConclusionsDefinitive pelvic radiotherapy as part of treatment in patients with stage IVB cervical cancer may improve oncologic outcomes compared with systemic chemotherapy (with or without palliative radiotherapy); however, this is based on low-quality data. Prospective evaluation would be ideal before the adoption of this intervention in standard clinical practice.

ObjectiveBibliometric literature in gynecologic oncology is limited. We aimed to study the association between the level of income of the country of authorship and citation metrics.MethodsA retrospective study including all articles and reviews published during 1977–2022 in theInternational Journal of Gynecological Cancer(IJGC) andGynecologic Oncologyjournals. Country of origin was defined as the corresponding author’s address. We classified articles into groups by level of income of the country of origin, as defined by the World Bank. The primary outcome measure was the median number of citations per year.ResultsA total of 9835 articles were included in the analysis (IJGCn=3786 (38.5%),Gynecologic Oncologyn=6049 (61.5%)). There were 8587 (87.3%) publications from high income countries, 1134 (11.5%) from upper-middle income countries, and 114 (1.2%) from lower-middle income countries. There were no publications from countries of low income. Most publications originated in the United States with 4089 (41.6%), followed by China (n=730, 7.4%), Italy (n=533, 5.4%), Canada (n=467, 4.7%), and Japan (n=461, 4.7%). Over the most recent 5 years there was a decrease in the representation of upper-middle income countries and lower-middle income countries; 16.3% (91/557) in 2018 versus 9.1% (38/417) in 2022 (p=0.005). In a multivariable regression analysis that included year of publication, open access publication model, study being supported by funding, publishing journal, review article, and level of income, all factors were associated with high citation per year score except the income classification of the article’s country of origin (adjusted OR 1.59–1.72, 95% CI 0.61 to 4.30).ConclusionHigh income countries have a disproportionate representation in gynecologic oncology publications. After adjusting for confounders, the country’s level of income was not independently associated with a high citation per year score. This implies that the number of citations per year is not compromised by the country’s level of income.

ObjectiveOpen surgery has become the standard approach for radical hysterectomy in early stage cervical cancer (International Federation of Gynecology and Obstetrics (FIGO) 2018 IA1 with lymphovascular space invasion-IIA1). Our primary objective was to compare the length of stay in patients undergoing open radical hysterectomy before and after implementation of an enhanced recovery after surgery (ERAS) program.MethodsThis was a single center, retrospective, before-and-after intervention study including patients who underwent open radical hysterectomy for cervical cancer from January 2009 to December 2020. Two groups were identified based on the time of ERAS implementation: pre-ERAS group included patients who were operated on between January 2009 and October 2014; post-ERAS group included patients who underwent surgery between November 2014 and December 2020.ResultsA total of 81 patients were included, of whom 29 patients were in the pre-ERAS group and 52 patients in the post-ERAS group. Both groups had similar clinical characteristics with no differences in terms of median age (42 years (interquartile range (IQR) 35–53) in pre-ERAS group vs 41 years (IQR 35–49) in post-ERAS group; p=0.47) and body mass index (26.1 kg/m2 (IQR 24.6–29.7) in pre-ERAS group vs 27.1 kg/m2 (IQR 23.5–33.5) in post-ERAS group; p=0.44). Patients in the post-ERAS group were discharged from the hospital earlier compared with those in the pre-ERAS group (median 3 days (IQR 2–3) vs 4 (IQR 3–4), pConclusionsPatients undergoing open radical hysterectomy on an ERAS pathway have a shorter length of hospital stay without increasing overall complications or readmissions rates.

BackgroundObservational 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 objectiveThe 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 hypothesisWe 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 designThe 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 criteriaPatients 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 endpointThe primary endpoint is non-inferiority of disease-free survival in minimally invasive vs laparotomic interval debulking surgery.Sample sizeTo demonstrate non-inferiority with a margin of 33% in the hazard ratio (HR=1.33), 549 patients will be randomized.

The major tenets in accurately assessing tumor size in patients with early stage cervical cancer currently include physical examination, imaging studies, and pathologic evaluation. It is estimated that when comparing clinical stage based on physical examination and final pathology, the concordance diminishes as stage increases: 85.4%, 77.4%, 35.3%, and 20.5% for stage IB1, IB2, IIA, and IIB, respectively. Vaginal involvement and larger tumor diameter are considered the main causes of stage inaccuracy. When considering imaging studies, magnetic resonance imaging (MRI) provides the highest level of accuracy in the assessment of cervical tumor size. Its accuracy in determining tumor location within the cervix is approximately 91% and in predicting tumor size 93%. MRI imaging is also significantly more accurate in measuring tumor size, delineating cervical tumor boundaries, and local tumor extension when compared with computed tomography (CT) scan. When comparing with pelvic ultrasound, the accuracy of both imaging techniques (MRI and pelvic ultrasound) in the assessment of tumor size in small versus large tumors is comparable. Pertaining to pathology, the depth of invasion should be measured by convention from the nearest surface epithelium, which equates to tumor thickness. In the setting where tumor is found both in the conization and hysterectomy specimen, the horizontal extent should be measured by summing the maximum horizontal measurement in the different specimens and the depth of invasion measured as the maximum depth in either specimen. A new pattern-based classification for endocervical adenocarcinomas recommends the description of patterns of invasion for human papillomavirus (HPV)-related adenocarcinomas as this is associated with differing risks of lymph node involvement.

Epithelial-to-mesenchymal transition (EMT) has been associated with cancer cell heterogeneity, plasticity, and metastasis. However, the extrinsic signals supervising these phenotypic transitions remain elusive. To assess how selected microenvironmental signals control cancer-associated phenotypes along the EMT continuum, we defined a logical model of the EMT cellular network that yields qualitative degrees of cell adhesions by adherens junctions and focal adhesions, two features affected during EMT. The model attractors recovered epithelial, mesenchymal, and hybrid phenotypes. Simulations showed that hybrid phenotypes may arise through independent molecular paths involving stringent extrinsic signals. Of particular interest, model predictions and their experimental validations indicated that: (i) stiffening of the extracellular matrix was a prerequisite for cells overactivating FAK_SRC to upregulate SNAIL and acquire a mesenchymal phenotype and (ii) FAK_SRC inhibition of cell–cell contacts through the receptor-type tyrosine-protein phosphatases kappa led to acquisition of a full mesenchymal, rather than a hybrid, phenotype. Altogether, these computational and experimental approaches allow assessment of critical microenvironmental signals controlling hybrid EMT phenotypes and indicate that EMT involves multiple molecular programs. Significance: A multidisciplinary study sheds light on microenvironmental signals controlling cancer cell plasticity along EMT and suggests that hybrid and mesenchymal phenotypes arise through independent molecular paths.

Presented by: Ignacio Zapardiel Cervical cancer is the most common cancer-related cause of death among young women with almost 570 000 new cases per year worldwide.1 The standard of care for patients with early stage disease is radical hysterectomy and pelvic lymphadenectomy with or without

Presented by: Kathleen M Schmeler The standard of care for patients with early-stage cervical cancer is radical hysterectomy with pelvic lymphadenectomy or sentinel lymph node mapping in experienced centers. For patients interested in future fertility, the National Comprehensive Cancer Network (

PURPOSE: There is a gap in knowledge regarding the impact of micrometastases (MIC) and isolated tumor cells (ITCs) found in the sentinel lymph nodes of patients with endometrial cancer. Here, we present a meta-analysis of the published literature on the rate of MIC and ITCs after lymphatic mapping and determine trends in postoperative management. METHODS: Literature search of Medline and PubMed was done using the terms: micrometastases, isolated tumor cells, endometrial cancer, and sentinel lymph node. Inclusion criteria were: English-language manuscripts, retrospectives, or prospective studies published between January 1999 and June 2019. We removed manuscripts on sentinel node mapping that did not specify information on micrometastases or isolated tumor cells, non-English-language articles, no data about oncologic outcomes, and articles limited to ten cases or less. RESULTS: A total of 45 manuscripts were reviewed, and 8 studies met inclusion criteria. We found that the total number of patients with MIC/ITCs was 286 (187 and 99, respectively). The 72% of patients detected with MIC/ITCs in sentinel nodes received adjuvant therapies. The MIC/ITCs group has a higher relative risk of recurrence of 1.34 (1.07, 1.67) than the negative group, even if the adjuvant therapy was given. CONCLUSION: We noted that there is an increased relative risk of recurrence in patients with low-volume metastases, even after receiving adjuvant therapy. Whether adjuvant therapy is indicated remains a topic of debate because there are other uterine factors implicated in the prognosis. Multi-institutional tumor registries may help shed light on this important question.

Over the past several years, a number of publications have had an impact on the management of endometrial, cervical, and ovarian cancers, representing true paradigm shifts for the gynecologic oncology community. The meeting “Paradigm shifts in gynecologic oncology: learning with friends” took

ObjectiveThe objective of the ConCerv Trial was to prospectively evaluate the feasibility of conservative surgery in women with early-stage, low-risk cervical cancer.MethodsFrom April 2010 to March 2019, a prospective, single-arm, multicenter study evaluated conservative surgery in participants from 16 sites in nine countries. Eligibility criteria included: (1) FIGO 2009 stage IA2–IB1 cervical carcinoma; (2) squamous cell (any grade) or adenocarcinoma (grade 1 or 2 only) histology; (3) tumor size <2 cm; (4) no lymphovascular space invasion; (5) depth of invasion <10 mm; (6) negative imaging for metastatic disease; and (7) negative conization margins. Cervical conization was performed to determine eligibility, with one repeat cone permitted. Eligible women desiring fertility preservation underwent a second surgery with pelvic lymph node assessment, consisting of sentinel lymph node biopsy and/or full pelvic lymph node dissection. Those not desiring fertility preservation underwent simple hysterectomy with lymph node assessment. Women who had undergone an ‘inadvertent’ simple hysterectomy with an unexpected post-operative diagnosis of cancer were also eligible if they met the above inclusion criteria and underwent a second surgery with pelvic lymph node dissection only.Results100 evaluable patients were enrolled. Median age at surgery was 38 years (range 23–67). Stage was IA2 (33%) and IB1 (67%). Surgery included conization followed by lymph node assessment in 44 women, conization followed by simple hysterectomy with lymph node assessment in 40 women, and inadvertent simple hysterectomy followed by lymph node dissection in 16 women. Positive lymph nodes were noted in 5 patients (5%). Residual disease in the post-conization hysterectomy specimen was noted in 1/40 patients—that is, an immediate failure rate of 2.5%. Median follow-up was 36.3 months (range 0.0–68.3). Three patients developed recurrent disease within 2 years of surgery—that is, a cumulative incidence of 3.5% (95% CI 0.9% to 9.0%).DiscussionOur prospective data show that select patients with early-stage, low-risk cervical carcinoma may be offered conservative surgery.

The 2019 update of the Enhanced Recovery After Surgery (ERAS) Society guidelines for gynecologic oncology is the most downloaded manuscript from the journal since its inception, with over 75 000 downloads and counting.[1][1] This, together with its high citation count in a relatively short period

OBJECTIVE: To determine the feasibility of pharmacologic beta-adrenergic blockade in women with newly diagnosed stage II-IV epithelial ovarian cancer (EOC) throughout primary treatment. METHODS: Patients initiated propranolol prior to beginning chemotherapy or surgery. Feasibility was assessed as proportion able to complete 6 chemotherapy cycles while on adrenergic suppression. Descriptive statistics summarized surveys, and paired changes were analyzed using signed rank tests. Random-intercept Tobit models examined immune response. RESULTS: Median age was 59.9; 88.5% were stage IIIC/IV; and 38.5% underwent primary debulking. Thirty-two patients were enrolled; 3 excluded because they never took propranolol; an additional 3 didn’t meet inclusion criteria, leaving 26 evaluable. Eighteen of 26 (69%), 90% credible interval (CI) of 53–81%, completed 6 chemotherapy cycles plus propranolol (an 82% posterior probability that the true proportion of success is ≥60%). Among the 23 patients with baseline and six month follow up data, overall QOL, anxiety, and depression improved (P

Background The identification of extrauterine disease is critical to the management of patients with high-risk endometrial cancer. The purpose of the current study was to determine the accuracy of preoperative positron emission tomography (PET)/computed tomography (CT) in the detection of extrauterine disease. Methods Women with high-risk endometrial cancer were enrolled prospectively and underwent preoperative PET/CT followed by surgery, including sentinel lymph node biopsy and lymphadenectomy. Primary tumor factors on PET/CT were correlated with lymph node pathology. The sensitivity, specificity, positive predictive value, and negative predictive value were calculated for the detection of lymphadenopathy and peritoneal disease by PET/CT. Results A total of 112 patients were enrolled and underwent PET/CT between April 2013 and May 2016, 108 of whom were evaluable. On PET/CT, 21 patients (19.4%) were found to have extrauterine disease, 18 (17%) had positive lymph nodes, and 8 (7%) had peritoneal disease. A total of 108 patients underwent surgery, 103 of whom (95%) underwent lymphadenectomy. The sensitivity of PET/CT to detect positive lymph nodes was 45.8%, with a specificity of 91.1%, positive predictive value of 61.1%, and negative predictive value of 84.7%. The false-negative rate was 54.2%. There was no difference in primary tumor characteristics on imaging noted between patients with positive and negative lymph nodes. The sensitivity of PET/CT to detect peritoneal disease was 37.5%, with a specificity of 97.8%, positive predictive value of 75%, and negative predictive value of 90.0%. The false-negative rate was 62.5%. Conclusions Preoperative PET/CT did not reliably predict the presence of extrauterine disease in women with high-risk endometrial cancer. Given the high false-negative rates, PET/CT should not be used in the preoperative treatment planning of these patients.

OBJECTIVE. To identify clinical and demographic characteristics associated with the absence of opioid usage on the day before discharge among patients undergoing open gynecologic surgery within an enhanced recovery after surgery (ERAS) program. METHODS. This was a single institution retrospective cohort study including all patients who underwent elective open gynecologic surgery as part of an ERAS program between November 1, 2014 and September 30, 2018 and who were discharged between post-operative day 2 and 7. Patients were excluded if they reported preexisting chronic opioid use or underwent total pelvic exenteration. Descriptive statistics were used and multivariable logistic regression was used to identify factors associated with the absence of opioid usage on the day before discharge, after adjustment for relevant covariates. RESULTS. A total of 971 were included with a median length of stay of 3 days, and of these 526 (54.2%) used opioids on day before discharge and 445 (45.8%) did not. Absence of opioid use on the day before discharge was associated with age (P < .001), race (P = .04), Charlson Co-morbidity Index (P < .001), marital status (P = .004), and smoking status (P = .002) by univariate analysis. In a multivariable model, older age (adjusted OR 1.04; 95% CI 1.02–1.06; P < .001), current smoker status (adjusted OR 0.42; 95% CI 0.20–0.81; P = .01), and white or Caucasian race (adjusted OR 0.59; 95% CI 0.38–0.91; P = .02) were significantly associated with the absence of opioid use on the day prior to discharge. CONCLUSIONS. Nearly half of patients undergoing open gynecologic surgery within an established ERAS program did not consume any opioids on day before discharge. Safe, evidence-based reductions in post-operative opioid prescribing may be feasible for a subset of gynecologic surgery patients.

// Marilyne Labrie 1 , Tae-Beom Kim 2 , Zhenlin Ju 2 , Sanghoon Lee 3 , Wei Zhao 3 , Yong Fang 1 , Yiling Lu 3 , Ken Chen 2 , Pedro Ramirez 4 , Michael Frumovitz 4 , Larissa Meyer 4 , Nicole D. Fleming 4 , Anil K. Sood 4 , Robert L. Coleman 4 , Gordon B. Mills 1 , 3 and Shannon N. Westin 4 1 Knight Cancer Institute and Cell, Developmental and Cancer Biology, Oregon Health and Science University, Portland, OR, USA 2 Department of Bioinformatics and Computational Biology, University of Texas, MD Anderson Cancer Center, Houston, TX, USA 3 Department of Systems Biology, University of Texas, MD Anderson Cancer Center, Houston, TX, USA 4 Department of Gynecologic Oncology and Reproductive Medicine, University of Texas, MD Anderson Cancer Center, Houston, TX, USA Correspondence to: Shannon N. Westin, email: swestin@mdanderson.org Keywords: poly (ADP-ribose) polymerase inhibitor; combination therapy; adaptive response; ovarian cancer; targeted therapy Received: March 12, 2019 Accepted: May 02, 2019 Published: May 28, 2019 ABSTRACT Poly (ADP-ribose) polymerase inhibitor (PARPi)-based combination therapies are demonstrating efficacy in patients, however, identifying the right combination for the right patient remains a critical challenge. Thus, it is urgent to develop approaches able to identify patients likely to benefit from specific combination therapies. Several groups, including ours, have demonstrated that targeting adaptive responses induced by PARPi increases depth and duration of response. In this study, we instituted a talazoparib (PARPi) monotherapy window of opportunity trial to identify informative adaptive responses in high grade serous ovarian cancer patients (HGSOC). Patients were treated for 7 to 14 days with PARPi monotherapy prior to surgery with tissue samples from multiple sites being collected pre- and post-treatment in each patient. Analysis of these samples demonstrated that individual patients displayed different adaptive responses with limited interlesional heterogeneity. Ability of combination therapies designed to interdict adaptive responses to decrease viability was validated using model systems. Thus, assessment of adaptive responses to PARPi provides an opportunity for patient-specific selection of combination therapies designed to interdict patient-specific adaptive responses to maximize patient benefit.

BackgroundThis is the first updated Enhanced Recovery After Surgery (ERAS) Society guideline presenting a consensus for optimal perioperative care in gynecologic/oncology surgery.MethodsA database search of publications using Embase and PubMed was performed. Studies on each item within the ERAS gynecologic/oncology protocol were selected with emphasis on meta-analyses, randomized controlled trials, and large prospective cohort studies. These studies were then reviewed and graded according to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system.ResultsAll recommendations on ERAS protocol items are based on best available evidence. The level of evidence for each item is presented accordingly.ConclusionsThe updated evidence base and recommendation for items within the ERAS gynecologic/oncology perioperative care pathway are presented by the ERAS® Society in this consensus review.

Objective To compare symptom burden and functional recovery in women undergoing primary cytoreductive surgery (PCS) or neoadjuvant chemotherapy (NACT) and interval cytoreductive surgery (ICS) within an enhanced recovery after surgery program (ERAS). Methods Symptom burden was measured using the MD Anderson Symptom Inventory-Ovarian Cancer, a 27-item validated tool that was administered preoperatively, daily while hospitalized, and weekly for 8 weeks after hospital discharge. Mixed-effect modeling was performed. Results 196 patients (71 PCS, 125 ICS) participated. Patients in the PCS group were younger, median age of 59 vs. 63 in ICS group. Median length of stay was 4 days for PCS and 3 days for ICS group. PCS pts had a significantly higher median surgical complexity score (4 vs. 2, p = 0.002), and longer median surgical time (257 min vs. 220 min, p = 0.03). While patients undergoing PCS had significantly different symptom burden profiles prior to surgery compared to those undergoing ICS, there were no significant differences in symptoms in the immediate in-hospital and extended post-hospital discharge period. Irrespective of the timing of surgery in relation to chemotherapy, patients undergoing intermediate or high complexity surgery had more nausea, fatigue, and higher total interference scores compared to patients undergoing low complexity surgery. Conclusion Within a center with a standardized, systematic method for patient selection for PCS and a standardized ERAS care pathway, there were not significant differences in surgery-related symptoms related to recovery between patients undergoing PCS or ICS. However, patient-reported symptom burden and symptom interference did meaningfully differentiate based on surgical complexity score.

OBJECTIVE: Using patient-reported outcomes (PROs) in perioperative care is increasingly common. We report the development, validation, and application of an MD Anderson Symptom Inventory version for use in patients undergoing surgery for gynecologic cancer or benign conditions (MDASI-PeriOp-GYN). METHODS: Our process included: (1) generating PeriOp-GYN–specific candidate items from qualitative interviews with patients, followed by input from an expert panel; (2) dropping items that lacked independent clinical relevance; (3) validating psychometric properties (reliability, validity) of the resulting MDASI-PeriOp-GYN; and (4) conducting cognitive debriefing interviews with patients to confirm ease of comprehension, relevance, and acceptability. RESULTS: Qualitative interviews with 40 patients generated 9 new PeriOp-GYN symptom items (bloating, abdominal cramping, constipation, hot flashes, dizziness, grogginess/confusion, urinary pain, difficulty urinating, and diarrhea) that, along with the core MDASI items, formed the new MDASI-PeriOpGYN. A total of 150 patients (minimally invasive surgery (MIS)=69, open surgery=81) participated in the validation study; 123 also provided retest data. Cronbach alphas were 0.89 for symptoms and 0.86 for interference. Test-retest reliability was 0.88 for all symptom severity items. Known-group validity was supported by the detection of significant differences in symptom and interference levels by performance status (P

Background HPV infection causes several cancers which include cervical, vaginal, vulval, penile and oropharyngeal cancer (OPC). Understanding the burden of HPV-related cancers is important for guiding cancer prevention and treatment interventions. Methods To inform policy, we analysed trends of age-standardised incidence (ASIR) and mortality (ASMR) rates for HPV-related head and neck (HNC) and anogenital cancers (AGC) in South Africa between 1994 and 2013. Results A total of 1 028 330 incident cancers and 617 044 cancer-related deaths were reported during the study period. The overall ASIR (-5.5%) and ASMR (-2.2%) for HNC declined, in part related to the anti-smoking legislation. In contrast, incidence (2.9%) and mortality (0.8%) rates for AGC increased with the rising HIV prevalence. ASIR for oral cavity cancer (OCC: -6.3%) and laryngeal cancer (LC: -11.3%) declined, including mortality associated with these cancers (OCC:-1.9%, and LC:-2.6%). However, oropharyngeal cancer showed a slower rate of decline in ASIR (-4.4%) and ASMR did not change. Compared to women, ASIR and ASMR for HNC were 3-fold higher among men. ASIR for both anal (7.5%) and vulval cancer (16.1%) increased. Median age at diagnosis of vulval cancer declined by 18 years (p-value = 0.01). Mortality rates for anal (3.9%) and vulval (2.6%) cancer increased. ASIR (-3.2%) and ASMR (-2.0%) for penile cancer declined. Rates for vaginal cancer did not change. Conclusions Anal and vulval cancers have increased over the reporting period. There is need to continuously monitor trends of these cancers. Implementation of HPV vaccination could significantly reduce the burden of HPV-related cancers.

To evaluate the prevalence and associated prognostic indicators in patients with vulvar carcinoma with and without evidence of perineural invasion (PNI).A retrospective review identified 421 patients with invasive vulvar carcinoma evaluated at a single institution between 1993 and 2011. Medical records were reviewed for demographic data, pathologic information and presence or absence of PNI, treatment type, and recurrence/outcome information. Variables were compared between patients with PNI to those without PNI.Of the 421 patients included in the study, 32 (7.6%) had tumors with PNI. There were no significant differences in age, race/ethnicity, smoking history, histologic subtype, or grade between the group of patients with PNI and the group without PNI. The group with PNI was more likely to have lichen sclerosus (25.0% vs. 15.4%, p = 0.024), stage III/IV disease (59.4% vs. 36.0%, p = 0.007), lymph node involvement (50.0% vs. 21.6%, p = 0.002), and lymphovascular space invasion (LVSI) (53.1% vs. 15.9%, p 0.001). A higher proportion of patients in the PNI group underwent primary or adjuvant radiation therapy (68.8% vs. 45.0%, p = 0.016). The median follow-up was 67.1 months (range 1.0 to 284.3). Patients with PNI had significantly shorter overall survival (OS), median 25.5 vs. 94.3 months (p 0.001), and progression-free survival (PFS), median 17.5 vs. 29.0 months (p = 0.004). After adjusting for stage, patients with PNI had a greater risk for death and progression (OS: hazard ratio, 2.71; p 0.001; PFS: hazard ratio, 1.64; p-value = 0.020).PNI should be considered an independent poor prognostic factor for patients with vulvar carcinoma, and should be included as part of the pathologic analysis.

Prostate cancer (PCa) is the second leading cause of cancer deaths in the U.S., disproportionally affecting African American (AA) men. Glucocorticoids (GCs) are administered to PCa patients and have been implicated in therapy resistance. This may be critical to AA men with PCa since they have elevated endogenous GCs levels compared to Caucasian American (CA) men. GCs bind to the glucocorticoid receptor (GR) to exert their actions. The mechanisms of GR-mediated chemoresistance, and its possible contribution to PCa mortality disparities are unknown. We demonstrated that GCs upregulate the chemoresistance-associated protein and transcription co-activator LEDGF/p75 in PCa cells and identified consensus GR binding sites in the promoter region of this protein. Given that both GR and LEDGF/p75 are components of the RNA polymerase II transcription complex, we hypothesized that GR transcriptionally upregulates LEDGF/p75 and then interacts with it to enhance taxane resistance in PCa cells. Pharmacological and genetic inhibition of GR in a panel of docetaxel (DTX)-sensitive and -resistant PCa cells decreased the expression of LEDGF/p75, confirming its status as a candidate GR target gene. However, silencing of LEDGF/p75 had no effects on GR expression. Immunoprecipitation studies revealed that GR and LEDGF/p75 interact in DTX-resistant PCa cells. This interaction was confirmed by confocal microscopy. Immunohistochemical analysis of GR and LEDGF/p75 expression in normal and tumor prostate tissues was performed, and the results are currently being analyzed. Our studies use a mechanistic approach to evaluate the potential contribution of the GR-LEDGF/p75 axis to PCa chemoresistance. Evaluating the co-expression of these proteins in racially diverse PCa tissues may also reveal race-related differential expression, providing insights into the potential contribution of this axis to PCa chemoresistance and mortality disparities. Citation Format: Evelyn S. Sanchez Hernandez, Greisha L. Ortiz Hernandez, Pedro T. Ochoa, Christian R. Gomez, Carlos A. Casiano. Contribution of the GR/LEDGFp75 axis to prostate cancer chemoresistance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2348.

The efficacy of anti-androgen receptor (AR) therapies and taxane-based chemotherapy for the treatment of advanced prostate cancer (PCa) is hindered by the development of therapy resistance. Our previous studies demonstrated that docetaxel (DTX)-resistant PCa cells activates a transcriptomic program associated with stemness and display cancer stem cell (CSC) properties, consistent with the notion that CSCs within prostate tumors contribute to chemoresistance. Glucocorticoid receptor (GR) signaling is a critical mediator of resistance to AR-targeted therapy, and has been recently implicated in the development of PCa cell tumorsphere formation and chemoresistance. Like GR, β-catenin is overexpressed in metastatic and therapy-resistant tumors, and is considered a key regulator of cancer stemness and androgen-targeted therapy resistance. Given the structural and functional overlap between GR and AR, a known interacting partner of β-catenin, we hypothesized that GR also interacts with β-catenin to support stemness and chemoresistance in PCa cells. We observed that treatment with the glucocorticoid dexamethasone induces enhanced nuclear accumulation of both GR and β-catenin in DTX-resistant PCa cells compared to their DTX-sensitive counterparts. Knockdown studies revealed that GR and β-catenin do no regulate each other at the protein level. However, using whole cell and nuclear co-immunoprecipitation, we demonstrated the interaction between GR and β-catenin in both DTX-resistant and DTX-sensitive PC3, DU145, and 22RV1 cells. Pharmacological inhibition and RNA interference-mediated silencing of GR with concomitant inhibition of β-catenin enhanced DTX cytotoxicity in resistant PCa cells grown in both adherent and spheroid cultures, and decreased CD44+/CD24- cell populations in tumorspheres. These results indicate that both GR and β-catenin interact and influence stemness, and may be promising therapeutic targets to overcome PCa chemoresistance. Citation Format: Shannalee R. Martinez, Catherine C. Elix, Pedro T. Ochoa, Evelyn S. Sanchez-Hernandez, Hossam R. Alkashgari, Greisha L. Ortiz-Hernandez, Lubo Zhang, Carlos A. Casiano. The glucocorticoid receptor and β-catenin interact in prostate cancer cells and their co-inhibition attenuates stemness and docetaxel resistance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 399.

Background: Despite high rates of remission after frontline management, most patients with advanced stage ovarian cancer recur. Second look laparoscopy (SLL) can provide more sensitive detection of minimal residual disease (MRD) allowing for more individualized prognostication and possible therapeutic intervention. It may also assess tumor biology and microenvironment associated with undetectable chemoresistant MRD phase of ovarian cancer. The objective of this study was to determine SLL feasibility, and clinicopathologic and molecular characteristics of MRD after frontline therapy in ovarian cancer. Methods: SLL was offered to patients with stage III-IV high grade epithelial ovarian cancer who achieved complete response after frontline surgery and 6 cycles of carboplatin and paclitaxel chemotherapy. Patients were offered standard of care or investigational management options based on homologous recombination deficiency (HRD) and MRD status at SLL. Preliminary translational studies included RNAseq for comparison of serial, matched tumor from primary or interval TRS and SLL derived MRD+ biopsies at the time of SLL. In addition, Nanostring analyses of SLL surgical biopsies both with and without residual tumor were performed. Molecular profiling employed hierarchical clustering, principle component analysis, non-parametric testing, and pathway analyses. Results: Between 4/2017- 7/2021, 39 patients underwent SLL. The majority had stage III disease (74%), high grade serous histology (90%) and underwent neoadjuvant chemotherapy with interval tumor reductive surgery (TRS; 54%). MRD was present in 49% (n=19) of patients and was more frequent among neoadjuvant chemotherapy recipients (73% vs 26%, P=0.015) and patients with homologous recombination proficient tumors (81% vs 25%, P=0.01). Most patients without MRD were dispositioned to observation; 4 patients with HRD received a PARP inhibitor per standard of care. All other patients with MRD received bevacizumab as part of a clinical trial, except for one patient who received a PARP inhibitor. Median follow-up was 6.74 months (range 0.66 - 28.62). Presence of MRD was associated with worse PFS (HR 3.7, 95% CI 1.3- 10.9; 5.5 vs 24.6 months; P= 0.02). Based on transcriptional signature, MRD are immunologically distinct from untreated tumors or those collected at interval TRS (after 3 cycles of chemo) but also displayed heterogeneity with two distinct subclusters. Conclusions: SLL to assess for MRD has potential to further individualize post-frontline therapy, and identify patients at high risk for progression for early intervention clinical trials. Transcriptional profiling suggests that MRD phase of ovarian cancer is characterized by a distinct, heterogeneous, and evolving tumor and immune microenvironment. Citation Format: Roni Nitecki, Minghao Dang, Sanghoon Lee, Bryan Fellman, J Alejandro Rauh-hain, Jolyn Taylor, Lois Ramondetta, Michaela Grinsfelder, Lauren Cobb, David M. Boruta, Pamela T. Soliman, Aaron Shafer, Nicole D. Fleming, Shannon N. Westin, Anil K. Sood, Chris Tanguma, Pedro T. Ramrez, Karen H. Lu, Linghua Wang, Amir A. Jazaeri. Initial clinicopathologic and molecular characterization of minimal residual disease detected by second look laparoscopy after completion of frontline surgery and chemotherapy in patients with advanced stage ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 4135.

In select patients with advanced ovarian cancer, primary cytoreductive surgery remains a standard approach with the aim of complete resection of all gross visible tumor.[1][1] Prior data have demonstrated that survival outcomes are driven by geographical access and the use of specialized referral

Objectives: The androgen receptor (AR) is more widely expressed than the estrogen or progesterone receptor in endometrial cancer (EC), including up to 90% of endometrioid type. Enzalutamide binds to the AR thereby nuclear translocation of receptors and blocking the association of the AR with DNA. We sought to evaluate the efficacy of paclitaxel, carboplatin and enzalutamide in a phase II study of advanced or recurrent endometrioid EC. Methods: Women with chemo-naive, advanced-stage or recurrent endometrioid EC with measurable disease and adequate end organ function were eligible. Documented AR expression was not required. A safety lead in of the triplet was performed to confirm dose. In phase II, patients received 28 days of enzalutamide (160mg daily) as a single agent before starting triplet therapy. Pre- and post-treatment biopsies were obtained during the single agent lead in for evaluation of molecular markers including AR receptor expression and activation, expression of AR-related genes/proteins, and DNA copy number alterations and mutations. Patients then received carboplatin (AUC 6 IV Q3wk), paclitaxel (175 mg/m2), and enzalutamide (160mg daily). Response per RECIST 1.1 was assessed every 3 cycles for a maximum of 9 cycles. Evaluable patients received at least 6 cycles of triplet therapy. Progression free survival (PFS) was calculated from date of treatment initiation to earliest date of progression, death, or last contact. This study was approved and funded in part by the National Comprehensive Cancer Network (NCCN) Oncology Research Program from general research support provided by Astellas Pharma Global Development, Inc. Results: A total 81 patients were screened with 49 patients treated to date (safety lead in n=7; phase II n=42). Median age was 64 years (range 41-81) and the majority of patients had grade 2 histology (53.1%) and recurrent disease (81.6%). There were no dose-limiting toxicities observed during the safety lead in. Patients received a median of 9 cycles of triplet therapy (range 0-9). 8 patients (16.3%) did not receive chemotherapy due to rapid progression during single agent enzalutamide (n=3), unrelated death (n=2), withdrawal (n=2), and unrelated stroke (n=1). PFS for the entire cohort was 11.47 months (95% CI 9.86 - 17.94; Figure 1a) and 6-month PFS probability was 0.77 (95% CI 0.61-0.87). Among 35 evaluable patients, confirmed objective response rate was 71% (95% CI 54–85%), 6 months PFS probability was 0.83 (95% CI 0.66-0.92) and median PFS was 14.42 months (95% CI 11.2-25.5; Figure 1B). The most common adverse events were as expected for chemotherapy alone, including neutropenia (20%), anemia (18%), fatigue (18%), neuropathy (10%), hyperglycemia (14%), nausea (8%), and thrombocytopenia (8%). Download : Download high-res image (41KB) Download : Download full-size image Conclusions: The combination of enzalutamide, carboplatin, and paclitaxel was tolerable and had promising clinical outcomes in chemo-naive advanced or recurrent endometrioid EC. Further analyses are ongoing regarding predictors of response and resistance to androgen-inhibitor therapy. Clinical Trials Registration: NCT02684227.

Fertility-sparing management of early-stage gynecologic cancers is becoming more prevalent as increasing evidence demonstrates acceptable oncologic and reproductive outcomes in appropriately selected patients. However, in the absence of randomized controlled trials, most of the commonly used treatment algorithms are based only on observational studies. As women are increasingly postponing childbearing, the need for evidence-based guidance on the optimal selection of appropriate candidates for fertility-sparing therapies is paramount. It is imperative to seriously consider the fertility potential of a given individual prior to making major oncologic treatment decisions that may deviate from the accepted standard of care. It is a disservice to patients to undergo a fertility-sparing procedure in hopes of ultimately achieving a live birth, only to determine later they have poor baseline fertility potential or other substantial barriers to conception including excess financial toxicity. Many women with oncologic diagnoses are of advanced maternal age and their obstetric and neonatal risks must be considered. In the era of advanced assisted reproductive technologies, patients should be provided realistic expectations regarding success rates while understanding the potential oncologic perils. A multidisciplinary approach to the conservative treatment of early-stage gynecologic cancers with early referral to reproductive specialists as well as maternal-fetal medicine specialists is warranted. In this review, we discuss the recommended fertility evaluation for patients with newly diagnosed, early-stage gynecologic cancers who are considering fertility-sparing management.

ObjectiveTo determine post-discharge patient-reported symptoms before and after implementation of restrictive opioid prescribing among women undergoing minimally invasive gynecologic surgery.MethodsWe compared clinical outcomes and symptom burden among a cohort of 389 women undergoing minimally invasive gynecologic surgery at a single institution before and after implementation of a restrictive opioid prescribing quality improvement initiative in July 2018. Post-discharge symptom burdens were collected up to 42 days after discharge using the MD Anderson Symptom Inventory and analyzed using linear mixed effects models.ResultsThe majority of women included in this study were white non-smokers and the median age was 55 (range 23–83). Most women underwent hysterectomy (64%), had surgery for malignancy (71%), and were discharged from the hospital on the day of surgery (65%). Women in the restrictive opioid prescribing group had a median reduction in morphine equivalent dose prescribed at discharge of 83%, corresponding to a median reduction in 25 tablets of 5 mg oxycodone per person. There was no difference between opioid prescribing groups in either the rate of refill requests (P=1) or hospital re-admission (P=1) up to 30 days after discharge. After adjustment for co-variates, there was no statistically significant difference in post-discharge symptom burden including patient-reported pain (P=0.08), sleep (P=0.30), walking interference (P=0.64), activity interference (P=0.12), or affective interference (P=0.67). There was a trend toward less reported constiptation in the restrictive opioid prescribing group that did not reach statistical significance (P=0.05).ConclusionWe found that restrictive post-operative opioid prescribing was not associated with differences in longitudinal symptom burden among women undergoing minimally invasive gynecologic surgery. These results provide the most comprehensive picture to date of post-operative symptom recovery under different opioid prescribing approaches, lending additional support for existing recommendations to reduce opioid prescribing following gynecologic surgery.