The impact of body mass index on robotic surgery outcomes in endometrial cancer.

OBJECTIVES: To compare surgical outcomes of patients with endometrial cancer who underwent robotic surgery across different BMI categories. METHODS: A retrospective study including all consecutive patients with endometrial cancer who underwent robotic surgery at a tertiary cancer center between December 2007 and December 2022. The study analyzed outcome measures, including blood loss, surgical times, length of hospitalization, perioperative complications, and conversion rates with the Kruskal-Wallis test for BMI group differences and the Chi-squared test for associations between categorical variables. RESULTS: A total of 1329 patients with endometrial cancer were included in the study. Patients were stratified by BMI: <30.0 (n = 576; 43.3%), 30.0-39.9 (n = 449; 33.8%), and ≥ 40.0 (n = 304; 22.9%). There were no significant differences in post-anesthesia care unit (PACU) stay (p = 0.105) and hospital stay (p = 0.497) between the groups. The rate of post-op complications was similar across the groups, ranging from 8.0% to 9.5% (p = 0.761). The rate of conversion to laparotomy was also similar across the groups, ranging from 0.7% to 1.0% (p = 0.885). Women with a BMI ≥40.0 had a non-clinically relevant but greater median estimated blood loss (30 mL vs. 20 mL; p < 0.001) and longer median operating room (OR) time (288 min vs. 270 min; p < 0.001). Within the OR time, the median set-up time was longer for those with a higher BMI (58 min vs. 50 min; p < 0.001). However, skin-to-skin time (209 min vs. 203 min; p = 0.202) and post-op time (14 min vs. 13 min; p = 0.094) were comparable between groups. CONCLUSION: BMI does not affect the peri-operative outcome of patients undergoing robotic staging procedures for endometrial cancer.

Association between BMI and oncologic outcomes in epithelial ovarian cancer: a predictors-matched case-control study.

OBJECTIVE: We aimed to study the association between obesity and survival in ovarian cancer (OC) patients, accounting for confounders as disease stage, histology, and comorbidities. METHODS: Retrospective matched case-control study of consecutive patients, with epithelial OC. Obese (body mass index [BMI] ≥ 35 kg m-2) patients were matched in a 1:4 ratio with patients having lower BMIs (BMI < 35 kg m-2) based on disease stage, cytoreduction state, tumor histology and ASA score. We compared the 3-year and total recurrence-free survival and overall survival through Kaplan-Meier survival curves and Cox proportional hazards. RESULTS: Overall, 153 consecutive patients were included, of whom 32 (20.9%) had a BMI ≥ 35. and 121 a BMI < 35. The median follow-up time was 39 months (interquartile range 18-67). Both study groups were similar in multiple prognostic factors, including American Society of Anesthesiologists physical status, completion of cytoreduction, histology and stage of disease (p = 0.981, p = 0.992, p = 0.740 and p = 0.984, respectively). Ninety-five (62.1%) patients underwent robotic surgery and conversion rate from robotic to laparotomy was similar in both groups 2 (6.3%) in obese group vs. 6 (5.0%) in lower BMI patients, p = 0.673. During the follow-up time, the rate of recurrence was similar in both groups; 21 (65.6%) in obese group vs. 68 (57.1%), p = 0.387 and the rate of death events was similar; 16 (50.0%) in obese group vs. 49 (40.5%), p = 0.333). The 3-year OS was higher in the obese group (log rank p = 0.042) but the 3-year RFS was similar in both groups (log rank p = 0.556). Median total OS was similar in both groups 62 months (95% confidence interval 25-98 months) in obese vs. 67 months (95% confidence interval 15-118) in the lower BMI group, log rank p = 0.822. Median RFS was similar in both groups; 61 months (95% confidence interval 47-74) in obese, vs. 54 (95% confidence interval 43-64), log rank p = 0.842. In Cox regression analysis for OS, including obesity, age, laparotomy and neoadjuvant treatment - only neoadjuvant treatment was independently associated with longer OS: odds ratio 1.82 (95% confidence interval 1.09-3.05) and longer RFS: odds ratio 2.16 (95% confidence interval 1.37-3.41). CONCLUSIONS: In the present study on consecutive cases of ovarian cancer, obesity did not seem to be associated with outcome, except for an apparent improved 3-year survival that faded away thereafter.

Grade and Estrogen Receptor Expression Identify a Subset of No Specific Molecular Profile Endometrial Carcinomas at a Very Low Risk of Disease-Specific Death.

Endometrial carcinoma (EC) can be divided into 4 prognostic molecular subtypes, and no specific molecular profile (NSMP) type is the most commonly occurring type (∼50%). Although described as having an intermediate to favorable prognosis, this subtype encompasses pathologically and molecularly diverse tumors. We aimed to identify factors associated with outcomes within the NSMP ECs that might be used to stratify prognosis and direct treatment. Clinicopathologic, immunohistochemical, and genetic features of a large series of NSMP EC were used to identify parameters that could identify the subset associated with a very favorable outcome (disease-specific death rate <5% at 5 years, termed low-risk NSMP). A total of 1110 NSMP ECs were profiled. In a univariate analysis, stage, grade, lymphovascular invasion, estrogen receptor (ER) and progesterone receptor (PR) expression, L1CAM overexpression, and mutations in PIK3CA were associated with disease-specific survival. Two critical features, grade and ER expression, identified a low-risk NSMP subset (grade 1-2, ER-positive [>1%], 84% of cases), which showed a 5-year disease-specific death rate of 1.6% across all stages and 1.4% within stage I. The remaining cases (high-risk NSMPs, grade 3, and/or ER-negative status) were responsible for most of the disease-specific deaths (disease-specific death rate at 5 years, 22.9%; hazard ratio compared with that of low-risk NSMPs: 16.3; 95% CI, 8.4-31.7). Within NSMP EC, the low-risk and high-risk categories were of prognostic significance independent of the stage on a multivariate analysis. Low-grade and ER-positive NSMP ECs are a homogeneous low-risk group associated with an exceptionally favorable prognosis in which de-escalation and/or endocrine therapy strategies can be applied. Grade 3 and/or ER-negative status identifies a high-risk NSMP subset, including rare high-grade histotypes (eg, clear cell, dedifferentiated, and mesonephric-like), responsible for most NSMP-related deaths. Subclassification of NSMPs allows for the category of low-risk EC molecular subtypes to be dramatically expanded because it now includes both POLEmut and the much more common low-risk NSMP EC.

Is sentinel lymph node assessment useful in patients with a preoperative diagnosis of endometrial intraepithelial neoplasia?

OBJECTIVE: To determine the prevalence of underlying high-intermediate (high-IM) and high-risk endometrial cancer (EC) in patients with preoperative diagnosis of Endometrial intraepithelial neoplasia (EIN) and to assess the impact of the information retrieved from the sentinel lymph node (SLN) on adjuvant therapy. METHODS: Retrospective cohort study of women undergoing hysterectomy, optional bilateral salpingo-oophorectomy (BSO) and lymph nodes assessment for EIN between December 2007 and August 2021. RESULTS: One hundred and sixty two (162) eligible patients were included, of whom 101 (62.3%) had a final diagnosis of EIN, while 61 (37.7%) were ultimately diagnosed with carcinoma. Out of 15 patients with high-IM to high-risk disease (9.25% of all EIN), 12 had grade 2-3 EC including 8 with >50% myometrial invasion, 2 with serous subtype, 1 with cervical invasion and 2 with pelvic lymph nodes involvement. Of the 3 patients with grade 1 EC, one patient had disease involving the adnexa and 2 patients had tumor invading >50% of the myometrium and with lymphovascular space invasion (LVSI). Ten patients received vaginal brachytherapy after surgery, 3 patients with extrauterine spread were treated with systemic chemotherapy followed by vaginal brachytherapy and pelvic external-beam radiotherapy and 2 patients with early-stage serous carcinoma received chemotherapy followed by vaginal brachytherapy. CONCLUSIONS: Information from SLN, even when negative, can be helpful in the management of patients with EC after preoperative EIN, as some patients are found to have high-IM to high-risk disease on final pathology. These patients would require either re-staging surgery or adjuvant external beam radiotherapy, both could be avoided by proper staging.

Molecular subtype stratified outcomes according to adjuvant therapy in endometrial cancer.

OBJECTIVES: Recent data support the predictive implications of molecular subtype assignment in endometrial cancer (EC). Our objective was to retrospectively assess clinical outcomes according to adjuvant treatment received within EC molecular subtypes. METHODS: Clinical outcomes (disease-specific and progression-free survival DSS/PFS) of EC patients from a single institution and population-based cohorts that had undergone molecular classification were assessed with respect to adjuvant therapy received and 2016 ESMO risk group. RESULTS: 2472 ECs were assessed; 184 (7.4%) POLEmut, 638 (25.8%) MMRd, 1223 (49.5%) NSMP and 427 (17.3%) p53abn. N = 774 (34.6%) of the cohort were ESMO 2016 high risk and 109 (4.8%) were advanced or metastatic. In patients with MMRd EC, assessed across and within stage, there was no observed benefit in DSS or PFS with the addition of chemotherapy +/- radiation compared to radiation alone in ESMO high risk (p = 0.694) or ESMO high, advanced, metastatic risk groups combined (p = 0.852). In patients with p53abn EC, adjuvant chemotherapy given with radiation was associated with significantly longer DSS compared to radiation alone in ESMO high risk (p = 0.007) and ESMO high, advanced and metastatic risk groups combined (p = 0.015), even when restricted to stage I disease (p < 0.001) and when compared in serous vs. non-serous histotypes (p = 0.009). CONCLUSIONS: Adjuvant chemotherapy is associated with more favorable outcomes for patients with p53abn EC, including stage I disease and non-serous histotypes, but does not appear to add benefit within MMRd ECs for any stage of disease, consistent with PORTEC-3 molecular subanalysis. Prospective trials, assessing treatment efficacy within molecular subtype are needed, however these 'real-world' data should be considered when discussing adjuvant treatment with patients.

Endocervical sampling using brush versus curette: a single centre experience and literature review.

Endocervical sampling is performed traditionally with an endocervical curette (ECC). The current study objective is to compare the histopathological performance of endocervical brush (ECB) and endocervical curette (ECC). A retrospective review was performed including patients included that underwent colposcopy with endocervical sampling using either method. A total of 127 samples were obtained with ECC and 98 with ECB. Histopathological diagnosis was obtained in 124 (97.6%) ECC samples and in 94 (95.9%) ECB samples (p = 0.46). The incidence of benign results was similar between ECC and ECB (117 (92.1%) versus 88 (89.8%) respectively (p = 0.28)). When combining information from endocervical sampling with cervical biopsies, the detection rate of high-grade pathologies was similar between the groups with 14 cases (17.7%) for ECC and 8 cases (17.0%) for ECB (p = 0.43). A scope review of the topic was performed, illustrating that studies favour either method. In conclusion, ECB and ECC perform similarly for providing a histopathological diagnosis on endocervical samples.IMPACT STATEMENTWhat is already known on this subject? Endocervical samples in colposcopy were traditionally obtained using an endocervical curette. Similarly, a brush can be used for histological sampling of the endocervical canal. However, it is unclear how the ability to obtain a histopathological diagnosis compares between the two techniques.What do the results of this study add? This single-institution experience with using endocervical brush and curette for endocervical sampling finds that both methods are acceptable and have a high ability to provide a histopathological diagnosis. Precisely, 4.1% of brush and 2.4% of curette samples had insufficient tissue.What are the implications of these findings for clinical practice and further research? The endocervical brush is an adequate sampling method for colposcopy, and can be safely used instead of the curette, based on clinician preference. Further studies could investigate how these methods compare from a patient perspective.

Variability in endometrial carcinoma pathology practice: opportunities for improvement with molecular classification.

We assessed the landscape of diagnostic pathology practice and how molecular classification could potentially impact management of patients with endometrial cancer by collecting patient samples, clinicopathologic data, and patient outcomes from EC patients diagnosed in 2016 at 10 Canadian tertiary cancer centers and 19 community hospitals. ProMisE molecular subtype (POLEmut, MMRd, p53abn, No Specific Molecular Profile (NSMP)) was assigned retrospectively. 1357 patients were fully evaluable including 85 POLEmut (6.3%), 380 MMRd (28.0%), 643 NSMP (47.4%), and 249 p53abn ECs (18.3%). Immunohistochemistry (IHC) for MMR proteins was undertaken at the time of primary diagnosis in 2016 in only 42% of the cohort (570/1357; range 3.5-95.4%/center). p53 IHC had only been performed in 21.1% of the cohort (286/1357; range 10.1-41.9%/center). Thus, based on the retrospective molecular subtype assignment, 54.7% (208/380) of MMRd EC had not been tested with MMR IHC (or MSI) and 48.2% (120/249) of p53abn ECs were not tested with p53 IHC in 2016. Molecular subtype diversity within histotypes was profound; most serous carcinomas were p53abn (91.4%), but only 129/249 (51.8%) p53abn EC were serous. Low-grade (Gr1-2) endometrioid carcinomas were mostly NSMP (589/954, 61.7%) but included all molecular subtypes, including p53abn (19/954, 2.0%). Molecular subtype was significantly associated with clinical outcomes (p < 0.001) even in patients with stage I disease (OS p = 0.006, DSS p < 0.001, PFS p < 0.001). Assessment of national pathologic practice in 2016 shows highly variable use of MMR and p53 IHC and demonstrates significant opportunities to improve and standardize biomarker reporting. Inconsistent, non-reflexive IHC resulted in missed opportunities for Hereditary Cancer Program referral and Lynch Syndrome diagnosis, and missed potential therapeutic implications (e.g., chemotherapy in p53abn EC, immune blockade for MMRd EC). Routine integration of molecular subtyping into practice can improve the consistency of EC pathology assessment and classification.

Variation in practice in endometrial cancer and potential for improved care and equity through molecular classification.

OBJECTIVES: We measured the variation in practice across all aspects of endometrial cancer (EC) management and assessed the potential impact of implementation of molecular classification. METHODS: Centers from across Canada provided representative tumor samples and clinical data, including preoperative workup, operative management, hereditary cancer program (HCP) referrals, adjuvant therapy, surveillance and outcomes, for all EC patients diagnosed in 2016. Tumors were classified into the four ProMisE molecular subtypes. RESULTS: A total of 1336 fully evaluable EC patients were identified from 10 tertiary cancer centers (TC; n = 1022) and 19 community centers (CC; n = 314). Variation of surgical practice across TCs was profound (14-100%) for lymphadenectomy (LND) (mean 57% Gr1/2, 82% Gr3) and omental sampling (20% Gr1/2, 79% Gr3). Preoperative CT scans were inconsistently obtained (mean 32% Gr1/2, 51% Gr3) and use of adjuvant chemo or chemoRT in high risk EC ranged from 0-55% and 64-100%, respectively. Molecular subtyping was performed retrospectively and identified 6% POLEmut, 28% MMRd, 48% NSMP and 18% p53abn ECs, and was significantly associated with survival. Within patients retrospectively diagnosed with MMRd EC only 22% had been referred to HCP. Of patients with p53abn EC, LND and omental sampling was not performed in 21% and 23% respectively, and 41% received no chemotherapy. Comparison of management in 2016 with current 2020 ESGO/ESTRO/ESP guidelines identified at least 26 and 95 patients that would have been directed to less or more adjuvant therapy, respectively (10% of cohort). CONCLUSION: Molecular classification has the potential to mitigate the profound variation in practice demonstrated in current EC care, enabling reproducible risk assessment, guiding treatment and reducing health care disparities.

Surgical and oncological outcomes of sentinel lymph node sampling in elderly patients with intermediate to high-risk endometrial carcinoma.

OBJECTIVE: We aimed to evaluate the surgical and oncological outcomes of elderly patients with intermediate to high-risk endometrial cancer undergoing staging with sentinel lymph node (SLN) sampling and pelvic lymphadenectomy. METHODS: We conducted a retrospective study of elderly (>65-year-old) patients diagnosed with endometrial cancer between December 2007 and August 2017. These patients had been treated at a single center in Montreal, Canada. We compared the surgical and oncological outcomes of three cohorts undergoing surgical staging in non-overlapping eras: 1) lymphadenectomy, 2) lymphadenectomy and SLN sampling, 3) SLN sampling alone. Using life tables, Kaplan-Meier survival curves and log-rank tests, we analyzed 2-year progression-free survival, overall survival, and disease-specific survival. RESULTS: Our study included 278 patients with a median age of 73 years (range; 65-91): 84 (30.2%) underwent lymphadenectomy, 120 (43.2%) underwent SLN sampling with lymphadenectomy, and 74 (26.6%) had SLN sampling alone. The SLN sampling alone group had shorter operative times with a median duration of 199 minutes (range, 75-393) compared with 231 (range, 125-403) and 229 (range, 151-440) minutes in the SLN sampling with lymphadenectomy and lymphadenectomy cohorts; respectively (p<0.001). The SLN sampling alone group also had lower estimated blood loss with a median loss of 20 mL (range, 5-150) vs 25 mL (range, 5-800) and 40 mL (range, 5-400) in the SLN sampling with lymphadenectomy and lymphadenectomy cohorts, respectively (p=0.002). The 2 year overall survival and progression-free survival were not significantly different between the three groups (p=0.45, p=0.51, respectively). On multivariable analysis after adjusting for age, American Society of Anesthesiologists (ASA) score, stage, grade, and lymphovascular space invasion, adding SLN sampling was associated with better overall survival, (HR 0.2, CI [0.1 to 0.6], p=0.006) and progression-free survival (HR 0.5, CI [0.1 to 1.0], p=0.05). CONCLUSION: Sentinel lymph node-based surgical staging is feasible and associated with better surgical outcomes and comparable oncological outcomes in elderly patients with intermediate and high-risk endometrial cancer.

Multiple lines of chemotherapy for patients with high-grade ovarian cancer: Predictors for response and effect on survival.

Guidelines for the treatment of tubo-ovarian cancer patients beyond third line are lacking. We aimed to evaluate the effect of response in each line on patient's outcome as well as identify variables that predict response for additional line of chemotherapy. A cohort study was performed including all patients with advanced high-grade ovarian cancer. Survival analysis was performed using Kaplan-Meier curves and log-rank tests. Odds ratios and hazard ratios were calculated using multilevel, mixed-effects logistic regression and Cox regression, adjusting for repeated measures within individual patients. Two-hundred thirty-eight patients were included and underwent up to 10 lines of chemotherapy. The median progression-free survival was 15.6 and overall survival (OS) was 55.6 months. Response rates dropped with each additional line and by line 5, most patients (61%) became refractory and only 16% had any type of response (complete 4% or partial 12%). By line 2, whether a patient had partial disease (PR), stable disease (SD) or progressive disease (PD) did not have an effect on the OS. From line 2, whether a patient had PR, SD or PD did not have an effect on chemotherapy-free interval. Number of previous lines and time from previous line were the only variables that significantly correlated with both outcome of patients and response to the next line. In conclusion, time interval from the previous line of chemotherapy is the major clinical factor that predicts beneficial effect of another line of treatment in patients with ovarian cancer.

Absence of prognostic value of lymphovascular space invasion in patients with endometrial cancer and negative sentinel lymph nodes.

OBJECTIVE: To evaluate if the prognostic value of lymphovascular space invasion (LVSI) is different in endometrial cancer patients with negative lymph nodes following sentinel lymph node (SLN) mapping or lymph node dissection (LND) as staging procedure. MATERIAL AND METHODS: A retrospective study of 510 patients diagnosed with endometrial carcinoma in our institution between 2007 and 2014. We excluded patients that were diagnosed with positive nodes (Stage IIIc). We compared patients' characteristics and survival outcomes as function of their LVSI status (positive LVSI vs negative LVSI subgroups) in each cohort separately. RESULTS: 413 patients met the inclusion criteria, out of whom 239 underwent SLN and 174 patients underwent LND only. In the SLN group, life table analysis showed 5-year OS and PFS of 80% and 72% in patients with LVSI compared to 96%, and 93% without LVSI. Same trend was observed among patients with LND with 5-year OS and PFS of 74% and 64% in patients with LVSI compared to 97%, and 90% without LVSI. On multivariable analysis, adjusted for age, FIGO stage, grade and maximal tumor size, the favorable survival of negative LVSI remained only in the LND cohort (SLN cohort: HR 1.2, CI [0.3-4.0], P = 0.8 and HR 1.7, CI [0.7-4.3], p = 0.2 for OS and PFS, respectively; LND cohort: HR 3.1, CI [1.4-6.5], p < 0.001 and HR 2.5, CI [1.2-4.9], p = 0.01 for OS and PFS, respectively). CONCLUSIONS: The prognostic value of LVSI disappears when patients undergo staging with SLN and are found to have negative nodes in contrast to those who have undergone LND. Future studies should confirm our observation on patients with negative sentinel nodes, and plan on tailoring adjuvant treatment to this specific subgroup.

Carboplatin plus paclitaxel weekly dose-dense chemotherapy for high-grade ovarian cancer: A re-evaluation.

INTRODUCTION: We compared oncologic and clinical outcomes in patients with advanced ovarian cancer who received dose-dense weekly paclitaxel with 3-weekly carboplatin with those who received standard 3-weekly chemotherapy. MATERIAL AND METHODS: Comparison of all consecutive patients with advanced (International Federation of Gynecology and Obstetrics stages III-IV) ovarian cancer who received a dose-dense protocol between 2010 and 2016 with an immediate historical cohort of consecutive patients who received standard chemotherapy. Patients who received less than three cycles of treatment were excluded. RESULTS: In all, 246 patients were included in the study, of whom 128 received the dose-dense protocol and 118 were treated with the standard Q3-week protocol. Patients in the dose-dense group had significantly better progression-free survival than those receiving the standard protocol (median progression-free survival 22 vs 15 months; log rank = 0.026). The overall survival of patients in the dose-dense group was also better than that of the patients in the standard protocol group; however, this difference was not statistically significant (median overall survival 66 vs 54 months; log rank = 0.185). The dose-dense protocol remained significantly associated with favorable survival outcome in multivariable analysis adjusted for stage, histologic type, cytoreductive results and neoadjuvant chemotherapy. The use of the dose-dense protocol was associated with higher rates of gastrointestinal, dermatologic, neurologic and hematologic side effects. CONCLUSION: Despite the limitations associated with the comparison to a historical cohort, a dose-dense chemotherapy protocol resulted in a significantly improved progression-free survival and the overall survival tended to be better, but this difference did not reach statistical significance compared with the standard chemotherapy protocol, and may be considered as a treatment alternative, albeit with some increased side effects.

Surgical Technique for Sentinel Lymph Node Sampling in Presumed Early-stage Ovarian Cancer.

STUDY OBJECTIVE: Surgical staging for apparent early-stage ovarian cancer includes systematic pelvic and para-aortic lymph node evaluation to detect occult stage III disease [1]. Although, lymphadenectomy procedure is associated with increased duration of surgery and a 13% risk of lymphocyst formation [2]. Sentinel lymph node (SLN) biopsy is still investigational, and no standardized approach has been studied. Recent mounting evidence has approved the applicability of SLN technique in early-stage ovarian cancer [3,4]. The objective of this video is to demonstrate a surgical technique for robotic performance of SLN biopsy in presumed early-stage ovarian cancer. DESIGN: Stepwise demonstration of the robotic technique for SLN sampling in presumed early-stage ovarian cancer. This video report is part of an institutional, investigational review board-approved study. SETTING: Academic tertiary referral center. INTERVENTIONS: This video presents our team's robotic technique for SLN sampling in a 37-year-old woman who presented to our center with a 10-cm right complex adnexal mass, suspicious for malignancy. A 27-gauge spinal needle was inserted through the abdominal wall under direct visualization. We injected 0.5 mL of dilute indocyanine green solution (Novadaq Technologies, Mississauga, Ontario, Canada) (1.25 mg/mL) subperitoneally into the utero-ovarian ligament. The SLN was checked with the fluorescence-guided camera of the Xi DaVinci robotic system (Sunnyvale, CA). Eight to 10 minutes after the injection, a right para-aortic SLN was identified, and dissection was performed. After dissection, the node was extracted and sent to pathology for evaluation by ultra-staging. The final pathology revealed a stage IA low-grade serous ovarian cancer. CONCLUSION: SLN sampling appears to be feasible in presumed early-stage ovarian cancer and may allow the avoidance of systematic lymph node dissection in this set of patients.

Endometrial Cancer in Germline BRCA Mutation Carriers: A Systematic Review and Meta-analysis.

OBJECTIVE: Risk-reducing salpingo-oophorectomy (RRSO) is standard treatment among women with BRCA mutations. The aim of this meta-analysis is to evaluate the risk of endometrial cancer (EC) in BRCA1 or BRCA2 germline mutation carriers and to examine the justifiability of prophylactic hysterectomy at the time of RRSO. DATA SOURCES: PubMed, Cochrane Central Register of Controlled Trials, BIOSIS, Medline (Ovid), Web of Science, ClinicalTrials.gov, and Google Scholar were searched. Eleven articles were selected and analyzed using the OpenMetaAnalyst 2012 software. METHODS OF STUDY SELECTION: Randomized controlled studies, cohort studies, and case-control studies evaluating the risk of EC and specifically uterine papillary serous carcinoma (UPSC) in germline BRCA1/2 mutation carriers were included. Articles were excluded if they did not meet the inclusion criteria, or if data were not reported and the authors did not respond to inquiries. We assessed the methodological quality of the included studies on the basis of the Newcastle-Ottawa scale. Dichotomous results from each of the studies eligible for the meta-analysis were expressed as the proportion of patients with EC or UPSC per total number of BRCA mutation carriers, with 95% confidence interval (CI). The Mantel-Haenszel statistical method was used. TABULATION, INTEGRATION, AND RESULTS: Eleven studies reported the outcome of interest and were included in the final meta-analysis. In total, 13 871 carriers of BRCA1 and BRCA2 mutations were identified. The pooled prevalence rates of EC and UPSC in BRCA1/2 mutation carriers were 82/13 827 (0.59%) and 19/11 582 (0.16%), respectively. The EC prevalence was 46/7429 (0.62%) in BRCA1 mutation carriers and 17/3546 (0.47%) in BRCA2 mutation carriers, with relative risk of 1.18 (95% CI, 0.7-2.0). For UPSC, the prevalence was 15/7429 (0.2%) and 3/3546 (0.08%) among BRCA1 and BRCA2 mutation carriers, respectively, (relative risk 1.39; 95% CI, 0.5-3.7). CONCLUSION: Most studies in this meta-analysis suggest a slightly increased risk of EC in BRCA mutation carriers, mainly for BRCA1. The decision regarding concurrent hysterectomy should be tailored individually to each patient on the basis of the patient's age, type of mutation, future need for hormone replacement treatment, history of breast cancer, tamoxifen use, and personal operative risks.

Directive clinique no 408 : Prise en charge des maladies gestationnelles trophoblastiques.

OBJECTIF: Cette directive passe en revue l'évaluation clinique et la prise en charge des maladies gestationnelles trophoblastiques, notamment les traitements chirurgicaux et médicamenteux des tumeurs bénignes, prémalignes et malignes. L'objectif de la présente directive clinique est d'aider les fournisseurs de soins de santé à rapidement diagnostiquer les maladies gestationnelles trophoblastiques, à normaliser les traitements et le suivi et à assurer des soins spécialisés précoces aux patientes dont l'atteinte est maligne ou métastatique. PROFESSIONNELS CONCERNéS: Gynécologues généralistes, obstétriciens, médecins de famille, sages-femmes, urgentologues, anesthésistes, radiologistes, anatomopathologistes, infirmières autorisées, infirmières praticiennes, résidents, gynécologues-oncologues, oncologues médicaux, radio-oncologues, chirurgiens, omnipraticiens en oncologie, infirmières en oncologie, pharmaciens, auxiliaires médicaux et autres professionnels de la santé qui traitent des patientes atteintes d'une maladie gestationnelle trophoblastique. La présente directive vise également à fournir des renseignements aux parties intéressées qui prodiguent des soins de suivi à ces patientes après le traitement. POPULATION CIBLE: Femmes en âge de procréer atteintes d'une maladie gestationnelle trophoblastique. OPTIONS: Les femmes ayant reçu un diagnostic de maladie gestationnelle trophoblastique doivent être orientées vers un gynécologue afin qu'il réalise une évaluation initiale, envisage une intervention chirurgicale primaire (évacuation ou hystérectomie) et effectue un suivi. Il y a lieu d'orienter les femmes ayant reçu un diagnostic de tumeur trophoblastique gestationnelle vers un gynécologue-oncologue afin qu'il effectue la stadification tumorale, établisse le score de risque et envisage l'intervention chirurgicale primaire ou un traitement systémique (mono- ou polychimiothérapie) et la nécessité d'éventuels traitements supplémentaires. Il est recommandé de discuter de chaque cas de néoplasie gestationnelle trophoblastique lors d'une réunion multidisciplinaire de cas oncologiques et de l'inscrire dans une base de données centralisée (régionale et/ou nationale). DONNéES PROBANTES: Des recherches ont été effectuées au moyen des bases de données Embase et MEDLINE, du Cochrane Central Register of Controlled Trials et de la Cochrane Database of Systematic Reviews afin de trouver les études publiées depuis 2002 utilisant un ou plusieurs des mots clés suivants : trophoblastic neoplasms, choriocarcinoma, trophoblastic tumor, placental site, gestational trophoblastic disease, hydatidiform mole, drug therapy, surgical therapy, radiotherapy, cure, complications, recurrence, survival, prognosis, pregnancy outcome, disease outcome, treatment outcome et remission. La recherche initiale a été effectuée en avril 2017; une mise à jour a été faite en mai 2019. Les données probantes pertinentes ont été sélectionnées aux fins d'inclusion selon l'ordre suivant : méta-analyses, revues systématiques, directives cliniques, essais cliniques randomisés, études de cohortes prospectives, études observationnelles, revues non systématiques, études de séries de cas et rapports. D'autres articles pertinents ont été trouvés en recoupant les revues répertoriées. Le nombre total d'études relevées était de 673, dont 79 études sont citées dans la présente revue. MéTHODES DE VALIDATION: Le contenu et les recommandations ont été rédigés et acceptés par les auteurs. La direction et le conseil d'administration de la Société de gynéco-oncologie du Canada ont passé en revue le contenu de la version préliminaire et ont soumis des commentaires à prendre en considération. Le conseil d'administration de la Société des obstétriciens et gynécologues du Canada a approuvé la version définitive aux fins de publication. La qualité des données probantes a été évaluée au moyen des critères de l'approche GRADE (Grading of Recommendations Assessment, Development and Evaluation). Consulter les tableaux dans l'annexe en ligne pour connaître les critères de notation et d'interprétation des recommandations. BéNéFICES, RISQUES, COûTS: Les présentes recommandations aideront les médecins à diagnostiquer rapidement les maladies gestationnelles trophoblastiques et à orienter de façon urgente les patientes ayant reçu un diagnostic de maladie gestationnelle trophoblastique en gynécologie oncologique pour une prise en charge spécialisée. Le traitement des néoplasies gestationnelles trophoblastiques en centre spécialisé combiné à l'utilisation de bases de données centralisées permet de recueillir et de comparer des données sur les résultats thérapeutiques des patientes atteintes de ces tumeurs rares et d'optimiser les soins aux patientes. DÉCLARATIONS SOMMAIRES (CLASSEMENT GRADE ENTRE PARENTHèSES): RECOMMANDATIONS (CLASSEMENT GRADE ENTRE PARENTHèSES).

Guideline No. 408: Management of Gestational Trophoblastic Diseases.

OBJECTIVE: This guideline reviews the clinical evaluation and management of gestational trophoblastic diseases, including surgical and medical management of benign, premalignant, and malignant entities. The objective of this guideline is to assist health care providers in promptly diagnosing gestational trophoblastic diseases, to standardize treatment and follow-up, and to ensure early specialized care of patients with malignant or metastatic disease. INTENDED USERS: General gynaecologists, obstetricians, family physicians, midwives, emergency department physicians, anaesthesiologists, radiologists, pathologists, registered nurses, nurse practitioners, residents, gynaecologic oncologists, medical oncologists, radiation oncologists, surgeons, general practitioners in oncology, oncology nurses, pharmacists, physician assistants, and other health care providers who treat patients with gestational trophoblastic diseases. This guideline is also intended to provide information for interested parties who provide follow-up care for these patients following treatment. TARGET POPULATION: Women of reproductive age with gestational trophoblastic diseases. OPTIONS: Women diagnosed with a gestational trophoblastic disease should be referred to a gynaecologist for initial evaluation and consideration for primary surgery (uterine evacuation or hysterectomy) and follow-up. Women diagnosed with gestational trophoblastic neoplasia should be referred to a gynaecologic oncologist for staging, risk scoring, and consideration for primary surgery or systemic therapy (single- or multi-agent chemotherapy) with the potential need for additional therapies. All cases of gestational trophoblastic neoplasia should be discussed at a multidisciplinary cancer case conference and registered in a centralized (regional and/or national) database. EVIDENCE: Relevant studies from 2002 onwards were searched in Embase, MEDLINE, the Cochrane Central Register of Controlled Trials, and Cochrane Systematic Reviews using the following terms, either alone or in combination: trophoblastic neoplasms, choriocarcinoma, trophoblastic tumor, placental site, gestational trophoblastic disease, hydatidiform mole, drug therapy, surgical therapy, radiotherapy, cure, complications, recurrence, survival, prognosis, pregnancy outcome, disease outcome, treatment outcome, and remission. The initial search was performed in April 2017 and updated in May 2019. Relevant evidence was selected for inclusion in the following order: meta-analyses, systematic reviews, guidelines, randomized controlled trials, prospective cohort studies, observational studies, non-systematic reviews, case series, and reports. Additional significant articles were identified through cross-referencing the identified reviews. The total number of studies identified was 673, with 79 studies cited in this review. VALIDATION METHODS: The content and recommendations were drafted and agreed upon by the authors. The Executive and Board of Directors of the Society of Gynecologic Oncology of Canada reviewed the content and submitted comments for consideration, and the Board of Directors for the Society of Obstetricians and Gynaecologists of Canada approved the final draft for publication. The quality of evidence was rated using the criteria described in the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology framework. See the online appendix tables for key to grading and interpretation of recommendations. BENEFITS: These guidelines will assist physicians in promptly diagnosing gestational trophoblastic diseases and urgently referring patients diagnosed with gestational trophoblastic neoplasia to gynaecologic oncology for specialized management. Treating gestational trophoblastic neoplasia in specialized centres with the use of centralized databases allows for capturing and comparing data on treatment outcomes of patients with these rare tumours and for optimizing patient care. SUMMARY STATEMENTS (GRADE RATINGS IN PARENTHESES): RECOMMENDATIONS (GRADE RATINGS IN PARENTHESES).

Sentinel Lymph Node Sampling as an Alternative to Lymphadenectomy in Patients With Endometrial Cancer and Obesity.

OBJECTIVE: Although its use in endometrial cancer staging is relatively new, sentinel lymph node (SLN) sampling has been shown to be highly accurate and is associated with few complications. However, some studies report lower rates of detection with SLN sampling among patients with obesity. The aim of the current study is to evaluate the feasibility of SLN sampling in endometrial cancer for patients with obesity, and to determine whether omitting lymph node dissection (LND) in surgical staging using SLN sampling impacts oncologic outcomes. METHODS: we conducted a retrospective study of patients with obesity (BMI ≥35 kg/m2), diagnosed with endometrial carcinoma between 2007 and 2017, that compared surgical and oncologic outcomes of 2 cohorts: patients who underwent LND and patients who underwent SLN without lymphadenectomy. The primary outcome was operative time. Secondary outcomes included intraoperative bleeding; lymph node assessment information; intraoperative and postoperative adverse events; and oncologic outcomes including progression-free survival (PFS), overall survival (OS), and disease-specific survival (DSS). PFS was defined as the time from surgery to the recurrence or death from any cause. OS was defined as time from diagnosis to death or the last date the patient was known to be alive, and DSS was defined as the time from the surgery to death from the disease. RESULTS: Out of 223 patients with a median BMI of 40.6 kg/m2, 140 underwent LND and 83 underwent SLN alone. The median operative time for patients in the SLN group was shorter than that of patients in the LND group (190.5 [range 108-393] vs. 238 [131-440] min; P < 0.001), and the SLN group had lower median estimated blood loss than the LND group (30 [range 0-300] vs. 40 [range 0-800] mL; P = 0.03). At the 24-month follow-up cut-off, 98% of patients were alive and 95.5% were disease free, with no significant differences in OS, DSS, and PFS between the 2 groups (P = 0.7, P = 0.8, and P = 0.4, respectively). CONCLUSIONS: In patients with obesity, omitting LND from surgical staging with SLN sampling was associated with shorter operative times and less bleeding and did not affect survival at 2 years.

The added value of sentinel node mapping in endometrial cancer.

OBJECTIVE: To evaluate long-term oncological outcomes and the added value of sentinel lymph node sampling (SLN) compared to pelvic lymph node dissection (LND) in patients with endometrial cancer (EC). METHODS: During the evaluation phase of SLN for EC, we performed LND and SLN and retrospectively compared the oncologic outcome with the immediate non-overlapping historical era during which patients underwent LND. RESULTS: From 2007 to 2010, 193 patients underwent LND and from December 2010 to 2014, 250 patients had SLN mapping with completion LND. Both groups had similar clinical characteristics. During a median follow-up period of 6.9 years, addition of SLN was associated with more favorable oncological outcomes compared to LND with 6-year overall survival (OS) of 90% compared to 81% (p = 0.009), and progression free survival (PFS) of 85% compared to 75% (p = 0.01) respectively. SLN was associated with improved OS (HR 0.5, 95% CI 0.3-0.8, p = 0.004), and PFS (HR 0.6, 95% CI 0.4-0.9, p = 0.03) in a multivariable analysis, adjusted for age, ASA score, stage, grade, non-endometrioid histology, and LVSI. Patients who were staged with SLN were less likely to have a recurrence in the pelvis or lymph node basins compared to patients who underwent LND only (6-year recurrence-free survival 95% vs 90%, p = 0.04). CONCLUSION: Addition of SLN to LND was ultimately associated with improved clinical outcomes compared to LND alone in patients with endometrial cancer undergoing surgical staging, suggesting that the data provided by the analysis of the SLN added relevant clinical information, and improved the decision on adjuvant therapy.

The impact of wait times on oncological outcome in high-risk patients with endometrial cancer.

OBJECTIVE: To evaluate the impact of surgical wait times on outcome of patients with grade 3 endometrial cancer. METHODS: All consecutive patients surgically treated for grade 3 endometrial cancer between 2007 and 2015 were included. Patients were divided into two groups based on the time interval between endometrial biopsy and surgery: wait time from biopsy to surgery ≤12 weeks (84 days) vs more than 12 weeks. Survival analyses were conducted using log-rank tests and Cox proportional hazards models. RESULTS: A total of 136 patients with grade 3 endometrial cancer were followed for a median of 5.6 years. Fifty-one women (37.5%) waited more than 12 weeks for surgery. Prolonged surgical wait times were not associated with advanced stage at surgery, positive lymph nodes, increased lymphovascular space invasion, and tumor size (P = .8, P = 1.0, P = .2, P = .9, respectively). In multivariable analysis adjusted for clinical and pathological factors, wait times did not significantly affect disease-specific survival (adjusted hazard ratio [HR]: 1.2, 95% confidence interval [CI], 0.6-2.5, P = .6), overall survival (HR: 1.1, 95% CI, 0.6-2.1, P = .7), or progression-free survival (HR: 0.9, 95% CI, 0.5-1.7, P = .8). CONCLUSION: Prolonged surgical wait time for poorly differentiated endometrial cancer seemed to have a limited impact on clinical outcomes compared to biological factors.

CA-125 reduction during neoadjuvant chemotherapy is associated with success of cytoreductive surgery and outcome of patients with advanced high-grade ovarian cancer.

INTRODUCTION: The objective was to assess whether an early response to neoadjuvant chemotherapy in women with advanced ovarian cancer may predict short- and long-term clinical outcome. MATERIAL AND METHODS: This is a retrospective study of all women with stage III-IV tubo-ovarian cancer treated with neoadjuvant chemotherapy at a single center in Montreal between 2003 and 2014. Logistic regression models were used to evaluate the association between cancer antigen 125 (CA-125) levels during neoadjuvant chemotherapy and debulking success. Cox proportional hazard models were used to estimate hazard ratios and their respective 95% CI for death and recurrence. Harrell's concordance indices were calculated to evaluate which variables best predicted the chemotherapy-free interval and overall survival in our population. RESULTS: In all, 105 women were included. Following the first, second, and third cycles of neoadjuvant chemotherapy, CA-125 levels had a median reduction of 43.2%, 85.4%, and 92.9%, respectively, compared with CA-125 levels at diagnosis. As early as the second cycle, CA-125 was associated with overall survival (hazard ratio 1.03, 95% CI 1.01-1.05, per 50 U/mL increment). By the third cycle, CA-125 did not only predict overall survival (hazard ratio 1.04, 95% CI 1.01-1.08), but it predicted overall survival better than the success of debulking surgery (Harrell's concordance index 0.646 vs 0.616). Both absolute CA-125 levels and relative reduction in CA-125 levels after 2 and 3 cycles predicted the chance to achieve complete debulking (P < .05). CONCLUSIONS: Reduction of CA-125 levels during neoadjuvant chemotherapy provides an early predictive tool that strongly correlates with successful cytoreductive surgery and long-term clinical outcome in women with advanced high-grade serous and endometrioid ovarian cancer.