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AIMS: This paper reports a study assessing Finnish unemployed nurses' sense of coherence and the factors relating to it. BACKGROUND: During the 1990s, due to the widespread economic downturn in Finland, the nursing profession suffered from a high level of unemployment. Previous research has clearly indicated that unemployment is detrimental to health. It creates stress by disturbing a person's sense of identity and self-esteem and by disrupting social networks. In Finland, many studies have been conducted on the impact of unemployment, but have not examined the sense of coherence of unemployed nurses. METHODS: Data were collected in one Employment and Economic Development Centre area in Finland in 1998. Structured questionnaires were used to collect data among Finnish unemployed nurses (n = 183), and included the General Health Questionnaire, measuring nurses' mental health; socio-demographic questions; and the 13-item version of the Sense of Coherence scale based on Antonovsky's salutogenic model to measure sense of coherence. RESULTS: Although the majority of unemployed nurses had a strong sense of coherence, many felt that during their period of unemployed they did not feel at ease, did not know what to do and had a sense of being unfairly treated. Daily household chores, on the whole, were perceived as meaningful. Income and the state of mental health were positively correlated with nurses' sense of coherence: the better the family income and state of mental health, the stronger was their sense of coherence. Because of the low response rate (less than 50%), the results might be skewed by those whose higher sense of coherence made them more motivated to complete the questionnaires. CONCLUSIONS: Many of the nurses reported low sense of coherence and poor general health. Special interventions should be designed to improve their sense of coherence and high motivation level, and to maintain their professional competence when they return to work. This kind of support may prevent further out-migration and nursing shortages from Finland and other industrialized countries. [ABSTRACT FROM AUTHOR]

Background: Fragmentation of cancer care (FC) occurs when patients receive treatment across several different hospitals. Regionalization of surgery for patients with high grade endometrial cancer means that patients must travel longer distances to receive care; these patients often require adjuvant treatment after surgery., Objectives: To determine whether the fragmentation of surgery and adjuvant treatment impacts survival in patients with high grade non-endometrioid endometrial cancer., Methods: This population-based retrospective cohort study included patients diagnosed between 2003-2017 with high-grade non-endometrioid endometrial cancer who received adjuvant treatment post-operatively. Non-fragmented care (NFC) was defined as receiving surgery and adjuvant treatment at the same institution. The primary outcome was overall survival (OS)., Results: We identified 1,795 patients, of whom 583 (32.5%) had FC. Patients with NFC were more likely to have had surgery by a Gynecologic Oncologist (92.4 vs 58.8%, p<0.001), surgical staging (66.6 vs 44.8%, p<0.001), and less travel for surgery (mean 30.8 km vs 93.7 km, p<0.001). They were less likely to receive chemotherapy (26.3 vs 30%, p<0.001) and chemoradiation (38.4 vs 41.3%, p<0.001). Median survival was 9 years. There was no significant difference in OS between patients who received FC and NFC. 92.4 and 93.5% of the patients in the FC and NFC groups were treated at a specialized gynecologic oncology center for at least part of their treatment (surgery, adjuvant treatment or both)., Conclusions: We have previously shown that regionalization of surgery in high-grade endometrial cancer is associated with improved survival. Fragmentation of surgery and adjuvant treatment in this population does not have an adverse effect on survival. After receiving surgical treatment with a Gynecologic Oncologist, these patients may receive adjuvant treatment closer to home to decrease financial and travel burden., (Copyright © 2024. Published by Elsevier Inc.)

Purpose: Vulvar squamous cell carcinoma (VSCC), a rare gynecologic malignancy, has been rising in incidence. Molecular classification on the basis of human papilloma virus (HPV) and tumor protein 53 (p53) status has identified three clinically distinct subtypes, but we still treat all VSCCs the same. Here, we review molecular classification of VSCC, outline treatment landscape, and highlight potential for targeted therapies in advanced VSCC., Design: We conducted a comprehensive review of the literature on treatment of advanced VSCC with particular focus on the implications of molecular stratification on the basis of HPV and p53 status on the treatment landscape of advanced VSCC., Results: Incorporation of HPV and p53 status in locoregional treatment decision making has the potential to advise (de)escalation strategies. The role of immunotherapy, alone and in combination, requires further exploration particularly earlier in the course of the disease. In advanced stages, potential for targeted therapies in VSCCs include inhibitors of vascular endothelial growth factor, endothelial growth factor receptor, cell cycle, and DNA damage response, particularly in HPV-negative (HPV-) VSCCs. Targeting the phosphoinositide 3 kinase/mammalian target of rapamycin pathway is attractive in HPV-positive and HPV-/p53 wildtype VSCCs. Trials incorporating antibody-drug conjugates (eg, trophoblast cell-surface antigen 2, human epidermal growth factor receptor 2) should be considered, and basket trials in perineal squamous cell cancers are warranted. Preclinical models are limited and should be expanded to inform trial design., Conclusion: Like other rare cancers, vulvar cancer lags behind in the identification and optimization of precision medicine strategies. Molecular-based preclinical models and rationally designed clinical trials, incorporating high-quality translational studies, are urgently required. These trials will require international collaboration to ensure feasibility and improvement of outcomes for women diagnosed with this disease.

Objective: To determine the accuracy of pelvic sentinel lymph node biopsy (SLN) in detecting positive para-aortic (PA) lymph nodes in high-grade uterine cancer, and to determine the recurrence rate in patients with high-grade uterine cancers who did not receive adjuvant chemotherapy based on negative pelvic SLNs., Methods: This was a retrospective cohort study of patients with newly diagnosed, high-grade endometrial cancer who underwent surgery, including pelvic SLNs with or without PA node dissection, at a tertiary care institution between 2015 and 2020. Baseline demographics, surgical management, pathology data, and outcomes were analyzed using descriptive statistics, and survival analysis., Results: Postoperative histology of the 110 patients meeting inclusion criteria was 45.5% grade 3 endometrioid, 36.4% serous, 10.9% clear cell, and 7.3% carcinosarcoma. On final pathology, 63.7% were stage 1, and 23.6% were stage 3C with positive nodes. A total of 63 patients (57.3%) had a PA lymph node dissection (56 bilateral, 7 unilateral) in addition to the pelvic SLN. Among this group, 5.8% (95% confidence interval 1.2%-16.0%) had a positive PA node despite a negative pelvic SLN. Among those with a negative pelvic SLN and no adjuvant chemotherapy (n = 75), the rate of distant recurrence was 14.7%, and 3-year recurrence-free survival was 71.9%., Conclusion: The rate of isolated PA node metastasis in high-grade endometrial cancers despite a negative pelvic SLN may be significantly higher than the accepted rate of isolated PA node metastasis in low-grade endometrial cancer. This supports adjuvant treatment decisions continuing to incorporate primary tumor pathology and molecular classification., (© 2024 The Author(s). International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.)

Perioperative blood transfusion in ovarian cancer patients was associated with a 28% increase in all-cause mortality. The negative impact of perioperative blood transfusion extends beyond the immediate postoperative period., Objectives: The effect of perioperative blood transfusions on long-term oncologic outcomes of patients with advanced ovarian cancer undergoing cytoreductive surgery remains uncertain. Our study aims to determine the association between perioperative blood transfusion and all-cause mortality in this population., Methods: Using province-wide administrative databases, patients with advanced ovarian cancer who underwent surgery between 2007 and 2021 as part of first-line treatment were identified. Perioperative transfusion was defined as any transfusion from date of surgery to discharge from hospital. Multivariable Cox proportional hazards regression models were used to determine if there was an independent association of transfusion with all-cause mortality, accounting significant confounders., Results: A total of 5891 patients had cytoreductive surgery for advanced ovarian cancer between 2007 and 2021, of which 2898 (49.2%) had interval cytoreductive surgery (ICS) and 2993 (50.8%) had primary cytoreductive surgery (PCS). Perioperative blood transfusion was given to 37.3% of patients (40.5% ICS and 34.2% PCS). On multivariable analysis, there was an increased hazard of all-cause mortality for patients receiving perioperative transfusion compared to those who did not (hazard ratio: 1.28; 95% CI: 1.20-1.37). The association of increased all-cause mortality was observed starting 1 year after surgery, was sustained thereafter, and seen in both ICS and PCS groups., Conclusion: Perioperative blood transfusion after cytoreductive surgery for ovarian cancer is common in Ontario, Canada and was significantly associated with an increase in all-cause mortality. Blood transfusion is a poor prognostic factor, and the negative impact of blood transfusion persists beyond the immediate postoperative period., (© 2024 Wiley Periodicals LLC.)

Objective: To assess clinical outcomes of inguinal lymph node surgical resection compared to primary groin radiotherapy for locally advanced, surgically unresectable vulvar cancer., Methods: All patients treated with radiation for vulvar cancer were identified between Jan 1, 2000 - Dec 31, 2020 at 2 academic centres. Inclusion criteria were those treated with curative intent primary radiotherapy +/- chemotherapy, tumors >4 cm, and surgically unresectable squamous cell vulvar carcinoma. Groin recurrence-free survival (RFS) was compared for groin surgery and primary groin radiotherapy using the Kaplan Meier method and log rank test. Groin failures are described by treatment modality, radiation dose and lymph node size., Results: Of 476 patients treated with radiation for vulvar cancer, 112 patients (23.5%) met inclusion and exclusion criteria. The median (95% CI) follow up was 1.9 (1.4-2.5) years. Complete clinical response was significantly higher (80.0%) in patients with surgical groin resection compared to patients treated with primary groin radiotherapy (58.2%) (p = 0.04). On multivariable analysis, after adjusting for clinical and/or radiologically abnormal lymph nodes (p = 0.67), surgical groin resection was significantly associated with lower groin recurrence (HR 0.2 (95%CI 0.05-0.92), p = 0.04). The 3-year groin recurrence-free survival (RFS) was significantly higher at 94.4% (87.1-100) in patients with surgical groin resection compared to 79.2% (69.1-90.9) in patients treated with primary radiation (p = 0.02)., Conclusions: In locally advanced squamous cell vulvar cancer, surgical groin management improves groin RFS compared to radiotherapy alone., Competing Interests: Declaration of competing interest None of the authors have any conflicts of interest to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: The American Society of Clinical Oncology recommends all patients with high-grade serous ovarian carcinoma (HGSC) undergo germline genetic testing. Genetic consultation rates in Ontario, Canada, only reached 13.3% in 2011. In 2016, PARP inhibitor maintenance therapy became available in Ontario for BRCA-positive HGSC patients. Given expanding treatment options, we re-examined genetic consultation rates among HGSC patients., Methods: This retrospective cohort study identified patients diagnosed with HGSC between 2012 and 2019 using population-based administrative data from Ontario. Genetics consultations were identified using Ontario Health Insurance Plan billing codes. Consultation rates over time were analyzed using Cochran-Armitage trend test and segmental regression analysis. Multivariable analysis identified factors associated with attending genetics consultation., Results: This study included 4645 HGSC patients. The mean age was 64.2 years (±SD 12.3); 56.3% had stage 3-4 disease. Overall, approximately 35% attended genetics consultations. The genetic consultation rate per year increased significantly from 21.6% to 42.6% (P < 0.001). Shorter times between diagnosis and genetics consult were observed after PARP inhibitors became available (68.1 vs 34.1 weeks, P < 0.001). Patients treated at designated cancer centers (odds ratio [OR] 2.11, P < 0.001), diagnosed in later years (OR 1.33, P < 0.001), and from higher income groups (P < 0.05) were more likely to attend genetics consultation; older patients were less likely (OR 0.98, P < 0.001). After PARP inhibitors became available, consultation rates plateaued (P < 0.001)., Conclusions: Between 2012 and 2019, genetic consultation rates improved significantly among HGSC patients; however, a large proportion of patients never attended consultation. Further exploration of barriers to care is warranted to improve consultation rates and ensure equitable access to care., (© 2024 International Federation of Gynecology and Obstetrics.)

Introduction: Early reports of PD-1 inhibition in ovarian clear cell carcinomas (OCCC) demonstrate promising response. We evaluated the combination of pembrolizumab and IDO-1 inhibitor epacadostat in patients with recurrent OCCC., Methods: This single arm, two-stage, phase 2 trial included those with measurable disease and 1-3 prior regimens. Patients received intravenous pembrolizumab 200 mg every 3 weeks and oral epacadostat 100 mg twice a day. Primary endpoint was overall response rate (ORR), secondary endpoints were toxicity, progression-free survival (PFS) and overall survival (OS). The study was powered to detect an absolute 25% increase in response (15% to 40%)., Results: Between September 28, 2018 and April 10, 2019, 14 patients enrolled at first stage. Rate of accrual was 2.3 patients per month. Median age was 65 years (44-89), 10 (71.4%) had ≥2 prior regimens. ORR was 21% (95% CI 5-51%) within 7 months of study entry with 3 partial responses, and 4 had stable disease (disease control rate 50%). Median PFS was 4.8 months (95% CI: 1.9-9.6), OS 18.9 months (95% CI: 1.9-NR). Most common grade ≥ 3 adverse events were electrolyte abnormalities and gastrointestinal pain, nausea, vomiting, bowel obstruction. In July 2019, the study reached the pre-specified criteria to re-open to second stage; however, the study closed prematurely in February 2021 due to insufficient drug supply., Conclusions: Pembrolizumab and epacadostat demonstrated an ORR of 21% in this small cohort of recurrent OCCC. The rapid rate of accrual highlights the enthusiasm and need for therapeutic studies in patients with OCCC., Competing Interests: Declaration of competing interest Dr. Lilian Gien received consulting fees from Merck – Advisor Board – October 2021. She also received Speaker Honorarium – January 2021 – from Merck. Dr. Danielle Enserro received funding from NCI for Cooperative Group/NCTN Grant Funding for all aspects of this trial including travel to Group meetings, trial design, statistical design and analysis, study monitoring, writing/editing of abstracts/manuscripts, etc. Dr. Matthew S. Block received grants or contracts from Merck – drug only contract for investigator-sponsored trial; Regeneron, Sorrento, Transgene, TILT Biotherapeutics, Alkermes, Bristol-Myers Squibb, Genentech, nFerence, Pharmacyclics and Viewpoint Molecular Therapeutics – institutional payment for clinical trial. He also has a patent filed for Dendritic Cell Based Vaccines Combined with Penbrolizumab for the Treatment of Advanced Ovarian Cancer – patent filed; author has waived rights to personal financial gain. He has participated on a Data Safety Monitoring Board or Advisory Board from TILT Biotherapeutics, Sorrento, and Viewpoint Molecular Therapeutics – no payment received. Dr. Linda Duska has multiple grants from sponsors for clinical trials. These grants go to her institution and not to her. These include, but are not limited to: (research funding (to institution) for investigator initiated trials for Merck, clinical trial grants (to institution) from Genentech/Roche, AbbVie/(GOG 3005), Acrivon, Advaxis, Aduro BioTech, Alkermes, Blueprint, Constellation, Eisai, GlaxoSmithKlein/Novartis, Immunogen, Inovio, Iovance, Karyopharm, KSQ Therapeutics, Lycera, Merck, Morab, MorphoTek, Naveris, Nurix, OncoQuest, Pfizer, Syndax, Tesaro, and Zentalis. She has Royalties or licenses (all up to date) with Wiley and ASCO (Editor of ASCO Connection). She received consulting fees from Regeneron, Aadi Bioscience and Merck for serving on Scientific Advisory Boards. She received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Advance Medical, CEA Group and Clinical Care Options (CME). She has participated on a Data Safety Monitoring Board or Advisory Board for Innovio DSMB (to institution) and Aegenus DSMB (to institution). She served as Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid as Secretary Treasurer for SGO (unpaid) and Editorial Board, British Journal of OB/GYN. Dr. Andrea E. Wahner-Hendrickson received Grants or contracts from TORL Therapeutics (funding to institution for clinical trial, OXCIA (advisory board – unpaid), Prolynx (funding to institution for clinical trial and Mayo Ovarian SPORE (P50 CA1363939). She participated on a Data Safety Monitoring Board or Advisory Board for OXCIA (unpaid). She also served in a Leadership or fiduciary role in other board, society, committee or advocacy group – MOCA (unpaid). Dr. Premal H. Thaker received grants to his institution from Merck and GlaxoSmithKline. She received consulting fees from Immunon. She also participated on a Data Safety Monitoring Board or Advisory Board with AstraZeneca, Clovis Oncology, GlaxoSmithKline, Seagen, Agenus, Immunon, Immuogen, Mersana, Novocure, R-Pharm, Zentalis, Aadi Pharmaceuticals, Merck, Caris Iovance and Verastem. She also has stock or stock options with Immunon. Dr. Floor Backes received grants or contracts from Merck, Eisai, ImmunoGen, Clovis, Beigene, Natera, Tempus and AstraZeneca (research grants paid to the institution). Royalties or licenses from UptoDate (personal fees). She also received consulting fees from Agenus, Merck, Clovis, Immunogen, Eisai, AstraZeneca, GlaxoSmithKline, Myriad, BioNTech and Daiichi Sankyo (Advisory boards – personal fees). She received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Clinical Educational Concepts, Clinical Care Options, Medscape/WebMD, Med Learngin, 13Health, CMR Institute, Global Learning Initiative/Prova, OncLive, Targeted Oncology and Research To Practice (CME lectures – personal fees). She received support for attending meetings and/or travel from GlaxoSmithKline. She participated on a Data Safety Monitoring Board – see consulting fees. She served in a Leadership or fiduciary role on other board, society, committee or advocacy group, paid or unpaid from Society of Gynecologic Oncology (Board member – unpaid), NRG Oncology Developmental Therapeutics Committee – Co-Chair and IGCS Education360 – Co-Chair. Dr. Carolyn Y. Muller received a grant to her institution from New Mexico Minority Underserved NCORP to support enrollment to all NCI NCTN trials. She has a contract to her institution to enroll to GOG Partners trials from GOG Partners Foundation (Segan, GSK, Mersana, Alkemes, Merck, Verastem, Immunogen, etc). She received contracts to her institution for enrollment to specific clinical trials from Linneus Therapeutics. She serves as Chair, Board of Directors of the New Mexico Cancer Research Alliance (unpaid position that manages an affiliate consortium to provide access to clinical trials across the states many health systems). Dr. Paul DiSilvestro serves on the NRG Oncology Board of Directors in a leadership or fiduciary role. Dr. David M. Gershenson's institution received a grant from Novartis. He has royalties or licenses from Elsevier and UpToDate. He received consulting fees to himself from Verastem. He received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Yale University and University of Washington. He serves in a Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid from International Consortium for Low Grade Serous Ovarian Cancer. He has stock in Bristol Myers Squibb, Johnson & Johnson and Proctor & Gamble. He has other financial or non-financial interests himself in Audi AB, Verastem AB, Springworks AB and Onconova AB. Dr. Kathleen N. Moore has grants/contracts from Clovis Oncology Pharmaceutical, Eli Lilly and Company, Genentech, GSK plc Pharmaceutical, Merck, PTC Therapeutics Pharmaceuticals, Verastem Oncology and Biotech. She received support for attending meetings and/or travel from Duality, GSK and Regeneron. She participates on a Data Safety Monitoring Board or Advisory Board for AstraZeneca, Aravive, Aadi Bioscience, Alkermes, Blueprint Medicines, Caris, Clovis Oncology Pharmaceutical, Duality, Eisai Pharmaceutical, EMD Serono Inc., Eli Lilly and Company, Genentech Biotechology, GSK plc Pharmaceutical, ImmunoGen Biotechnology, InxMed, I-MAB Biotech, Iovance, Jiangsu Hengrui Medicine Pharmaceutical, Merck, Mereo BioPharma Group, Mersana Therapeutics Inc., Myriad Genetics, Novartis Pharmaceuticals, Onconova Therapeutics Inc., OncXerna Therapeutics, Inc., Regeneron, VBL, and Verastem Oncology. She serves in a leadership or fiduciary role for GOG Partners and ASCO. Dr. Carol Aghajanian received Clinical Trial funding to her institution (MSK) from: Abbvie – MSKPI – GOG 3005; AstraZeneca – MSK PI, SOLO1/GOG 3004; National Coordinating Investigator and MSK PI, DO81RC00001; ENGOT-ov46; AGO-OVAR 23; GOG-3025; Clovis – MSK PI, ARIEL 2 &3; Genentech/Roche – MSK PI, GOG3015 (IMagyn050). She also participates on an Advisory Board for Blueprint Medicine – Advisory Board 6/30/21 (no consulting fee); Mrck – Global Cervical and Ovaian Cancer Virtual Advisory Board 7/10/23 (no consulting fee) and AstraZeneca – AZ Evolve dmc 4/26/23-ongoing, She also serves on the GOG Foundation, Board of Directors (unpaid, occasional travel cost reimbursement to attend meetings) and NRG Oncology Board of Directors (unpaid)., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: The aim of this study is to describe management and survival in adult patients with malignant ovarian germ cell tumors (MOGCT) undergoing surgery by general gynecologists (GG) versus gynecologic oncologists (GO)., Methods: This is a population-based retrospective cohort study, including patients (age ≥ 18 years old) with MOGCT identified in the provincial cancer registry of Ontario, (1996-2020). Baseline characteristics, surgical and chemotherapy treatment were compared between those with surgery by GG or GO. Cox proportional hazards (CPH) model was used to determine if surgeon specialty was associated with overall survival (OS)., Results: Overall, 363 patients were included. One-hundred and sixty (44%) underwent surgery by GO and 203 (56%) by GG. There were higher rates of stage II-IV in the GO group (27.5% vs 3.9%, p < 0.001, and higher proportion of chemotherapy (64.4% vs 37.4%, p < 0.0001). Five-year OS was 90% and 93% in the GO vs GG groups, respectively (p = 0.39). CPH model showed factors associated with increased risk of death were older age at diagnosis (HR 1.09, 95% CI 1.07-1.12) and chemotherapy (HR 3.12, 95% CI 1.44-6.75). Surgeon specialty was not independently associated with all-cause death (HR 1.04, 95% 0.51-2.15, p = 0.91)., Conclusions: In this group of MOGCT, 5-year OS was not significantly different between patients having surgery by GO compared to GG. Nevertheless, survival rates were lower than expected in the GG group despite their low-risk features. Further exploration is warranted regarding the reasons for this and whether patients with suspected MOGCT may benefit from early assessment by GO for optimal management., Competing Interests: Declaration of competing interest The authors report no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The Society of Gynecologic Oncology (SGO) Journal Club webinar series is an open forum that invites national experts to discuss the literature pertaining to important topics in the management of gynecologic cancers. On August 14th, 2023, SGO hosted a journal club focused on the management of upfront and recurrent vulvar cancer. Our discussants included Dr. Brian M Slomovitz from Mount Sinai Medical Center in Miami Beach, Dr. Emi Yoshida from the University of California San Francisco Helen Diller Family Comprehensive Cancer Center, and Dr. Lilian Gien from the University of Toronto Sunnybrook Odette Cancer Center. During the discussion,we reviewed the progression of vulvar cancer surgery from en bloc resection of the vulva and groins, to partial radical vulvectomy and sentinel lymph nodes. We also reviewed the management of node positive vulvar cancer including published and accruing Groningen International Study on Sentinel Nodes in Vulvar Cancer (GROINSS) trials and other sentinel trials from the Gynecologic Oncology Group (GOG). Here we will also review the literature on the management of recurrent vulvar cancer, highlighting current treatment options and ongoing clinical trials. The following is a report of the journal club presentation., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Objectives: (1) To determine the role of human papillomavirus (HPV) testing after excisional treatment of cervical precancer. (2) To determine clinical factors associated with persistence of cervical precancer post-treatment., Methods: A retrospective chart review was conducted including patients who had a loop electrosurgical excision procedure (LEEP) for cervical precancer (cervical intraepithelial neoplasia 3/adenocarcinoma in situ/high-grade squamous intraepithelial lesions [HSIL]). All patients treated between 2016 and 2018 at a tertiary centre colposcopy unit were included. Persistence/recurrence of disease was defined as high-grade cytology or histology identified during the time of follow-up. Univariate and multivariate regression models were performed to identify factors associated with persistence/recurrence and HPV positivity at exit testing., Results: A total of 284 patients were included. The median follow-up time was 19 months. Of the LEEP specimens, 90.8% (n = 258) demonstrated HSIL and 3.9% (n = 11) had adenocarcinoma in situ. 28.5% (n = 81) of the LEEP specimens had positive margins. In follow-up, 72.9% had negative cytology, 17.6% had atypical squamous cells of undetermined significance/low-grade SIL, 1.8% had atypical squamous cells, HSIL cannot be excluded/low-grade SIL-H, and 6.7% had HSIL. At the final follow-up, 27.8% (n = 79) were HPV+. Overall rate of persistence/recurrence was 11.3% (n = 32); median time to persistence/recurrence was 6.5 months. Multivariate regression models demonstrated that follow-up HPV positivity (OR = 22.0) and positive margins (OR = 3.7) were significantly associated with persistence/recurrence. Similarly, in univariate regression models, positive margins were significant (OR = 2.2) for predicting HPV positivity in exit testing., Conclusions: Persistence/recurrence of precancer can occur due to incomplete treatment of lesions by local excision and by the persistence of HPV infection. Surveillance strategies for women treated for cervical precancer require a risk-based approach and should rely on HPV testing., (Copyright © 2023 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

Background: The aim of the study was to evaluate the safety of fertility-sparing surgery in invasive mucinous ovarian carcinomas (MOC)., Methods: Retrospective review was performed of MOCs diagnosed between 1999 and 2019 at two tertiary cancer centers. Pathology was reviewed to rule out metastasis from gastrointestinal tract. The demographics and survival outcomes were compared between women who underwent fertility-sparing surgery and those who underwent radical surgery (at least hysterectomy, bilateral salpingo-oophorectomy +/- staging). Cox proportional hazard models were constructed to evaluate the effect of fertility sparing surgery on survival., Results: Of 134 with stage I disease, 42 (31%) underwent fertility-sparing surgery with unilateral salpingo-oophorectomy. Compared to women who underwent radical surgery, these women were younger with low grade, early-stage disease. Two patients (5%) in the fertility-sparing cohort experienced a recurrence and 1 of these 2 patients died due to disease progression. There was no difference in either OS or RFS between those that underwent fertility-sparing surgery and radical surgery. In a multivariable analysis adjusting for age and use of adjuvant chemotherapy, fertility-sparing surgery was not significantly associated with OS (HR 0.18; 95% CI 0.01-2.78) or RFS (HR 0.19; 95% CI 0.03-1.45). There were 4 patients (9%) with documented full-term delivery with median interval to conception of 11 months., Conclusions: Fertility-sparing surgery in stage I MOC is not associated with worse outcomes compared to radical surgery and is reasonable to offer to those with early stage disease who wish to retain fertility., Competing Interests: Declaration of Competing Interest No conflict of interest from authors., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Standard first-line chemotherapy for endometrial cancer is paclitaxel plus carboplatin. The benefit of adding pembrolizumab to chemotherapy remains unclear., Methods: In this double-blind, placebo-controlled, randomized, phase 3 trial, we assigned 816 patients with measurable disease (stage III or IVA) or stage IVB or recurrent endometrial cancer in a 1:1 ratio to receive pembrolizumab or placebo along with combination therapy with paclitaxel plus carboplatin. The administration of pembrolizumab or placebo was planned in 6 cycles every 3 weeks, followed by up to 14 maintenance cycles every 6 weeks. The patients were stratified into two cohorts according to whether they had mismatch repair-deficient (dMMR) or mismatch repair-proficient (pMMR) disease. Previous adjuvant chemotherapy was permitted if the treatment-free interval was at least 12 months. The primary outcome was progression-free survival in the two cohorts. Interim analyses were scheduled to be triggered after the occurrence of at least 84 events of death or progression in the dMMR cohort and at least 196 events in the pMMR cohort., Results: In the 12-month analysis, Kaplan-Meier estimates of progression-free survival in the dMMR cohort were 74% in the pembrolizumab group and 38% in the placebo group (hazard ratio for progression or death, 0.30; 95% confidence interval [CI], 0.19 to 0.48; P<0.001), a 70% difference in relative risk. In the pMMR cohort, median progression-free survival was 13.1 months with pembrolizumab and 8.7 months with placebo (hazard ratio, 0.54; 95% CI, 0.41 to 0.71; P<0.001). Adverse events were as expected for pembrolizumab and combination chemotherapy., Conclusions: In patients with advanced or recurrent endometrial cancer, the addition of pembrolizumab to standard chemotherapy resulted in significantly longer progression-free survival than with chemotherapy alone. (Funded by the National Cancer Institute and others; NRG-GY018 ClinicalTrials.gov number, NCT03914612.)., (Copyright © 2023 Massachusetts Medical Society.)

Introduction: Venous thromboembolic events represent the second most frequent cause of mortality in cancer patients. Recent literature shows that direct oral anticoagulants (DOAC) are at least as effective and safe as low molecular weight heparin for postoperative thromboprophylaxis. However, this practice has not been broadly adopted in gynecologic oncology. The aim of this study was to evaluate clinical effectiveness and safety of apixaban for extended thromboprophylaxis in comparison to enoxaparin after laparotomies for gynecologic oncology patients., Methods: The Gynecologic Oncology Division at a large tertiary center transitioned from enoxaparin 40 mg daily to apixaban 2.5 mg BID for 28 days after laparotomies for gynecologic malignancies in November 2020. This real-world study compared patients post-transition (November 2020 to July 2021 (n = 112)) to a historical cohort (January to November 2020 (n = 144)), using the institutional National Surgical Quality Improvement Program (NSQIP) database. All Canadian gynecologic oncology centers were surveyed to assess postoperative DOAC utilization., Results: Patient characteristics were similar between groups. No difference was found between total venous thromboembolism rates (4% vs. 3%, p = 0.49). No difference was found in postoperative readmission (5% vs. 6%, p = 0.50). Of the 7 readmissions in the enoxaparin group, one was due to bleeding requiring transfusion; there were no readmissions for bleeding in the apixaban group. No patient required a reoperation for bleeding. Thirteen percent of the 20 Canadian centers have transitioned to extended apixaban thromboprophylaxis., Conclusions: Apixaban for 28-day postoperative thromboprophylaxis was found to be an effective and safe alternative to enoxaparin after laparotomies in a real-world cohort of gynecologic oncology patients., Competing Interests: Declaration of Competing Interest YL has received research funding from Canadian Blood Services and consultant fees from Choosing Wisely Canada. Other co-authors have no conflicts of interest to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: Mucinous ovarian carcinoma is a rare subtype of epithelial ovarian cancer with scarce literature guiding its management. We aimed to investigate the optimal surgical management of clinical stage I mucinous ovarian carcinoma by examining the prognostic significance of lymphadenectomy and intra-operative rupture on patient survival., Methods: We conducted a retrospective cohort study of all pathology-reviewed invasive mucinous ovarian carcinomas diagnosed between 1999 and 2019 at two tertiary care cancer centers. Baseline demographics, surgical management details, and outcomes were collected. Five-year overall survival, recurrence-free survival, and the association of lymphadenectomy and intra-operative rupture on survival were examined., Results: Of 170 women with mucinous ovarian carcinoma, 149 (88%) had clinical stage I disease. Forty-eight (32%; n=149) patients had a pelvic and/or para-aortic lymphadenectomy, but only 1 patient with grade 2 disease was upstaged due to positive pelvic lymph nodes. Intra-operative tumor rupture was documented in 52 cases (35%). On multivariable analysis, after adjusting for age, final stage, and use of adjuvant chemotherapy, there was no significant association between intra-operative rupture with overall survival (HR 2.2 (0.6-8.0); p=0.3) or recurrence-free survival (HR 1.3 (0.5-3.3); p=0.6), or lymphadenectomy with overall survival (HR 0.9 (0.3-2.8); p=0.9) or recurrence-free survival (HR 1.2 (0.5-3.0); p=0.7). Advanced stage was the only factor that was significantly associated with survival., Conclusions: In clinical stage I mucinous ovarian carcinoma, systematic lymphadenectomy has low utility, as very few patients are upstaged and recurrence typically occurs in the peritoneum. Furthermore, intra-operative rupture does not appear to independently confer a worse survival, and therefore these women may not benefit from adjuvant treatment based on rupture alone., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Standard treatment of early-stage vulvar cancer is a radical, wide, local excision of the primary tumor and a sentinel lymph node (SLN) procedure for the groins. An inguinofemoral lymphadenectomy is no longer necessary for patients who have a negative SLN or micrometastasis ( ≤ 2 mm). When there is macrometastasis (>2 mm) in the SLN, an inguinofemoral lymphadenectomy is indicated; however, this procedure is associated with major morbidity, such as wound healing, lymphoceles, and lymphedema., Primary Objective: To investigate the safety of replacing inguinofemoral lymphadenectomy by chemoradiation in patients with early-stage vulvar cancer with a macrometastasis (>2 mm) and/or extracapsular extension in the sentinel node., Study Hypothesis: Combination of 56 Gy of radiation to the inguinal site and concurrent cisplatin chemotherapy without completion inguinofemoral lymphadenectomy will be feasible and safe, with low groin recurrence rates., Trial Design: This is a single-arm, prospective phase II treatment trial with stopping rules for unacceptable groin recurrences. Eligible patients will receive 56 Gy of radiation to the involved inguinal site and chemotherapy with concurrent cisplatin., Major Inclusion/exclusion Criteria: Eligible patients undergoing sentinel node procedure will have stage I, unifocal, invasive (>1 mm depth of invasion) squamous cell carcinoma of the vulva with tumor size <4 cm, and no suspicious nodes on imaging. Those eligible for the trial are those with a metastasis >2 mm in the sentinel node and/or extracapsular extension, or more than one sentinel node with micrometastasis ≤2 mm., Primary Endpoint: Groin recurrence rate in the first 2 years after primary treatment., Sample Size: 157 patients with macrometastases in their SLN., Estimated Dates for Completing Accrual and Presenting Results: January 1, 2029., Trial Registration Number: NCT05076942., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Investigating for mismatch repair protein deficiency (MMRd), microsatellite instability (MSI), and Lynch syndrome (LS) is widely accepted in endometrial cancer, but knowledge is limited on its value in epithelial ovarian cancer (EOC). The primary objective was to evaluate the prevalence of mismatch repair protein deficiency (MMRd), microsatellite instability (MSI)-high, and Lynch syndrome (LS) in epithelial ovarian cancer (EOC), as well as the diagnostic accuracy of LS screening tests. The secondary objective was to determine the prevalence of MMRd, MSI-high, and LS in synchronous ovarian endometrial cancer and in histological subtypes., Methods: We systematically searched the MEDLINE, Epub Ahead of Print, MEDLINE In-Process and Other Non-Indexed Citations, Cochrane Central Register of Controlled Trials, and Embase databases. We included studies analysing MMR, MSI, and/or LS by sequencing., Results: A total of 55 studies were included. The prevalence of MMRd, MSI-high, and LS in EOC was 6% (95% confidence interval (CI) 5-8%), 13% (95% CI 12-15%), and 2% (95% CI 1-3%) respectively. Hypermethylation was present in 76% of patients with MLH1 deficiency (95% CI 64-84%). The MMRd prevalence was highest in endometrioid (12%) followed by non-serous non-mucinous (9%) and lowest in serous (1%) histological subtypes. MSI-high prevalence was highest in endometrioid (12%) and non-serous non-mucinous (12%) and lowest in serous (9%) histological subtypes. Synchronous and endometrioid EOC had the highest prevalence of LS pathogenic variants at 7% and 3% respectively, with serous having lowest prevalence (1%). Synchronous ovarian and endometrial cancers had highest rates of MMRd (28%) and MSI-high (28%). Sensitivity was highest for IHC (91.1%) and IHC with MSI (92.8%), while specificity was highest for IHC with methylation (92.3%)., Conclusion: MMRd and germline LS testing should be considered for non-serous non-mucinous EOC, particularly for endometrioid., Precis: The rates of mismatch repair deficiency, microsatellite instability high, and mismatch repair germline mutations are highest in endometrioid subtype and non-serous non-mucinous ovarian cancer. The rates are lowest in serous histologic subtype., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Cancer surgery cancellation can have negative consequences for the patient, the surgeon and the health care system. There is a paucity of literature on cancer surgery cancellation and its association with wait times, perioperative outcomes, survival and costs of care. Therefore, the objective of this study was to determine the incidence of same-day cancer surgery cancellation in a universal health care context and its association with short and long-term outcomes., Methods: This was a population-based retrospective cancer cohort study in Ontario, Canada (2010-2016). There were 199 599 patients in the control cohort and 3539 patients in the cohort that experienced a cancellation. We assessed the cohorts for differences in survival, perioperative complications and costs of care., Results: The overall cancellation rate was 1.74% and was predicted by cancer type (genitourinary), lower income quintile, and more central region of residence. Wait times in the cancelled cohort were longer than in the control cohort; however, this difference was not associated with worse survival outcomes. Patients in the cancelled cohort had higher complication rates while in hospital (7.3 %) than those in the control cohort (4.9%; p < 0.01). After adjusting for important confounders, the cancelled cohort was more costly ($1100)., Conclusion: Same-day cancer surgery cancellation rates were low. They were associated with longer wait times, higher complication rates and increased costs of care. Survival was not worse in the cancelled cohort, suggesting that appropriate cancer urgency prioritization occurs. Preventable causes of cancellation should be targeted to improve outcomes in patients with cancer., Competing Interests: Competing interests: None declared., (© 2022 CMA Impact Inc. or its licensors.)

Opinion Statement: The treatment of endometrial cancer has recently undergone a paradigm shift from using traditional clinical-pathologic factors to molecular characterization for prognosis and selection of treatment. Recent approval of pembrolizumab, dostarlimab, and the combination of lenvatinib and pembrolizumab has drastically changed the treatment options and response rate for advanced and recurrent endometrial cancer, especially for DNA mismatch repair-deficient (MMRd) tumors. For p53 abnormal tumors, which have the worst prognosis, there are several new treatment approaches including lenvatinib and pembrolizumab, trastuzumab, and possibly a future role for PARP inhibitors in the homologous recombination deficiency (HRD) p53 abnormal population. In DNA polymerase epsilon-mutated (POLEmut) tumors which have an excellent prognosis, there's a possibility to de-escalate treatment, and in the small chance of recurrence, these tumors may be susceptible to immune checkpoint inhibitors. Further research is needed to better characterize biomarkers for prognosis and identify targeted treatments within the p53 wild-type (p53 WT)/no specific molecular profile (NSMP) cohort. Upcoming studies are evaluating adjuvant treatment by molecular subtype and will determine the next steps for precision medicine in endometrial cancer., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The majority of patients with advanced, high-grade epithelial-tubo ovarian cancer (EOC) respond well to initial treatment with platinum-based chemotherapy; however, up to 80% of patients will experience a recurrence. Poly(ADP-ribose) Polymerase (PARP) inhibitors have been established as a standard of care maintenance therapy to prolong remission and prevent relapse following a response to first-line platinum-chemotherapy. Olaparib and niraparib are the PARP inhibitors currently approved for use in the first-line maintenance setting in Canada. Selection of maintenance therapy requires consideration of patient and tumour factors, presence of germline and somatic mutations, expected drug toxicity profile, and treatment access. This paper discusses the current clinical evidence for first-line PARP inhibitor maintenance therapy in patients with advanced, high-grade EOC and presents consensus statements and a treatment algorithm to aid Canadian oncologists on the selection and use of PARP inhibitors within the Canadian EOC treatment landscape.

Importance: Adjuvant radiation plays an important role in reducing locoregional recurrence in patients with uterine cancer. Although hypofractionated radiotherapy may benefit health care systems and the global community while decreasing treatment burden for patients traveling for daily radiotherapy, it has not been studied prospectively nor in randomized trials for treatment of uterine cancers, and the associated toxic effects and patient quality of life are unknown., Objective: To evaluate acute genitourinary and bowel toxic effects and patient-reported outcomes following stereotactic hypofractionated adjuvant radiation to the pelvis for treatment of uterine cancer., Design, Setting, and Participants: The Stereotactic Pelvic Adjuvant Radiation Therapy in Cancers of the Uterus (SPARTACUS) phase 1/2 nonrandomized controlled trial of patients accrued between May 2019 and August 2021 was conducted as a multicenter trial at 2 cancer centers in Ontario, Canada. In total, 61 patients with uterine cancer stages I through III after surgery entered the study., Interventions: Stereotactic adjuvant pelvic radiation to a dose of 30 Gy in 5 fractions administered every other day or once weekly., Main Outcomes and Measures: Assessments of toxic effects and patient-reported quality of life (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires C30 and endometrial EN24) were collected at baseline, fractions 3 and 5, and at 6 weeks and 3 months of follow-up. Descriptive analysis was conducted, calculating means, SDs, medians, IQRs, and ranges for continuous variables and proportions for categorical variables. Univariate generalized linear mixed models were generated for repeated measurements on the quality-of-life scales., Results: A total of 61 patients were enrolled (median age, 66 years; range, 51-88 years). Tumor histologic results included 39 endometrioid adenocarcinoma, 15 serous or clear cell, 3 carcinosarcoma, and 4 dedifferentiated. Sixteen patients received sequential chemotherapy, and 9 received additional vault brachytherapy. Median follow-up was 9 months (IQR, 3-15 months). Of 61 patients, worst acute gastrointestinal tract toxic effects of grade 1 were observed in 33 patients (54%) and of grade 2 in 8 patients (13%). For genitourinary worst toxic effects, grade 1 was observed in 25 patients (41%) and grade 2 in 2 patients (3%). One patient (1.6%) had an acute grade 3 gastrointestinal tract toxic effect of diarrhea at fraction 5 that resolved at follow-up. Only patient-reported diarrhea scores were both clinically (scores ≥10) and statistically significantly worse at fraction 5 (mean [SD] score, 35.76 [26.34]) compared with baseline (mean [SD] score, 6.56 [13.36]; P < .001), but this symptom improved at follow-up., Conclusions and Relevance: Results of this phase 1/2 nonrandomized controlled trial suggest that stereotactic hypofractionated radiation was well tolerated at short-term follow-up for treatment of uterine cancer. Longer follow-up and future randomized studies are needed to further evaluate this treatment., Trial Registration: ClinicalTrials.gov Identifier: NCT04866394.

Introduction: The diagnostic role of lymph node (LN) assessment is established in endometrial cancer. Our study assesses whether surgical removal of metastatic LNs has oncologic benefit in high-grade endometrial cancer., Materials and Methods: High-grade endometrial cancer cases (2000-2010) were collected from two tertiary cancer centres. In patients with at least one positive LN, recurrence free survival (RFS) was compared by the number of LNs removed. Factors predicting nodal recurrence (NR) were explored. Univariate statistical analyses by log rank test and multivariable cox proportional hazards model were performed using SAS version 9.4., Results: Of 570 patients identified, 334 patients underwent staging lymphadenectomy, 74 (22.2%) patients had at least one positive LN. The median RFS with at least one positive lymph node was 87.1 months (95% CI ≥ 14.3) when greater than 15 LNs were removed, compared to 16.9 months (95% CI, 13.6-35.6) and 17.3 months (95% CI, 8.5-39.8) when 5-15 and less than 5 LNs were removed, respectively (p = 0.02). In the cohort of 570 patients, there were 167 disease recurrences with location described on imaging, 98 (58.7%) had a NR and 69 (41.3%) recurred at other sites. Multivariable modeling identified that only positive LNs at surgical staging predicted NR (HR 3.8, 95% CI 1.4-10.2)., Conclusion: In high-grade endometrial cancer, positive LNs predict NR, and RFS is longer with a more extensive LN dissection in women with positive LNs. Future prospective studies should evaluate the oncologic benefit of surgical removal of metastatic LNs in high-grade endometrial cancer., Competing Interests: Declaration of competing interest None of the authors have any conflicts of interest to disclose., (Copyright © 2021 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Objectives: Timely treatment of epithelial ovarian cancer (EOC) by gynecologic oncologists (GOs) with a combination of surgery and/or chemotherapy has been advocated. Nonetheless, some patients are not assessed by GOs prior to starting their treatment or have surgery by non-GOs. This study aims to determine trends over time in non-mucinous EOC care and to evaluate the impact of care on survival., Methods: Using province-wide administrative data, patients diagnosed with non-mucinous EOC between 2007 and 2018 were identified. Multivariate Cox proportional hazards regression models were used to evaluate the impact of GO assessment prior to initiating treatment or having surgery done by a non-GO on mortality., Results: A total of 10,086 EOC patients were included between 2007 and 2018. During the study period, there was an 8% increase in GO assessment (79% in 2007 to 87% in 2018-19, p ≤  0.001) and a 19% increase in surgeries performed by GOs (69% in 2007 to 88% in 2018-19, p ≤ 0.001). On multivariate analysis, there was an increased hazard of all-cause mortality for patients not assessed by GOs before first treatment (Hazard ratio (HR): 1.61; 95% CI 1.46-1.79). There was an increased hazard of all-cause mortality if ovarian cancer surgery was performed by non-GOs (HR 2.03; 95% CI 1.80-2.30)., Conclusion: Assessment by GO before starting initial treatment is associated with improved survival in women with non-mucinous EOC as the type of surgeon performing primary ovarian cancer surgery. Assessment by GO for all patients with new or suspected ovarian cancer diagnosis before initiation of primary treatment should be advocated., Competing Interests: Declaration of competing interest The authors report no conflicts of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background and Objectives: To compare the immediate operating room (OR), inpatient, and overall costs between three surgical modalities among women with endometrial cancer (EC) and Class III obesity or higher., Methods: A multicentre prospective observational study examined outcomes of women, with early stage EC, treated surgically. Resource use was collected for OR costs including OR time, equipment, and inpatient costs. Median OR, inpatient, and overall costs across surgical modalities were analyzed using an Independent-Samples Kruskal-Wallis Test among patients with BMI ≥ 40., Results: Out of 520 women, 103 had a BMI ≥ 40. Among women with BMI ≥ 40: median OR costs were $4197.02 for laparotomy, $5524.63 for non-robotic assisted laparoscopy, and $7225.16 for robotic-assisted laparoscopy (p < 0.001) and median inpatient costs were $5584.28 for laparotomy, $3042.07 for non-robotic assisted laparoscopy, and $1794.51 for robotic-assisted laparoscopy (p < 0.001). There were no statistically significant differences in the median overall costs: $10 291.50 for laparotomy, $8412.63 for non-robotic assisted laparoscopy, and $9002.48 for robotic-assisted laparoscopy (p = 0.185)., Conclusion: There was no difference in overall costs between the three surgical modalities in patient with BMI ≥ 40. Given the similar costs, any form of minimally invasive surgery should be promoted in this population., (© 2021 Wiley Periodicals LLC.)

Objective: Practice guidelines advocating for regionalization of endometrial cancer surgery to gynecologic oncologists practicing in designated gynecologic oncology centres were published in Ontario in June 2013. Our objectives were to determine whether this policy affected surgical wait times, and whether longer wait time to surgery is a predictor of survival in high grade endometrial cancer patients., Methods: This was a population-based retrospective cohort study, which included patients diagnosed with high-grade non-endometrioid endometrial cancer who had a hysterectomy between 2003 and 2017. Multivariable Cox proportional hazards regression with a spline function was used to model the relationship between surgical wait time and overall survival (OS)., Results: We identified 3518 patients who underwent hysterectomy for high-grade non-endometrioid endometrial cancer. Patients who had surgery with a gynecologic oncologist had a median surgical wait time from diagnosis to hysterectomy of 53 days compared to 57 days pre-regionalization (p = 0.0007), and from first gynecologic oncology consultation to hysterectomy of 29 days compared to 32 days pre-regionalization (p = 0.0006). Survival was inferior for patients who had surgery within 14 days of diagnosis (HR death 2.7 for 1-7 days, 95% CI 1.61-4.51, and HR death 1.96 for 8-14 days, 95% CI 1.50-2.57), reflective of disease severity. Decreased survival occurred with surgical wait times of more than 45 days from the patient's first gynecologic oncology appointment (HR death 1.19 for 46-60 days, 95% CI 1.04-1.36, and HR death 1.42 for 61-75 days, 95% CI 1.11-1.83)., Conclusions: Regionalization of surgery for high-grade endometrial cancer has not had an impact on surgical wait times. Patients who have surgery more than 45 days after surgical consultation have reduced survival., Competing Interests: Declaration of Competing Interest None of the authors have any conflict of interest to declare., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: To assess the diagnostic accuracy of intraoperative pathologic examination of sentinel lymph nodes (SLNs) and patient outcomes in vulva cancer., Methods: This retrospective study included patients with unifocal, <4 cm, invasive vulvar squamous cell carcinoma and clinically negative groin nodes treated with SLN biopsy from January 2008-March 2020. Intraoperative SLN frozen section and final pathology were compared. If the SLN was negative, inguinal femoral lymphadenectomy (IFLD) was omitted. Recurrence location and groin recurrence free survival (RFS) were assessed., Results: The SLN cohort included 173 patients, with 258 groins. On frozen section, there were 36/258 positive and 222 negative groins. On final pathology, there were 39/258 positive: 31 macrometastases, 6 micrometastases, 2 isolated tumor cells (ITCs) and 219 negative groins. The sensitivity, specificity, PPV and NPV for intraoperative detection of metastatic disease, was 89.7% and 99.5%, 97.2% and 98.2%, respectively. There was 1 false positive and 4 false negative frozen section results where final pathology revealed 2 ITCs, 1 micrometastasis and 1 macrometastasis. Based on intraoperative results, thirty patients (17.3%) underwent immediate IFLD. Median follow up was 38.0 (1-137.8) months. The 3-year groin RFS was 91.6% (95% CI 86.2-97.4%) for negative SLNs and 64.6% (95% CI 46.5-89.7%) for positive SLNs on frozen section. Similarly, the 3-year groin RFS was 91.7% (95% CI 86.3-97.4%) for negative, 58.4% (95% CI 38.5-87.7%) for macrometastases and 100% for micrometastases/ITCs on final pathology., Conclusions: Intraoperative assessment of SLNs is accurate to determine need for IFLD and does not compromise patient outcomes in vulvar cancer., Competing Interests: Declaration of Competing Interest None of the authors have any conflicts of interest to disclose., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: Patients with gynecologic malignancies have high rates of post-operative venous thromboembolism. Currently, there is no consensus for peri-operative thromboprophylaxis specific to gynecologic oncology. We aimed to compare rates of symptomatic pulmonary embolus within 30 days post-operatively, and to identify risk factors for pulmonary embolus., Methods: The Division of Gynecologic Oncology at Sunnybrook Health Sciences Centre implemented dual thromboprophylaxis for laparotomies in December 2017. We conducted a prospective study of laparotomies for gynecologic malignancies from December 2017 to October 2018, with comparison to historical cohort from January 2016 to November 2017 using the institutional National Surgical Quality Improvement Program database (NSQIP). Pre-intervention, patients received low molecular weight heparin during admission and extended 28-day prophylaxis was continued at the surgeon's discretion. Post-intervention, all patients received both mechanical thromboprophylaxis with sequential compression devices during admission and 28-day prophylaxis with low molecular weight heparin., Results: There were 371 and 163 laparotomies pre- and post-intervention, respectively. Patient characteristics (age, body mass index, diabetes, smoking, tumor stage), rate of malignant cases, operative blood loss and duration, and length of stay were similar between groups. After implementation, pulmonary emboli rates decreased from 5.1% to 0% (p=0.001). There were more cytoreductive procedures pre-intervention (p≤0.0001) but surgical complexity scores were similar (p=0.82). Univariate analysis revealed that surgery pre-intervention (OR 4.25, 95% CI 1.04 to 17.43, p=0.04), length of stay ≥5 days (OR 11.94, 95% CI 2.65 to 53.92, p=0.002), and operative blood loss ≥500 mL (OR 2.85, 95% CI 1.05 to 7.8, p=0.04) increased risk of pulmonary embolus. On multivariable analysis, surgery pre-intervention remained associated with more pulmonary emboli (OR 4.16, 95% CI 1.03 to 16.79, p=0.045), when adjusting for operative blood loss., Conclusion: Dual thromboprophylaxis after laparotomy significantly reduced rates of pulmonary embolus in this high-risk patient population., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Low-grade serous ovarian cancer (LGSOC) is a rare form of ovarian cancer that accounts for 5-10% of epithelial ovarian cancers. LGSOCs are difficult to treat as they respond poorly to traditional chemotherapy treatments. This systematic review aims to appraise the literature describing the efficacy of hormone maintenance therapy (HMT) in patients with LGSOC given after cytoreductive surgery., Methods: Medline, EMBASE, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews were searched from inception to November 2020. No language restrictions were applied. Publications describing HMT in the primary setting following cytoreductive surgery with or without chemotherapy in women with LGSOC were included. Publications describing HMT in recurrence, non-LGSOC carcinomas, and in-vitro or animal studies were excluded along with case reports, case series, and conference proceedings. We summarized oncologic outcomes, HMT used, and hormone receptor status where reported. Studies were assessed for risk of bias and quality of evidence., Results: The literature search identified 14,799 records. Four cohort studies met eligibility criteria. A total of 558 patients were included, of which 127 were treated with HMT. There was significant heterogeneity between studies demonstrated by differences in HMT regimens used, dosing, and study population, leading to various outcomes following treatment with HMT., Conclusions: Treatment of LGSOC remains a challenge. One retrospective study demonstrated improved progression-free survival following HMT for LGSOC, while two others failed to show significant improvements. However, there is limited data available in the literature which restricts the generalizability of these results. Therefore, well-designed, prospective, and randomized trials are needed to confirm the benefit of HMT in patients with this rare subgroup of ovarian cancer., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: Malignant bowel obstruction in patients with gynecologic malignancies can impose a large symptomatic burden. The objectives of this study were to identify factors associated with shorter length of hospital stay and overall survival in gynecologic oncology patients with malignant bowel obstructions., Methods: A retrospective chart review was performed from December 2014 to March 2019 on patients admitted to a tertiary care center with a malignant bowel obstruction and advanced gynecologic malignancy. Data collection included patient and tumor characteristics, malignant bowel obstruction management (such as conservative management with bowel rest, nasogastric tube, pharmacotherapy or active intervention with surgery, chemotherapy, radiation, total parenteral nutrition or interventional stents), length of hospital stay, and survival outcomes. Statistical analysis included comparisons with Student's t-test and χ 2 test, multivariable analysis, and survival analysis., Results: A total of 107 patients with gynecologic cancer with malignant bowel obstruction were included. The majority of patients (63%, n=67) had ovarian cancer. The median length of hospital stay was 12 days (range 1-23), with a median overall survival after malignant bowel obstruction diagnosis of 7 months (range 0.1-64.1). Patients with active interventions had a longer length of stay compared with those with conservative management (13 vs 6 days, p<0.001). However, patients who received multiple active interventions had increased overall survival (9.1 vs 2.9 months, p=0.049)., Conclusion: Patients who received multimodal treatment for malignant bowel obstruction had an increased length of stay and improvement in survival of over 6 months. This emphasizes the importance of a multidisciplinary approach to actively manage malignant bowel obstruction in advanced gynecologic cancer., Competing Interests: Competing interests: MT, CL, HJM, and LTG have nothing to disclose. SL reports grants from industry-sponsored trials, personal fees from Roche Holding AG, personal fees from GSK, personal fees from AstraZeneca, personal fees from Merck & Co, outside the submitted work. No payment was received for the current manuscript., (© IGCS and ESGO 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Compare recurrence-free survival (RFS) and morbidity between radical hysterectomy (RH) and simple hysterectomy (SH) for clinically diagnosed stage II endometrial cancer., Methods: A multicentre, retrospective study, from 2000 to 2015, involving patients with endometrial cancer with cervical involvement preoperatively and stromal invasion on final pathology. Wilcoxon rank-sum test, Fisher exact test, Kaplan-Meier survival functions, and Cox proportional hazards models were used for analysis., Results: Ninety of 1613 patients had clinical stage II endometrial cancer; 57 underwent RH and 33 underwent SH, with no difference in adjuvant treatment or morbidity. About half of patients (51%) had pathologic stage III-IV disease. Mean follow-up was 3.3 and 3.8 years for SH and RH, respectively. Thirty-three percent of patients with RH and SH experienced a recurrence. Most recurrences were distant: 90% with SH and 79% with RH. There was no difference in RFS between groups (2-year: SH 65% vs. RH 75%; 5-year: SH 54% vs. RH 63%; P = 0.72). Controlling for stage, adjuvant treatment, and margin status, RH was not associated with RFS (HR 0.62; 95% CI 0.28-1.35). Among 44 patients with pathologic stage II disease, 7 had a recurrence (4 SH and 3 RH); 6 of 7 had distant recurrences., Conclusions: Fifty-one percent of patients with clinical stage II endometrial cancer had advanced disease on final pathology, highlighting the importance of surgical staging. RH was not associated with RFS or reduced morbidity. Most recurrences were distant. Although RH could be performed to achieve negative surgical margins, SH may be sufficient for central, small tumours given the high risk of advanced disease and distant recurrence. Research efforts should further elucidate the ideal management of these patients., (Copyright © 2021 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

Aim: Cystoscopic placement of ureteric stents during colorectal surgery (CRS) may aid in the intraoperative identification of the ureters and thus prevent ureteric injury, but may also be associated with prolonged operating time, increased cost and adverse events. No formal recommendations exist regarding the use of ureteric stents prior to CRS. Our aim was to determine the effect of prophylactic ureteric stent insertion on the risk of ureteric injury among adult patients undergoing CRS., Method: A systematic search using the Ovid platform was completed. The primary outcome was risk of ureteric injury. Secondary outcomes included the risk of acute kidney injury (AKI), urinary tract infection (UTI), sepsis, length of stay (LOS) and mortality. The Paule-Mandel pooling and a random effects model was used to produce odds ratios (ORs) with 95% confidence intervals (CIs) for binary outcomes. Standardized mean differences (MD) were reported for continuous variables. Analyses were completed using R3.5., Results: Nine retrospective cohort studies evaluating 98 507 patients were included. The incidence of ureteric injury was 0.6%. Overall, 5.1% of patients underwent ureteric stenting. There was no change in the odds of ureteric injury among stented patients compared with controls (OR 1.30, 95% CI 0.39-4.29, I 2  = 25%). Operating time was significantly longer (MD 49.3 min, 95% CI 35.3-63.4, I 2  = 96%) in the intervention group. There was no difference in rates of AKI, UTI, sepsis, LOS or mortality between groups., Conclusion: Given the retrospective nature of the identified studies, the benefit of prophylactic ureteric stenting remains uncertain. Prophylactic ureteric stenting was not associated with increased patient morbidity but did significantly increase operating time., (© 2020 The Association of Coloproctology of Great Britain and Ireland.)

Objective: Ovarian clear cell carcinoma has unique clinical and molecular features compared with other epithelial ovarian cancer histologies. Our objective was to describe the incidence of second primary malignancy in patients with ovarian clear cell carcinoma., Methods: Retrospective cohort study of patients with ovarian clear cell carcinoma at two tertiary academic centers in Toronto, Canada between May 1995 and June 2017. Demographic, histopathologic, treatment, and survival details were obtained from chart review and a provincial cancer registry. We excluded patients with histologies other than pure ovarian clear cell carcinoma (such as mixed clear cell histology), and those who did not have their post-operative follow-up at these institutions., Results: Of 209 patients with ovarian clear cell carcinoma, 54 patients developed a second primary malignancy (25.8%), of whom six developed two second primary malignancies. Second primary malignancies included: breast (13), skin (9), gastrointestinal tract (9), other gynecologic malignancies (8), thyroid (6), lymphoma (3), head and neck (4), urologic (4), and lung (4). Eighteen second primary malignancies occurred before the index ovarian clear cell carcinoma, 35 after ovarian clear cell carcinoma, and 7 were diagnosed concurrently. Two patients with second primary malignancies were diagnosed with Lynch syndrome. Smoking and radiation therapy were associated with an increased risk of second primary malignancy on multivariable analysis (OR 3.69, 95% CI 1.54 to 9.07, p=0.004; OR 4.39, 95% CI 1.88 to 10.6, p=0.0008, respectively). However, for patients developing second primary malignancies after ovarian clear cell carcinoma, radiation therapy was not found to be a significant risk factor (p=0.17). There was no significant difference in progression-free survival (p=0.85) or overall survival (p=0.38) between those with second primary malignancy and those without., Conclusion: Patients with ovarian clear cell carcinoma are at increased risk of second primary malignancies, most frequently non-Lynch related. A subset of patients with ovarian clear cell carcinoma may harbor mutations rendering them susceptible to second primary malignancies. Our results may have implications for counseling and consideration for second primary malignancy screening., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: In June 2013, Ontario Health (Cancer Care Ontario), the agency responsible for advancing cancer care in Ontario, Canada, published practice guidelines recommending that gynecologic oncologists at tertiary care centers manage the treatment of patients with high-grade endometrial cancers. This study examines the effects of this regionalization of care on patient outcomes., Objective: This study aimed to evaluate the impact of the regionalization of surgery for high-grade endometrial cancer on patient and treatment outcomes., Study Design: In this retrospective cohort study, patients diagnosed with nonendometrioid high-grade endometrial cancer from 2003 to 2017 were identified using province-wide administrative databases. To allow 6 months for knowledge translation, 2 periods were defined, with January 1, 2014, as the cutoff. Methods for segmented regression were used to test the effect of the guidelines. Multivariable Cox proportional hazards regression was used to evaluate whether regionalization of care had an impact on patient survival., Results: There were 3518 patients with nonendometrioid high-grade endometrial cancer identified. The case mix as represented by patient comorbidities and the disease stage distribution did not differ significantly between the 2 regionalization periods. There was a significant increase (69%-85%; P<.001) in the proportion of primary surgeries performed by gynecologic oncologists after regionalization, which was not explained by secular trends. After regionalization, the proportion of patients who had surgical staging (50%-63%; P<.001) and the proportion of patients who received adjuvant treatment (65%-71%; P<.001) increased significantly. After adjusting for age, stage, and comorbidities, there was a decrease in the hazard of mortality (hazard ratio, 0.85 [95% confidence interval, 0.73-0.99]; P=.04) after regionalization., Conclusion: The publication of a regionalization policy for the treatment of high-grade endometrial cancers in Ontario led to an increase in the proportion of surgeries performed by gynecologic oncologists. This also translated into a significant improvement in patient survival., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: There has been a contemporary shift in clinical practice towards tailoring treatment in patients with early cervical cancer and low-risk features to non-radical surgery. The objective of this study was to evaluate the oncologic, fertility, and obstetric outcomes after cervical conization and sentinel lymph node (SLN) biopsy in patients with early stage low-risk cervical cancer., Methods: We conducted a retrospective review in patients with early cervical cancer treated with cervical conization and lymph node assessment between November 2008 and February 2020. Eligibility criteria included patients with a histologic diagnosis of invasive squamous cell carcinoma, adenocarcinoma or adenosquamous carcinoma, International Federation of Gynecology and Obstetrics 2009 stage IA1 with positive lymphovascular space invasion (LVSI), stage IA2, or stage IB1 (≤2 cm) with less than two-thirds (<10 mm) cervical stromal invasion., Results: A total of 44 patients were included in the analysis. The median age was 31 years (range 19-61) and 20 patients (45%) were nulliparous. One patient had a 25 mm tumor while the remaining patients had tumors smaller than 20 mm. Eighteen (41%) patients had LVSI. Median follow-up was 44 months (range 6-137). A total of 17 (39%) patients had negative margins on the diagnostic excisional procedure, and none had residual disease on the repeat cone biopsy. Three (6.8%) patients had micrometastases detected in the SLNs and underwent ipsilateral lymphadenectomy; all remaining non-SLN lymph nodes were negative. Six (13.6%) patients required more definitive surgical or adjuvant treatment due to high-risk pathologic features. There were no recurrences documented. Three patients developed cervical stenosis. The live birth rate was 85% and 16 (94%) of 17 patients had live births at term., Conclusion: Cervical conization with SLN biopsy appears to be a safe treatment option in selected patients with early cervical cancer. Future results of prospective trials may shed definitive light on fertility-sparing options in this group of patients., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Importance: Whether sentinel lymph node biopsy (SLNB) can replace lymphadenectomy for surgical staging in patients with high-grade endometrial cancer (EC) is unclear., Objective: To examine the diagnostic accuracy of, performance characteristics of, and morbidity associated with SLNB using indocyanine green in patients with intermediate- and high-grade EC., Design, Setting, and Participants: In this prospective, multicenter cohort study (Sentinel Lymph Node Biopsy vs Lymphadenectomy for Intermediate- and High-Grade Endometrial Cancer Staging [SENTOR] study), accrual occurred from July 1, 2015, to June 30, 2019, with early stoppage because of prespecified accuracy criteria. The study included patients with clinical stage I grade 2 endometrioid or high-grade EC scheduled to undergo laparoscopic or robotic hysterectomy with an intent to complete staging at 3 designated cancer centers in Toronto, Ontario, Canada., Exposures: All patients underwent SLNB followed by lymphadenectomy as the reference standard. Patients with grade 2 endometrioid EC underwent pelvic lymphadenectomy (PLND) alone, and patients with high-grade EC underwent PLND and para-aortic lymphadenectomy (PALND)., Main Outcomes and Measures: The primary outcome was sensitivity of the SLNB algorithm. Secondary outcomes were additional measures of diagnostic accuracy, sentinel lymph node detection rates, and adverse events., Results: The study enrolled 156 patients (median age, 65.5 years; range, 40-86 years; median body mass index [calculated as weight in kilograms divided by height in meters squared], 27.5; range, 17.6-49.3), including 126 with high-grade EC. All patients underwent SLNB and PLND, and 101 patients (80%) with high-grade EC also underwent PALND. Sentinel lymph node detection rates were 97.4% per patient (95% CI, 93.6%-99.3%), 87.5% per hemipelvis (95% CI, 83.3%-91.0%), and 77.6% bilaterally (95% CI, 70.2%-83.8%). Of 27 patients (17%) with nodal metastases, 26 patients were correctly identified by the SLNB algorithm, yielding a sensitivity of 96% (95% CI, 81%-100%), a false-negative rate of 4% (95% CI, 0%-19%), and a negative predictive value of 99% (95% CI, 96%-100%). Only 1 patient (0.6%) was misclassified by the SLNB algorithm. Seven of 27 patients with node-positive cancer (26%) were identified outside traditional PLND boundaries or required immunohistochemistry for diagnosis., Conclusions and Relevance: In this prospective cohort study, SLNB had acceptable diagnostic accuracy for patients with high-grade EC at increased risk of nodal metastases and improved the detection of node-positive cases compared with lymphadenectomy. The findings suggest that SLNB is a viable option for the surgical staging of EC.

Objectives: Minimally invasive radical hysterectomy is associated with decreased survival in patients with early cervical cancer. The objective of this study was to determine whether the use of an intra-uterine manipulator at the time of laparoscopic or robotic radical hysterectomy is associated with inferior oncologic outcomes., Methods: A retrospective cohort study was carried out of all patients with cervical cancer (squamous cell carcinoma, adenocarcinoma or adenosquamous carcinoma) International Federation of Gynecology and Obstetrics 2009 stages IA1 (with positive lymphovascular space invasion) to IIA who underwent minimally invasive radical hysterectomy at two academic centers between January 2007 and December 2017. Treatment, tumor characteristics, and survival data were retrieved from hospital records., Results: A total of 224 patients were identified at the two centers; 115 had surgery with the use of an intra-uterine manipulator while 109 did not; 53 were robotic and 171 were laparoscopic. Median age was 44 years (range 38-54) and median body mass index was 25.8 kg/m 2 (range 16.6-51.5). Patients in whom an intra-uterine manipulator was not used at the time of minimally invasive radical hysterectomy were more likely to have residual disease at hysterectomy (p<0.001), positive lymphovascular space invasion (p=0.02), positive margins (p=0.008), and positive lymph node metastasis (p=0.003). Recurrence-free survival at 5 years was 80% in the no intra-uterine manipulator group and 94% in the intra-uterine manipulator group. After controlling for the presence of residual cancer at hysterectomy, tumor size and high-risk pathologic criteria (positive margins, parametria or lymph nodes), the use of an intra-uterine manipulator was no longer significantly associated with worse recurrence-free survival (HR 0.4, 95% CI 0.2 to 1.0, p=0.05). The only factor which was consistently associated with recurrence-free survival was tumor size (HR 2.1, 95% CI 1.5 to 3.0, for every 10 mm increase, p<0.001)., Conclusion: After controlling for adverse pathological factors, the use of an intra-uterine manipulator in patients with early cervical cancer who underwent minimally invasive radical hysterectomy was not an independent factor associated with rate of recurrence., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The FIGO 2019 update on cervical cancer staging removed horizontal tumor extent (HZTE) as a staging variable. Evidence is needed to substantiate this change. The prognostic significance of HZTE and a related variable, circumferential tumor extent (%CTE), is similarly unknown. We aimed to investigate the association of HZTE and %CTE with survival outcomes in cervical cancer patients., Methods: We identified patients treated with primary surgery for stage I cervical cancer in a single institution during a 9-year period. HZTE and, when available, %CTE were obtained from pathology records. Cases were staged using 2019 FIGO staging. Correlations between HZTE, %CTE and FIGO stage with recurrence-free (RFS) and disease-specific survival (DSS) were determined using univariable and multivariable analyses., Results: 285 patients were included with a median follow-up of 48 (range 7-123) months. HZTE was statistically associated with RFS and DSS on univariate and multivariate analysis. None of the 168 stage IA patients in our series had tumor recurrence or death during follow-up, including 42 with HZTE ≥7 mm. None of the patients with a tumor horizontal extent <7 mm experienced recurrence or death. %CTE correlated only with RFS on univariate analysis. 2019 FIGO stage did not independently correlate with RFS or DSS in our sample., Conclusions: HZTE is an independent predictor of survival in cervical carcinoma. In stage IA tumors, however, HZTE does not offer superior prognostic value, supporting the 2019 FIGO recommendations to remove this variable from staging in these cases. HZTE may be useful in larger tumors in which staging depends on maximum tumor size. %CTE is not an independent prognostic variable in cervical cancer, and we advise against its use., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Aims: Grading of primary ovarian mucinous carcinoma (OMC) is inconsistent among practices. The International Collaboration on Cancer Reporting recommends grading OMC using the International Federation of Gynecology and Obstetrics (FIGO) system for endometrial endometrioid carcinoma, when needed. The growth pattern (expansile versus infiltrative), a known prognostic variable in OMC, is not considered in any grading system. We herein analysed the prognostic value of various grading methods in a well-annotated cohort of OMC., Methods and Results: Institutional OMCs underwent review and grading by the Silverberg and FIGO schemes and a novel system, growth-based grading (GBG), defined as G1 (expansile growth or infiltrative invasion in ≤10%) and G2 (infiltrative growth >10% of tumour). Of 46 OMCs included, 80% were FIGO stage I, 11% stage II and 9% stage III. On follow-up (mean = 52 months, range = 1-190), five patients (11%) had adverse events (three recurrences and four deaths). On univariate analysis, stage (P = 0.01, Cox proportional analysis), Silverberg grade (P = 0.01), GBG grade (P = 0.001) and percentage of infiltrative growth (P < 0.001), but not FIGO grade, correlated with disease-free survival. Log-rank analysis showed increased survival in patients with Silverberg grade 1 versus 2 (P < 0.001) and those with GBG G1 versus G2 (P < 0.001). None of the parameters evaluated was significant on multivariate analysis (restricted due to the low number of adverse events)., Conclusions: Silverberg and the new GBG system appear to be prognostically significant in OMC. Pattern-based grading allows for a binary stratification into low- and high-grade categories, which may be more appropriate for patient risk stratification. Despite current practices and recommendations to utilise FIGO grading in OMC, our study shows no prognostic significance of this system and we advise against its use., (© 2020 John Wiley & Sons Ltd.)

Background: Vulvar melanoma (VuM) and vaginal melanoma (VaM) represent a unique subgroup of malignant melanomas with important differences in biology and treatment., Objective: The objective of this study was to describe the epidemiology and prognosis of VuM and VaM in a large representative cohort., Methods: Women with invasive VuM or VaM were identified from the Surveillance, Epidemiology and End Results-18 population representing 27.8% of the US population. Data on age, ethnicity, stage, location, histopathology, primary surgery, and lymphadenectomy were collected. The Kaplan-Meier method was used to analyze disease-specific and overall survival. Univariate and multivariate regression models were used to identify factors with a significant association with disease-specific survival., Results: A total of 1400 VuM and 463 VaM were included for further analysis; 78.6% and 49.7% of women with VuM and VaM underwent surgery, but only 52.9% of women with non-metastatic VuM and 42.9% of women with non-metastatic VaM undergoing surgery had lymph node assessment; one third of these had positive nodes. Superficial spreading was the most common subtype in VuM, and nodular melanoma in VaM (p < 0.001). The median disease-specific survival was 99 months (95% confidence interval 60-138) and 19 months (95% confidence interval 16-22), respectively. Survival was significantly associated with age at diagnosis, ethnicity, stage, surgery, lymph node metastases, histologic subtype, ulceration, mitotic count, and tumor thickness in VuM, and stage, surgery, and lymph node involvement in VaM. In the Cox model, lymph node status and number of mitoses remained independent predictors of outcome in VuM; in VaM, only lymph node status remained significant., Conclusions: The overall prognosis of VuM and VaM remains poor. The American Joint Committee on Cancer staging system is applicable and should be used for VuM; however, lymph node status and mitotic rate are the most important predictors of survival. Lymph node status should be assessed and patients with positive nodes may be candidates for adjuvant treatment.

Introduction: As sentinel lymph node biopsy is evolving to an accepted standard of care, clinicians are being faced with more frequent cases of small volume nodal metastatic disease. The objective of this study is to describe the management and to measure the effect on recurrence rates of nodal micrometastasis and isolated tumor cells in patients with early stage cervical cancer at two high-volume centers., Methods: We conducted a review of prospectively collected patients with surgically treated cervical cancer who were found to have micrometastasis or isolated tumor cells on ultrastaging of the sentinel lymph node. Our practice is to follow patients for ≥5 years post-operatively either at our center or another cancer center closer to home., Results: Nineteen patients with small volume nodal disease were identified between 2006 and 2018. Median follow-up was 62 months. Ten (53%) had nodal micrometastatic disease, while nine (47%) had isolated tumor cells detected in the sentinel lymph node. Seven patients (37%) underwent completion pelvic lymphadenectomy and four of them also had para-aortic lymphadenectomy; there were no positive non-sentinel lymph nodes. The majority (74%) received adjuvant treatment, mostly driven by tumor factors. We observed two recurrences. Recurrence-free survival was comparable with historical cohorts of node negative patients, and adjuvant treatment did not seem to impact the recurrence rate (p=0.5)., Conclusion: Given the uncertainties around the prognostic significance of small volume nodal disease in cervical cancer, a large proportion of patients receive adjuvant treatment. We found no positive non-sentinel lymph nodes, suggesting that pelvic lymphadenectomy or para-aortic lymphadenectomy may not be of benefit in patients diagnosed with small volume nodal metastases. Recurrence-free survival in this group did not seem to be affected. However, given the small numbers of patients and lack of level 1 evidence, decisions should be individualized in accordance with patient preferences and tumor factors., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Recent studies demonstrating shorter survival among cervical cancer patients undergoing minimally invasive versus open radical hysterectomy could not account for surgeon volume and require confirmation in other jurisdictions with larger sample sizes, longer follow-up, and data on disease recurrence., Objective: To determine if surgical approach is associated with oncologic outcomes in cervical cancer patients undergoing minimally invasive or open radical hysterectomy, while accounting for mechanistic factors including surgeon volume., Study Design: We performed a population-based retrospective cohort study of cervical cancer patients undergoing primary radical hysterectomy by a gynecologic oncologist from 2006 to 2017 in Ontario, Canada. A multivariable marginal Cox proportional hazards model and cause-specific hazards model were used to evaluate the association of surgical approach with all-cause death and recurrence respectively, clustering at the surgeon level. We tested for interactions between surgical approach and either pathologic stage or surgeon volume., Results: We identified 958 patients (minimally invasive 475; open 483) with mean age 45.9 and a median follow-up of 6 years. Of minimally invasive procedures, 89.6% were performed laparoscopically and 10.4% robotically. The unadjusted 5-year cumulative incidences of all-cause death (minimally invasive 12.5%; open 5.4%), cervical cancer death (minimally invasive 9.3%; open 3.3%), and recurrence (minimally invasive 16.2%; open 8.4%) were significantly increased for minimally invasive radical hysterectomy in patients with stage IB disease, but not the cohort overall. After adjusting for patient factors and surgeon volume, minimally invasive radical hysterectomy was associated with increased rates of death (hazard ratio [HR], 2.20; 95% confidence interval [CI], 1.15-4.19) and recurrence (HR, 1.97; 95% CI, 1.10-3.50) compared to open radical hysterectomy in patients with stage IB disease (n = 534), but not IA disease (n = 244; HR, 0.73; 95% CI, 0.13-4.01; HR, 0.34; 95% CI, 0.10-1.10)., Conclusion: Minimally invasive radical hysterectomy is associated with increased rates of death and recurrence in patients with stage IB cervical cancer even after controlling for surgeon volume; open radical hysterectomy should be the recommended approach in this population. Although there may be a subset of patients with microscopic early-stage disease for whom minimally invasive radical hysterectomy remains safe, additional studies are required., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Lymph node metastasis is the most important prognostic factor in patients with vulvar squamous cell carcinoma (SCC). Previous excision of the vulvar tumor may disrupt lymphatic channels and alter the accuracy of the sentinel lymph node (SLN) biopsy. The purpose of this study was to measure outcomes after SLN biopsy in patients with and without previous excision of the vulvar tumor., Methods: Retrospective study of patients at a single institution with primary vulvar cancer, clinically negative nodes, and vulvar tumors < 4 cm treated with surgical excision who had SLN biopsy (2008-2015)., Results: There were 106 cases of concomitant wide local excision (WLE) and SLN biopsy and 24 additional cases of patients who had previous vulvar surgery and no visible tumor; these patients underwent scar re-excision and SLN biopsy. Median follow-up was 31 months. Patients who had previous tumor excision were more likely to be of younger age (p = 0.0001), have a smaller tumor (p = 0.002), and less depth of invasion (p = 0.02). In the wide local excision of the scar specimen, 11 patients (46%) had no residual disease left, 8 patients (33%) had only vulvar intraepithelial neoplasia (VINIII), 4 patients (17%) had carcinoma in situ with focal invasion and 1 patient (4%) had invasive carcinoma within the second specimen, resected with clear margins. There were no groin recurrences in patients who underwent scar re-excision and who had a negative SLN biopsy., Conclusion: SLN biopsy is feasible and safe in patients who have had previous excision of the vulvar tumor and present with a scar. When a SLN is detected by injecting the remaining scar, this accurately reflects the nodal status and does not negatively impact oncologic outcomes., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Patients with recurrent clear cell ovarian cancer have poor prognosis and limited effective systemic treatment options., Objectives: To characterize patterns of recurrence and compare overall survival and post-recurrence survival parameters in patients with recurrent ovarian clear cell carcinoma., Methods: Clinical data on patients with ovarian clear cell carcinoma between June 1995 and August 2014 were collected. Patients with clear cell ovarian cancer recurrence were included in this study. Patients with different histologic sub-type, persistent or progressive disease on completion of the initial treatment were excluded. Descriptive statistics, univariate and multivariable analyses, and Kaplan-Meier survival probability estimates were completed. The log-rank test was used to quantify survival differences on univariable analysis. To search for significant covariates related to the overall survival and post-recurrence survival, a univariable Cox proportional hazard model was performed., Results: A total of 209 patients met inclusion criteria. Of these, 61 (29%) patients who were free of disease at completion of the initial treatment had recurrence. Patterns of recurrence were as follows: 38 (62%) patients had multiple-site recurrence, 12 (20%) had single-site recurrence, and 11 (18%) had nodal recurrence only. The median overall survival was 44.7 months (95% CI 33.4 to 64.2) and was significantly associated with pattern of recurrence (p=0.005). The median post-recurrence survival was 18.4 months (95% CI 12.5 to 26.7): 54.4 months (95% CI 11 to 125.5) in single-site recurrence, 13.7 months (95% CI 6.8 to 16.5) in multiple-site recurrence, and 30.1 (95% CI 7.2 to 89) months in nodal recurrence (p=0.0002). In the multivariable analysis, pattern of recurrence was a predictor of post-recurrence survival.Six patients (9.8%) had a prolonged disease-free interval after recurrence (disease-free for more than 30 months after completion of treatment for recurrence). Prolonged recurrences were noted in 4 (33%) of 12 patients with single-site recurrence, 1 (9%) of 11 patients with nodal recurrence, and in 1 (2.7%) of 38 patients with multiple-site recurrence. Three of the six patients with a prolonged disease-free interval after recurrence were treated surgically at the time of recurrence., Conclusion: Ovarian clear cell carcinoma predominantly recurs in multiple sites and it is associated with a high mortality rate and short post-recurrence survival. When recurrences are limited to a single site, or only to lymph nodes, the median post-recurrence survival is longer. Disease-free interval after recurrence is longer in patients with single-site recurrence who are treated surgically at the time of recurrence., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Determine rates of radical minimally invasive surgery (MIS) for cervix cancer in Ontario, and whether these rates varied over time and by region. Assess whether changes in the use of MIS impacted length of hospital stay and readmissions., Methods: Retrospective population-based cohort study of women undergoing radical surgery for cervical cancer between 2002 and 2015. Radical MIS versus laparotomy were compared. Trends in rate of MIS over time, length of hospital stay, and readmission within 30 days were determined. Multivariate logistic regression was used to determine factors associated with MIS approach., Results: 805 women underwent radical abdominal surgery versus 538 radical minimally invasive surgery. Radical MIS increased over the study period, from 17.7% in 2002 to 61.5% in 2015. The most significant predictor of MIS approach was hospital site, with a 14-fold difference in sites with highest and lowest uptake of MIS. Mean length of hospital stay was significantly shorter after radical MIS compared to radical abdominal surgery (1.1 v. 4.2 days). Hospital readmission within 30 days was reduced over the study period for MIS but remained stable following abdominal surgery., Conclusions: Although rates of radical MIS increased in Ontario over the time period studied, this seems to have been driven by a few high volume centres. Cervical cancer is rare and it takes time to develop the skills to carry out the procedure effectively. Abandonment of minimally invasive radical hysterectomy may have a significant impact on surgical training and subsequent proficiency in the skills unique to this procedure., (Copyright © 2019 Elsevier Inc. All rights reserved.)