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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.

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.

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.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.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).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.

BackgroundStandard 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 ObjectiveTo 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 HypothesisCombination 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 DesignThis 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 CriteriaEligible 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 2 mm in the sentinel node and/or extracapsular extension, or more than one sentinel node with micrometastasis ≤2 mm.Primary EndpointGroin recurrence rate in the first 2 years after primary treatment.Sample Size157 patients with macrometastases in their SLN.Estimated Dates for Completing Accrual and Presenting ResultsJanuary 1, 2029.Trial Registration NumberNCT05076942.

Objectives: To measure the diagnostic accuracy of intraoperative frozen section examination of sentinel lymph nodes (SLN) in vulvar cancer and to describe associated patient outcomes. Methods: This retrospective cohort study included patients with invasive squamous cell carcinoma of the vulva who underwent SLN biopsy with intraoperative frozen section at one cancer centre from Jan 2008 - Feb 2020. Exclusion criteria were tumor size >4cm, multifocal tumor, palpable groin lymph nodes and neoadjuvant therapy. The SLN procedure was performed by injection of the primary vulvar tumor or scar with technetium-99m, ICG and/or blue dye. We compared the intraoperative SLN frozen section diagnosis and the paraffin section report for concordance. Recurrence location was described and recurrence free survival (RFS) was compared using the Kaplan-Meier method. Results: A total of 173 patients (258 groins) met inclusion and exclusion criteria. On frozen section, there were 36/258 positive groins on frozen section and 222 negative groins. On final pathology, there were 39/258 positive groin nodes: 30 macro-metastases, 7 micro-metastases, 2 isolated tumor cells (ITCs). There were 219 negative groins. The sensitivity and specificity for frozen section detecting any metastatic disease compared to final pathology, was 89.7% and 99.5%, respectively. The positive-predictive value (PPV) was 97.2% and the negative-predictive-value (NPV) was 98.2%. There were 4 cases of false negative frozen section where final pathology revealed two cases of ITCs, 1 micro-metastasis and 1 macro-metastasis. A total of 30 patients (17.3%) underwent a full inguinal femoral lymphadenectomy during the same operation due to the frozen section results and avoided a second operation. A total of 2 patients (1.2%) required a second operation for lymphadenectomy due to false negative results on frozen section. Median (range) follow up was 38.0 (1-137.8) months. Median RFS was 14.9 (3.6 to 98.2) months. There were 46 recurrences in the study population, of which 29 were confined to the vulva, 9 groin recurrences and 8 distant recurrences. Among patients with a negative SLN biopsy on both frozen section and final pathology, there were 10 (3.9 %) groin and/or distant recurrences. A total of 6 nodal recurrences were ipsilateral, 1 was contralateral, 2 were bilateral and 1 recurrence was distant. After exclusion of patients with local recurrence only, the RFS at 3 years was 91.6% (95% CI 86.2-97.4%) for patients with negative SLN on frozen section and 64.6% (95% CI 46.5-89.7%) for positive SLN on frozen section. On final pathology, patients with negative SLN had a 3-year RFS of 91.7% (95% CI 86.3-97.4%), macro-metastases 58.4% (95% CI 38.5-87.7%), and micro-metastases/ITCs was 100%. Conclusions: Intraoperative frozen section of SLNs in vulvar cancer is an accurate intraoperative guide to determine if complete inguinal femoral lymphadenectomy should be performed. SLN biopsy reduced the need for a second surgical procedure and does not appear to compromise patient outcomes.

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.

ObjectiveThere 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.MethodsWe 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 (ResultsA 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.ConclusionCervical 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.

ObjectivesMalignant 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.MethodsA 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 χ2 test, multivariable analysis, and survival analysis.ResultsA 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, pConclusionPatients 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.

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, I2 = 25%). Operating time was significantly longer (MD 49.3 min, 95% CI 35.3-63.4, I2 = 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.

ObjectivesPatients 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.MethodsThe 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.ResultsThere 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.ConclusionDual thromboprophylaxis after laparotomy significantly reduced rates of pulmonary embolus in this high-risk patient population.

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

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.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.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%;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.

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.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.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).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.

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.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).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).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.

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

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.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).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.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.

BackgroundPatients with recurrent clear cell ovarian cancer have poor prognosis and limited effective systemic treatment options.ObjectivesTo characterize patterns of recurrence and compare overall survival and post-recurrence survival parameters in patients with recurrent ovarian clear cell carcinoma.MethodsClinical 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.ResultsA 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.ConclusionOvarian 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.

To evaluate trends in uptake of sentinel lymph node (SLN) procedures over time and associated factors in women with vulvar cancer.A retrospective population-based cohort study identified women with invasive squamous cell carcinoma (SCC) of the vulva using health administrative data for the province of Ontario, Canada, between 2008 and 2016. Patients who underwent SLN procedures were compared to those who had groin node dissection (GND). Multivariable analysis was used to identify factors associated with SLN procedures.1385 patients with SCC of the vulva were identified; 1079 had a surgical procedure. Only those with groin node assessment were included in the study cohort (n = 732, 68%). SLN procedures were done in 52%. When comparing SLN versus GND, the rate of SLNs was significantly different by year of diagnosis (P 0.001), associated comorbidity (P 0.001) and institution (P 0.0001). The rates of SLNs by institution with gynecologic oncologist were variable and ranged from 32% to 79% among 9 centers. There were no differences in age, income quintile, and urban/rural residence. The proportion of SLN procedures increased from 30.1% (CI 18.9-45.6) in 2008 to 65.2% (CI 36.5-107.6) in 2016. On multivariate analysis, factors significantly associated with SLN procedures were more recent year of diagnosis (OR 7.9, CI 2.7-23.5) associated comorbidities (OR 2.7, CI 1.5-5.0) and institution (Site 5, OR 19.6 [CI 3.6-108.3] and Site 6, [OR 6, CI 1.1-33.4]).The proportion of SLN procedures in women with vulvar cancer has increased over time, but uptake is not uniform across institutions. Barriers to uptake should be explored.

Objective To assess the impact of a surgical site infection (SSI) prevention bundle for Gynecologic Oncology patients at a large academic tertiary centre in Toronto, Canada. Methods A SSI prevention bundle was implemented in February 2017 including: preoperative chlorhexidine shower, prophylactic antibiotics, glycemic control, normothermia, and separate closing tray. Data were collected prospectively using the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) institutional data, and chart review of surgeries between January 2016 and September 2017 was performed. The primary outcome was rate of SSIs, secondary outcomes were: superficial, deep and organ space SSIs, sepsis, wound disruption, length of stay, 30-day readmission and reoperation. Logistic regression analysis was conducted to identify predictors of SSIs. Results 339 baseline and 224 post-intervention patients were included. 53 incurred one or more SSIs: 43 superficial, 6 deep, and 14 organ-space. The bundle decreased overall SSIs by 55% (12.1% to 5.4%, p = 0.008) and superficial SSIs by 54% (9.7% to 4.5%, p = 0.023). Improvement was sustained for 6 quarters. No significant difference was found in other secondary outcomes. On multivariable analysis, surgery in the pre-bundle period, BMI ≥30, laparotomies and longer operative duration were independent risk factors for overall SSIs (OR 2.23, 95% CI 1.06–5.06, –OR 3.01, 95% CI 1.57 – 5.87, OR 3.70, 95% CI 1.56 – 10.18 and – OR 2.16, 95% 1.11 – 4.19, respectively). Conclusions This prevention bundle successfully decreased SSIs in patients undergoing gynecologic cancer surgery. We recommend improving quality of care by wide implementation of SSI prevention bundles in Gynecologic Oncology patients.

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.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.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.Stereotactic adjuvant pelvic radiation to a dose of 30 Gy in 5 fractions administered every other day or once weekly.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.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.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.ClinicalTrials.gov Identifier: NCT04866394.

Purpose/Objective(s) Adjuvant radiation plays a significant role in reducing locoregional recurrences in uterine cancers. Standard treatment consists of daily radiation for 5 weeks which can be challenging for patients and the healthcare system, especially during the COVID pandemic. Hypofractionated radiotherapy has been evaluated and established in other pelvic malignancies. This study aims to evaluate the acute urinary and bowel toxicities, and patient reported outcomes following stereotactic hypofractionated adjuvant radiation for endometrial cancer. Materials/Methods This is a prospective phase I/II trial in which patients with endometrial cancer planned for adjuvant radiation received 30 Gy in 5 fractions, every other day or once weekly. Treatment was delivered at two centers with volumetric arc radiation therapy with a body-vacuum immobilization, bowel enema and 3D image-guidance. Toxicity assessment, outcomes and patient reported quality of life (QOL, EORTC core QLQ-C30 and endometrial EN24) were collected at baseline, fractions (F) 3 and 5, and at regular follow-up intervals. Higher scores represent better global QOL/health status or worse symptoms (scale 0 – 100). Changes in QOL over time were investigated with linear mixed-effects models. A P-value threshold of 0.05 was used for statistical significance. A change in QOL score of ≥ 10 points was considered clinically significant. Results The median age of the 41 enrolled patients is 66 (range: 51 – 88). Histologies included 29 endometrioid adenocarcinoma, 8 serous/clear cell, 1 carcinosarcoma, and 3 dedifferentiated. Thirty patients had stage 1 disease while 3 had stage 2 and 8 stage 3. Seven patients received sequential chemotherapy and 3 had additional vault brachytherapy. Median follow-up is 9 months, with worst toxicity (GI or GU) of grade 1 and 2 in 63% and 24% respectively. No patients have experienced a grade 3 or higher toxicity. Patient-reported diarrhea and gastrointestinal domain scores were statistically significantly worse than baseline at F5 (mean paired difference = 27.2; 8.7, P Conclusion Stereotactic hypofractionated radiation for uterine cancers is feasible and well-tolerated with short-term follow-up. Longer follow-up and future randomized studies are needed to further evaluate this treatment.

Background It is unclear whether sentinel lymph node biopsy (SLNB) can replace lymphadenectomy in women with high grade endometrial cancer (EC). We performed a prospective multicenter cohort study (the SENTOR trial) to evaluate the diagnostic accuracy of SLNB using indocyanine green in intermediate and high grade EC (NCT01886066). Methods Patients with clinical stage I grade 2 endometrioid or high grade EC scheduled for minimally invasive hysterectomy at three academic centers in Toronto, Canada, were prospectively enrolled for SLNB followed by pelvic (PLND) and para-aortic lymphadenectomy (PALND) as the reference standard. The study was powered to determine sensitivity of the SLNB algorithm as the primary endpoint. Results We enrolled 156 patients (126 high grade); all underwent SLNB and PLND, and 106 (84%) with high grade EC underwent PALND. Sentinel lymph node detection rates were 97% per patient (95% CI 94–99), 88% per hemipelvis (95% CI 83–91), and 78% bilaterally (95% CI 70–84). Of 27 patients (17%) with nodal metastases, 26 were correctly identified by the SLNB algorithm, yielding a sensitivity of 96% (95% CI 81–100), false negative rate of 4% (95% CI 0–19), and negative predictive value of 99% (95% CI 96–100). Only one patient (0.6%) was misclassified by the SLNB algorithm. Two of 27 node-positive patients (7.5%) were identified outside traditional PLND boundaries, and five of 27 (18.5%) required immunohistochemistry for diagnosis. Conclusion SLNB has comparable, if not superior, diagnostic accuracy relative to lymphadenectomy in high grade EC patients. SLNB is a viable option for the surgical staging of EC.

Objectives Practice guidelines advocating for the regionalization of endometrial cancer surgery to gynecologic oncologists (GO) practicing in designated gynecologic oncology centres were released by Cancer Care Ontario in June 2013. We sought to determine the impact this policy had on contemporary surgical wait times, and whether longer wait time to surgery is a predictor of survival in patients with high risk endometrial cancer. Study Methods This was a retrospective cohort study, which included patients diagnosed with non-endometrioid high-risk endometrial cancer (serous, carcinosarcoma, clear cell, and undifferentiated) between 2003 and 2017. A cut point of January 2014 was chosen to allow 6 months for knowledge translation and define 2 regionalization periods. Results We identified 3518 patients with high risk endometrial cancer. Patients who had surgery with a GO had a median surgical wait time from diagnosis to hysterectomy of 55 days compared to 59 days pre-regionalization (p=0.0002), and from first GO consultation to hysterectomy of 29 days compared to 32 days pre-regionalization (p=0.0006). Survival was worst for patients who had surgery within 14 days of diagnosis (HR death 1.94, 95%CI 1.48–2.54), indicating disease severity. Decreased survival occurred with surgical wait times of more than 45 days from the patient’s first GO appointment (HR death 1.19, 95%CI 1.04–1.36). Conclusion Regionalization of surgery for high risk endometrial cancer has not had a negative impact on surgical wait times. Impact on survival is seen with patients who have surgery more than 45 days after surgical consultation.

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.

ObjectiveOvarian 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.MethodsRetrospective 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.ResultsOf 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.ConclusionPatients 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.

ObjectivesMinimally 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.MethodsA 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.ResultsA 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/m2 (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 (pConclusionAfter 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.

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.This study aimed to evaluate the impact of the regionalization of surgery for high-grade endometrial cancer on patient and treatment outcomes.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.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.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.

ObjectiveHigh grade and non-endometrioid endometrial cancers carry a poor prognosis, and the lack of randomized prospective data has led to a wide range of practice regarding adjuvant therapy. The objective of this study was to evaluate the outcomes of different treatment strategies in patients with high-risk, early-stage endometrial cancer.MethodsPatients with high-grade endometrioid, serous endometrial cancer and carcinosarcoma diagnosed between 2000 and 2012 were identified from databases in three gynecologic oncology divisions, in Toronto and in Israel. Adjuvant treatment practices differed across the centers, creating a heterogeneous cohort. A comparison of stage I patients stratified by adjuvant treatment was undertaken. Log-rank tests and Cox proportional hazards models were employed to compare recurrence and survival across treatment groups.Results490patients with high risk endometrial cancer were identified, among them 213 patients with stage I disease. Israeli patients received more chemotherapy (41% vs 10% in stage I disease; PConclusionsIn this retrospective analysis, neither adjuvant radiation nor chemotherapy were associated with improved outcome in stage I, high risk endometrial cancer.

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.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.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 extent7 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.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.

Summary Background Accurate identification of sentinel lymph nodes in patients with cancer improves detection of metastatic disease and decreases surgical morbidity. We sought to establish whether indocyanine green fluorescent dye is non-inferior to isosulfan blue dye in detecting sentinel lymph nodes in women with cervical and uterine cancers. Methods In this non-inferiority, within-patient comparison study, patients aged 18 years or older with clinical stage I endometrial or cervical cancer undergoing curative surgery were randomly assigned 1:1 to lymphatic mapping with isosulfan blue dye (visualised by white light) followed by indocyanine green (visualised by near-infrared imaging), or indocyanine green followed by isosulfan blue dye. Permuted block randomisation with stratification by study site was done with a computerised random number generator. All participants were masked to their randomisation assignment until after the procedure; however, investigators were not masked to the procedure used. Laparoscopic surgery with the PINPOINT near-infrared fluorescence imaging system (Stryker, Kalamazoo, MI, USA) was used in all cases. The primary outcome was efficacy of intraoperative indocyanine green with near-infrared fluorescence imaging versus that of isosulfan blue dye in the identification of lymph nodes, defined as the number of lymph nodes identified by indocyanine green and isosulfan blue dye, respectively (and confirmed as lymphoid tissue by histology), divided by the number of lymph nodes identified intraoperatively and excised. The study had a 5% non-inferiority margin needed to show non-inferiority of the frequency of lymph node detection with indocyanine green to that with isosulfan blue dye with 80% power at a 5% two-sided significance level. Analyses were done in both per-protocol and modified intention-to-treat populations. The trial was registered with ClinicalTrials.gov, number NCT02209532, and is completed and closed. Findings Between Dec 21, 2015, and June 19, 2017, 180 patients were enrolled and randomly assigned to the two groups (90 to each group); 176 patients received the intervention and were evaluable (modified intention-to-treat population). 13 patients with major protocol violations were subsequently excluded from the per-protocol population. 517 sentinel nodes were identified in the per-protocol population (n=163), of which 478 (92%) were confirmed to be lymph nodes on pathological processing: 219 (92%) of 238 nodes that were both blue and green, all seven nodes that were blue only, and 252 (95%) of 265 nodes that were green only (p=0·33). Seven sentinel lymph nodes were neither blue nor green but were removed for appearing suspicious or enlarged on visual examination. In total, 471 (97%) of 485 lymph nodes were identified with the green dye and 226 (47%) with the blue dye (difference 50%, 95% CI 39–62; p Interpretation Indocyanine green dye with near-infrared fluorescence imaging identified more sentinel nodes than isosulfan blue dye in women with cervical and uterine cancers, with no difference in the pathological confirmation of nodal tissue between the two mapping substances. Funding Novadaq.

ObjectiveMucinous 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.MethodsWe 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.ResultsOf 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.ConclusionsIn 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.

Objectives: Recommendation for referral of patients with upper Mullerian tract High Grade Serous Carcinoma (HGSC) for genetic counseling and germline BRCA1/2 mutation testing has existed for over a decade. In Nov 2018, tumor (somatic) BRCA1/2 mutation testing became provincially funded in Ontario, Canada, based on the approval of Poly (ADP-ribose) polymerase inhibitor (PARPi) therapy (Olaparib) as maintenance therapy in newly diagnosed and recurrent platinum sensitive HGSC patients with BRCA1/2 germline and somatic mutations. This is a summary of a single cancer center's institutional experience with the clinical rollout of this process. Methods: 252 patients undergoing surgery for HGSC at our centre between Nov 2018 - Oct 2020 underwent tumor tissue, germline or combined BRCA1/2 mutation testing at external provincially accredited molecular laboratories in the greater Toronto area. We performed comprehensive chart reviews with emphasis on 1) utilization of tumor and/or germline test ordering 2) tumor tissue test report structure and recommendations 3) laboratory handling of failed tumor tissue tests. Results: The results are summarized in Figure 1. Tumor tissue testing only was performed at Labs A and B, germline and tumor tissue testing at Lab C, and germline testing only at Lab D. 234 (93 %) cases underwent tumor tissue BRCA1/2 mutation testing, either in conjunction with germline testing (140, 56 %), or alone (94, 37%). 18 (7%) HGSC patients were assessed only for BRCA1/2 germline mutations. Tumor tissue testing was ordered by gynecologic oncologists from Nov 2018 to April 2020 and by pathologists from May 2020 to October 2020. From Nov 2018 – Aug 2019 services of Labs B and C were used for tumor tissue testing. Workflow readjustments occurred in Sept 2019, and services of Lab A were henceforth predominantly engaged. Germline variants were reported according to the ACMG guidelines 2015/2017. For reporting of somatic variants, Lab A used the AMP/ASCO/CAP guidelines, whereas Labs B and C used ACMG 2015/2017 guidelines. Statements about eligibility for PARPi were reported by Labs A and B, and not by Lab C or Lab D. Overall, testing fail rate was approximately 6 % (14 out of 252 samples) with insufficient material in 4 samples and poor DNA quality in 10 samples. Tumor tissue testing on alternative tumor samples was suggested by Labs A and C, and no recommendations were made by Lab B. Download : Download high-res image (161KB) Download : Download full-size image Conclusions: There was a high order rate (over 90 %) of the newly available BRCA1/2 mutation tumor testing at our institution in the initial rollout period. However, among the three external laboratories that carried out the testing, there was non-uniformity of utilization for reporting guidelines of somatic mutations, recommendations for PARPi administration and suggestions for management of failed tests. Our institutional experience underscores the need for establishing provincial and national guidelines with respect to tumor tissue BRCA1/2 mutation testing in accredited laboratories.

Objectives: Mucinous ovarian carcinoma (MOC) is the most common histology in young women eligible for fertility-sparing surgery. The aim of the study was to evaluate the safety and reproductive outcomes after fertility-sparing surgery in invasive mucinous ovarian carcinomas. Methods: A retrospective review was performed of all MOCs diagnosed between 1999 and 2019 at two tertiary care cancer centers. Pathology was reviewed to rule out cases with metastasis from gastrointestinal tract primary. 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). Five-year overall survival (OS) and recurrence free survival (RFS) were calculated from Kaplan-Meier curves and comparisons made using log-rank test. Cox proportional hazard models were constructed to evaluate the effect of fertility sparing surgery on survival. Results: Of 149 women with apparent stage I disease upon presentation, 43 (29%) underwent fertility-sparing surgery in the form of unilateral salpingo-oophorectomy±omentectomy and lymphadenectomy. Compared to women who underwent radical surgery, these women were younger (30 years vs 55 years; p Conclusions: Fertility-sparing surgery in apparent stage I MOC is not associated with worse survival outcomes; however, it is important that candidates are carefully selected based on pathologic factors. In those with aggressive histologic components, radical surgery should be considered.

IntroductionAs 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.MethodsWe 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.ResultsNineteen 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).ConclusionGiven 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.

Objectives Patients with gynecologic malignancies have high rates of postoperative venous thromboembolism. Currently, there is no consensus for perioperative thromboprophylaxis. The Gynecologic Oncology division at Sunnybrook Health Sciences Centre in Toronto, Canada, implemented a dual thromboprophylaxis strategy for laparotomies in 12/2017. We aimed to compare rates of pulmonary embolus(PE) within 30 days postoperatively, and to identify risk factors for PE. Methods Prospective study of laparotomies for gynecologic malignancies from 12/2017–10/2018, with comparison to historical cohort from 01/2016–11/2017 using the institutional National Surgical Quality Improvement Program database(NSQIP). Preintervention, patients received low molecular weight heparin(LMWH) during admission and those deemed high-risk continued 30-day prophylaxis. Postintervention, all patients received both mechanical thromboprophylaxis with sequential compression devices during admission and 30-day prophylaxis with LMWH. Results There were 371 and 163 laparotomies pre-and post-intervention. After implementation, PE rates decreased from 5.1% to 0% (p=0.001). PEs were diagnosed by CT scan prompted by symptoms, at a median of 2 days postoperatively. Patient characteristics (age, BMI, diabetes, smoking, tumor stage), rate of malignant cases, operative blood loss and duration, and length of stay(LOS) were similar between groups. There were more cytoreductive procedures preintervention (p ≤0.0001). Univariate analysis revealed that surgery preintervention (OR:4.25, 95%CI 1.04–17.43, p=0.04), LOS≥5 days (OR:11.94, 95%CI 2.65–53.92, p=0.002), and operative blood loss ≥500mL (OR:2.85, 95%CI 1.05–7.8, p=0.04) increased risk of PE. On multivariable analysis, surgery preintervention remained associated with more PEs(OR:4.16, 95%CI 1.03–16.79, p=0.05), when adjusting for operative blood loss. Conclusions Aggressive dual thromboprophylaxis after laparotomy appears to significantly reduce PE in this high-risk patient population.

Objectives: Practice guidelines advocating for the regionalization of endometrial cancer surgery to gynecologic oncologists practicing in designated gynecologic oncology centres were released by Cancer Care Ontario in June 2013. We sought to determine the impact this policy had on contemporary surgical wait times. Moreover, a discussion about the impact of delays in treatment has never been more timely than in the context of the current COVID19 pandemic, which has burdened health care systems around the world. Our primary objective was to establish whether longer wait time to surgery is a predictor of survival in patients with high grade endometrial cancer. Methods: This was a retrospective cohort study, which included patients diagnosed with non-endometrioid high-grade endometrial cancer (serous, carcinosarcoma, clear cell, and undifferentiated) between 2003 and 2017. A total of 2 regionalization periods were defined, before and after January 2014 to allow 6 months for knowledge translation after guideline publication. Patients were identified in population-based administrative provincial data sources. Multivariable Cox proportional hazards regression with a spline function was used to model the relationship between wait time and overall survival, as measured from time of surgery. Results: We identified 3518 patients with high grade endometrial cancer. Median wait time between diagnosis and surgery for the entire cohort did not significantly change with regionalization of care (50 vs 52 days, p=0.14). Patients who had surgery with a gynecologic oncologist had a median surgical wait time from diagnosis to hysterectomy of 55 days compared to 59 days pre-regionalization (p=0.0002), and from first gynecologic oncology consultation to hysterectomy of 29 days compared to 32 days pre-regionalization (p=0.0006). Survival was worst for patients who had surgery within 14 days of diagnosis (HR death 2.7, 95% CI 1.61-4.51 for 1-7 days and HR death 1.96, 95% CI 1.5-2.57 for 8-14 days), indicating 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, 95% CI 1.04-1.36 for 46-60 days and HR death 1.42, 95% CI 1.11-1.82). Download : Download high-res image (109KB) Download : Download full-size image Conclusions: Regionalization of surgery for high grade endometrial cancer has not had a negative impact on surgical wait times. Impact on survival is seen with patients who have surgery more than 45 days after surgical consultation.

Objectives: Timely treatment of primary epithelial ovarian cancer (EOC) by gynecologic oncologists (GOs) with a combination of surgery and/or platinum/taxane-based chemotherapy at expert centers has been advocated. Nonetheless, some patients have their oncologic surgery by non-GOs or are not assessed by GOs prior to starting their initial cancer treatment. The aim of the study was to evaluate the impact of care by gynecologic oncologists on the survival of primary non-mucinous EOC in Ontario. Methods: In this population-based retrospective cohort study, patients diagnosed with non-mucinous EOC between 2007-2018 were identified using province-wide administrative databases. Assessment by GOs was defined as any consultation 6 months prior to diagnosis date and up to first treatment (surgery or chemotherapy). Type of surgeon performing surgeries related to ovarian cancer were identified (general gynecologists, general surgeons, or GOs). Multivariate cox proportional hazards regression models were used to evaluate the impact of GO consultations prior to initiating treatment or having surgery done by a GO on the survival of ovarian cancer. Age, socioeconomic status (SES), year of diagnosis, comorbidity score and days from diagnosis to surgery were covariates in the models. FIGO stage was available in 70% of our cohort. Sensitivity analysis was performed adjusting for stage and the other covariates. Results: A total of 10,086 EOC patients were included between 2007-2018 with a median age of 63 years (range 53-72). Primary treatment included surgery alone in 26% of patients (2,593/10,086), while 63% (6,397/10,086) had neoadjuvant chemotherapy and/or adjuvant chemotherapy and 11% (1,096/10,086) had chemotherapy alone. A total of 8,990 ovarian cancer patients underwent surgery as part of their primary treatment. During the study period, there was an increase in GO consultations (79% in 2007 to 87% in 2018-19) and surgeries performed by GOs (69% in 2007 to 88% in 2018-19). On multivariate analysis, there was an increase in all-cause mortality for patients not assessed by GOs before first treatment (Hazard ratio (HR): 2.18; 95% CI 1.98-2.41). There was also an increase in all-cause mortality if ovarian cancer surgery was performed by non-GOs (HR 2.37; 95% CI 2.11- 2.67) after adjusting for age, SES, year of diagnosis, comorbidity score and days from diagnosis to surgery. In a sensitivity analysis where FIGO stage was added to the models, there remained a significant increase in all-cause mortality for patients not assessed by GOs before first treatment (HR 1.44; 95% CI 1.26-1.66) and an increase in all-cause mortality if ovarian cancer surgery was performed by non-GOs (HR 2.23; 95% CI 1.88-2.65). Conclusions: Assessment by GO before starting initial treatment (chemotherapy or surgery) was associated with improved survival in women with non-mucinous EOC. Type of surgeons performing primary ovarian cancer surgery had a significant impact on survival.

TPS5601 Background: Low-grade serous carcinoma of the ovary or peritoneum (LGSOC) is a rare subtype of epithelial carcinoma. Differences in epidemiology, pathogenesis, disease presentation, and clinical outcomes have been characterized between women diagnosed with LGSOC and those with the p53-driven high-grade serous carcinoma (HGSOC). Ultimately, patients with LGSOC should be treated differently than those with HGSOC. Several studies suggest that LGSOC is relatively chemoresistant and that most tumors robustly express estrogen and progesterone receptors. Recently, retrospective reports suggest that utilization of the aromatase inhibitor, letrozole, as monotherapy or in addition to platinum/taxane-based chemotherapy in those with primary advanced-stage LGSOC results in preliminarily promising survival outcomes. Methods: This study is a two-arm, randomized, open-label, Phase III clinical trial. The primary objective is to assess whether letrozole monotherapy (2.5 mg po daily) is non-inferior to carboplatin (AUC 5-6) and paclitaxel (175 mg/m2) followed by letrozole maintenance therapy with respect to progression free survival in women with primary, Stage II-IV LGSOC who have undergone an attempt at maximal surgical cytoreduction. Secondary endpoints include incidence of adverse events, objective response rate in those with measurable disease after surgery, response duration, overall survival, and adherence to letrozole maintenance therapy. Study subjects must have undergone a bilateral salpingo-oophorectomy, and p53 IHC testing of tumors is required to rule out those with aberrant p53 expression commonly observed in HGSOC tumors. Study strata include residual disease status and country of enrollment. Four hundred and fifty patients will be enrolled in the United States, Canada and South Korea through the NRG Oncology trials network. Correlative aims include analyzing the association of ER/PR tumoral expression with aromatase inhibitor therapy response and determining ESR1 mutational status in those who develop letrozole resistance. The study includes two interim analyses; at 20% information time, a futility analysis will be conducted, and at 40% information time, both efficacy and futility will be assessed. This is one of the first randomized trials performed in women with primary, advanced LGSOC, and the study is open with 71 patients enrolled at the time of abstract submission. Clinical trial information: NCT04095364.