Shifting incidence and survival of epithelial ovarian cancer (1995-2014): A SurvMark-2 study.

The aim of the study is to provide a comprehensive assessment of incidence and survival trends of epithelial ovarian cancer (EOC) by histological subtype across seven high income countries (Australia, Canada, Denmark, Ireland, New Zealand, Norway and the United Kingdom). Data on invasive EOC diagnosed in women aged 15 to 99 years during 1995 to 2014 were obtained from 20 cancer registries. Age standardized incidence rates and average annual percentage change were calculated by subtype for all ages and age groups (15-64 and 65-99 years). Net survival (NS) was estimated by subtype, age group and 5-year period using Pohar-Perme estimator. Our findings showed marked increase in serous carcinoma incidence was observed between 1995 and 2014 among women aged 65 to 99 years with average annual increase ranging between 2.2% and 5.8%. We documented a marked decrease in the incidence of adenocarcinoma "not otherwise specified" with estimates ranging between 4.4% and 7.4% in women aged 15 to 64 years and between 2.0% and 3.7% among the older age group. Improved survival, combining all EOC subtypes, was observed for all ages combined over the 20-year study period in all countries with 5-year NS absolute percent change ranging between 5.0 in Canada and 12.6 in Denmark. Several factors such as changes in guidelines and advancement in diagnostic tools may potentially influence the observed shift in histological subtypes and temporal trends. Progress in clinical management and treatment over the past decades potentially plays a role in the observed improvements in EOC survival.

A comparison of synoptic reports and dictated reports to enhance and standardize surgical documentation and quality of care in epithelial ovarian cancer.

OBJECTIVE: The purpose of this study is to assess the degree to which synoptic reports (SRs) and dictated reports (DRs) document elements of the Ovarian Cancer Pan-Canadian Standards Data Elements (OCPCDE) checklist, and to compare their completeness. Analysis of dictated versus synoptic reporting has never been performed for suspected epithelial ovarian cancer (EOC) based on literature review at the time of data collection (1-12). METHODS: A retrospective chart review was performed including 254 charts of women 18 years or older, from 2012 to 2017, undergoing surgery for suspected EOC. Charts from five gynecologic oncologists, at a single tertiary care centre were used. The OCPCDE checklist was used to evaluate their completeness. Comparison of completeness between SRs and DRs was done using linear regression with a fixed effect of surgeon to account for intraclass correlation. RESULTS: The data showed that SRs included 20.1% more data elements than DRs. Data elements that may be perceived as being more critical were more likely to be documented in SRs. Residual disease data was documented in 51.7% DR versus 99.1% of SR. Descriptive data upon entering the abdomen was more frequently documented in DRs. CONCLUSION: This study shows that synoptic reporting includes more data elements deemed important by the OCPCDE checklist authors for suspected epithelial ovarian cancer surgery in our centre. We would recommend continuation of SRs in our department, and implementation of synoptic reporting in other gynecologic oncology centres where surgery for suspected epithelial ovarian cancer is performed.

Exploring the role of a multidisciplinary hereditary gynecologic oncology clinic in epithelial ovarian cancer risk-reducing surgical decision-making practices: A mixed-methods study.

Individuals that have gynecologic reproductive organs with pathogenic variants in BRCA1 or BRCA2 ("BRCA-positive") have an increased risk of developing high-grade serous ovarian cancer (HGSOC). The majority of HGSOC develops in the fallopian tubes and later spreads to the ovaries and peritoneal cavity. Therefore, risk-reducing salpingo-oophorectomy (RRSO) is recommended for those who are BRCA-positive to preventatively remove their ovaries and fallopian tubes. The Hereditary Gynecology Clinic (HGC) is a provincial program in Winnipeg, Canada, that specifically targets care to the unique needs of such individuals through an interdisciplinary team of gynecological oncologists, menopause specialists, and registered nurses. A mixed-methods study design was used to explore the decision-making processes of these BRCA-positive individuals who have been recommended (or who completed) RRSO and experiences with healthcare providers at the HGC influenced this decision. Individuals who are BRCA-positive without a previous diagnosis of HGSOC and who had previously received genetic counselling were recruited from the HGC and the provincial cancer genetics program (Shared Health Program of Genetics & Metabolism). Forty-three people completed a survey and 15 participated in an in-depth interview about their experiences and decisions surrounding RRSO. Surveys were analyzed to compare scores on validated scales related to decision-making and cancer-related worry. Qualitative interviews were transcribed, coded, and analyzed using interpretive description. Participants described the complex decisions faced by those who are BRCA-positive, which are intertwined with life experiences and circumstances including age, marital status, and family disease history. Participants interpreted their HGSOC risk through a personalized "lens" of contextual factors that impacted perceptions about the practical and emotional implications of RRSO and the need for surgery. Mean scores on validated scales evaluating the HGC's impact on decisional outcomes and preparedness for decision-making about RRSO were not significant, indicating that the HGC played a supportive role, rather than helping with decision-making itself. Therefore, we present a novel framework that consolidates the various influences on decision-making and connects them to the psychological and practical implications of RRSO in the context of the HGC. Strategies for improving support, decisional outcomes, and the overall experiences of individuals who are BRCA-positive attending the HGC are also described.

Olaparib treatment for platinum-sensitive relapsed ovarian cancer by BRCA mutation and homologous recombination deficiency status: Phase II LIGHT study primary analysis.

OBJECTIVE: Olaparib treatment resulted in significant improvement in objective response rates (ORRs) and progression-free survival (PFS) over non­platinum chemotherapy in patients with BRCA1/BRCA2-mutated (BRCAm) platinum-sensitive relapsed ovarian cancer (PSROC) and ≥2 prior lines of platinum-based chemotherapy in the phase III SOLO3 study. LIGHT (NCT02983799) prospectively evaluated olaparib treatment for patients with PSROC and known BRCAm and homologous recombination deficiency (HRD) status. METHODS: In this phase II open-label multicenter study, patients with PSROC and ≥1 prior line of platinum-based chemotherapy were assigned to cohorts by presence of germline BRCAm (gBRCAm), somatic BRCAm (sBRCAm), HRD-positive tumors without BRCAm, or HRD-negative tumors. The primary endpoint was investigator-assessed ORR. Secondary endpoints included disease control rate (DCR) and PFS. Tumors were analyzed using Myriad BRACAnalysis CDx and myChoice HRD assays; HRD-positive tumors were defined using a genomic instability score of ≥42. RESULTS: Of 272 enrolled patients, 271 received olaparib and 270 were included in efficacy analyses. At data cut-off, ORRs in the gBRCAm, sBRCAm, HRD-positive, and HRD-negative cohorts were 69.3%, 64.0%, 29.4%, and 10.1%, respectively. DCRs were 96.0%, 100.0%, 79.4%, and 75.3% in each cohort, respectively. Median PFS was 11.0, 10.8, 7.2, and 5.4 months, respectively. The most common (≥ 20%) treatment-emergent adverse events included nausea, fatigue/asthenia, vomiting, anemia, constipation, diarrhea, and decreased appetite. CONCLUSIONS: Olaparib treatment demonstrated activity across all cohorts. The greatest efficacy was observed in the BRCAm cohorts, regardless of gBRCAm/sBRCAm. For patients without a BRCAm, greater efficacy was observed in the HRD-positive than the HRD-negative cohorts. The safety profile was consistent with that established in previous olaparib studies.

A population-based study of outcomes in adjuvant radiotherapy for stage II endometrial carcinoma.

OBJECTIVE: Our study aimed to analyze recurrence and survival outcomes in stage II endometrial cancer patients treated with adjuvant radiotherapy at CancerCare Manitoba, a Canadian provincial cancer program. METHODS: This retrospective population-based cohort study identified all International Federation of Gynecology and Obstetrics (FIGO) 2009 stage II endometrioid type endometrial carcinoma diagnosed between January 1995 and December 2019. All patients underwent surgery followed by vaginal vault brachytherapy alone or external beam pelvic radiotherapy plus vaginal vault brachytherapy. We used Kaplan-Meier curves to describe overall survival and recurrence-free survival, and cumulative incidence to describe recurrence. Cox regression was used to predict overall survival and recurrence-free survival competing risk regression to predict recurrence. RESULTS: A total of 121 patients were included (78 vaginal brachytherapy alone and 43 external beam pelvic radiotherapy plus vaginal brachytherapy) with a median age of 62 (range 24-85). The median follow-up was 55.2 months (range 7.1-147.9) in the vaginal brachytherapy group and 41.9 months (range 7.4-127.0) in the pelvic radiotherapy group. Lymph node dissection was performed in 79 (65.3%) patients. There were 14 (17.9%) recurrences (8 vaginal vault, 3 pelvic, 3 distant) with vaginal brachytherapy and 7 (16.3%) recurrences (3 vaginal vault, 2 pelvic, 2 distant) with external beam pelvic radiotherapy. The 5 year overall survival was 73.1% with vaginal vault brachytherapy vs 73.7% with external beam pelvic radiotherapy plus vaginal brachytherapy (p=0.31), the 5 year recurrence-free survival was 65.0% vs 68.2% (p=0.61), and the 5 year recurrence risk was 20.3% vs 19.4% (p=0.94). On univariable and multivariable analysis, only age was a statistically significant predictor for overall survival and recurrence-free survival (p<0.05), but not lymphovascular space invasion (HR, 2.97; 95% CI, 0.99 to 8.93 for overall survival, p=0.15). The type of adjuvant radiotherapy did not predict for recurrence (p=0.94). CONCLUSIONS: There was no significant difference in overall survival, recurrence-free survival, and recurrence risk between vaginal vault brachytherapy vs external beam pelvic radiotherapy plus vaginal vault brachytherapy in patients with stage II endometrial cancer.

The Canadian Gynecologic Oncology Peri-operative Management Survey: re-examining Enhanced Recovery After Surgery (ERAS) recommendations.

OBJECTIVE: Enhanced Recovery After Surgery (ERAS) is a global surgery quality improvement program associated with improved clinical outcomes across the spectrum of disciplines, including gynecologic oncology. The objective of this study was to re-survey the practice of ERAS Gynecologic Oncology guidelines across Canada, after the initial guidelines publication (2016), subsequent guidelines update (2019), and Society of Gynecologic Oncology of Canada (GOC) education events. METHODS: A survey was created and developed through the GOC Communities of Practice ERAS section and distributed to all members between March and November 2021. The results of this survey were compared with the survey performed in 2015 RESULTS: The initial GOC survey in 2015 included 77/92 active gynecologic oncologists (84%) representing all provinces in Canada. The current updated survey had responses from 59/118 active gynecologic oncologists (51%) also from every province. Compared with the original survey there was a statistically significant improvement in uptake of 10 ERAS recommendations: smoking/alcohol cessation, modern fasting guidelines (allowance of clear fluids and solid food pre-operatively), carbohydrate loading, pre-operative warming, early feeding, post-operative laxative use, avoidance of nasogastric tubes and abdominal drains, foley catheter removal at 6 hours, and active mobilization (all p<0.003). Only two fields (stopping oral contraceptive medications pre-operatively and foley catheter removal post-operative day 1) showed worsening uptake across the two surveys (p<0.01). The ERAS recommendations that did not change in the examined time frame included routine use of mechanical bowel preparation, venous thromboembolism prophylaxis, pre-operative antibiotics, and additional antibiotic dosing for prolonged surgery. CONCLUSIONS: This survey demonstrates increased uptake of 10 of the ERAS guideline recommendations among Canadian gynecologic oncology providers. These findings may translate to improvements in clinical outcomes and healthcare system-level benefits including increased hospital capacity and cost savings.

Canadian Enhanced Recovery After Surgery (ERAS) Cesarean Delivery Perioperative Management Survey.

Enhanced Recovery After Surgery (ERAS) is a global surgical quality improvement initiative that has spread across numerous surgical disciplines. The uptake of ERAS in cesarean delivery in Canada is presently unknown. This study surveyed the current practices of Society of Obstetricians and Gynaecologists of Canada (SOGC) members with regards to ERAS guidelines for preoperative, intraoperative, and postoperative cesarean delivery care. Survey responses highlight perioperative practice variations across Canada. Active implementation of ERAS cesarean delivery guidelines could potentially lessen variations in perioperative care, improve patient outcomes, and minimize health care costs.

Perioperative Incidence of Venous Thromboembolism in Patients With Ovarian Cancer Using Four Different Data Collection Methods: A Manitoba Ovarian Cancer Outcomes (MOCO) Group Study.

OBJECTIVE: To evaluate the incidence of venous thromboembolism (VTE) in 90-day pre-operative period and at 30 and 90 days post surgery in patients who underwent debulking for ovarian cancer, analyze the impact of extended prophylaxis that was initiated in 2012, and examine the influence of data collection technique on reported rates of VTE. METHODS: This retrospective database and records study examined rates of VTE in epithelial ovarian cancer patients in Manitoba, Canada between 2004 and 2016. Cases of VTE were identified using ICD codes, drug prescriptions, and records reviews; 4 different data collection methods were used. Analysis was performed with analysis of variance, Kruskal-Wallis and χ2 tests, and interrupted time series models. RESULTS: Data collection identified 823 debulking surgeries, with a final cohort of 779 patients; data were analyzed before and after extended prophylaxis intervention. Overall rates of VTE varied by collection method and were 1.82%-5.47%, 0.36%-3.16%, 0.85%-1.46%, and 1.46%-2.79%, respectively. During this timeframe, we noted a significant increase in the use of neoadjuvant chemotherapy (P = 0.010) and stage migration to stage 3 (P < 0.001). CONCLUSION: We report the rates of VTE utilizing 4 different data collection methods. We found a low overall rate, with some trends requiring further investigation. This study highlights the importance of data collection method on the reported rates of VTE in research.

Chromosome instability is prevalent and dynamic in high-grade serous ovarian cancer patient samples.

OBJECTIVE: High-grade serous ovarian cancer (HGSOC) is the most lethal gynaecological malignancy in women with a high level of mortality, metastatic disease, disease recurrence and multi-drug resistance. Many previous studies have focused on characterising genome instability in recurrent resistant HGSOC and while this has advanced our understanding of HGSOC, our fundamental knowledge of the mechanisms driving genome instability remains limited. Chromosome instability (CIN; an increased rate of chromosome gains and losses) is a form of genome instability that is commonly associated with recurrence and multi-drug resistance in many cancer types but has just begun to be characterised in HGSOC. METHOD: To examine the relationship between CIN and HGSOC, we employed single-cell quantitative imaging microscopy approaches capable of capturing the cell-to-cell heterogeneity associated with CIN, to assess the prevalence and dynamics of CIN within individual and patient-matched HGSOC ascites and solid tumour samples. RESULTS: CIN occurs in 90.9% of ascites samples and 100% of solid tumours, while in-depth analyses identified statistically significant temporal dynamics within the serial ascites samples. In general, aneuploidy and CIN increase with disease progression and frequently decrease following chemotherapy treatments in responsive disease. Finally, our work identified higher levels of CIN in solid tumours relative to ascites samples isolated from the same individual, which identifies a novel difference existing between solid tumours and ascites samples. CONCLUSIONS: Our findings provide novel insight into the relationship between CIN and HGSOC, and uncover a previously unknown relationship existing between CIN in solid tumours and metastatic disease (ascites).

The Risk of Postoperative Infectious Complications Following Massive Intraoperative Blood Loss During Gynaecologic Laparotomy: Retrospective Cohort Study.

PURPOSE: To determine whether massive intraoperative blood loss (MIBL) was independently associated with postoperative infectious complications after gynaecologic laparotomy. METHODS: We conducted a retrospective cohort study of patients undergoing gynaecologic laparotomy who were exposed or not exposed to MIBL. The outcome of interest was composite postoperative febrile morbidity. Multiple logistic regression was used to determine the association between exposure and outcome while controlling for measured covariates. RESULTS: The primary outcome was identified to have occurred in 48% (144 of 298) of surgeries with MIBL compared with 12% (51 of 413) of surgeries without MIBL (P < 0.0001). MIBL was found to be strongly and independently associated with primary outcome (adjusted odds ratio 7.04; 95% confidence interval 4.62-10.74; P < 0.0001) after adjusting for age, body mass index, diabetes, immunosuppression, type of procedure, incision type, drains left in situ, and bowel complications. CONCLUSION: MIBL is strongly and independently associated with postoperative febrile morbidity after gynaecologic laparotomy.

Exploring variations in ovarian cancer survival by age and stage (ICBP SurvMark-2): A population-based study.

OBJECTIVE: The study aims to evaluate the differences in ovarian cancer survival by age and stage at diagnosis within and across seven high-income countries. METHODS: We analyzed data from 58,161 women diagnosed with ovarian cancer during 2010-2014, followed until 31 December 2015, from 21 population-based cancer registries in Australia, Canada, Denmark, Ireland, New Zealand, Norway, and United Kingdom. Comparisons of 1-year and 3-year age- and stage-specific net survival (NS) between countries were performed using the period analysis approach. RESULTS: Minor variation in the stage distribution was observed between countries, with most women being diagnosed with 'distant' stage (ranging between 64% in Canada and 71% in Norway). The 3-year all-ages NS ranged from 45 to 57% with Australia (56%) and Norway (57%) demonstrating the highest survival. The proportion of women with 'distant' stage was highest for those aged 65-74 and 75-99 years and varied markedly between countries (range:72-80% and 77-87%, respectively). The oldest age group had the lowest 3-year age-specific survival (20-34%), and women aged 65-74 exhibited the widest variation across countries (3-year NS range: 40-60%). Differences in survival between countries were particularly stark for the oldest age group with 'distant' stage (3-year NS range: 12% in Ireland to 24% in Norway). CONCLUSIONS: International variations in ovarian cancer survival by stage exist with the largest differences observed in the oldest age group with advanced disease. This finding endorses further research investigating international differences in access to and quality of treatment, and prevalence of comorbid conditions particularly in older women with advanced disease.

Guidelines for vulvar and vaginal surgery: Enhanced Recovery After Surgery Society recommendations.

This is the first collaborative Enhanced Recovery After Surgery Society guideline for optimal perioperative care for vulvar and vaginal surgeries. An Embase and PubMed database search of publications was performed. Studies on each topic within the Enhanced Recovery After Surgery vulvar and vaginal outline were selected, with emphasis on meta-analyses, randomized controlled trials, and prospective cohort studies. All studies were reviewed and graded according to the Grading of Recommendations, Assessment, Development and Evaluation system. All recommendations on the Enhanced Recovery After Surgery topics are based on the best available evidence. The level of evidence for each item is presented.

Response to Multi-Line Chemotherapy in Non-Serous Epithelial Ovarian Cancer.

OBJECTIVES: To describe the response rate to chemotherapy, rates of recurrence, and overall survival in patients with non-serous epithelial ovarian cancers. METHODS: This retrospective cohort study used the Manitoba Cancer Registry to identify all women with non-serous epithelial ovarian, fallopian, or peritoneal cancer treated between 1995 and 2010. Chart review entailed extracting information regarding therapy and outcomes. All patients with recurrence were identified and response to chemotherapy was assessed. RESULTS: We identified 392 patients with non-serous ovarian cancers, 192 of whom received chemotherapy in the first-line setting. Optimal debulking resulted in improvements in rates of recurrence and overall survival (P < 0.001). Histology did not have an effect on recurrence or overall survival. Forty-eight patients (25%) had a recurrence and received second-line therapy, and 21 (11%) received third-line therapy. Response rates were similar regardless of histology. In the second-line setting, 40.9%-83.3% of patients (other > mucinous > clear cell > endometrioid) and in the third-line setting, 33.3%-75.0% of patients (other > mucinous > clear cell > endometrioid) received >6 lines of chemotherapy. Twenty-three percent of patients experienced a recurrence within 2 years of first-line therapy. Two-year survival was 79.4% after first-line treatment, 27.6% after second-line treatment, and 19.5% after third-line treatment. CONCLUSION: Patients with clear cell ovarian cancer had chemotherapy continuation rates similar to those of previously reported studies. This is one of the first studies reporting response rates for mucinous and endometrioid subtypes. Recurrent disease responds to treatment with second- and third-line therapy, emphasizing the importance of offering patients subsequent lines of chemotherapy for disease management. Further studies are needed to determine the optimal regimen.

The temporal dynamics of chromosome instability in ovarian cancer cell lines and primary patient samples.

Epithelial ovarian cancer (EOC) is the most prevalent form of ovarian cancer and has the highest mortality rate. Novel insight into EOC is required to minimize the morbidity and mortality rates caused by recurrent, drug resistant disease. Although numerous studies have evaluated genome instability in EOC, none have addressed the putative role chromosome instability (CIN) has in disease progression and drug resistance. CIN is defined as an increase in the rate at which whole chromosomes or large parts thereof are gained or lost, and can only be evaluated using approaches capable of characterizing genetic or chromosomal heterogeneity within populations of cells. Although CIN is associated with numerous cancer types, its prevalence and dynamics in EOC is unknown. In this study, we assessed CIN within serial samples collected from the ascites of five EOC patients, and in two well-established ovarian cancer cell models of drug resistance (PEO1/4 and A2780s/cp). We quantified and compared CIN (as measured by nuclear areas and CIN Score (CS) values) within and between serial samples to glean insight into the association and dynamics of CIN within EOC, with a particular focus on resistant and recurrent disease. Using quantitative, single cell analyses we determined that CIN is associated with every sample evaluated and further show that many EOC samples exhibit a large degree of nuclear size and CS value heterogeneity. We also show that CIN is dynamic and generally increases within resistant disease. Finally, we show that both drug resistance models (PEO1/4 and A2780s/cp) exhibit heterogeneity, albeit to a much lesser extent. Surprisingly, the two cell line models exhibit remarkably similar levels of CIN, as the nuclear areas and CS values are largely overlapping between the corresponding paired lines. Accordingly, these data suggest CIN may represent a novel biomarker capable of monitoring changes in EOC progression associated with drug resistance.

International validation of Enhanced Recovery After Surgery Society guidelines on enhanced recovery for gynecologic surgery.

BACKGROUND: Enhanced Recovery After Surgery Society publishes guidelines on perioperative care, but these guidelines should be validated prospectively. OBJECTIVE: To evaluate the association between compliance with Enhanced Recovery After Surgery Gynecologic/Oncology guideline elements and postoperative outcomes in an international cohort. STUDY DESIGN: The study comprised 2101 patients undergoing elective gynecologic/oncology surgery between January 2011 and November 2017 in 10 hospitals across Canada, the United States, and Europe. Patient demographics, surgical/anesthesia details, and Enhanced Recovery After Surgery protocol compliance elements (pre-, intra-, and postoperative phases) were entered into the Enhanced Recovery After Surgery Interactive Audit System. Surgical complexity was stratified according to the Aletti scoring system (low vs medium/high). The following covariates were accounted for in the analysis: age, body mass index, smoking status, presence of diabetes, American Society of Anesthesiologists class, International Federation of Gynecology and Obstetrics stage, preoperative chemotherapy, radiotherapy, operating time, surgical approach (open vs minimally invasive), intraoperative blood loss, hospital, and Enhanced Recovery After Surgery implementation status. The primary end points were primary hospital length of stay and complications. Negative binomial regression was used to model length of stay, and logistic regression to model complications, as a function of compliance score and covariates. RESULTS: Patient demographics included a median age 56 years, 35.5% obese, 15% smokers, and 26.7% American Society of Anesthesiologists Class III-IV. Final diagnosis was malignant in 49% of patients. Laparotomy was used in 75.9% of cases, and the remainder minimally invasive surgery. The majority of cases (86%) were of low complexity (Aletti score ≤3). In patients with ovarian cancer, 69.5% had a medium/high complexity surgery (Aletti score 4-11). Median length of stay was 2 days in the low- and 5 days in the medium/high-complexity group. Every unit increase in Enhanced Recovery After Surgery guideline score was associated with 8% (IRR, 0.92; 95% confidence interval, 0.90-0.95; P<.001) decrease in days in hospital among low-complexity, and 12% (IRR, 0.88; 95% confidence interval, 0.82-0.93; P<.001) decrease among patients with medium/high-complexity scores. For every unit increase in Enhanced Recovery After Surgery guideline score, the odds of total complications were estimated to be 12% lower (P<.05) among low-complexity patients. CONCLUSION: Audit of surgical practices demonstrates that improved compliance with Enhanced Recovery After Surgery Gynecologic/Oncology guidelines is associated with an improvement in clinical outcomes, including length of stay, highlighting the importance of Enhanced Recovery After Surgery implementation.

Evolution of genetic assessment for BRCA-associated gynaecologic malignancies: a Canadian multisociety roadmap.

The landscape of genetic testing in ovarian cancer patients has changed dramatically in recent years. The therapeutic benefits of poly ADP-ribose polymerase (PARP) inhibitors in treatment of BRCA1/2-related ovarian cancers has resulted in an increased demand and urgency for genetic testing results, while technological developments have led to widespread use of multi-gene cancer panels and development of tumour testing protocols. Traditional genetic counselling models are no longer sustainable and must evolve to match the rapid evolution of genetic testing technologies and developments in personalized medicine. Recently, representatives from oncology, clinical genetics, molecular genetics, pathology, and patient advocacy came together to create a national multi-disciplinary Canadian consortium. By aligning stakeholder interests, the BRCA Testing to Treatment (BRCA TtoT) Community of Practice aims to develop a national strategy for tumour and germline BRCA1/2 testing and genetic counselling in women with ovarian cancer. This article serves to provide an overview of the recent evolution of genetic assessment for BRCA1/2-associated gynecologic malignancies and outline a Canadian roadmap to facilitate change, improve genetic testing rates, and ultimately improve outcomes for hereditary ovarian cancer patients and their families.

Uterine Inversion as a Result of a Large Prolapsed Carcinosarcoma of the Uterus.

BACKGROUND: Uterine inversion is most commonly seen in labour and delivery. However, it can be associated with uterine tumours, including gynaecologic malignancy. CASE: In a 66-year-old woman, uterine inversion identified at laparotomy that was found to be associated with uterine carcinosarcoma (malignant mixed mesodermal tumour) represents an unusual presentation. Surgical approach necessitated a vertical hysterotomy to amputate and deliver the uterine tumour. CONCLUSION: Uterine inversion in gynaecologic oncology may be associated with sarcoma or malignant mixed mesodermal tumour. This can represent a diagnostic and surgical challenge and should be considered.

No. 385-Indications for Pelvic Examination.

OBJECTIVE: The primary objective of this document is to clarify the indications for pelvic examination. INTENDED USERS: Physicians, including gynaecologists, obstetricians, family physicians, and emergency physicians; nurses, including registered nurses and nurse practitioners; midwives, including midwives in clinical practice and midwifery trainees; medical trainees, including medical students, residents, and fellows; and all other health care providers who care for women. TARGET POPULATION: This publication provides evidence and expert-based recommendations for pelvic examination in adult women (18 years and older) both with and without gynaecologic symptoms. OUTCOMES: This publication clarifies indications for pelvic examination in the context of recently published national task force statements on the utility of pelvic examination. We aim to ensure that women who have clinical indications for examination receive proper clinical investigation with minimal delays to diagnosis of treatable disease. EVIDENCE: For this committee opinion, relevant studies were identified in PubMed and Medline using the following terms, either alone or in combination, with the search limited to English-language materials and human subjects and no publication date cut-off: pelvic examination, bimanual examination, speculum examination, rectovaginal examination, ovarian cancer screening, asymptomatic women, periodic health examination. The search was performed in May and June 2018. Relevant evidence was selected for inclusion in the following order: meta-analyses, systematic reviews, guidelines and national task force statements, randomized controlled trials, prospective cohort studies, observational studies, non-systematic reviews, case series, and reports. Additional articles were identified by cross-referencing the identified publications. A formal systematic review was not conducted for all topics discussed due to the paucity of evidence and number of different subtopics discussed. The total number of publications included in this review was 66. VALIDATION METHODS: The content and recommendations were drafted and agreed upon by the principal authors. The Boards of the Society of Gynecologic Oncology of Canada (GOC), the College of Family Physicians of Canada (CFPC), and the Society of Obstetricians and Gynaecologists of Canada (SOGC) approved the final draft for publication after review by their respective representative committees. The quality of evidence was rated using the criteria described in the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology framework (Tables 1 and 2). The Summary of Findings is available upon request. BENEFITS, HARMS, AND COSTS: This committee opinion should benefit all women with and without gynaecologic symptoms who present to gynaecologists and primary care practitioners. It will help guide practitioners in identifying indications for pelvic examination to reduce unnecessary examination with related potential harm while also increasing indicated examination to reduce delays in diagnosis of treatable gynaecologic conditions. GUIDELINE UPDATE: This SOGC Committee Opinion will be automatically reviewed 5 years after publication to determine if all or part of the committee opinion should be updated. However, this review may be performed earlier if new high-impact research is published in the interim. SUMMARY STATEMENTS: 1. National and international statements and guidelines on pelvic examination should not be interpreted to suggest that the pelvic examination is irrelevant or noncontributory to physical assessment or that the pelvic examination in symptomatic women should be omitted. 2. Pelvic examination may include visual inspection, speculum examination, bimanual examination, single digit examination, and/or rectovaginal examination depending on the indication for examination. 3. No study published to date has adequately evaluated any component of the pelvic examination as a screening method for any type of malignant gynaecologic disease, except for the speculum examination for cervical cancer cytology screening. As such, any universal recommendations for or against pelvic examinations for other indications can only be made based on expert opinion and low-quality evidence. 4. In asymptomatic women at average risk for cervical cancer, cervical cytology screening reduces both the incidence of, and mortality from, cervical cancer by detecting pre-invasive, treatable lesions. 5. In asymptomatic women at average risk of malignancy, a visual and bimanual examination at the time of obtaining cervical cytology samples may add value to this screening manoeuvre: Women might not raise certain gynaecologic concerns until the time of pelvic examination; the examination provides an opportunity for patient education and practitioner skill maintenance; and, although inadequately studied to date, there may be positive effects on ovarian and vulvar malignancy that require further investigation. These potential benefits should be weighed against potential harms like patient discomfort and false positives/negatives that may result in inappropriate reassurance or unnecessary investigations/interventions. RECOMMENDATIONS: Symptomatic Women. 1) Any woman with gynaecologic complaints including, but not limited to, vulvar complaints, vaginal discharge, abnormal premenopausal bleeding, postmenopausal bleeding, infertility, pelvic organ prolapse symptoms, urinary incontinence, new and unexplained gastrointestinal symptoms (abdominal pain, increased abdominal size/bloating, and difficulty eating/early satiety), pelvic pain, or dyspareunia should undergo appropriate components of the pelvic examination to identify benign or malignant disease (strong, low). 2) Health care providers may consider discussing the risks and benefits of performing a baseline pelvic examination including visual and bimanual examination prior to prescribing hormonal replacement therapy/menopausal hormonal treatment (weak, very low). Asymptomatic Women. 3) Health care practitioners should perform cervical cytology cancer screening in accordance with provincial/territorial guidelines (strong, strong). 4) There is insufficient evidence to guide recommendations on screening pelvic examination for noncervical gynaecologic malignancy or any benign gynaecologic disease in healthy, asymptomatic women with average risk of malignancy. However, health care practitioners may consider performing a screening pelvic examination including visual, speculum, and bimanual examinations in concert with cervical cytology sampling intervals as recommended by provincial/territorial guidelines. This practice may identify clinically important benign or malignant disease not recognized or reported by the patient (weak, very low). 5) In women over age 70 who no longer require screening with cervical cytology, health care practitioners should consider continuing periodic screening of asymptomatic women for vulvar disease with inspection of the vulva, perineum, and anus to identify benign or malignant disease unrecognized by this population. There is insufficient evidence to guide recommendations on frequency of this examination (weak, low). 6) Women with a personal history of gynaecologic malignancy, a genetic diagnosis that increases gynaecologic malignancy risk, or a history of in utero diethylstilbestrol exposure may benefit from more frequent screening pelvic examinations to identify early primary, recurrent, or metastatic malignancy in the absence of symptoms. Because there is inadequate evidence to define these screening intervals, they should be in accordance with provincial/territorial guidelines and expert opinion (weak, very low). 7. Non-invasive and self-collection screening options for chlamydia and gonorrhea are acceptable in asymptomatic women, but pelvic examination, including visual inspection, speculum examination, and bimanual examination, is required in the presence of symptoms to rule out pelvic inflammatory disease or tubo-ovarian abscess (strong, low). 8) No pelvic examination is required prior to prescription of hormonal contraception in a healthy woman with no gynaecologic symptoms (strong, low).

No 385 - Indications de l'examen pelvien.

OBJECTIF: L'objectif principal du présent document est de clarifier les indications de l'examen pelvien. UTILISATEURS CONCERNéS: Médecins, y compris les gynécologues, obstétriciens, médecins de famille, urgentologues; infirmières, y compris les infirmières autorisées et les infirmières praticiennes; sages-femmes, y compris les sages-femmes en pratique clinique et les apprenties sages-femmes et les apprentis en médecine, y compris les étudiants de médecine, résidents, stagiaires (fellows); et tous les autres fournisseurs de soins de santé qui prodiguent des soins aux femmes. POPULATION CIBLE: La présente publication fournit des données probantes et des recommandations fondées sur des avis d'experts sur l'examen pelvien chez les femmes adultes (18 ans et plus) avec et sans symptômes gynécologiques. ISSUES: La présente publication clarifie les indications de l'examen pelvien dans le contexte des déclarations de groupes d'étude nationaux récemment publiées sur l'utilité de l'examen pelvien. L'objectif est de veiller à ce que les femmes qui présentent des indications cliniques d'examen fassent rapidement l'objet d'une évaluation clinique adéquate pour diagnostiquer les maladies traitables. DONNéES PROBANTES: Pour la présente opinion de comité, les études pertinentes ont été repérées dans PubMed et Medline à l'aide des termes suivants, seuls ou combinés, et les recherches ont été limitées aux publications en anglais portant sur des humains sans date limite de publication : pelvic examination, bimanual examination, speculum examination, rectovaginal examination, ovarian cancer screening, asymptomatic women, periodic health examination. La recherche a été effectuée en mai et en juin 2018. Les données probantes pertinentes ont été retenues dans l'ordre suivant : méta-analyses, revues systématiques, lignes directrices et déclarations des groupes d'étude nationaux, essais cliniques randomisés, études de cohorte prospective, études observationnelles, revues non systématiques, études de série de cas et rapports. Des articles supplémentaires ont été repérés en consultant les notices bibliographiques des publications sélectionnées. Une revue systématique officielle n'a pas été menée pour tous les sujets discutés en raison du manque de données probantes et du nombre de différents sous-thèmes abordés. Le nombre total de publications examinées dans le cadre de cette revue était de 66. MéTHODES DE VALIDATION: Les auteurs principaux ont rédigé le contenu et les recommandations et ils se sont entendus sur ces derniers. Les conseils d'administration de la Society of Gynecologic Oncology of Canada (GOC), de Collège des médecins de famille du Canada (CMFC) et de la Société des obstétriciens et gynécologues du Canada (SOGC) ont approuvé la version définitive aux fins de publication après que leurs comités représentatifs respectifs l'aient passée en revue. La qualité des données probantes utilisées dans le présent document a été évaluée au moyen des critères du cadre méthodologique GRADE (Grading of Recommendations, Assessment, Development, and Evaluation). (Tableaux 1 et 2) Le résumé des conclusions est disponible sur demande. AVANTAGES, PRéJUDICE ET COûTS: La présente opinion de comité devrait aider toutes les femmes qui souffrent ou non de symptômes gynécologiques qui se présentent chez le gynécologue et un fournisseur de soins primaires. Elle aidera les praticiens à déterminer les indications d'examen pelvien afin de réduire le nombre d'examens inutiles et susceptibles de porter préjudice tout en augmentant le nombre d'examens indiqués afin de réduire les retards de diagnostic des affections gynécologiques traitables. MISE à JOUR DE LA DIRECTIVE CLINIQUE: La présente opinion de comité de la SOGC sera automatiquement passée en revue cinq ans après sa publication pour déterminer si une partie ou l'ensemble de l'opinion de comité devrait être mis à jour. Cependant, cette revue peut être effectuée plus tôt si de nouvelles recherches révolutionnaires sont publiées entre-temps. DÉCLARATIONS SOMMAIRES: 1) Les déclarations et les directives nationales et internationales sur l'examen pelvien ne devraient pas être interprétées comme si l'examen pelvien est superflu, qu'il ne contribue pas à l'évaluation physique ou que l'examen pelvien chez les femmes symptomatiques devrait être omis. 2) L'examen pelvien peut comprendre les examens visuels, au spéculum, bimanuel, à un doigt ou rectovaginal selon l'indication d'examen. 3) Aucune étude publiée à ce jour n'a évalué adéquatement quelque composante que ce soit de l'examen pelvien comme méthode de dépistage pour quelconque type de maladie gynécologique maligne, à l'exception de l'examen au spéculum pour le dépistage cytologique du cancer du col de l'utérus. Ainsi, toute recommandation universelle, pour ou contre les examens pelviens pour d'autres indications ne peut qu'être faite selon l'opinion des spécialistes et des données probantes de faible qualité. 4) Chez les femmes asymptomatiques dont le risque de cancer du col de l'utérus est moyen, le dépistage cytologique du cancer du col de l'utérus réduit à la fois son incidence et son taux de mortalité en détectant les lésions préinvasives traitables. 5) Chez les femmes asymptomatiques dont le risque de tumeur ou affection maligne est moyen, un examen visuel et bimanuel au moment d'obtenir des échantillons cytologiques cervicaux peut apporter une valeur ajoutée à cette méthode de dépistage. Les femmes peuvent ne pas soulever certaines inquiétudes sur le plan gynécologique jusqu'au moment de l'examen pelvien; l'examen offre une occasion de sensibiliser les patientes et de maintenir les compétences du praticien; de plus, même si le sujet n'a pas encore été étudié adéquatement, il pourrait comporter des effets positifs sur les tumeurs ou affections malignes ovariennes et vulvaires qui nécessiteraient des analyses plus poussées. Ces avantages potentiels devraient être soupesés par rapport aux préjudices potentiels comme l'inconfort de la patiente et les faux positifs ou négatifs qui pourraient la rassurer à tort ou entraîner des analyses et des interventions non justifiées. RECOMMANDATIONS: Femmes symptomatiques 1) Toute femme qui exprime des plaintes de nature gynécologique, y compris, mais sans s'y limiter, des plaintes concernant la vulve, des pertes vaginales, des saignements préménopausiques anormaux, des saignements postménopausiques, l'infertilité, des symptômes de prolapsus des organes pelviens, l'incontinence urinaire, de nouveaux symptômes gastro-intestinaux inexpliqués (douleur abdominale, distension abdominale ou ballonnement et difficulté à manger ou satiété précoce), la douleur pelvienne ou la dyspareunie, devrait subir des composantes pertinentes de l'examen pelvien afin de détecter les maladies bénignes ou malignes (forte, basse). 2) Les fournisseurs de soins de santé peuvent envisager de discuter des risques et avantages de l'exécution d'un examen pelvien de base qui comprend un examen visuel et un examen bimanuel avant de prescrire une hormonothérapie substitutive ou un traitement hormonal de la ménopause (faible, très basse). Femmes asymptomatiques 3) Les professionnels de la santé devraient faire le dépistage cytologique du cancer du col de l'utérus conformément aux lignes directrices provinciales ou territoriales (forte, forte). 4) Les données sont insuffisantes pour orienter les recommandations sur l'examen pelvien aux fins de dépistage de tumeurs ou affections malignes de nature gynécologique non cervicales ou de toute maladie gynécologique bénigne chez les femmes asymptomatiques en santé dont le risque de tumeur ou affection maligne est moyen. Cependant, les professionnels de la santé peuvent envisager d'effectuer un examen pelvien aux fins de dépistage comprenant les examens visuel, bimanuel et au spéculum conjointement avec le prélèvement d'échantillons cytologiques cervicaux selon les intervalles recommandés dans les lignes directrices provinciales ou territoriales. Cette pratique pourrait permettre de détecter d'importantes maladies bénignes ou malignes non reconnues ou signalées par la patiente (faible, très basse). 5) Chez les femmes âgées de plus de 70 ans qui n'ont plus à subir de dépistage cytologique cervical, les professionnels de la santé devraient envisager de continuer chez les femmes asymptomatiques le dépistage périodique des maladies vulvaires en examinant la vulve, le périnée et l'anus afin de détecter les maladies bénignes ou malignes méconnues de cette population. Les données sont insuffisantes pour déterminer des recommandations sur la fréquence de cet examen (faible, basse). 6) Des examens pelviens de dépistage plus fréquents pour déceler les signes précoces de tumeurs ou affections malignes primitives, récidivantes ou métastatiques en l'absence de symptômes pourraient s'avérer bénéfiques pour les femmes qui ont des antécédents personnels de tumeurs malignes de nature gynécologique, un diagnostic génétique qui augmente le risque de tumeurs ou affections malignes gynécologiques ou des antécédents d'exposition in utero au diéthylstilbestrol. Puisque les données pour déterminer ces intervalles de dépistage sont inadéquates, on devrait les déterminer en fonction des lignes directrices provinciales ou territoriales et de l'opinion des spécialistes (faible, très basse). 7) Les options non effractives et par auto-prélèvement de dépistage de la chlamydia et de la gonorrhée sont acceptables chez les femmes asymptomatiques, mais l'examen pelvien, qui comprend les examens visuel, bimanuel et au spéculum, est requis en présence de symptômes pour écarter la possibilité d'une maladie inflammatoire pelvienne ou d'un abcès tubo-ovarien (forte, basse). 8) Aucun examen pelvien n'est requis avant la prescription de contraception hormonale chez une femme en santé qui ne présente aucun symptôme gynécologique (forte, basse).

Low-Risk Gestational Trophoblastic Neoplasia in Manitoba: Experience With Alternating Methotrexate and Dactinomycin.

OBJECTIVES: The aim of this study was to review the treatment and outcomes of low-risk gestational trophoblastic neoplasia (GTN) in Manitoba over more than 3 decades, with a focus on those treated with alternating methotrexate and dactinomycin, a protocol that has only rarely been described. MATERIALS AND METHODS: We retrospectively reviewed all patients with GTN referred to CancerCare Manitoba from January 1977 to December 2012. Cases were classified as low risk as per the modified WHO-FIGO prognostic scoring system (score, ≤6). Demographic, treatment, and outcomes data were abstracted, and descriptive statistics and time-to-event analysis were performed. The low-risk protocol used at CancerCare Manitoba consists of alternating single-agent use of methotrexate and dactinomycin, each for 5 days, on a 14-day cycle. RESULTS: Sixty-seven cases of GTN were identified, of which 52 were low risk. Thirty-nine patients were initiated on alternating methotrexate and dactinomycin. Thirty-four (87.2%) achieved primary cure on this regimen, with a median of 4.4 cycles administered (range, 2-7). Median time to response was 56 days. One patient achieved cure after receiving a repeat course of methotrexate as their final cycle. Second-line multiagent chemotherapy was required by 4 patients. Two patients experienced grade 3 toxicities, and none greater than grade 3. There were no recurrences. CONCLUSIONS: Alternating methotrexate and dactinomycin is an effective treatment protocol for low-risk GTN, with high rates of primary cure and acceptable toxicity.