Symptom-triggered testing detects early stage and low volume resectable advanced stage ovarian cancer.

OBJECTIVE: Symptom-triggered testing for ovarian cancer was introduced to the UK whereby symptomatic women undergo an ultrasound scan and serum CA125, and are referred to hospital within 2 weeks if these are abnormal. The potential value of symptom-triggered testing in the detection of early-stage disease or low tumor burden remains unclear in women with high grade serous ovarian cancer. In this descriptive study, we report on the International Federation of Gynecology and Obstetrics (FIGO) stage, disease distribution, and complete cytoreduction rates in women presenting via the fast-track pathway and who were diagnosed with high grade serous ovarian cancer. METHODS: We analyzed the dataset from Refining Ovarian Cancer Test accuracy Scores (ROCkeTS), a single-arm prospective diagnostic test accuracy study recruiting from 24 hospitals in the UK. The aim of ROCkeTS is to validate risk prediction models in symptomatic women. We undertook an opportunistic analysis for women recruited between June 2015 to July 2022 and who were diagnosed with high grade serous ovarian cancer via the fast-track pathway. Women presenting with symptoms suspicious for ovarian cancer receive a CA125 blood test and an ultrasound scan if the CA125 level is abnormal. If either of these is abnormal, women are referred to secondary care within 2 weeks. Histology details were available on all women who underwent surgery or biopsy within 3 months of recruitment. Women who did not undergo surgery or biopsy at 3 months were followed up for 12 months as per the national guidelines in the UK. In this descriptive study, we report on patient demographics (age and menopausal status), WHO performance status, FIGO stage at diagnosis, disease distribution (low/pelvic confined, moderate/extending to mid-abdomen, high/extending to upper abdomen) and complete cytoreduction rates in women who underwent surgery. RESULTS: Of 1741 participants recruited via the fast-track pathway, 119 (6.8%) were diagnosed with high grade serous ovarian cancer. The median age was 63 years (range 32-89). Of these, 112 (94.1%) patients had a performance status of 0 and 1, 30 (25.2%) were diagnosed with stages I/II, and the disease distribution was low-to-moderate in 77 (64.7%). Complete and optimal cytoreduction were achieved in 73 (61.3%) and 18 (15.1%). The extent of disease was low in 43 of 119 (36.1%), moderate in 34 of 119 (28.6%), high in 32 of 119 (26.9%), and not available in 10 of 119 (8.4%). Nearly two thirds, that is 78 of 119 (65.5%) women with high grade serous ovarian cancer, underwent primary debulking surgery, 36 of 119 (30.3%) received neoadjuvant chemotherapy followed by interval debulking surgery, and 5 of 119 (4.2%) women did not undergo surgery. CONCLUSION: Our results demonstrate that one in four women identified with high grade serous ovarian cancer through the fast-track pathway following symptom-triggered testing was diagnosed with early-stage disease. Symptom-triggered testing may help identify women with a low disease burden, potentially contributing to high complete cytoreduction rates.

Investigating age and ethnicity as novel high-risk phenotypes in mucinous ovarian cancer: retrospective study in a multi-ethnic population.

OBJECTIVES: Primary mucinous ovarian carcinoma represents 3% of ovarian cancers and is typically diagnosed early, yielding favorable outcomes. This study aims to identify risk factors, focussing on the impact of age and ethnicity on survival from primary mucinous ovarian cancer. METHODS: A retrospective observational study of patients treated at Sandwell and West Birmingham Hospitals NHS Trust and University Hospital Coventry and Warwickshire. Patients included were women aged ≥16 years, with primary mucinous ovarian cancer confirmed by specialist gynecological histopathologist and tumor immunohistochemistry, including cytokeratin-7, cytokeratin-20, and CDX2. Statistical analyses were performed using R integrated development environment, with survival assessed by Cox proportional hazards models and Kaplan-Meier plots. RESULTS: A total of 163 patients were analyzed; median age at diagnosis was 58 years (range 16-92), 145 (89%) were International Federation of Gynecology and Obstetrics stage I and 43 (26%) patients had infiltrative invasion. Women aged ≤45 years were more likely to have infiltrative invasion (RR=1.38, 95% CI 0.78 to 2.46), with increased risk of death associated with infiltrative invasion (HR=2.29, 95% CI 1.37 to 5.83). Compared with White counterparts, South Asian women were more likely to undergo fertility-sparing surgery (RR=3.52, 95% CI 1.48 to 8.32), and have infiltrative invasion (RR=1.25, 95% CI 0.60 to 2.58). South Asian women undergoing fertility-sparing surgery had worse prognosis than those undergoing traditional staging surgery (HR=2.20, 95% CI 0.39 to 13.14). In FIGO stage I disease, 59% South Asian and 37% White women received adjuvant chemotherapy (p=0.06). South Asian women exhibited a worse overall prognosis than White women (HR=2.07, 95% CI 0.86 to 4.36), particularly pronounced in those aged ≤45 years (HR=8.75, 95% CI 1.22 to 76.38). CONCLUSION: This study identified young age as a risk factor for diagnosis of infiltrative invasion. Fertility-sparing surgery in South Asian women is a risk factor for poorer prognosis. South Asian women exhibit poorer overall survival than their White counterparts.

Exploring global barriers to optimal ovarian cancer care: thematic analysis.

OBJECTIVE: To explore the barriers to ovarian cancer care, as reported in the open ended responses of a global expert opinion survey, highlighting areas for improvement in global ovarian cancer care. Potential solutions to overcome these barriers are proposed. METHODS: Data from the expert opinion survey, designed to assess the organization of ovarian cancer care worldwide, were analyzed. The survey was distributed across a global network of physicians. We examined free text, open ended responses concerning the barriers to ovarian cancer care. A qualitative thematic analysis was conducted to identify, analyze, and report meaningful patterns within the data. RESULTS: A total of 1059 physicians from 115 countries completed the survey, with 438 physicians from 93 countries commenting on the barriers to ovarian cancer care. Thematic analysis gave five major themes, regardless of income category or location: societal factors, inadequate resources in hospital, economic barriers, organization of the specialty, and need for early detection. Suggested solutions include accessible resource stratified guidelines, multidisciplinary teamwork, public education, and development of gynecological oncology training pathways internationally. CONCLUSIONS: This analysis provides an international perspective on the main barriers to optimal ovarian cancer care. The themes derived from our analysis highlight key target areas to focus efforts to reduce inequalities in global care. Future regional analysis involving local representatives will enable country specific recommendations to improve the quality of care and ultimately to work towards closing the care gap.

Training the gynecologic oncologists of the future - challenges and opportunities.

Several recent advances in gynecologic cancer care have improved patient outcomes. These include national screening and vaccination programs for cervical cancer as well as neoadjuvant chemotherapy for ovarian cancer. Conversely, these advances have cumulatively reduced surgical opportunities for training creating a need to supplement existing training strategies with evidence-based adjuncts. Technologies such as virtual reality and augmented reality, if properly evaluated and validated, have transformative potential to support training. Given the changing landscape of surgical training in gynecologic oncology, we were keen to summarize the evidence underpinning current training in gynecologic oncology.In this review, we undertook a literature search of Medline, Google, Google Scholar, Embase and Scopus to gather evidence on the current state of training in gynecologic oncology and to highlight existing evidence on the best methods to teach surgical skills. Drawing from the experiences of other surgical specialties we examined the use of training adjuncts such as cadaveric dissection, animation and 3D models as well as simulation training in surgical skills acquisition. Specifically, we looked at the use of training adjuncts in gynecologic oncology training as well as the evidence behind simulation training modalities such as low fidelity box trainers, virtual and augmented reality simulation in laparoscopic training. Finally, we provided context by looking at how training curriculums varied internationally.Whereas some evidence to the reliability and validity of simulation training exists in other surgical specialties, our literature review did not find such evidence in gynecologic oncology. It is important that well conducted trials are used to ascertain the utility of simulation training modalities before integrating them into training curricula.

Exploring international differences in ovarian cancer care: a survey report on global patterns of care, current practices, and barriers.

OBJECTIVE: Although global disparities in survival rates for patients with ovarian cancer have been described, variation in care has not been assessed globally. This study aimed to evaluate global ovarian cancer care and barriers to care. METHODS: A survey was developed by international ovarian cancer specialists and was distributed through networks and organizational partners of the International Gynecologic Cancer Society, the Society of Gynecologic Oncology, and the European Society of Gynecological Oncology. Respondents received questions about care organization. Outcomes were stratified by World Bank Income category and analyzed using descriptive statistics and logistic regressions. RESULTS: A total of 1059 responses were received from 115 countries. Respondents were gynecological cancer surgeons (83%, n=887), obstetricians/gynecologists (8%, n=80), and other specialists (9%, n=92). Income category breakdown was as follows: high-income countries (46%), upper-middle-income countries (29%), and lower-middle/low-income countries (25%). Variation in care organization was observed across income categories. Respondents from lower-middle/low-income countries reported significantly less frequently that extensive resections were routinely performed during cytoreductive surgery. Furthermore, these countries had significantly fewer regional networks, cancer registries, quality registries, and patient advocacy groups. However, there is also scope for improvement in these components in upper-middle/high-income countries. The main barriers to optimal care for the entire group were patient co-morbidities, advanced presentation, and social factors (travel distance, support systems). High-income respondents stated that the main barriers were lack of surgical time/staff and patient preferences. Middle/low-income respondents additionally experienced treatment costs and lack of access to radiology/pathology/genetic services as main barriers. Lack of access to systemic agents was reported by one-third of lower-middle/low-income respondents. CONCLUSIONS: The current survey report highlights global disparities in the organization of ovarian cancer care. The main barriers to optimal care are experienced across all income categories, while additional barriers are specific to income levels. Taking action is crucial to improve global care and strive towards diminishing survival disparities and closing the care gap.

Homologous recombination deficiency in newly diagnosed FIGO stage III/IV high-grade epithelial ovarian cancer: a multi-national observational study.

OBJECTIVE: Olaparib plus bevacizumab maintenance therapy improves survival outcomes in women with newly diagnosed, advanced, high-grade ovarian cancer with a deficiency in homologous recombination. We report data from the first year of routine homologous recombination deficiency testing in the National Health Service (NHS) in England, Wales, and Northern Ireland between April 2021 and April 2022. METHODS: The Myriad myChoice companion diagnostic was used to test DNA extracted from formalin-fixed, paraffin-embedded tumor tissue in women with newly diagnosed International Federation of Gynecology and Obstetrics (FIGO) stage III/IV high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer. Tumors with homologous recombination deficiency were those with a BRCA1/2 mutation and/or a Genomic Instability Score (GIS) ≥42. Testing was coordinated by the NHS Genomic Laboratory Hub network. RESULTS: The myChoice assay was performed on 2829 tumors. Of these, 2474 (87%) and 2178 (77%) successfully underwent BRCA1/2 and GIS testing, respectively. All complete and partial assay failures occurred due to low tumor cellularity and/or low tumor DNA yield. 385 tumors (16%) contained a BRCA1/2 mutation and 814 (37%) had a GIS ≥42. Tumors with a GIS ≥42 were more likely to be BRCA1/2 wild-type (n=510) than BRCA1/2 mutant (n=304). The distribution of GIS was bimodal, with BRCA1/2 mutant tumors having a higher mean score than BRCA1/2 wild-type tumors (61 vs 33, respectively, χ2 test p<0.0001). CONCLUSION: This is the largest real-world evaluation of homologous recombination deficiency testing in newly diagnosed FIGO stage III/IV high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer. It is important to select tumor tissue with adequate tumor content and quality to reduce the risk of assay failure. The rapid uptake of testing across England, Wales, and Northern Ireland demonstrates the power of centralized NHS funding, center specialization, and the NHS Genomic Laboratory Hub network.

British Gynaecological Cancer Society recommendations for women with gynecological cancer who received non-standard care during the COVID-19 pandemic.

During the COVID-19 pandemic, pressures on clinical services required adaptation to how care was prioritised and delivered for women with gynecological cancer. This document discusses potential 'salvage' measures when treatment has deviated from the usual standard of care. The British Gynaecological Cancer Society convened a multidisciplinary working group to develop recommendations for the onward management and follow-up of women with gynecological cancer who have been impacted by a change in treatment during the pandemic. These recommendations are presented for each tumor type and for healthcare systems, and the impact on gynecological services are discussed. It will be important that patient concerns about the impact of COVID-19 on their cancer pathway are acknowledged and addressed for their ongoing care.

Methods Used in Economic Evaluations of Testing and Diagnosis for Ovarian Cancer: A Systematic Review.

OBJECTIVE: There are multiple tests available that can help diagnose ovarian cancer, and the cost-effective analysis of these diagnostic interventions is essential for making well-informed decisions regarding resource allocation. There are multiple factors that can impact on the conclusions drawn from economic evaluations including test accuracy, the impact of the testing pathway on patient costs and outcomes, and delays along the ovarian cancer test-treat pathway. The objective of this study was to evaluate how test accuracy, the choice of perspective, and delays along the testing and diagnostic pathway have been incorporated in economic evaluations of testing for ovarian cancer. METHODS: A systematic review of published literature was undertaken to identify economic evaluations (eg, cost-effectiveness, cost-utility analysis) focused on testing and diagnosis for ovarian cancer. RESULTS: Seven studies met the inclusion criteria. Six studies incorporated test accuracy and its impact on patients to some extent. Four studies adopted a societal perspective, but only one considered the costs incurred by patients on the testing and diagnosis pathway. Where delays on the testing pathway were incorporated into the analysis, these were frequently due to false-negative test results leading to delays in patients accessing treatment. Any anxiety that patients might experience as a result of a positive test was not considered in these studies. CONCLUSIONS: The impact on patients of receiving a positive test in terms of anxiety and the costs incurred by patients having to attend for testing and diagnosis are rarely considered. Delays along the testing and diagnosis pathway can have a major effect on patient outcomes, and it is important that these are acknowledged in economic evaluations focused on testing. Future economic analysis should incorporate these key determinants in order that diagnostic tests for ovarian cancer can be robustly evaluated.

Analysis of outcome in women with borderline glandular change on cervical cytology.

OBJECTIVE: To review the outcome of women presenting with borderline glandular smear on cervical cytology and to investigate correlation between cytology, colposcopy and histology and subsequent smear history. STUDY DESIGN: A 5 year retrospective analysis of outcome in all women reported with borderline glandular changes on cytology between 2001 and 2005 at the John Radcliffe Hospital, Oxford, and Cheltenham General Hospital, Gloucestershire, was performed. Cytology, colposcopy, histology and follow-up cytology data at 6, 12 and 24 months after index smear were collated. RESULTS: Of 92 women with borderline glandular smears, 56 were referred for colposcopy. This accounts for 0.9% of the total referral (6293) to the colposcopy units. A significant rate of abnormal histology was noted, with CIN 1, 2, 3, CGIN or worse in 20 women (36%) and benign pathology in 18 women (32%). Colposcopy had a sensitivity of 82%, specificity of 39%, negative predictive value of 80% and positive predictive value of 49% in predicting abnormal (premalignant/malignant) histology. Only one woman with normal histology at presentation had subsequent abnormal cytology (1/31), whereas abnormal histology at presentation was strongly associated with subsequent abnormality on follow-up cytology over 24 months (8/21) with a p value=0.0058. CONCLUSION: Colposcopic examination and biopsy of colposcopically identified abnormalities is reliable, with negative colposcopy having a high negative predictive value. We also recommend thorough colposcopic examination before any invasive investigation as over treatment may impact on the future reproductive outcome [1].

Role of lymphangiogenesis in cancer.

Regional lymph node metastasis is a common event in solid tumors and is considered a marker for dissemination, increased stage, and worse prognosis. Despite rapid advances in tumor biology, the molecular processes that underpin lymphatic invasion and lymph node metastasis remain poorly understood. However, exciting discoveries have been made in the field of lymphangiogenesis in recent years. The identification of vascular endothelial growth factor ligands and cognate receptors involved in lymphangiogenesis, an understanding of the embryology of the mammalian lymphatic system, the recent isolation of pure populations of lymphatic endothelial cells, the investigation of lymphatic metastases in animal models, and the identification of markers that discriminate lymphatics from blood vessels at immunohistochemistry are current advances in the field of lymphangiogenesis, and as such are the main focus of this article. This review also evaluates evidence for lymphangiogenesis (ie, new lymphatic vessel formation in cancer) and critically reviews current data on the prognostic significance of lymphatic vascular density in tumors. A targeted approach to block pathways of lymphangiogenesis seems to be an attractive anticancer treatment strategy. Conversely, promotion of lymphangiogenesis may be a promising approach to the management of treatment-induced lymphedema in cancer survivors. Finally, the implications of these developments in cancer therapeutics and directions for future research are discussed.

Advances in the management of cervical cancer.

This review presents key advances in the management of cervical cancer. Traditionally, cervical cancer is staged clinically and has been treated either by radical hysterectomy or by radiotherapy. Improvements in imaging have led to more accurate therapeutic decision making and treatment planning. The evidence on fertility-preserving surgery for cervical cancer and chemoradiotherapy for locally advanced cancer is summarized here. An improved understanding of the viral aetiology of cervical cancer has led to the development of therapeutic vaccination, with limited success. There is increasing recognition of the psychosexual needs of women who have survived cervical cancer.