Sudha Sundar

Identifying the best diagnostic test for ovarian cancer – synopsis of Refining Ovarian Cancer Test accuracy Scores (ROCkeTS) research

Background Ovarian cancer survival is stage-dependent: Stage I patients have 90% 5-year survival versus 15% for stage IV. Over 70% of patients worldwide are diagnosed at advanced stages. Ovarian cancer presents with non-specific symptoms (abdominal bloating, early satiety, discomfort/pain, bowel/urinary changes). Current National Institute for Health and Care Excellence guidelines recommend that symptomatic women presenting to primary care are tested with cancer antigen 125 and ultrasound, then referred to secondary care for further triage if these tests are abnormal. Current standard of care risk prediction model used to triage women in National Health Service secondary care is Risk of Malignancy Index 1 combining cancer antigen 125 and simple ultrasound features, which at 250 threshold has 70% sensitivity and 90% specificity. Newer models offer potential for improved sensitivity, earlier diagnosis and better survival outcomes. Objectives To evaluate diagnostic strategies for ovarian cancer in women with non-specific symptoms through systematic review, United Kingdom Collaborative Trial of Ovarian Cancer Screening data set analysis, prospective studies and health economic evaluation comparing Risk of Malignancy Index 1 against newer approaches including Risk of Ovarian Malignancy Algorithm, Ovarian-Adnexal Reporting and Data System and International Ovarian Tumour Analysis models, including International Ovarian Tumour Analysis Assessment of Different NEoplasias in the adneXa. Methods Four concurrent work packages: (1) Cochrane systematic review; (2) United Kingdom Collaborative Trial of Ovarian Cancer Screening data set model development; (3) prospective multicentre diagnostic accuracy study (ROCkeTS) with parallel pre/postmenopausal cohorts; and (4) cost–consequence analysis. Allied analyses investigated psychological impact and cancer outcomes from symptom-triggered pathways. ROCkeTS recruited 2453 women across 23 hospitals (2015–23) with symptoms, raised cancer antigen 125 and/or abnormal imaging. Women completed questionnaires, donated blood and underwent transvaginal ultrasound scored by International Ovarian Tumour Analysis terminology by certified National Health Service sonographers with quality assurance. Reference standard was histology for surgical cases or 12-month wellbeing ascertainment. Primary outcome: primary invasive ovarian cancer versus benign or normal. Results The Cochrane systematic review (58 studies, 30,121 patients and 9061 ovarian cancer cases) demonstrated that most published diagnostic test accuracy studies failed to differentiate between pre- and postmenopausal women, and all were conducted in high-prevalence settings, limiting applicability to routine practice. In the ROCkeTS prospective study in premenopausal women, in the initial cohort recruited prior to protocol change ( n  = 857), Risk of Malignancy Index 1 at threshold 250 showed poor sensitivity (42.6%, 95% confidence interval 28.3 to 57.8) but high specificity (96.5%, 95% confidence interval 94.7 to 97.8). All other tests improved sensitivity but dropped specificity. International Ovarian Tumour Analysis Assessment of Different NEoplasias in the adneXa at 10% threshold achieved significantly higher sensitivity (89.1%, 95% confidence interval 76.4 to 96.4), higher than all other tests with acceptable specificity (73.2%, 95% confidence interval 69.9 to 76.4). In the ROCkeTS prospective cohort study in postmenopausal women ( n  = 1242), Risk of Malignancy Index 1 at 250 demonstrated better performance (82.9%, 95% confidence interval 76.7 to 88.0), but International Ovarian Tumour Analysis Assessment of Different NEoplasias in the adneXa at 10% had the best sensitivity at 96.1% (95% confidence interval 92.2 to 98.4) compared to Risk of Malignancy Index 1 with the least drop of specificity. Risk of Ovarian Malignancy Algorithm at manufacturer recommended threshold and Ovarian-Adnexal Reporting and Data System did not improve on Risk of Malignancy Index 1 sensitivity in postmenopausal women. Cancer prevalence differed between premenopausal (5.7%) and postmenopausal (17%) cohorts. Early-stage cancer (I/II) were diagnosed in 60.2% of premenopausal and 41% of postmenopausal cohorts. Cancer diagnosis rates were very low (1.6%) in women under 40 years. High anxiety and distress were noted, particularly in younger women. One in four women with high-grade serous ovarian cancers were diagnosed at early stage (I/II). Complete cytoreduction was achieved in 61.3% of cases, with optimal cytoreduction (≤ 1 cm residual disease) in an additional 15.1%. Cost–consequence analysis demonstrated that a two-step strategy deployed at the same ultrasound sitting, initially triaging out benign looking tumours on ultrasound, then calculating ovarian cancer risk with International Ovarian Tumour Analysis Assessment of Different NEoplasias in the adneXa ultrasound model at 10% demonstrated the best balance across cost, diagnostic yield and cancer deaths compared to other diagnostic strategies. Limitations Cohort study required key changes to protocol and post-pandemic recruitment was slow. Conclusions International Ovarian Tumour Analysis Assessment of Different NEoplasias in the adneXa ultrasound at 10% threshold, delivered by trained National Health Service sonographers demonstrated superior diagnostic performance compared to Risk of Malignancy Index 1 and should be considered as new standard of care for suspected ovarian cancer in pre- and postmenopausal women. A two-step strategy using International Ovarian Tumour Analysis Assessment of Different NEoplasias in the adneXa offers optimal balance across cost, diagnostic yield and cancer death reduction. Implementation requires sonographer training investment and quality assurance. Future research International Ovarian Tumour Analysis Assessment of Different NEoplasias in the adneXa implementation in primary care/community settings, artificial intelligence-enabled quality assurance, reconfiguration of referral pathways in primary care to reduce unnecessary referrals in younger women and consequent harm are important research areas. Systematic symptom elicitation capitalising on routine health interactions to reach underserved communities warrants further research. Funding This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number 13/13/01.

Diagnostic tests for ovarian cancer in premenopausal women with non-specific symptoms (ROCkeTS): prospective, multicentre, cohort study

Abstract Objective To investigate the accuracy of risk prediction models and scores for diagnosing ovarian cancer in premenopausal women presenting to secondary care with symptoms and abnormal test results. Design Prospective cohort study. Setting Secondary care in 23 hospitals in the UK between June 2015 and March 2023. Participants Premenopausal women presenting with non-specific symptoms, and raised serum levels of cancer antigen 125 or abnormal imaging results, were prospectively recruited, predominantly referred through the NHS urgent suspected cancer pathway from primary care. A head-to-head comparison of the accuracy of the six risk prediction models and scores was conducted using donated blood and ultrasound scans performed by NHS staff trained in the use of International Ovarian Tumour Analysis (IOTA) imaging terminology. The index tests used were Risk of Malignancy Index 1 (with pre-stated thresholds of 200, 250), Risk of Malignancy Algorithm (7.4%, 11.4%, 12.5%, 13.1%), IOTA Assessment of Different Neoplasias in the adnEXa (ADNEX) (3%, 10%), IOTA simple rules risk model (3%, 10%), IOTA simple rules, and cancer antigen 125 (CA 125, 87 IU/mL). Participants were classified as having primary invasive ovarian cancer versus having benign or normal pathology according to the reference standard determined from surgical specimens or biopsies by histology or cytology, if undertaken, or else at 12 month follow-up. After June 2018, because of covid restrictions and concerns about sample size, recruitment was restricted to only women undergoing surgery within three months of presentation to clinic (in whom ovarian cancer was more likely). Main outcome measures Diagnostic accuracy at predicting primary invasive ovarian cancer versus benign or normal histology, assessed by analysing the sensitivity, specificity, C index, area under receiver operating characteristic curve, positive and negative predictive values, and calibration plots in participants with conclusive reference standard results and available index test data. Results 88 of 1211 premenopausal women received diagnoses of primary ovarian cancer: 49 of 857 women in the pre-June 2018 cohort (prevalence of 5.7%) and 39 of 354 women in the post-June 2018 cohort (11.0%). For the diagnosis of primary ovarian cancer (n=799 women, after exclusion of 58 other diagnoses), Risk of Malignancy Index 1 at the 250 threshold had a sensitivity of 42.6% (95% confidence interval (CI) 28.3 to 57.8; specificity 96.5%, 94.7 to 97.8). Compared with Risk of Malignancy Index 1 at the 250 threshold, CA 125 and all other tests had higher sensitivity (CA 125 at 87 IU/mL threshold: 55.1%, 40.2 to 69.3, P=0.06; Risk of Malignancy Algorithm at 11.4% threshold: 79.2%, 65.0 to 89.5, P<0.001; IOTA ADNEX at 10% threshold: 89.1%, 76.4 to 96.4, P<0.001; IOTA simple rules risk at 10% threshold: 83.0%, 69.2 to 92.4, P<0.001; IOTA simple rules: 75.0%, 56.6 to 88.5, P=0.01) and lower specificity (CA 125 at 87 IU/mL threshold: 89.0%, 86.5 to 91.2, P<0.001; Risk of Malignancy Algorithm at 11.4% threshold: 73.1%, 69.6 to 76.3, P<0.001; IOTA ADNEX at 10% threshold: 75.1%, 71.4 to 78.6, P<0.001; IOTA simple rules risk at 10% threshold: 76.0%, 72.4 to 79.3, P<0.001; IOTA simple rules: 95.2%, 93.0 to 96.9, P=0.06). Results for IOTA simple rules were inconclusive in 120 of 799 participants. Analysis of the complete cohort (n=1211), including the 354 premenopausal women with a higher likelihood of developing ovarian cancer, yielded similar results. Conclusions Compared to Risk of Malignancy Index 1 at 250 threshold—the test currently used in NHS secondary care to triage women to tertiary care—most tests improve sensitivity but reduce specificity. Ultrasound triage with the IOTA ADNEX model at 10% in secondary care demonstrated the highest sensitivity gain, with a comparable decline in specificity to other comparator tests. Ultrasound with the IOTA ADNEX model at 10% should be considered the new standard of care test for triaging premenopausal women in secondary care. Implementation should incorporate staff training and quality assurance. Trial registration ISRCTN17160843 .

A Cost Consequence Analysis of Seven Diagnostic Strategies for Ovarian Cancer: A Model‐Based Economic Evaluation

ABSTRACT Objective To assess the costs and consequences of seven diagnostic strategies for ovarian cancer in pre‐ and post‐menopausal women with symptoms in secondary care. Design Economic evaluation alongside a prospective single‐arm diagnostic accuracy study. Setting NHS secondary care outpatients (2‐week referrals, clinics, GP referrals, cross‐specialty referrals) and inpatients (emergency presentations to secondary care). Sample Two cohorts of 857 pre‐menopausal and 1242 post‐menopausal women newly presenting to secondary care with symptoms of suspected ovarian cancer. Methods A model‐based cost‐consequence analysis (CCA) was conducted using a decision tree simulating patient pathways over 12 months. Diagnostic accuracy data were sourced from the ROCkeTS study and supplemented by literature. Main Outcome Measures Cancer deaths, correct diagnosis proportion, and diagnostic yield. Results No diagnostic strategy was optimal across all outcomes. Across both cohorts, the Risk of Malignancy Index (RMI) 200 was least expensive but had poor cancer death and diagnostic yield outcomes. The ADNEX 3% strategy had the highest diagnostic yield and lowest cancer mortality but was the most expensive. For pre‐menopausal women, the IOTA ADNEX 10% strategy outperformed ORADS, ROMA, and CA125 in cost and outcomes. For post‐menopausal women, the high cancer prevalence required a trade‐off. In sensitivity analysis, a two‐step IOTA ADNEX 10% strategy outperformed ORADS, ROMA, and CA125 across all three outcomes, making the strategy a more balanced choice in both cohorts. Conclusion At 12 months, no single diagnostic strategy was superior. Early diagnosis requires balancing cancer mortality, diagnostic yield, and cost. The IOTA ADNEX two‐step strategy at a 10% threshold provided the best trade‐off across these factors and is recommended for practice.

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

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

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. 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. 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). 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

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. 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. 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. 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.

Investigating the acceptability of cervical screening, using conventional clinician-taken cervical samples or urine self-sampling, at 6 weeks postnatal: A cross-sectional questionnaire

Objectives United Kingdom (UK) guidelines recommend delaying cervical screening due during pregnancy to 12 weeks postnatal, despite a lack of supporting evidence. This questionnaire-based study aimed to determine the feasibility of a clinical study of cervical screening and urine self-sampling for human papillomavirus (HPV) at 6 weeks postnatal, as pilot work suggested this would improve uptake, if offered at the routine postnatal check-up. Methods Females who were pregnant/recently pregnant were invited to participate in a web-based questionnaire. Questions assessed acceptability of postnatal cervical screening at 6 weeks postnatal, analysed with chi-square, Fisher's exact and Mann–Whitney tests. Free-text responses were coded using the Theoretical Framework of Acceptability (TFA) to conduct a qualitative content analysis. Results Among the 454 participants, 266 (58.6%) would be more likely to undergo cervical screening if offered at 6 weeks postnatal, and an even higher proportion expressed increased willingness if urine self-sampling were offered ( n  = 338; 74.4%). Two-thirds (308/454; 67.8%) would be willing to be screened at 6 weeks postnatal for a research study and 356/454 (78.4%) if it would be limited only to urine self-sampling. When considering screening modality, over half (245/454; 54%) would prefer urine self-sampling to cervical screening, although a fifth (93/454; 21%) preferred conventional sampling. Free-text responses were provided by 279 participants, and these highlighted that affective attitude and burden TFA constructs underpinned prospective acceptability of having screening at 6 weeks postnatal. Conclusions Offering cervical screening at the 6-week postnatal check-up has potential to increase cervical screening participation. Most participants would be interested in taking part in the research. The feasibility of screening at 6 weeks postnatal and concurrent acceptability should be tested in pilot clinical studies.

Investigating harms of testing for ovarian cancer – psychological outcomes and cancer conversion rates in women with symptoms of ovarian cancer: A cohort study embedded in the multicentre ROCkeTS prospective diagnostic study

AbstractObjectiveTo investigate psychological correlates in women referred with suspected ovarian cancer via the fast‐track pathway, explore how anxiety and distress levels change at 12 months post‐testing, and report cancer conversion rates by age and referral pathway.DesignSingle‐arm prospective cohort study.SettingMulticentre. Secondary care including outpatient clinics and emergency admissions.PopulationA cohort of 2596 newly presenting symptomatic women with a raised CA125 level, abnormal imaging or both.MethodsWomen completed anxiety and distress questionnaires at recruitment and at 12 months for those who had not undergone surgery or a biopsy within 3 months of recruitment.Main outcome measuresAnxiety and distress levels measured using a six‐item short form of the State–Trait Anxiety Inventory (STAI‐6) and the Impact of Event Scale – Revised (IES‐r) questionnaire. Ovarian cancer (OC) conversion rates by age, menopausal status and referral pathway.ResultsOverall, 1355/2596 (52.1%) and 1781/2596 (68.6%) experienced moderate‐to‐severe distress and anxiety, respectively, at recruitment. Younger age and emergency presentations had higher distress levels. The clinical category for anxiety and distress remained unchanged/worsened in 76% of respondents at 12 months, despite a non‐cancer diagnosis. The OC rates by age were 1.6% (95% CI 0.5%–5.9%) for age <40 years and 10.9% (95% CI 8.7%–13.6%) for age ≥40 years. In women referred through fast‐track pathways, 3.3% (95% CI 1.9%–5.7%) of pre‐ and 18.5% (95% CI 16.1%–21.0%) of postmenopausal women were diagnosed with OC.ConclusionsWomen undergoing diagnostic testing display severe anxiety and distress. Younger women are especially vulnerable and should be targeted for support. Women under the age of 40 years have low conversion rates and we advocate reducing testing in this group to reduce the harms of testing.

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

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. 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. 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. 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.

Association Between Purchase of Over-the-Counter Medications and Ovarian Cancer Diagnosis in the Cancer Loyalty Card Study (CLOCS): Observational Case-Control Study

Background Over-the-counter (OTC) medications are frequently used to self-care for nonspecific ovarian cancer symptoms prior to diagnosis. Monitoring such purchases may provide an opportunity for earlier diagnosis. Objective The aim of the Cancer Loyalty Card Study (CLOCS) was to investigate purchases of OTC pain and indigestion medications prior to ovarian cancer diagnosis in women with and without ovarian cancer in the United Kingdom using loyalty card data. Methods An observational case-control study was performed comparing purchases of OTC pain and indigestion medications prior to diagnosis in women with (n=153) and without (n=120) ovarian cancer using loyalty card data from two UK-based high street retailers. Monthly purchases of pain and indigestion medications for cases and controls were compared using the Fisher exact test, conditional logistic regression, and receiver operating characteristic (ROC) curve analysis. Results Pain and indigestion medication purchases were increased among cases 8 months before diagnosis, with maximum discrimination between cases and controls 8 months before diagnosis (Fisher exact odds ratio [OR] 2.9, 95% CI 2.1-4.1). An increase in indigestion medication purchases was detected up to 9 months before diagnosis (adjusted conditional logistic regression OR 1.38, 95% CI 1.04-1.83). The ROC analysis for indigestion medication purchases showed a maximum area under the curve (AUC) at 13 months before diagnosis (AUC=0.65, 95% CI 0.57-0.73), which further improved when stratified to late-stage ovarian cancer (AUC=0.68, 95% CI 0.59-0.78). Conclusions There is a difference in purchases of pain and indigestion medications among women with and without ovarian cancer up to 8 months before diagnosis. Facilitating earlier presentation among those who self-care for symptoms using this novel data source could improve ovarian cancer patients’ options for treatment and improve survival. Trial Registration ClinicalTrials.gov NCT03994653; https://clinicaltrials.gov/ct2/show/NCT03994653

British Gynaecological Cancer Society/British Association of Gynaecological Pathology consensus for germline and tumor testing for BRCA1/2 variants in ovarian cancer in the United Kingdom

The British Gynecological Cancer Society and the British Association of Gynecological Pathologists established a multidisciplinary consensus group comprising experts in surgical gynecological oncology, medical oncology, genetics, and laboratory science, and clinical nurse specialists to identify the optimal pathways to

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

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. 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 The myChoice assay was performed on 2829 tumors. Of these, 2474 (87%) and 2178 (77%) successfully underwent 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.

Quality of life from cytoreductive surgery in advanced ovarian cancer: Investigating the association between disease burden and surgical complexity in the international, prospective, SOCQER‐2 cohort study

AbstractObjectiveTo investigate quality of life (QoL) and association with surgical complexity and disease burden after surgical resection for advanced ovarian cancer in centres with variation in surgical approach.DesignProspective multicentre observational study.SettingGynaecological cancer surgery centres in the UK, Kolkata, India, and Melbourne, Australia.SamplePatients undergoing surgical resection (with low, intermediate or high surgical complexity score, SCS) for late‐stage ovarian cancer.Main Outcome MeasuresPrimary: change in global score on the European Organisation for Research and Treatment of Cancer (EORTC) core quality‐of‐life questionnaire (QLQ‐C30). Secondary: EORTC ovarian cancer module (OV28), progression‐free survival.ResultsPatients’ preoperative disease burden and SCS varied between centres, confirming differences in surgical ethos. QoL response rates were 90% up to 18 months. Mean change from the pre‐surgical baseline in the EORTC QLQ‐C30 was 3.4 (SD 1.8, n = 88) in the low, 4.0 (SD 2.1, n = 55) in the intermediate and 4.3 (SD 2.1, n = 52) in the high‐SCS group after 6 weeks (p = 0.048), and 4.3 (SD 2.1, n = 51), 5.1 (SD 2.2, n = 41) and 5.1 (SD 2.2, n = 35), respectively, after 12 months (p = 0.133). In a repeated‐measures model, there were no clinically or statistically meaningful differences in EORTC QLQ‐C30 global scores between the three SCS groups (p = 0.840), but there was a small statistically significant improvement in all groups over time (p < 0.001). The high‐SCS group experienced small to moderate decreases in physical (p = 0.004), role (p = 0.016) and emotional (p = 0.001) function at 6 weeks post‐surgery, which resolved by 6–12 months.ConclusionsThe global QoL of patients undergoing low‐, intermediate‐ and high‐SCS surgery improved at 12 months after surgery and was no worse in patients undergoing extensive surgery.Tweetable AbstractCompared with surgery of lower complexity, extensive surgery does not result in poorer quality of life in patients with advanced ovarian cancer.

Diagnostic performance of quantitative measures from [18F]FDG PET/CT, [18F]FEC PET/CT, and DW-MRI in the detection of lymph node metastases in endometrial and cervical cancer: data from the MAPPING study

Abstract Purpose To evaluate the diagnostic performance of quantitative measures derived from [ 18 F]FDG PET/CT, [ 18 F]FEC PET/CT, and DW-MRI in the detection of lymph node metastases in endometrial and cervical cancer with comparison to standard visual PET analysis with histology as the reference standard. Methods Subanalysis of quantitative data from the prospective multicentre MAPPING study. Nodal and tumour SUV max from [ 18 F]FDG PET/CT and [ 18 F]FEC PET/CT and ADC mean from DW-MRI were documented. Nodal-to-tumour ratios (NTR) and SUV max -to-ADC mean ratio (STAR) were calculated. Optimal cut-offs of quantitative measures were compared to visual assessment on a regional basis using histopathology as the reference standard. Results Scans from 112 patients (36 cervical and 76 endometrial cancers; 340 nodal regions) were eligible for quantitative image analysis. Lower ADC mean on DW-MRI was observed in metastatic nodes for cervical cancer but not for endometrial cancer. Quantitative measures were significantly higher in malignant than benign nodal regions on [ 18 F]FDG PET/CT and [ 18 F]FEC PET/CT in endometrial cancer. SUV max cut-offs showed similar performance to visual assessment in the diagnosis of metastatic lymph nodes in endometrial cancer whilst ADC mean cut-offs showed significantly lower specificity than visual assessment. Interobserver agreement was excellent for SUV max measurements on both [ 18 F]FDG PET/CT and [ 18 F]FEC PET/CT, but poor for ADC mean on DW-MRI. Conclusion Quantitative measures from [ 18 F]FDG PET/CT, [ 18 F]FEC PET/CT, or DW-MRI did not outperform visual assessment in the detection of nodal metastases in endometrial cancer. Therefore, the implementation of these quantitative measures as standalone diagnostic tools in routine clinical practice is not recommended.

Cancer Loyalty Card Study

Approximately 7,400 new cases of ovarian cancer are diagnosed each year in the United Kingdom (UK), and with over 4,000 women dying from the disease each year it is a particularly lethal form of cancer. The symptoms for ovarian cancer are not well known and vague, and most women are diagnosed at a late stage when the cancer has already spread around the abdominal cavity with poor prognosis. Novel methods are needed to improve earlier detection and thereby improve survival from this disease. The Cancer Loyalty Card Study (CLOCS) proposes to use loyalty card data from two participating high street retailers to investigate purchase behaviour as an opportunity for cancer symptom surveillance. The investigators aim to conduct a case-control study of ovarian cancer patients matched with women without ovarian cancer and to explore public preferences for how to communicate potential outcomes of the commercial and health data linkages back to individuals. Eligible participants will be women in the UK who own at least one loyalty card with the participating high street retailers. Of these women, those who have been diagnosed with ovarian cancer are eligible to participate in the study as cases, while women who have not been diagnosed with ovarian cancer are eligible to participate as controls. Upon choosing to participate, all participants will be asked to complete a short questionnaire about well-established ovarian cancer risk factors and common symptoms either in the clinic (cases) or online/from a packet in the mail(controls). This information will be used in risk assessment for ovarian cancer of participants, which will be used at the analysis stage.