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Background:There are limited data on surgical outcomes in gynaecological oncology. We report on predictors of complications in a multicentre prospective study.Methods:Data on surgical procedures and resulting complications were contemporaneously recorded on consented patients in 10 participating UK gynaecological cancer centres. Patients were sent follow-up letters to capture any further complications. Post-operative (Post-op) complications were graded (I-V) in increasing severity using the Clavien-Dindo system. Grade I complications were excluded from the analysis. Univariable and multivariable regression was used to identify predictors of complications using all surgery for intra-operative (Intra-op) and only those with both hospital and patient-reported data for Post-op complications.Results:Prospective data were available on 2948 major operations undertaken between April 2010 and February 2012. Median age was 62 years, with 35% obese and 20.4% ASA grade ⩾3. Consultant gynaecological oncologists performed 74.3% of operations. Intra-op complications were reported in 139 of 2948 and Grade II-V Post-op complications in 379 of 1462 surgeries. The predictors of risk were different for Intra-op and Post-op complications. For Intra-op complications, previous abdominal surgery, metabolic/endocrine disorders (excluding diabetes), surgical complexity and final diagnosis were significant in univariable and multivariable regression (P<0.05), with diabetes only in multivariable regression (P=0.006). For Post-op complications, age, comorbidity status, diabetes, surgical approach, duration of surgery, and final diagnosis were significant in both univariable and multivariable regression (P<0.05).Conclusions:This multicentre prospective audit benchmarks the considerable morbidity associated with gynaecological oncology surgery. There are significant patient and surgical factors that influence this risk. [ABSTRACT FROM AUTHOR]

Background: To evaluate outcomes of laparoscopic retroperitoneal para-aortic lymphadenectomy for stage 1b3-3b cervical cancer., Methods: Pathology databases searched for all para-aortic lymphadenectomy cases 2005-2016. Descriptive statistics were used to analyse baseline characteristics, cox models for treatment affect after accounting for variables, and Kaplan Meier curves for survival (STATA v15)., Results: 191 patients had 1b3-3b cervical cancer of which 110 patients had Para-aortic lymphadenectomy. 8 (7.3%) patients stage 1b3, 82 (74.6%) stage 2b, and 20 (18.1%) stage 3b cervical cancer. Mean lymph node count 11.7 (SD7.6). The intra-operative and post-operative 30 day complication rates were 8.8% (CI: 4.3%, 15.7%) and 5.3% (CI: 1.9%, 11.2%) respectively.Para-aortic nodes were apparently positive on CT/MRI in 5/110 (5%) cases. Cancer was found in 10 (8.9%, CI: 4.3%, 15.7%) cases on histology, all received extended field radiotherapy. Only 2 were identified on pre-operative CT/MRI imaging. 3 of 10 suspected node-positive cases on CT/MRI had negative histology. Para-aortic lymphadenectomy led to alteration in staging and radiotherapy management in 8 (8%, CI: 3.7%, 14.6%) patients. Mean overall survival 42.81 months (SD = 31.79 months). Survival was significantly higher for women undergoing PAN (50.57 (SD 30.7) months) compared to those who didn't (31.27 (SD 32.5) months)., Conclusion: Laparoscopic retroperitoneal para-aortic lymphadenectomy is an acceptable procedure which can guide treatment in women with locally advanced cervical cancer.

Background: We compared the relative benefits, harms and cost-effectiveness of hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery ± systemic chemotherapy versus cytoreductive surgery ± systemic chemotherapy or systemic chemotherapy alone in people with peritoneal metastases from colorectal, gastric or ovarian cancers by a systematic review, meta-analysis and model-based cost-utility analysis., Methods: We searched MEDLINE, EMBASE, Cochrane Library and the Science Citation Index, ClinicalTrials.gov and WHO ICTRP trial registers until 14 April 2022. We included only randomised controlled trials addressing the research objectives. We used the Cochrane risk of bias tool version 2 to assess the risk of bias in randomised controlled trials. We used the random-effects model for data synthesis when applicable. For the cost-effectiveness analysis, we performed a model-based cost-utility analysis using methods recommended by The National Institute for Health and Care Excellence., Results: The systematic review included a total of eight randomised controlled trials (seven randomised controlled trials, 955 participants included in the quantitative analysis). All comparisons other than those for stage III or greater epithelial ovarian cancer contained only one trial, indicating the paucity of randomised controlled trials that provided data. For colorectal cancer, hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy probably results in little to no difference in all-cause mortality (60.6% vs. 60.6%; hazard ratio 1.00, 95% confidence interval 0.63 to 1.58) and may increase the serious adverse event proportions compared to cytoreductive surgery ± systemic chemotherapy (25.6% vs. 15.2%; risk ratio 1.69, 95% confidence interval 1.03 to 2.77). Hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy probably decreases all-cause mortality compared to fluorouracil-based systemic chemotherapy alone (40.8% vs. 60.8%; hazard ratio 0.55, 95% confidence interval 0.32 to 0.95). For gastric cancer, there is high uncertainty about the effects of hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy versus cytoreductive surgery + systemic chemotherapy or systemic chemotherapy alone on all-cause mortality. For stage III or greater epithelial ovarian cancer undergoing interval cytoreductive surgery, hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy probably decreases all-cause mortality compared to cytoreductive surgery + systemic chemotherapy (46.3% vs. 57.4%; hazard ratio 0.73, 95% confidence interval 0.57 to 0.93). Hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy may not be cost-effective versus cytoreductive surgery + systemic chemotherapy for colorectal cancer but may be cost-effective for the remaining comparisons., Limitations: We were unable to obtain individual participant data as planned. The limited number of randomised controlled trials for each comparison and the paucity of data on health-related quality of life mean that the recommendations may change as new evidence (from trials with a low risk of bias) emerges., Conclusions: In people with peritoneal metastases from colorectal cancer with limited peritoneal metastases and who are likely to withstand major surgery, hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy should not be used in routine clinical practice ( strong recommendation ). There is considerable uncertainty as to whether hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy or cytoreductive surgery + systemic chemotherapy should be offered to patients with gastric cancer and peritoneal metastases (no recommendation) . Hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy should be offered routinely to women with stage III or greater epithelial ovarian cancer and metastases confined to the abdomen requiring and likely to withstand interval cytoreductive surgery after chemotherapy ( strong recommendation )., Future Work: More randomised controlled trials are necessary., Study Registration: This study is registered as PROSPERO CRD42019130504., Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 17/135/02) and is published in full in Health Technology Assessment ; Vol. 28, No. 51. See the NIHR Funding and Awards website for further award information.

Objective: UKCTOCS provides an opportunity to explore symptoms in preclinical invasive epithelial ovarian cancer (iEOC). We report on symptoms in women with pre-clinical (screen-detected) cancers (PC) compared to clinically diagnosed (CD) cancers., Methods: In UKCTOCS, 202638 postmenopausal women, aged 50-74 were randomly allocated (April 17, 2001-September 29, 2005) 2:1:1 to no screening or annual screening till Dec 31,2011, using a multimodal or ultrasound strategy. Follow-up was through national registries. An outcomes committee adjudicated on OC diagnosis, histotype, stage. Eligible women were those diagnosed with iEOC at primary censorship (Dec 31, 2014). Symptom details were extracted from trial clinical-assessment forms and medical records. Descriptive statistics were used to compare symptoms in PC versus CD women with early (I/II) and advanced (III/IV/unable to stage) stage high-grade-serous (HGSC) cancer. ISRCTN-22488978; ClinicalTrials.gov-NCT00058032., Results: 1133 (286PC; 847CD) women developed iEOC. Median age (years) at diagnosis was earlier in PC compared to CD (66.8PC, 68.7CD, p = 0.0001) group. In the PC group, 48% (112/234; 90%, 660/730CD) reported symptoms when questioned. Half PC (50%, 13/26PC; 36%, 29/80CD; p = 0.213) women with symptomatic HGSC had >1symptom, with abdominal symptoms most common, both in early (62%, 16/26, PC; 53% 42/80, CD; p = 0.421) and advanced (57%, 49/86, PC; 74%, 431/580, CD; p = 0.001) stages. In symptomatic early-stage HGSC, compared to CD, PC women reported more gastrointestinal (change in bowel habits and dyspepsia) (35%, 9/26PC; 9%, 7/80CD; p = 0.001) and systemic (mostly lethargy/tiredness) (27%, 7/26PC; 9%, 7/80CD; p = 0.017) symptoms., Conclusions: Our findings, add to the growing evidence, that we should reconsider what constitutes alert symptoms for early tubo-ovarian cancer. We need a more nuanced complex of key symptoms which is then evaluated and refined in a prospective trial., Competing Interests: Declaration of Competing Interest UM had stock ownership awarded by University College London (UCL) between until October 2021 in Abcodia, which holds the licence for ROCA. She and MP have received grants and AGM, MB, JK and AR have been funded by grants from the Medical Research Council (MRC), Cancer Research UK, National Institute for Health Research (NIHR) and The Eve Appeal. UM has also received grants from UK Innovate and National Health and Medical Research Council (NHMRC), Australia and salary support from UCL Hospital Biomedical Research Centre. UM, AGM and SA report funded research collaborations with industry - iLOF (intelligent Lab on Fiber), RNA Guardian, Micronoma, MercyBio Analytics and academics -Cambridge University, QIMR Berghofer Medical Research Institute Imperial College London, University of Innsbruck and Dana Farber USA. UM holds patent number EP10178345.4 for Breast Cancer Diagnostics. AGM is a member of ACED Gynaecological Cancer Working Group and is ACED Co-Director Research Domain Trials. MP was an Associate Member of the EME funding committee while the project was active. SJS reports that Massachusetts General Hospital (MGH) has co-licensed software for ROCA to Abcodia, now owned by GenInCode, with MGH licence revenue to MGH and research laboratories per MGH institutional policies. SJS receives grant support from National Cancer Institute (USA) and National Institute for Health Research (NIHR) (UK). He is paid for service on the clinical advisory board for Guardant Health. He serves on the Scientific Advisory Board for LUNGevity. He has stock options from SISCAPA Assay Technologies for participation on its Scientific Advisory Board. IJJ reports grants from Eve Appeal Charity, MRC, Cancer Research UK, and NIHR during the conduct of the study. He co-invented the ROCA in 1995. Massachusetts General Hospital and Queen Mary University of London granted a licence for the ROCA to Abcodia in 2014. IJJ is non-executive director, shareholder, and consultant to Abcodia and has rights to royalties from sales of the ROCA. He founded (1985), was a trustee of (2012–14), and is now an Emeritus trustee (2015–present) of The Eve Appeal, one of the funding agencies for UKCTOCS. LF reports MRC funding for the psychosocial arm of the UKCTOCS study 2001–13, paid to University of Sussex. NS received honoraria from Astra-Zeneca-MPC and GlaxoSmithKline for participation in advisory boards. AMcG was a member of NIHR HTA and EME Editoral Board (2012 to 2022). RM reports funding from The Eve Appeal, Rosetrees Trust, Barts Charity, Yorkshire Cancer Research, Ovacure, British Gynaecological Cancer Society (BGCS), GlaxoSmithKline (GSK), and Honoraria from Astrazeneca and EGL. All other authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Ovarian cancer continues to have a poor prognosis with the majority of women diagnosed with advanced disease. Therefore, we undertook the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) to determine if population screening can reduce deaths due to the disease. We report on ovarian cancer mortality after long-term follow-up in UKCTOCS., Methods: In this randomised controlled trial, postmenopausal women aged 50-74 years were recruited from 13 centres in National Health Service trusts in England, Wales, and Northern Ireland. Exclusion criteria were bilateral oophorectomy, previous ovarian or active non-ovarian malignancy, or increased familial ovarian cancer risk. The trial management system confirmed eligibility and randomly allocated participants in blocks of 32 using computer generated random numbers to annual multimodal screening (MMS), annual transvaginal ultrasound screening (USS), or no screening, in a 1:1:2 ratio. Follow-up was through national registries. The primary outcome was death due to ovarian or tubal cancer (WHO 2014 criteria) by June 30, 2020. Analyses were by intention to screen, comparing MMS and USS separately with no screening using the versatile test. Investigators and participants were aware of screening type, whereas the outcomes review committee were masked to randomisation group. This study is registered with ISRCTN, 22488978, and ClinicalTrials.gov, NCT00058032., Findings: Between April 17, 2001, and Sept 29, 2005, of 1 243 282 women invited, 202 638 were recruited and randomly assigned, and 202 562 were included in the analysis: 50 625 (25·0%) in the MMS group, 50 623 (25·0%) in the USS group, and 101 314 (50·0%) in the no screening group. At a median follow-up of 16·3 years (IQR 15·1-17·3), 2055 women were diagnosed with tubal or ovarian cancer: 522 (1·0%) of 50 625 in the MMS group, 517 (1·0%) of 50 623 in the USS group, and 1016 (1·0%) of 101 314 in the no screening group. Compared with no screening, there was a 47·2% (95% CI 19·7 to 81·1) increase in stage I and 24·5% (-41·8 to -2·0) decrease in stage IV disease incidence in the MMS group. Overall the incidence of stage I or II disease was 39·2% (95% CI 16·1 to 66·9) higher in the MMS group than in the no screening group, whereas the incidence of stage III or IV disease was 10·2% (-21·3 to 2·4) lower. 1206 women died of the disease: 296 (0·6%) of 50 625 in the MMS group, 291 (0·6%) of 50 623 in the USS group, and 619 (0·6%) of 101 314 in the no screening group. No significant reduction in ovarian and tubal cancer deaths was observed in the MMS (p=0·58) or USS (p=0·36) groups compared with the no screening group., Interpretation: The reduction in stage III or IV disease incidence in the MMS group was not sufficient to translate into lives saved, illustrating the importance of specifying cancer mortality as the primary outcome in screening trials. Given that screening did not significantly reduce ovarian and tubal cancer deaths, general population screening cannot be recommended., Funding: National Institute for Health Research, Cancer Research UK, and The Eve Appeal., Competing Interests: Declaration of interests UM has stock ownership awarded by University College London (UCL) in Abcodia, which holds the licence for ROCA. She has received grants from the Medical Research Council (MRC), Cancer Research UK, the National Institute for Health Research (NIHR), and The Eve Appeal. She holds patent number EP10178345.4 for Breast Cancer Diagnostics. MP has received grants and AG-M, MB, AR, CK, GC, and SKM have been funded by grants from MRC, Cancer Research UK, NIHR, and The Eve Appeal. RM has received grants from The Eve Appeal, Rosetrees Charity, and Barts Charity, and personal fees from AstraZeneca. SJS holds the (expired) patent for ROCA, patented and owned by Massachusetts General Hospital and Queen Mary University of London, licenced to Abcodia. He reports stock options from SISCAPA Assay Technologies, and personal fees from Abcodia, Guardant Health, and Freenome, outside the submitted work. IJJ reports grants from Eve Appeal Charity, Medical Research Council, Cancer Research UK, and NIHR during the conduct of the study. He co-invented the ROCA in 1995, it was patented by Massachusetts General Hospital and Queen Mary University of London and is owned by these universities. Massachusetts General Hospital and Queen Mary University of London granted a licence to ROCA to Abcodia in 2014. IJJ is non-executive director, shareholder, and consultant to Abcodia and has rights to royalties from sales of the ROCA. He founded (1985), was a trustee of (2012–14), and is now an Emeritus trustee (2015–present) of The Eve Appeal, one of the funding agencies for UKCTOCS. All other authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Randomised controlled trials of ovarian cancer (OC) screening have not yet demonstrated an impact on disease mortality. Meanwhile, the screening data from clinical trials represents a rich resource to understand the performance of modalities used. We report here on incidence screening in the ultrasound arm of UKCTOCS. 44,799 of the 50,639 women who were randomised to annual screening with transvaginal ultrasound attended annual incidence screening between 28 April 2002 and 31 December 2011. Transvaginal ultrasound was used both as the first and the second line test. Participants were followed up through electronic health record linkage and postal questionnaires. Out of 280,534 annual incidence screens, 960 women underwent screen-positive surgery. 113 had ovarian/tubal cancer (80 invasive epithelial). Of the screen-detected invasive epithelial cancers, 37.5% (95% CI: 26.9-49.0) were Stage I/II. An additional 52 (50 invasive epithelial) were diagnosed within one year of their last screen. Of the 50 interval epithelial cancers, 6.0% (95% CI: 1.3-16.5) were Stage I/II. For detection of all ovarian/tubal cancers diagnosed within one year of screen, the sensitivity, specificity, and positive predictive values were 68.5% (95% CI: 60.8-75.5), 99.7% (95% CI: 99.7-99.7), and 11.8% (95% CI: 9.8-14) respectively. When the analysis was restricted to invasive epithelial cancers, sensitivity, specificity and positive predictive values were 61.5% (95% CI: 52.6-69.9); 99.7% (95% CI: 99.7-99.7) and 8.3% (95% CI: 6.7-10.3), with 12 surgeries per screen positive. The low sensitivity coupled with the advanced stage of interval cancers suggests that ultrasound scanning as the first line test might not be suitable for population screening for ovarian cancer. Trial registration: ISRCTN22488978. Registered on 6 April 2000.

Objective: There are widespread efforts to increase symptom awareness of 'pelvic/abdominal pain, increased abdominal size/bloating, difficulty eating/feeling full and urinary frequency/urgency' in an attempt to diagnose ovarian cancer earlier. Long-term survival of women with these symptoms adjusted for known prognostic factors is yet to be determined. This study explored the association of symptoms, routes and interval to diagnosis and long-term survival in a population-based cohort of postmenopausal women diagnosed with invasive epithelial tubo-ovarian cancer (iEOC) in the 'no screen' (control) UKCTOCS arm., Methods: Of 101,299 women in the control arm, 574 were confirmed on outcome review to have iEOC between randomisation (2001-2005) and 31 December 2014. Data was extracted from medical notes and electronic records. A multivariable model was fitted for individual symptoms, time interval from symptom onset to diagnosis, route to diagnosis, speciality, morphological Type, age at diagnosis, year of diagnosis (period effect), stage, primary treatment, and residual disease., Results: Women presenting with symptoms listed in the NICE guidelines (HR1.48, 95%CI1.16-1.89, p = 0.001) or the modified Goff Index (HR1·68, 95%CI1·32-2.13, p < 0.0001) had significantly worse survival than those who did not. Each additional presenting symptom decreased survival (HR1·20, 95%CI1·12-1·28, p < 0.0001). In multivariable analysis, in addition to advanced stage, increasing residual disease and inadequate primary treatment, abdominal pain and loss of appetite/feeling full were significantly associated with increased mortality., Conclusions: The ovarian cancer symptom indices identify postmenopausal women with a poorer prognosis. This study however cannot exclude the possibility of better outcomes in those who are aware and act on their symptoms., Competing Interests: Declaration of competing interest UM has stocks in Abcodia awarded to her by UCL. IJ and SJS are co-inventors of the Risk of Ovarian Cancer Algorithm (ROCA) which has been licensed to Abcodia Ltd. by Massachusetts General Hospital (MGH) and Queen Mary University of London (QMUL). IJ has a financial interest in Abcodia. Ltd. as a shareholder and director and is entitled to a royalty payments via MGH and QMUL from any commercial use of the ROCA. SJS co-developed the ROCA with all rights assigned to MGH and QMUL. SJS receives personal fees from the LUNGevity Foundation and SISCAPA Assay Technologies as member of their Scientific Advisory Boards and from Abcodia as a consultant. All other authors declare no competing interests., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: There is uncertainty about whether cytoreductive surgery (CRS)+hyperthermic intraoperative peritoneal chemotherapy (HIPEC) improves survival and/or quality of life compared with standard of care (SoC) in people with peritoneal metastases who can withstand major surgery., Primary Objectives: To compare the relative benefits and harms of CRS+HIPEC versus SoC in people with peritoneal metastases from colorectal, ovarian or gastric cancers eligible to undergo CRS+HIPEC by a systematic review and individual participant data (IPD) meta-analysis., Secondary Objectives: To compare the cost-effectiveness of CRS+HIPEC versus SoC from a National Health Service (NHS) and personal social services perspective using a model-based cost-utility analysis., Methods and Analysis: We will perform a systematic review of literature by updating the searches from MEDLINE, Embase, Cochrane library, Science Citation Index as well as trial registers. Two members of our team will independently screen the search results and identify randomised controlled trials comparing CRS+HIPEC versus SoC for inclusion based on full texts for articles shortlisted during screening. We will assess the risk of bias in the trials and obtain data related to baseline prognostic characteristics, details of intervention and control, and outcome data related to overall survival, disease progression, health-related quality of life, treatment related complications and resource utilisation data. Using IPD, we will perform a two-step IPD, that is, calculate the adjusted effect estimate from each included study and then perform a random-effects model meta-analysis. We will perform various subgroup analyses, meta-regression and sensitivity analyses. We will also perform a model-based cost-utility analysis to assess whether CRS+HIPEC is cost-effective in the NHS setting., Ethics and Dissemination: This project was approved by the UCL Research Ethics Committee (Ethics number: 16023/001). We aim to present the findings at appropriate international meetings and publish the review, irrespective of the findings, in a peer-reviewed journal., Prospero Registration Number: CRD42019130504., Competing Interests: Competing interests: The clinical practice of the clinicians in the project: TM, MM, MS, OA and SO may be altered by the findings of the review., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Objective: Pathogenic BRCA variants account for 5.8-24.8% of ovarian cancers. The identification of such a variant can have a significant impact on the affected individual and their relatives, determining eligibility for targeted therapies, predicting treatment response, and granting access to disease prevention strategies. Cancer services are responding to the increased demand for genetic testing with the introduction of mainstreamed genetic testing via oncology clinics. This study aimed to evaluate patient experience of the mainstreamed genetic testing pathway at a tertiary referral center in London, UK., Methods: Study participants were patients diagnosed with high-grade non-mucinous ovarian cancer, tested via a mainstreamed genetic testing pathway at the tertiary referral center between February 2015 and June 2017. Eligible participants were invited to complete the retrospective study questionnaire. Five quantitative measures with additional free-text items were used to evaluate the patient experience of mainstreamed genetic testing., Results: The tertiary referral center tested 170 ovarian cancer patients. Twenty-three pathogenic BRCA mutations were identified (23/170, 13.5%). One-hundred and six patients (106/170, 62.4%) met the study inclusion criteria. Twenty-nine of those invited to participate (29/106, 27.4%) returned the retrospective study questionnaire. Pathogenic BRCA1/2 variants were identified within four respondents (4/29, 13.8%). Motivations for genetic testing related to improved medical management, and the ability to provide relatives with genetic information. Participants did not appear to be adversely affected by result disclosure post-mainstreamed genetic testing. Two individuals with a pathogenic variant reported that the support provided by the tertiary referral center post-result disclosure could have been improved., Conclusion: Results of the current study support further psychosocial research into the expansion of the mainstreamed genetic testing pathway. The results, although promising, have also highlighted the importance of genetic awareness within the multi-disciplinary team and the provision of timely psychological support from genetic specialists., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Preservation of fertility in cancer patients of reproductive age is a concern for both the patient and the clinician. In this study, we aimed to study the effectiveness of laparoscopic ovarian transposition or ovariopexy in preserving ovarian function in women undergoing pelvic radiotherapy with or without chemotherapy for pelvic tumours., Methods: The records of patients who underwent laparoscopic ovarian transposition or ovariopexy prior to pelvic radiation therapy between 2002 and 2018 were reviewed retrospectively., Results: Thirty-nine women or adolescent girls with a diagnosis of cervical cancer (n=15), Hodgkin's lymphoma (n=6) or other types of pelvic tumours (n=18) were included in the study. The majority of patients had bilateral (n=25) or unilateral (n=8) ovarian transposition prior to radiotherapy. Nine out of 10 (90%) patients with soft tissue tumors, Ewing sarcoma or ependymoma, five out of seven (71.4%) patients with Hodgkin's lymphoma, two patients (100%) with rectal and anal cancer, and six out of 15 (40%) with cervical cancer retained ovarian function. Patients with cervical cancer, those who received concomitant chemotherapy and those older than 30 years were more likely to experience ovarian failure. Five patients conceived spontaneously and two women had four live births., Conclusion: Laparoscopic repositioning of the ovaries out of the radiation field in order to protect ovarian function in patients receiving radiotherapy appears to be effective in the majority of patients. The procedure seems safe and should be considered either as a sole procedure or in association with other fertility preservation methods prior to pelvic radiotherapy., (Copyright © 2019 Facts, Views & Vision.)

Background: Ovarian cancer is the fifth most common cause of cancer death for women in the UK. Up to 18% of cases can be attributed to germline mutations in BRCA1 and BRCA2 genes. Identifying patients who carry a BRCA mutation provides important information about potential response to treatment and eligibility for therapies such as poly ADP ribose polymerase (PARP) inhibitors. Implementation of systematic genetic testing of patients with ovarian cancer via oncology clinics (mainstreamed genetic testing, MGT) is increasing., Methods and Results: This service evaluation reports on the first year of MGT at a tertiary oncology centre in London, UK. In total, 122 patients with high-grade non-mucinous ovarian cancer underwent BRCA germline testing via MGT. Eighteen patients (14.8%) were found to carry a deleterious BRCA1 / BRCA2 mutation. Four BRCA carriers did not meet previous criteria for genetic testing and would have been missed. Six BRCA carriers accessed PARP inhibitors post-MGT. Only 22% of patients with a variant of unknown significance (VUS) were referred to clinical genetics services., Conclusions: MGT appears to be a feasible way of providing BRCA testing to patients with ovarian cancer. Greater clarity of how oncologists use VUS results is needed, as well as further research on psychosocial implications of MGT for patients with ovarian cancer, which may include somatic testing in the future., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2019. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: To assess the within-trial cost-effectiveness of an NHS ovarian cancer screening (OCS) programme using data from UKCTOCS and extrapolate results based on average life expectancy., Methods: Within-trial economic evaluation of no screening (C) vs either (1) an annual OCS programme using transvaginal ultrasound (USS) or (2) an annual ovarian cancer multimodal screening programme with serum CA125 interpreted using a risk algorithm (ROCA) and transvaginal ultrasound as a second-line test (MMS), plus comparison of lifetime extrapolation of the no screening arm and the MMS programme using both a predictive and a Markov model., Results: Using a CA125-ROCA cost of £20, the within-trial results show USS to be strictly dominated by MMS, with the MMS vs C comparison returning an incremental cost-effectiveness ratio (ICER) of £91 452 per life year gained (LYG). If the CA125-ROCA unit cost is reduced to £15, the ICER becomes £77 818 per LYG. Predictive extrapolation over the expected lifetime of the UKCTOCS women returns an ICER of £30 033 per LYG, while Markov modelling produces an ICER of £46 922 per QALY., Conclusion: Analysis suggests that, after accounting for the lead time required to establish full mortality benefits, a national OCS programme based on the MMS strategy quickly approaches the current NICE thresholds for cost-effectiveness when extrapolated out to lifetime as compared with the within-trial ICER estimates. Whether MMS could be recommended on economic grounds would depend on the confirmation and size of the mortality benefit at the end of an ongoing follow-up of the UKCTOCS cohort.

Background: Current standard neoadjuvant treatment for advanced ovarian cancer is 3-weekly platinum-based chemotherapy (CP3w). Patients unable to have interval debulking surgery (IDS) or with significant residual disease have a poor outcome to CP3w treatment. We investigated the outcome in patients who were switched to dose-dense chemotherapy., Methods: We retrospectively analysed 30 patients treated at UCLH in 2009-2013, who switched to dose-dense chemotherapy after neoadjuvant CP3w, having achieved a poor response/progressed and unable to proceed to IDS (n=21), or had >1 cm residual disease after IDS (n=9). Treatment was 3-weekly carboplatin and weekly paclitaxel (n=23), or both drugs weekly (n=7). For comparison, we included 30 matched patients treated with CP3w followed by IDS (n=24, without or ≤1 cm residual disease; n=6, with >1 cm residual disease). Time to progression (TTP) and overall survival (OS) were measured from the date of diagnosis until progression (CT scan or CA-125) and death from any cause, respectively., Results: Baseline characteristics were similar in both groups. The response rate to dose-dense chemotherapy was 70% (Gynecological Cancer Intergroup criteria). In the dose-dense group, 24 patients had tumour progression and 16 died; the corresponding numbers in the control group were 24 and 11. Median TTP was 15.8 months with dose-dense therapy, higher than expected for this patient group, and the same as in the control group (15.7 months) undergoing IDS, p=0.27. Median TTP in patients with residual disease postsurgery was 16.5 months (dose-dense) and 10.8 months (controls), p=0.02. TTP in dose-dense patients who did not have surgery was 10.4 months. Median OS was 31.3 (dose-dense) and 59.6 months (controls), p=0.06. Dose-dense chemotherapy was well tolerated: only three patients interrupted treatment due to toxicity., Conclusion: Switching to dose-dense chemotherapy in patients who failed to respond to CT3w neoadjuvant chemotherapy appears to be an effective strategy and requires further investigation., Competing Interests: Competing interests: None declared.

Objective: To assess the outcome of patients with advanced ovarian cancer (OC) who were treated without surgery, having received upfront chemotherapy and no interval debulking surgery (IDS)., Methods: Retrospective analysis of medical and chemotherapy records of consecutive patients with OC between 2005 and 2013 at UCL Hospitals London, UK who received neoadjuvant chemotherapy (NACT) was then found to be unsuitable for IDS following review by the multidisciplinary team., Results: Eighty-three patients (18%) out of 467 receiving NACT did not undergo IDS. Median age was 70years (range 33-88); out of these 83 patients, 43 (51.8%) presented with stage IV disease. Forty-three of these 83 patients received carboplatin and paclitaxel (CP) (51.8%) and 37 received carboplatin alone (C) (44.6%); 3 patients (3.6%) received other platinum-based combinations. Reasons for not proceeding to surgery were: poor response to chemotherapy after 3-4 cycles of NACT (61/83, 73.5%); comorbidities (12/83, 14.5%); patient decision (4/83, 4.8%). Six patients (7.2%) received <3 cycles of NACT due to a worsening clinical condition. The median overall survival (OS) for patients not undergoing IDS was 18months (95% CI 10-20months). Forty-four of 83 patients (53%) received >2 lines of chemotherapy. In a univariate analysis CP, age <70years, and absence of comorbidities were factors influencing OS. In a multivariate analysis only having received CP remained independently associated with OS (HR 0.49, 95% CI 0.29-0.84)., Conclusions: Chemotherapy alone can provide reasonable disease control in patients unsuitable for IDS and CP should be used if possible., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objectives: The aims of this study were to determine the role of omental sampling in staging of uterine serous carcinoma (USC) and to evaluate its impact on patient outcomes., Materials and Methods: A retrospective study of 106 women with USC who underwent primary surgery between 2005 and 2014 was done. Overall survival, disease-free survival, and progression and recurrence patterns were studied in 84 patients with follow-up over 1 year. Diagnostic characteristics were evaluated for preoperative imaging and operative findings. Univariate and multivariate analyses were performed to evaluate risk factors for omental metastasis. Survival curves were used to compare omental sampling status and the presence of omental metastasis., Results: Of the 106 patients, 66 underwent surgical staging with omental biopsy (54; 82%) or omentectomy (12, 18%). Eight (12%) patients had metastatic disease in the omental samplings. All 6 patients with macrometastasis had visible lesions or palpable nodules and preoperative computed tomography (CT) was suspicious in 3. In 2 (3%) patients, omentum was not suspicious on CT or intraoperatively but had micrometastases. The negative predictive value regarding the staging CT scan was 92% and of the operative findings was 97%. On multivariate analysis, no variable was associated with omental involvement. Disease progressed or recurred in 40 (48%) patients. The most frequent sites of recurrence or progression were the omentum (23; 27%), peritoneum (26; 31%), pelvis (15, 18%), lung (15, 18%), and liver (12, 14%). Comparing the groups with or without omental assessment, no significant difference was found regarding progression and recurrence patterns, overall survival, and disease-free survival., Conclusions: Omental involvement in USC upstages patients to stage IV disease and traditional risk factors fail to predict extrauterine disease. Although omental sampling does not influence disease progression or survival, a comprehensive intraoperative evaluation of the omentum is advised as most cases have grossly visible lesions.

Objective: A noninvasive tool that allows individuals to be monitored who are at risk of developing a malignancy is an unmet need. Such a test would need to consist of a molecular signature that allows for gradual judgment to assess the efficacy of preventive strategies. Here we performed a proof-of-principle study to test whether a DNA methylation (DNAme) signature in fluid collected from the vagina is able to identify women with cervical or endometrial cancer., Materials and Methods: DNA from vaginal fluid samples from 111 women (30, 8, 73 with endometrial cancer, cervical cancer, and benign gynecological conditions, respectively) were analyzed for DNAme using the Illumina 450k DNA methylation bead array assay, which allows the assessment of DNAme at more than 480.000 CpG sites. We developed a cervical and an endometrial cancer DNAme signature by comparing normal and cancerous cervical and endometrial samples from the publicly available The Cancer Genome Atlas data and developed deviation scores to assess the potential of discriminating cancer from a control sample using a vaginal fluid DNAme signature., Results: More than 60% of variations in DNAme in our vaginal fluid cannot be explained by those clinical or technical factors that we were aware of. Both the cervical and the endometrial cancer DNAme signature resulted in receiver operating characteristic area under the curve between 0.75 and 0.83 to discriminate controls and the cancers for which the signature has been designed for., Conclusions: Whole DNAme signatures based on array technologies in body fluids are able to discriminate cancer cases from controls.

Background: Ovarian cancer has a poor prognosis, with just 40% of patients surviving 5 years. We designed this trial to establish the effect of early detection by screening on ovarian cancer mortality., Methods: In this randomised controlled trial, we recruited postmenopausal women aged 50-74 years from 13 centres in National Health Service Trusts in England, Wales, and Northern Ireland. Exclusion criteria were previous bilateral oophorectomy or ovarian malignancy, increased risk of familial ovarian cancer, and active non-ovarian malignancy. The trial management system confirmed eligibility and randomly allocated participants in blocks of 32 using computer-generated random numbers to annual multimodal screening (MMS) with serum CA125 interpreted with use of the risk of ovarian cancer algorithm, annual transvaginal ultrasound screening (USS), or no screening, in a 1:1:2 ratio. The primary outcome was death due to ovarian cancer by Dec 31, 2014, comparing MMS and USS separately with no screening, ascertained by an outcomes committee masked to randomisation group. All analyses were by modified intention to screen, excluding the small number of women we discovered after randomisation to have a bilateral oophorectomy, have ovarian cancer, or had exited the registry before recruitment. Investigators and participants were aware of screening type. This trial is registered with ClinicalTrials.gov, number NCT00058032., Findings: Between June 1, 2001, and Oct 21, 2005, we randomly allocated 202,638 women: 50,640 (25·0%) to MMS, 50,639 (25·0%) to USS, and 101,359 (50·0%) to no screening. 202,546 (>99·9%) women were eligible for analysis: 50,624 (>99·9%) women in the MMS group, 50,623 (>99·9%) in the USS group, and 101,299 (>99·9%) in the no screening group. Screening ended on Dec 31, 2011, and included 345,570 MMS and 327,775 USS annual screening episodes. At a median follow-up of 11·1 years (IQR 10·0-12·0), we diagnosed ovarian cancer in 1282 (0·6%) women: 338 (0·7%) in the MMS group, 314 (0·6%) in the USS group, and 630 (0·6%) in the no screening group. Of these women, 148 (0·29%) women in the MMS group, 154 (0·30%) in the USS group, and 347 (0·34%) in the no screening group had died of ovarian cancer. The primary analysis using a Cox proportional hazards model gave a mortality reduction over years 0-14 of 15% (95% CI -3 to 30; p=0·10) with MMS and 11% (-7 to 27; p=0·21) with USS. The Royston-Parmar flexible parametric model showed that in the MMS group, this mortality effect was made up of 8% (-20 to 31) in years 0-7 and 23% (1-46) in years 7-14, and in the USS group, of 2% (-27 to 26) in years 0-7 and 21% (-2 to 42) in years 7-14. A prespecified analysis of death from ovarian cancer of MMS versus no screening with exclusion of prevalent cases showed significantly different death rates (p=0·021), with an overall average mortality reduction of 20% (-2 to 40) and a reduction of 8% (-27 to 43) in years 0-7 and 28% (-3 to 49) in years 7-14 in favour of MMS., Interpretation: Although the mortality reduction was not significant in the primary analysis, we noted a significant mortality reduction with MMS when prevalent cases were excluded. We noted encouraging evidence of a mortality reduction in years 7-14, but further follow-up is needed before firm conclusions can be reached on the efficacy and cost-effectiveness of ovarian cancer screening., Funding: Medical Research Council, Cancer Research UK, Department of Health, The Eve Appeal., (Copyright © 2016 Jacobs Menon et al. Open Access article published under the terms of CC BY. Published by Elsevier Ltd.. All rights reserved.)

Background: This is a feasibility study to determine whether circulating tumour cells (CTCs) are detectable and suitable for molecular profiling in advanced endometrial cancer (aEC)., Method: Between October 2012 and February 2014, 30 patients with aEC had baseline and up to 3 follow-up samples. CTCs and stathmin expression were evaluated using the CellSearch platform. Epithelial cell adhesion molecule (EpCAM) and stathmin immunohistochemistry were performed on FFPE tumour tissue., Results: Eighteen from 30 (60%) patients had detectable CTCs during study [1 CTC (n = 7), 2 (n = 4), 3 (n = 1), 4 (n = 2), 7 (n = 1), 8 (n = 1), 22 (n = 1), 172 (n = 1) in 7.5 ml blood]. Ten from 18 patients had between 50 and 100% of detectable CTCs that were stathmin positive. More CTC-positive than CTC-negative patients had non-endometrioid versus endometrioid histology, tumour size ≥5 versus <5 cm, higher-stage disease and worse survival [hazard ratio 3.3, p > 0.05, 95% confidence interval 0.7-16.2]. Twenty-one tumour blocks were tested for EpCAM and stathmin immunohistochemistry (IHC). Stathmin tumour immunostaining scores (TIS) on IHC were higher in CTC-positive patients., Conclusion: CTC enumeration and molecular profiling with stathmin on the CellSearch platform is feasible in aEC. Stathmin TIS on IHC, a known prognostic marker in EC, was associated with CTC positivity., (© 2016 S. Karger AG, Basel.)

Purpose: Cancer screening strategies have commonly adopted single-biomarker thresholds to identify abnormality. We investigated the impact of serial biomarker change interpreted through a risk algorithm on cancer detection rates., Patients and Methods: In the United Kingdom Collaborative Trial of Ovarian Cancer Screening, 46,237 women, age 50 years or older underwent incidence screening by using the multimodal strategy (MMS) in which annual serum cancer antigen 125 (CA-125) was interpreted with the risk of ovarian cancer algorithm (ROCA). Women were triaged by the ROCA: normal risk, returned to annual screening; intermediate risk, repeat CA-125; and elevated risk, repeat CA-125 and transvaginal ultrasound. Women with persistently increased risk were clinically evaluated. All participants were followed through national cancer and/or death registries. Performance characteristics of a single-threshold rule and the ROCA were compared by using receiver operating characteristic curves., Results: After 296,911 women-years of annual incidence screening, 640 women underwent surgery. Of those, 133 had primary invasive epithelial ovarian or tubal cancers (iEOCs). In all, 22 interval iEOCs occurred within 1 year of screening, of which one was detected by ROCA but was managed conservatively after clinical assessment. The sensitivity and specificity of MMS for detection of iEOCs were 85.8% (95% CI, 79.3% to 90.9%) and 99.8% (95% CI, 99.8% to 99.8%), respectively, with 4.8 surgeries per iEOC. ROCA alone detected 87.1% (135 of 155) of the iEOCs. Using fixed CA-125 cutoffs at the last annual screen of more than 35, more than 30, and more than 22 U/mL would have identified 41.3% (64 of 155), 48.4% (75 of 155), and 66.5% (103 of 155), respectively. The area under the curve for ROCA (0.915) was significantly (P = .0027) higher than that for a single-threshold rule (0.869)., Conclusion: Screening by using ROCA doubled the number of screen-detected iEOCs compared with a fixed cutoff. In the context of cancer screening, reliance on predefined single-threshold rules may result in biomarkers of value being discarded., (© 2015 by American Society of Clinical Oncology.)