@article{a002d6b650ff4bce98c49dd833f67e1e,
title = "The avoiding late diagnosis of ovarian cancer (ALDO) project; a pilot national surveillance programme for women with pathogenic germline variants in BRCA1 and BRCA2",
abstract = "Background Our study aimed to establish 'real-world' performance and cost-effectiveness of ovarian cancer (OC) surveillance in women with pathogenic germline BRCA1/2 variants who defer risk-reducing bilateral salpingo-oophorectomy (RRSO). Methods Our study recruited 875 female BRCA1/2-heterozygotes at 13 UK centres and via an online media campaign, with 767 undergoing at least one 4-monthly surveillance test with the Risk of Ovarian Cancer Algorithm (ROCA) test. Surveillance performance was calculated with modelling of occult cancers detected at RRSO. The incremental cost-effectiveness ratio (ICER) was calculated using Markov population cohort simulation. Results Our study identified 8 OCs during 1277 women screen years: 2 occult OCs at RRSO (both stage 1a), and 6 screen-detected; 3 of 6 (50%) were ≤stage 3a and 5 of 6 (83%) were completely surgically cytoreduced. Modelled sensitivity, specificity, Positive Predictive Value (PPV) and Negative Predictive Value (NPV) for OC were 87.5% (95% CI, 47.3 to 99.7), 99.9% (99.9-100), 75% (34.9-96.8) and 99.9% (99.9-100), respectively. The predicted number of quality-adjusted life years (QALY) gained by surveillance was 0.179 with an ICER cost-saving of -£102,496/QALY. Conclusion OC surveillance for women deferring RRSO in a 'real-world' setting is feasible and demonstrates similar performance to research trials; it down-stages OC, leading to a high complete cytoreduction rate and is cost-saving in the UK National Health Service (NHS) setting. While RRSO remains recommended management, ROCA-based surveillance may be considered for female BRCA-heterozygotes who are deferring such surgery.",
keywords = "Costs and Cost Analysis, Early Diagnosis, Economics, Genetic Predisposition to Disease, Women's Health",
author = "Sue Philpott and Maria Raikou and Ranjit Manchanda and Michelle Lockley and Naveena Singh and Malcolm Scott and Evans, {D Gareth} and Julian Adlard and Munaza Ahmed and Richard Edmondson and Athena Lamnisos and Janos Balega and Brady, {Angela F} and Aarti Sharma and Louise Izatt and Anjana Kulkarni and Vishakha Tripathi and Solomons, {Joyce S} and Helen Hanson and Katie Snape and Lucy Side and Steve Skates and Alistair McGuire and Rosenthal, {Adam N}",
note = "Funding Information: We thank the participants without whom the project would not have been possible. We thank the lead clinicians at collaborating centres and their teams for identifying potential participants, sending out invitation letters, providing ultrasound services and seeing participants in clinic when required. We thank the NHS North Central London (NCL) Cancer Alliance for their continued support and encouragement throughout the project (Nasa Turabi, Emily Collins, Mairead Lyons, Helga Laszlo and Donna Chung). We thank members of the project steering committee (Usha Menon, Nasa Turabi, Jodie Moffat (Cancer Research UK), Caroline Presho (Patient representative), Gareth Evans, Richard Edmondson, Emma Woodward, Julie Barnes and Athena Lamnisos). We also thank the charities who publicised the project to potential participants (Cancer Research UK, The Eve Appeal, Target Ovarian Cancer, Ovarian Cancer Action, Ovacome and BRCA Umbrella). Adam Rosenthal was supported by the NIHR Biomedical Research Centre at University College London Hospitals National Health Service Foundation Trust and University College London. Funding Information: The project was co-funded by Abcodia Ltd and North Central London Cancer Alliance. Abcodia Ltd had no role in the design of the project, nor in the interpretation of the findings or the drafting/editing of the manuscript. Sue Philpott has previously held a consulting role with Abcodia Ltd Adam Rosenthal has previously held a consulting role with Abcodia Ltd and Everything Genetic Ltd. Ranjit Manchanda has received funding from Yorkshire Cancer Research, GSK, Eve Appeal, Cancer Research UK, NHS Innovation Accelerator (NIA), Barts & the London Charity, Rose Trees Trust outside this work for research related to genetic testing and honorarium for advisory board membership or lectures from Astrazeneca/MSD/GSK/EGL. Naveena Singh has served on advisory boards for Astra-Zeneca-MSD and Glaxo SmithKline. Gareth Evans has a consultancy role with AstraZeneca. Helen Hanson has served on advisory boards for AstraZeneca. Steve Skates works at Massachusetts General Hospital which has co-licensed the software for early detection of ovarian cancer to Abcodia and has served on clinical advisory boards for Guardant Health and LUNGevity, has collaborated on early detection research with Freenome, participates in the Independent Data Monitoring Committee for GRAIL and has stock option for serving on the scientific Advisory Board for SISCAPA Assay Technologies. The other authors declare no competing interests. Funding Information: This project was funded by Abcodia Ltd and North Central London Cancer Alliance. Publisher Copyright: {\textcopyright} Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. Publisher Copyright: {\textcopyright} Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.",
year = "2023",
month = may,
day = "11",
doi = "10.1136/jmg-2022-108741",
language = "English",
volume = "60",
pages = "440--449",
journal = "Journal of Medical Genetics",
issn = "1468-6244",
publisher = "BMJ ",
number = "5",
}
