eprintid: 10204755
rev_number: 7
eprint_status: archive
userid: 699
dir: disk0/10/20/47/55
datestamp: 2025-02-14 10:57:49
lastmod: 2025-02-14 10:57:49
status_changed: 2025-02-14 10:57:49
type: article
metadata_visibility: show
sword_depositor: 699
creators_name: Bedia, Jacob S
creators_name: Jacobs, Ian J
creators_name: Ryan, Andy
creators_name: Gentry-Maharaj, Aleksandra
creators_name: Burnell, Matthew
creators_name: Singh, Naveena
creators_name: Manchanda, Ranjit
creators_name: Kalsi, Jatinderpal K
creators_name: Dawnay, Anne
creators_name: Fallowfield, Lesley
creators_name: Mcguire, Alistair J
creators_name: Campbell, Stuart
creators_name: Parmar, Mahesh KB
creators_name: Menon, Usha
creators_name: Skates, Steven J
title: Estimating the ovarian cancer CA-125 preclinical detectable phase, in-vivo tumour doubling time, and window for detection in early stage: an exploratory analysis of UKCTOCS
ispublished: pub
divisions: UCL
divisions: B02
divisions: D11
divisions: D65
divisions: J38
keywords: Science & Technology, Life Sciences & Biomedicine, Medicine, General & Internal, Medicine, Research & Experimental, General & Internal Medicine, Research & Experimental Medicine, CA-125 antigen, Blood, Carcinoma, Ovarian epithelial*, Early detection of cancer*, Longitudinal studies, Ovarian neoplasms*, Epidemiology, UKCTOCS, Mass screening, Biomarker, Preclinical history of cancer, Preclinical detectable phase, Natural history of cancer, Early diagnosis, UK COLLABORATIVE TRIAL, MUTATIONS, MORTALITY, SYMPTOMS, PROSTATE, ROUTES, WOMEN, RISK, LUNG
note: Copyright © 2025 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND
license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
abstract: Background: The ovarian cancer (OC) preclinical detectable phase (PCDP), defined as the interval during which cancer is detectable prior to clinical diagnosis, remains poorly characterised. We report exploratory analyses from the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). Methods: In UKCTOCS between Apr-2001 and Sep-2005, 101,314 postmenopausal women were randomised to no screening (NS) and 50,625 to annual multimodal screening (MMS) (until Dec-2011) using serum CA-125 interpreted by the Risk of Ovarian Cancer Algorithm (ROCA). All provided a baseline blood sample. Women with invasive epithelial OC diagnosed between randomisation and trial censorship (Dec-2014) in the MMS and NS arms with two or more CA-125 measurements, including one within two years of diagnosis were included. OC-free women (2:1 to cases) from the MMS arm provided information on baseline CA-125 distribution. CA-125 measurements were obtained from MMS results, secondary analysis of baseline samples, and medical records. PCDP duration and in-vivo tumour doubling time were estimated using the change-point model underlying ROCA. Early-stage (Stage I and II) PCDP was estimated from a Bayesian model for the probability of early stage given a CA-125 measurement. Findings: Of 541 women (2371 CA-125 measurements) with high-grade serous cancer (HGSC), 93% (504/541) secreted CA-125 into the circulation. Median CA-125 PCDP duration for clinically-diagnosed HGSC was 15.2 (IQR 13.1–16.9, 95% IPR 9.6–21.8) months, of which 11.9 (IQR 10.5–13.1, 95% IPR 7.5–16.5) months was in early stage. The median HGSC in-vivo tumour doubling time for cancers secreting CA-125 was 2.9 (IQR 2.3–3.7, 95% IPR 1.5–7.6) months. Interpretation: We report a comprehensive characterisation of the OC CA-125 PCDP. The 12-month window for early-stage detection and short tumour doubling time of HGSC provide a benchmark for researchers evaluating novel screening approaches including need to reduce diagnostic workup interval. Equally the findings provide urgent impetus for clinicians to reduce intervals from presentation to treatment onset. Funding: NCI Early Detection Research Network, Concord (MA) Detect Ovarian Cancer Early Fund, MRC Clinical Trials Unit at UCL Core Funding.
date: 2025-02
date_type: published
publisher: ELSEVIER
official_url: https://doi.org/10.1016/j.ebiom.2024.105554
oa_status: green
full_text_type: pub
language: eng
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 2353129
doi: 10.1016/j.ebiom.2024.105554
medium: Print-Electronic
pii: S2352-3964(24)00590-5
lyricists_name: Gentry-Maharaj, Aleksandra
lyricists_name: Menon, Usha
lyricists_name: Parmar, Mahesh
lyricists_id: AGENT07
lyricists_id: UMENO29
lyricists_id: MKBPA56
actors_name: Menon, Usha
actors_name: Spencer, Susan
actors_id: UMENO29
actors_id: SMSPE80
actors_role: owner
actors_role: impersonator
funding_acknowledgements: U01 CA152990 [National Cancer Institute (NCI) Early Detection Research Network]; U2C CA271871 [National Cancer Institute (NCI) Early Detection Research Network]; [Concord (MA) Detect Ovarian Cancer Early Fund]; U01 CA260758 [NCI]; MC_UU_00004/01 [MRC Clinical Trials Unit at UCL]; G9901012 [MRC]; G0801228 [MRC]; C1479/A2884 [Cancer Research UK]; [UK Department of Health]; [Eve Appeal]; 16/46/01 [NIHR (Health Technology Assessment grant)]
full_text_status: public
publication: eBioMedicine
volume: 112
article_number: 105554
pages: 13
event_location: Netherlands
issn: 2352-3964
citation:        Bedia, Jacob S;    Jacobs, Ian J;    Ryan, Andy;    Gentry-Maharaj, Aleksandra;    Burnell, Matthew;    Singh, Naveena;    Manchanda, Ranjit;                                 ... Skates, Steven J; + view all <#>        Bedia, Jacob S;  Jacobs, Ian J;  Ryan, Andy;  Gentry-Maharaj, Aleksandra;  Burnell, Matthew;  Singh, Naveena;  Manchanda, Ranjit;  Kalsi, Jatinderpal K;  Dawnay, Anne;  Fallowfield, Lesley;  Mcguire, Alistair J;  Campbell, Stuart;  Parmar, Mahesh KB;  Menon, Usha;  Skates, Steven J;   - view fewer <#>    (2025)    Estimating the ovarian cancer CA-125 preclinical detectable phase, in-vivo tumour doubling time, and window for detection in early stage: an exploratory analysis of UKCTOCS.                   eBioMedicine , 112     , Article 105554.  10.1016/j.ebiom.2024.105554 <https://doi.org/10.1016/j.ebiom.2024.105554>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10204755/1/Estimating%20the%20ovarian%20cancer%20CA-125%20preclinical%20detectable%20phase%2C%20in-vivo%20tumour%20doubling%20time%2C%20and%20window%20for%20detection%20in.pdf