TY  - JOUR
KW  - Science & Technology
KW  -  Life Sciences & Biomedicine
KW  -  Medicine
KW  -  General & Internal
KW  -  Medicine
KW  -  Research & Experimental
KW  -  General & Internal Medicine
KW  -  Research & Experimental Medicine
KW  -  CA-125 antigen
KW  -  Blood
KW  -  Carcinoma
KW  -  Ovarian epithelial*
KW  -  Early detection of cancer*
KW  -  Longitudinal studies
KW  -  Ovarian neoplasms*
KW  -  Epidemiology
KW  -  UKCTOCS
KW  -  Mass screening
KW  -  Biomarker
KW  -  Preclinical history of cancer
KW  -  Preclinical detectable phase
KW  -  Natural history of cancer
KW  -  Early diagnosis
KW  -  UK COLLABORATIVE TRIAL
KW  -  MUTATIONS
KW  -  MORTALITY
KW  -  SYMPTOMS
KW  -  PROSTATE
KW  -  ROUTES
KW  -  WOMEN
KW  -  RISK
KW  -  LUNG
A1  - Bedia, Jacob S
A1  - Jacobs, Ian J
A1  - Ryan, Andy
A1  - Gentry-Maharaj, Aleksandra
A1  - Burnell, Matthew
A1  - Singh, Naveena
A1  - Manchanda, Ranjit
A1  - Kalsi, Jatinderpal K
A1  - Dawnay, Anne
A1  - Fallowfield, Lesley
A1  - Mcguire, Alistair J
A1  - Campbell, Stuart
A1  - Parmar, Mahesh KB
A1  - Menon, Usha
A1  - Skates, Steven J
JF  - eBioMedicine
SN  - 2352-3964
UR  - https://doi.org/10.1016/j.ebiom.2024.105554
PB  - ELSEVIER
ID  - discovery10204755
N2  - 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.
N1  - 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/).
EP  - 13
AV  - public
VL  - 112
Y1  - 2025/02//
TI  - 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
ER  -