Risk algorithm using serial biomarker measurements doubles the number of screen-detected cancers compared with a single-threshold rule in the United Kingdom collaborative trial of ovarian cancer screening

Menon, Usha, Ryan, Andy, Kalsi, Jatinderpal, Gentry-Maharaj, Aleksandra, Dawnay, Anne, Habib, Mariam, Apostolidou, Sophia, Singh, Naveena, Benjamin, Elizabeth, Burnell, Matthew, Davies, Susan, Sharma, Aarti, Gunu, Richard, Godfrey, Keith, Lopes, Alberto, Oram, David, Herod, Jonathan, Williamson, Kevin, Seif, Mourad W, Jenkins, Howard, Mould, Tim, Woolas, Robert, Murdoch, John B, Dobbs, Stephen, Amso, Nazar N, Leeson, Simon, Cruickshank, Derek, Scott, Ian, Fallowfield, Lesley, Widschwendter, Martin, Reynolds, Karina, McGuire, Alistair, Campbell, Stuart, Parmar, Mahesh, Skates, Steven J and Jacobs, Ian (2015) Risk algorithm using serial biomarker measurements doubles the number of screen-detected cancers compared with a single-threshold rule in the United Kingdom collaborative trial of ovarian cancer screening. Journal of Clinical Oncology, 33 (18). pp. 2062-2071. ISSN 0732-183X

[img]
Preview
PDF - Published Version
Available under License Creative Commons Attribution.

Download (813kB) | Preview

Abstract

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.

Item Type: Article
Keywords: ovarian cancer screening, risk algorithm, serial biomarkers
Schools and Departments: Brighton and Sussex Medical School > Sussex Health Outcomes Research & Education in Cancer (SHORE-C)
Subjects: R Medicine > RC Internal medicine
R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology Including cancer and carcinogens
Depositing User: Kathryn Monson
Date Deposited: 18 Jun 2015 13:26
Last Modified: 10 Mar 2017 07:00
URI: http://sro.sussex.ac.uk/id/eprint/54598

View download statistics for this item

📧 Request an update
Project NameSussex Project NumberFunderFunder Ref
UnsetRQ01-G0543Medical Research CouncilG000073