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J Clin Oncol. 2015 Jun 20;33(18):2062-71. doi: 10.1200/JCO.2014.59.4945. Epub 2015 May 11.

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.

Author information

1
Usha Menon, Andy Ryan, Jatinderpal Kalsi, Aleksandra Gentry-Maharaj, Mariam Habib, Sophia Apostolidou, Matthew Burnell, Susan Davies, Richard Gunu, Martin Widschwendter, Elizabeth Benjamin, Mahesh Parmar, and Ian Jacobs, University College London; Anne Dawnay and Tim Mould, University College London Hospital; Naveena Singh, Barts and the London School of Medicine and Dentistry; David Oram and Karina Reynolds, St Bartholomew's Hospital; Alistair McGuire, London School of Economics; Stuart Campbell, Create Health Clinic; Aarti Sharma, University Hospital of Wales; Nazar N. Amso, Cardiff University, Cardiff; Keith Godfrey, Queen Elizabeth Hospital, Gateshead; Alberto Lopes, Royal Cornwall Hospital, Truro; Jonathan Herod, Liverpool Women's Hospital, Liverpool; Karin Williamson, Nottingham City Hospital, Nottingham; Mourad W. Seif, St Mary's Hospital, Manchester; Howard Jenkins and Ian Scott, Royal Derby Hospital, Derby; Robert Woolas, Queen Alexandra Hospital, Portsmouth; John B. Murdoch, St Michael's Hospital, Bristol; Stephen Dobbs, Belfast City Hospital, Belfast; Simon Leeson, Llandudno Hospital, Ysbyty Gwynedd; Derek Cruickshank, James Cook University Hospital, Middlesbrough; Lesley Fallowfield, University of Sussex, Falmer, United Kingdom; Steven J. Skates, Massachusetts General Hospital and Harvard Medical School, Boston, MA; and Ian Jacobs, UNSW Australia, Sydney, NSW, Australia. u.menon@ucl.ac.uk.
2
Usha Menon, Andy Ryan, Jatinderpal Kalsi, Aleksandra Gentry-Maharaj, Mariam Habib, Sophia Apostolidou, Matthew Burnell, Susan Davies, Richard Gunu, Martin Widschwendter, Elizabeth Benjamin, Mahesh Parmar, and Ian Jacobs, University College London; Anne Dawnay and Tim Mould, University College London Hospital; Naveena Singh, Barts and the London School of Medicine and Dentistry; David Oram and Karina Reynolds, St Bartholomew's Hospital; Alistair McGuire, London School of Economics; Stuart Campbell, Create Health Clinic; Aarti Sharma, University Hospital of Wales; Nazar N. Amso, Cardiff University, Cardiff; Keith Godfrey, Queen Elizabeth Hospital, Gateshead; Alberto Lopes, Royal Cornwall Hospital, Truro; Jonathan Herod, Liverpool Women's Hospital, Liverpool; Karin Williamson, Nottingham City Hospital, Nottingham; Mourad W. Seif, St Mary's Hospital, Manchester; Howard Jenkins and Ian Scott, Royal Derby Hospital, Derby; Robert Woolas, Queen Alexandra Hospital, Portsmouth; John B. Murdoch, St Michael's Hospital, Bristol; Stephen Dobbs, Belfast City Hospital, Belfast; Simon Leeson, Llandudno Hospital, Ysbyty Gwynedd; Derek Cruickshank, James Cook University Hospital, Middlesbrough; Lesley Fallowfield, University of Sussex, Falmer, United Kingdom; Steven J. Skates, Massachusetts General Hospital and Harvard Medical School, Boston, MA; and Ian Jacobs, UNSW Australia, Sydney, NSW, Australia.

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.

PMID:
25964255
PMCID:
PMC4463475
DOI:
10.1200/JCO.2014.59.4945
[Indexed for MEDLINE]
Free PMC Article

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