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

被引：140

作者：

Menon, Usha ^{[1
]}

Ryan, Andy ^{[1
]}

Kalsi, Jatinderpal ^{[1
]}

Gentry-Maharaj, Aleksandra ^{[1
]}

Dawnay, Anne ^{[2
]}

Habib, Mariam ^{[1
]}

Apostolidou, Sophia ^{[1
]}

Singh, Naveena ^{[3
]}

Benjamin, Elizabeth ^{[1
]}

Burnell, Matthew ^{[1
]}

Davies, Susan ^{[1
]}

Sharma, Aarti ^{[7
]}

Gunu, Richard ^{[1
]}

Godfrey, Keith ^{[9
]}

Lopes, Alberto ^{[10
]}

Oram, David ^{[4
]}

Herod, Jonathan ^{[11
]}

Williamson, Karin ^{[12
]}

Seif, Mourad W. ^{[13
]}

Jenkins, Howard ^{[14
]}

Mould, Tim ^{[2
]}

Woolas, Robert ^{[15
]}

Murdoch, John B. ^{[16
]}

Dobbs, Stephen ^{[17
]}

Amso, Nazar N. ^{[8
]}

Leeson, Simon ^{[18
]}

Cruickshank, Derek ^{[19
]}

Scott, Ian

Fallowfield, Lesley ^{[20
]}

Widschwendter, Martin ^{[1
]}

Reynolds, Karina ^{[4
]}

McGuire, Alistair ^{[5
]}

Campbell, Stuart ^{[6
]}

Parmar, Mahesh ^{[1
]}

Skates, Steven J. ^{[21
,22
]}

Jacobs, Ian ^{[1
,14
,23
]}

机构：

[1] UCL, London W1T 7DN, England

[2] Univ Coll London Hosp, London, England

[3] Barts & London Queen Marys Sch Med & Dent, London, England

[4] St Bartholomews Hosp, London, England

[5] London Sch Econ, London, England

[6] Create Hlth Clin, Waterloo, ON, Canada

[7] Univ Wales Hosp, Cardiff, S Glam, Wales

[8] Cardiff Univ, Cardiff CF10 3AX, S Glam, Wales

[9] Queen Elizabeth Hosp, Gateshead, England

[10] Royal Cornwall Hosp, Truro, England

[11] Liverpool Womens Hosp, Liverpool, Merseyside, England

[12] City Hosp Nottingham, Nottingham, England

[13] St Marys Hosp, Manchester, England

[14] Royal Derby Hosp, Derby, England

[15] Queen Alexandra Hosp, Portsmouth, Hants, England

[16] St Michaels Hosp, Bristol, Avon, England

[17] Belfast City Hosp, Belfast BT9 7AD, Antrim, North Ireland

[18] Llandudno Hosp, Ysbyty Gwynedd, England

[19] James Cook Univ Hosp, Middlesbrough, Cleveland, England

[20] Univ Sussex, Falmer, England

[21] Massachusetts Gen Hosp, Boston, MA 02114 USA

[22] Harvard Univ, Sch Med, Boston, MA 02115 USA

[23] UNSW Australia, Sydney, NSW, Australia

来源：

JOURNAL OF CLINICAL ONCOLOGY | 2015年 / 33卷 / 18期

基金：

英国医学研究理事会;

关键词：

ANTIGEN VELOCITY; PROSTATE; MORTALITY; LUNG; RECRUITMENT; MULTICENTER; IMPACT; ROCA;

D O I：

10.1200/JCO.2014.59.4945

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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. (C) 2015 American Society of Clinical Oncology.

引用

页码：2062 / U114

页数：14

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