在英国卵巢癌筛查协作试验中，与单阈值规则相比，使用系列生物标志物测量的风险算法使筛查发现的癌症数量增加了一倍。
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.
作者信息
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 Karin, 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, Jacobs Ian
机构信息
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.
出版信息
J Clin Oncol. 2015 Jun 20;33(18):2062-71. doi: 10.1200/JCO.2014.59.4945. Epub 2015 May 11.
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.
目的
癌症筛查策略通常采用单一生物标志物阈值来识别异常情况。我们研究了通过风险算法解读的系列生物标志物变化对癌症检出率的影响。
患者与方法
在英国卵巢癌筛查协作试验中，46237名50岁及以上的女性采用多模式策略（MMS）进行发病率筛查，其中每年的血清癌抗原125（CA - 125）通过卵巢癌风险算法（ROCA）进行解读。女性根据ROCA进行分类：低风险，返回年度筛查；中度风险，重复检测CA - 125；高风险，重复检测CA - 125并进行经阴道超声检查。风险持续增加的女性接受临床评估。所有参与者通过国家癌症和/或死亡登记处进行随访。使用受试者操作特征曲线比较单一阈值规则和ROCA的性能特征。
结果
经过296911人年的年度发病率筛查后，640名女性接受了手术。其中，133人患有原发性浸润性上皮性卵巢或输卵管癌（iEOC）。总共22例间隔期iEOC在筛查后1年内发生，其中1例由ROCA检测到，但在临床评估后进行了保守处理。MMS检测iEOC的敏感性和特异性分别为85.8%（95%CI，79.3%至90.9%）和99.8%（95%CI，99.8%至99.8%），每例iEOC进行4.8次手术。仅ROCA检测到87.1%（155例中的135例）的iEOC。在最后一次年度筛查时，使用固定的CA - 125临界值超过35 U/mL、超过30 U/mL和超过22 U/mL分别可识别41.3%（155例中的64例）、48.4%（155例中的75例）和66.5%（155例中的103例）。ROCA的曲线下面积（0.915）显著高于单一阈值规则（0.869）（P = 0.0027）。
结论
与固定临界值相比，使用ROCA进行筛查使筛查发现的iEOC数量增加了一倍。在癌症筛查的背景下，依赖预定义的单一阈值规则可能会导致有价值的生物标志物被丢弃。
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