TY - JOUR
T1 - 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
AU - Menon, Usha
AU - Ryan, Andy
AU - Kalsi, Jatinderpal
AU - Gentry-Maharaj, Aleksandra
AU - Dawnay, Anne
AU - Habib, Mariam
AU - Apostolidou, Sophia
AU - Singh, Naveena
AU - Benjamin, Elizabeth
AU - Burnell, Matthew
AU - Davies, Susan
AU - Sharma, Aarti
AU - Gunu, Richard
AU - Godfrey, Keith
AU - Lopes, Alberto
AU - Oram, David
AU - Herod, Jonathan
AU - Williamson, Karin
AU - Seif, Mourad W.
AU - Jenkins, Howard
AU - Mould, Tim
AU - Woolas, Robert
AU - Murdoch, John B.
AU - Dobbs, Stephen
AU - Amso, Nazar N.
AU - Leeson, Simon
AU - Cruickshank, Derek
AU - Scott, Ian
AU - Fallowfield, Lesley
AU - Widschwendter, Martin
AU - Reynolds, Karina
AU - McGuire, Alistair
AU - Campbell, Stuart
AU - Parmar, Mahesh
AU - Skates, Steven J.
AU - Jacobs, Ian
PY - 2015/6/20
Y1 - 2015/6/20
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84930654984&partnerID=8YFLogxK
U2 - 10.1200/JCO.2014.59.4945
DO - 10.1200/JCO.2014.59.4945
M3 - Article
C2 - 25964255
AN - SCOPUS:84930654984
SN - 0732-183X
VL - 33
SP - 2062
EP - 2071
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 18
ER -
