The diagnostic performance of CA125 for the detection of ovarian and non-ovarian cancer in primary care: A population-based cohort study

This is the final version. Available on open access from the Public Library of Science via the DOI in this recordData Availability: Data cannot be shared publicly as they are analysed under licence. All data used in this study are available from CPRD (www.cprd.com). Permission to access data is through the Independent Scientific Advisory Committee (ISAC, contact via: isac@cprd.com). Derived data used to prepare article figures are available from the University of Cambridge Repository: www.repository.cam.ac.uk (https://doi.org/10.17863/CAM.56363).BACKGROUND: The serum biomarker cancer antigen 125 (CA125) is widely used as an investigation for possible ovarian cancer in symptomatic women presenting to primary care. However, its diagnostic performance in this setting is unknown. We evaluated the performance of CA125 in primary care for the detection of ovarian and non-ovarian cancers. METHODS AND FINDINGS: We studied women in the United Kingdom Clinical Practice Research Datalink with a CA125 test performed between 1 May 2011-31 December 2014. Ovarian and non-ovarian cancers diagnosed in the year following CA125 testing were identified from the cancer registry. Women were categorized by age: <50 years and ≥50 years. Conventional measures of test diagnostic accuracy, including sensitivity, specificity, and positive predictive value, were calculated for the standard CA125 cut-off (≥35 U/ml). The probability of a woman having cancer at each CA125 level between 1-1,000 U/ml was estimated using logistic regression. Cancer probability was also estimated on the basis of CA125 level and age in years using logistic regression. We identified CA125 levels equating to a 3% estimated cancer probability: the "risk threshold" at which the UK National Institute for Health and Care Excellence advocates urgent specialist cancer investigation. A total of 50,780 women underwent CA125 testing; 456 (0.9%) were diagnosed with ovarian cancer and 1,321 (2.6%) with non-ovarian cancer. Of women with a CA125 level ≥35 U/ml, 3.4% aged