CA125 and age-based models for ovarian cancer detection in primary care: a population-based external validation study
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Background
Cancer antigen-125 (CA125) is widely used to investigate symptoms of possible ovarian cancer (OC) in primary care. However, cancer risk varies with age as well as CA125 level. We externally validated the Ovatools models, which provide CA125- and age-specific OC risk.
Methods
The performance of Ovatools in predicting OC diagnosis within 12 months of primary care CA125 was examined using English healthcare data for women <50 and ≥50 years. Discrimination and calibration were examined, accuracy was calculated at varying risk thresholds and compared to CA125 ≥35U/ml. We estimated OCs missed/detected by Ovatools in hypothetical diagnostic pathways, including a two-threshold pathway where moderate risk (1-2.9%) triggered primary care ultrasound, and higher risk (≥3%) triggered urgent cancer referral.
Results
342,278 women were included, 0.63% had OC. The AUC was 0.95 in women ≥50 and 0.89 in women <50. When sensitivity/specificity was matched to CA125 ≥35U/ml, Ovatools showed marginally improved performance across other accuracy metrics (≥50 years). In a two-threshold pathway (≥50 years), 18.3% identified for urgent referral and 1% identified for ultrasound had OC.
Discussion
Ovatools performed well on external validation. Ovatools could be used to support informed decision-making and to triage women for further investigation based on cancer risk.
