Abstract

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.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

This research arises from the CanTest Collaborative, funded by Cancer Research UK [C8640/A23385], and from the Policy Research Unit funded by the National Institute for Health Research [PR-PRU-1217-21601]. The views expressed are those of the authors and not necessarily those of Cancer Research UK, the NIHR or the Department of Health and Social Care. EJC is supported by a National Institute for Health and Care Research (NIHR) Advanced Fellowship (NIHR300650) and the NIHR Manchester Biomedical Research Centre (NIHR203308).

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The study was approved by the Independent Scientific Advisory Committee (ISAC) for the Medicines and Healthcare Products Regulatory Agency (protocol number 21_001655). All data were provided to researchers in an anonymised form, and individual consent was not required.

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AbbreviationsAUCArea under the curveCA125Cancer antigen 125CIConfidence intervalCITLCalibration-in-the-largeCPRDClinical Research Practice DatalinkICDInternational Classification of DiseasesGPGeneral practitionerNCRASNational Cancer Registration and AnalysisNICENational Institute for Health and Care ExcellenceNPVNegative predictive valueOCOvarian cancerO/EObserved divided by expected casesPPVPositive predictive valuePSAProstate specific antigenROCReceiver operating curveSEStandard errorTRIPODTransparent Reporting of a Multivariable Prediction Model for Individual Prognosis or DiagnosisUKUnited KingdomU/mlUnits per millilitre