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Could Ovarian Cancer Prediction Models Improve the Triage of Symptomatic Women in Primary Care? A Modelling Study Using Routinely Collected Data

1
The Primary Care Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK
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University of Exeter Medical School, University of Exeter, Exeter EX1 1TX, UK
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Gynaecological Oncology Research Group, Division of Cancer Sciences, University of Manchester, Manchester M13 9WL, UK
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Manchester Academic Health Sciences Centre, Department of Obstetrics and Gynaecology, Manchester University NHS Foundation Trust, Manchester M13 9WL, UK
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Institute of Population Health Sciences, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AB, UK
*
Author to whom correspondence should be addressed.
Academic Editor: Line Bjørge
Cancers 2021, 13(12), 2886; https://doi.org/10.3390/cancers13122886
Received: 4 May 2021 / Revised: 4 June 2021 / Accepted: 6 June 2021 / Published: 9 June 2021
(This article belongs to the Section Cancer Causes, Screening and Diagnosis)
Earlier detection of ovarian cancer has the potential to improve patient outcomes, including survival. However, determining which women presenting in primary care to refer for specialist assessment and investigation is a clinical dilemma. In this study, we used routinely collected English primary care data from 29,962 women with symptoms of possible ovarian cancer who were tested for the ovarian cancer biomarker CA125. We developed diagnostic prediction models to estimate the probability of the disease. A relatively simple model, consisting of age and CA125 level, performed well for the identification of ovarian cancer. Including additional risk factors within the model did not materially improve model performance. Following further validation, this model could be used to help triage symptomatic women in primary care based on their risk of undiagnosed ovarian cancer, identifying those at high risk for urgent specialist investigation and those at lower (but still elevated) risk for non-urgent investigation or monitoring.
CA125 is widely used as an initial investigation in women presenting with symptoms of possible ovarian cancer. We sought to develop CA125-based diagnostic prediction models and to explore potential implications of implementing model-based thresholds for further investigation in primary care. This retrospective cohort study used routinely collected primary care and cancer registry data from symptomatic, CA125-tested women in England (2011–2014). A total of 29,962 women were included, of whom 279 were diagnosed with ovarian cancer. Logistic regression was used to develop two models to estimate ovarian cancer probability: Model 1 consisted of age and CA125 level; Model 2 incorporated further risk factors. Model discrimination (AUC) was evaluated using 10-fold cross-validation. The sensitivity and specificity of various model risk thresholds (≥1% to ≥3%) were compared with that of the current CA125 cut-off (≥35 U/mL). Model 1 exhibited excellent discrimination (AUC: 0.94) on cross-validation. The inclusion of additional variables (Model 2) did not improve performance. At a risk threshold of ≥1%, Model 1 exhibited greater sensitivity (86.4% vs. 78.5%) but lower specificity (89.1% vs. 94.5%) than CA125 (≥35 U/mL). Applying the ≥1% model threshold to the cohort in place of the current CA125 cut-off, 1 in every 74 additional women identified had ovarian cancer. Following external validation, Model 1 could be used as part of a ‘risk-based triage’ system in which women at high risk of undiagnosed ovarian cancer are selected for urgent specialist investigation, while women at ‘low risk but not no risk’ are offered non-urgent investigation or interval CA125 re-testing. Such an approach has the potential to expedite ovarian cancer diagnosis, but further research is needed to evaluate the clinical impact and health–economic implications. View Full-Text
Keywords: ovarian cancer; CA125; cancer antigen 125; primary care; diagnostic prediction model; early detection; risk assessment; triage; diagnostic pathways ovarian cancer; CA125; cancer antigen 125; primary care; diagnostic prediction model; early detection; risk assessment; triage; diagnostic pathways
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MDPI and ACS Style

Funston, G.; Abel, G.; Crosbie, E.J.; Hamilton, W.; Walter, F.M. Could Ovarian Cancer Prediction Models Improve the Triage of Symptomatic Women in Primary Care? A Modelling Study Using Routinely Collected Data. Cancers 2021, 13, 2886. https://doi.org/10.3390/cancers13122886

AMA Style

Funston G, Abel G, Crosbie EJ, Hamilton W, Walter FM. Could Ovarian Cancer Prediction Models Improve the Triage of Symptomatic Women in Primary Care? A Modelling Study Using Routinely Collected Data. Cancers. 2021; 13(12):2886. https://doi.org/10.3390/cancers13122886

Chicago/Turabian Style

Funston, Garth, Gary Abel, Emma J. Crosbie, Willie Hamilton, and Fiona M. Walter 2021. "Could Ovarian Cancer Prediction Models Improve the Triage of Symptomatic Women in Primary Care? A Modelling Study Using Routinely Collected Data" Cancers 13, no. 12: 2886. https://doi.org/10.3390/cancers13122886

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