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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

SIMPLE SUMMARY: 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 En...

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Autores principales: Funston, Garth, Abel, Gary, Crosbie, Emma J., Hamilton, Willie, Walter, Fiona M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8228892/
https://www.ncbi.nlm.nih.gov/pubmed/34207611
http://dx.doi.org/10.3390/cancers13122886
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author Funston, Garth
Abel, Gary
Crosbie, Emma J.
Hamilton, Willie
Walter, Fiona M.
author_facet Funston, Garth
Abel, Gary
Crosbie, Emma J.
Hamilton, Willie
Walter, Fiona M.
author_sort Funston, Garth
collection PubMed
description SIMPLE SUMMARY: 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. ABSTRACT: 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.
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spelling pubmed-82288922021-06-26 Could Ovarian Cancer Prediction Models Improve the Triage of Symptomatic Women in Primary Care? A Modelling Study Using Routinely Collected Data Funston, Garth Abel, Gary Crosbie, Emma J. Hamilton, Willie Walter, Fiona M. Cancers (Basel) Article SIMPLE SUMMARY: 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. ABSTRACT: 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. MDPI 2021-06-09 /pmc/articles/PMC8228892/ /pubmed/34207611 http://dx.doi.org/10.3390/cancers13122886 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Funston, Garth
Abel, Gary
Crosbie, Emma J.
Hamilton, Willie
Walter, Fiona M.
Could Ovarian Cancer Prediction Models Improve the Triage of Symptomatic Women in Primary Care? A Modelling Study Using Routinely Collected Data
title Could Ovarian Cancer Prediction Models Improve the Triage of Symptomatic Women in Primary Care? A Modelling Study Using Routinely Collected Data
title_full Could Ovarian Cancer Prediction Models Improve the Triage of Symptomatic Women in Primary Care? A Modelling Study Using Routinely Collected Data
title_fullStr Could Ovarian Cancer Prediction Models Improve the Triage of Symptomatic Women in Primary Care? A Modelling Study Using Routinely Collected Data
title_full_unstemmed Could Ovarian Cancer Prediction Models Improve the Triage of Symptomatic Women in Primary Care? A Modelling Study Using Routinely Collected Data
title_short Could Ovarian Cancer Prediction Models Improve the Triage of Symptomatic Women in Primary Care? A Modelling Study Using Routinely Collected Data
title_sort could ovarian cancer prediction models improve the triage of symptomatic women in primary care? a modelling study using routinely collected data
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8228892/
https://www.ncbi.nlm.nih.gov/pubmed/34207611
http://dx.doi.org/10.3390/cancers13122886
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