Lin Liu1,2, Karen Messer1,2, John A Baron3, David A Lieberman4, Elizabeth T Jacobs5, Amanda J Cross6,7, Gwen Murphy8, Maria Elena Martinez1,2, Samir Gupta9,10,11. 1. Division of Biostatistics and Bioinformatics, Department of Family Medicine and Public Health, University of California San Diego, La Jolla, CA, USA. 2. University of California San Diego Moores Cancer Center, La Jolla, CA, USA. 3. Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, USA. 4. Division of Gastroenterology and Hepatology, Veterans Affairs Medical Center and Oregon Health and Science University, Portland, OR, USA. 5. University of Arizona Cancer Center, Arizona College of Public Health, University of Arizona, Tucson, AZ, USA. 6. Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. 7. Cancer Screening and Prevention Research Group, Department of Surgery and Cancer, Imperial College London, London, UK. 8. Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, National Institutes of Health, Rockville, MD, USA. 9. University of California San Diego Moores Cancer Center, La Jolla, CA, USA. s1gupta@ucsd.edu. 10. Veteran Affairs San Diego Healthcare System, 3350 La Jolla Village Dr, MC 111D, San Diego, CA, 92161, USA. s1gupta@ucsd.edu. 11. Division of Gastroenterology, Department of Internal Medicine, University of California San Diego, La Jolla, CA, USA. s1gupta@ucsd.edu.
Abstract
PURPOSE: Following colonoscopic polypectomy, US Multisociety Task Force (USMSTF) guidelines stratify patients based on risk of subsequent advanced neoplasia (AN) using number, size, and histology of resected polyps, but have only moderate sensitivity and specificity. We hypothesized that a state-of-the-art statistical prediction model might improve identification of patients at high risk of future AN and address these challenges. METHODS: Data were pooled from seven prospective studies which had follow-up ascertainment of metachronous AN within 3-5 years of baseline polypectomy (combined n = 8,228). Pooled data were randomly split into training (n = 5,483) and validation (n = 2,745) sets. A prognostic model was developed using best practices. Two risk cut-points were identified in the training data which achieved a 10 percentage point improvement in sensitivity and specificity, respectively, over current USMSTF guidelines. Clinical benefit of USMSTF versus model-based risk stratification was then estimated using validation data. RESULTS: The final model included polyp location, prior polyp history, patient age, and number, size and histology of resected polyps. The first risk cut-point improved sensitivity but with loss of specificity. The second risk cut-point improved specificity without loss of sensitivity (specificity 46.2 % model vs. 42.1 % guidelines, p < 0.001; sensitivity 75.8 % model vs. 74.0 % guidelines, p = 0.64). Estimated AUC was 65 % (95 % CI: 62-69 %). CONCLUSION: This model-based approach allows flexibility in trading sensitivity and specificity, which can optimize colonoscopy over- versus underuse rates. Only modest improvements in prognostic power are possible using currently available clinical data. Research considering additional factors such as adenoma detection rate for risk prediction appears warranted.
PURPOSE: Following colonoscopic polypectomy, US Multisociety Task Force (USMSTF) guidelines stratify patients based on risk of subsequent advanced neoplasia (AN) using number, size, and histology of resected polyps, but have only moderate sensitivity and specificity. We hypothesized that a state-of-the-art statistical prediction model might improve identification of patients at high risk of future AN and address these challenges. METHODS: Data were pooled from seven prospective studies which had follow-up ascertainment of metachronous AN within 3-5 years of baseline polypectomy (combined n = 8,228). Pooled data were randomly split into training (n = 5,483) and validation (n = 2,745) sets. A prognostic model was developed using best practices. Two risk cut-points were identified in the training data which achieved a 10 percentage point improvement in sensitivity and specificity, respectively, over current USMSTF guidelines. Clinical benefit of USMSTF versus model-based risk stratification was then estimated using validation data. RESULTS: The final model included polyp location, prior polyp history, patient age, and number, size and histology of resected polyps. The first risk cut-point improved sensitivity but with loss of specificity. The second risk cut-point improved specificity without loss of sensitivity (specificity 46.2 % model vs. 42.1 % guidelines, p < 0.001; sensitivity 75.8 % model vs. 74.0 % guidelines, p = 0.64). Estimated AUC was 65 % (95 % CI: 62-69 %). CONCLUSION: This model-based approach allows flexibility in trading sensitivity and specificity, which can optimize colonoscopy over- versus underuse rates. Only modest improvements in prognostic power are possible using currently available clinical data. Research considering additional factors such as adenoma detection rate for risk prediction appears warranted.
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