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Figure 1.
Flow of Patients Through the Study
Flow of Patients Through the Study

FIT indicates fecal immunochemical test; KPNC, Kaiser Permanente Northern California; KPSC, Kaiser Permanente Southern California.

Figure 2.
Time to Colonoscopy After a Positive FIT and Adjusted Riska of Advanced Adenoma, Any Colorectal Cancer, and Advanced-Stage Colorectal Cancer
Time to Colonoscopy After a Positive FIT and Adjusted Riska of Advanced Adenoma, Any Colorectal Cancer, and Advanced-Stage Colorectal Cancer

BMI indicates body mass index (calculated as weight in kilograms divided by height in meters squared); FIT, fecal immunochemical test; OR, odds ratio. Models for any colorectal cancer include the entire population. Advanced adenoma was defined as adenomas with advanced histology (ie, tubulovillous and villous adenomas). Models for advanced adenoma exclude 2191 patients diagnosed with colorectal cancer. Advanced-stage cancers were defined as stage III (regional lymph node involvement) or stage IV (distant metastasis) according to the American Joint Committee on Cancer staging system or, for those without such staging, as code 3 (disease in the regional lymph nodes), code 4 (regional disease with direct extension and spread to the regional lymph nodes), or code 7 (distant metastasis) according to the 2013 Surveillance, Epidemiology, and End Results Program Coding and Staging Manual. Models for advanced-stage colorectal cancer exclude 14 patients with colorectal cancer of unknown stage. The adjusted advanced-stage colorectal cancer model dropped 244 patients with unknown BMI because no patient with unknown BMI had this outcome.

aAdjusted for sex; age; race/ethnicity; BMI; region; FIT screening year; completion of previous FIT screening (ever and in the prior year); and in the year prior to FIT screening, receipt of the flu or pneumonia vaccine, presence of gastrointestinal symptoms (bleeding or blood in stool, unexplained weight loss, abdominal pain, diarrhea, diverticulitis, inflammatory bowel disease, or Lynch syndrome), diagnosis of iron-deficiency anemia or diabetes, current smoker, number of primary care visits, and number of days hospitalized.

bRates (95% CIs) were per 1000 patients who had a colonoscopy after a positive FIT.

Figure 3.
Time to Colonoscopy After a Positive FIT and Adjusted Riska of Colorectal Cancer Stages 0-IV
Time to Colonoscopy After a Positive FIT and Adjusted Riska of Colorectal Cancer Stages 0-IV

BMI indicates body mass index (calculated as weight in kilograms divided by height in meters squared); FIT, fecal immunochemical test; OR, odds ratio. Models for stage-specific colorectal cancer exclude patients with colorectal cancer of any stage other than the specified stage. The adjusted models for colorectal cancer stages 0, III, and IV dropped 242 patients with unknown BMI because no patient with unknown BMI had these outcomes. The adjusted colorectal cancer stage IV model dropped 2435 patients with unknown race/ethnicity because no patient with unknown race/ethnicity had this outcome.

aAdjusted for sex; age; race/ethnicity; BMI; region; FIT screening year; completion of previous FIT screening (ever and in the prior year); and in the year prior to FIT screening, receipt of the flu or pneumonia vaccine, presence of gastrointestinal symptoms (bleeding or blood in stool, unexplained weight loss, abdominal pain, diarrhea, diverticulitis, inflammatory bowel disease, or Lynch syndrome), diagnosis of iron-deficiency anemia or diabetes, current smoker, number of primary care visits, and number of days hospitalized.

bRates (95% CIs) were per 1000 patients who had a colonoscopy after a positive FIT.

Table 1.  
Characteristics Among Patients Who Received a Colonoscopy After a Positive FIT Result
Characteristics Among Patients Who Received a Colonoscopy After a Positive FIT Result
Table 2.  
Colorectal Cancer Outcomes in Patients Who Received a Colonoscopy After a Positive FIT Result
Colorectal Cancer Outcomes in Patients Who Received a Colonoscopy After a Positive FIT Result
Table 3.  
Time to Colonoscopy Among Patients Receiving a Positive FIT Result
Time to Colonoscopy Among Patients Receiving a Positive FIT Result
1.
Centers for Disease Control and Prevention.  Colorectal cancer statistics. https://www.cdc.gov/cancer/colorectal/statistics/index.htm. Accessed March 24, 2017.
2.
Bibbins-Domingo  K, Grossman  DC, Curry  SJ,  et al; US Preventive Services Task Force.  Screening for colorectal cancer: US Preventive Services Task Force Recommendation Statement.  JAMA. 2016;315(23):2564-2575.PubMedGoogle ScholarCrossref
3.
Canadian Task Force on Preventive Health Care, Bacchus  CM, Dunfield  L,  et al.  Recommendations on screening for colorectal cancer in primary care.  CMAJ. 2016;188(5):340-348.PubMedGoogle ScholarCrossref
4.
Stracci  F, Zorzi  M, Grazzini  G.  Colorectal cancer screening: tests, strategies, and perspectives.  Front Public Health. 2014;2:210.PubMedGoogle ScholarCrossref
5.
US Preventive Services Task Force.  Screening for colorectal cancer: US Preventive Services Task Force recommendation statement.  Ann Intern Med. 2008;149(9):627-637.PubMedGoogle ScholarCrossref
6.
Veterans Health Administration.  VHA Directive 2007-004: Colorectal Cancer Screening. Washington, DC: Dept of Veterans Affairs; 2007.
7.
Paterson  WG, Depew  WT, Paré  P,  et al; Canadian Association of Gastroenterology Wait Time Consensus Group.  Canadian consensus on medically acceptable wait times for digestive health care.  Can J Gastroenterol. 2006;20(6):411-423.PubMedGoogle ScholarCrossref
8.
Peterson  K, Carson  S, Humphrey  L, Helfand  M.  Patients with positive screening fecal occult blood tests: evidence brief on the relationship between time delay to colonoscopy and colorectal cancer outcomes. https://www.hsrd.research.va.gov/publications/esp/fecaloccult.pdf. Accessed March 24, 2017.
9.
Gellad  ZF, Almirall  D, Provenzale  D, Fisher  DA.  Time from positive screening fecal occult blood test to colonoscopy and risk of neoplasia.  Dig Dis Sci. 2009;54(11):2497-2502.PubMedGoogle ScholarCrossref
10.
Wattacheril  J, Kramer  JR, Richardson  P,  et al.  Lagtimes in diagnosis and treatment of colorectal cancer: determinants and association with cancer stage and survival.  Aliment Pharmacol Ther. 2008;28(9):1166-1174.PubMedGoogle ScholarCrossref
11.
Gordon  NP.  How does the adult Kaiser Permanente membership in Northern California compare with the larger community?https://www.dor.kaiser.org/external/uploadedFiles/content/research/mhs/_2011_Revised_Site/Documents_Special_Reports/comparison_kaiser_vs_nonKaiser_adults_kpnc(1).pdf. Accessed March 24, 2017.
12.
Koebnick  C, Langer-Gould  AM, Gould  MK,  et al.  Sociodemographic characteristics of members of a large, integrated health care system: comparison with US Census Bureau data.  Perm J. 2012;16(3):37-41.PubMedGoogle ScholarCrossref
13.
Krieger  N.  Overcoming the absence of socioeconomic data in medical records: validation and application of a census-based methodology.  Am J Public Health. 1992;82(5):703-710.PubMedGoogle ScholarCrossref
14.
Levin  TR, Jamieson  L, Burley  DA, Reyes  J, Oehrli  M, Caldwell  C.  Organized colorectal cancer screening in integrated health care systems.  Epidemiol Rev. 2011;33(1):101-110.PubMedGoogle ScholarCrossref
15.
Valori  R, Rey  JF, Atkin  WS,  et al.  European guidelines for quality assurance in colorectal cancer screening and diagnosis: first edition—quality assurance in endoscopy in colorectal cancer screening and diagnosis.  Endoscopy. 2012;44(suppl 3):SE88-105. PubMedGoogle ScholarCrossref
16.
National Cancer Institute.  SEER program coding and staging manual. https://seer.cancer.gov/archive/manuals/2013/SPCSM_2013_maindoc.pdf. Accessed March 10, 2017.
17.
Corley  DA, Jensen  CD, Marks  AR,  et al.  Variation of adenoma prevalence by age, sex, race, and colon location in a large population: implications for screening and quality programs.  Clin Gastroenterol Hepatol. 2013;11(2):172-180. PubMedGoogle ScholarCrossref
18.
Choi  KS, Lee  HY, Jun  JK, Shin  A, Park  EC.  Adherence to follow-up after a positive fecal occult blood test in an organized colorectal cancer screening program in Korea, 2004-2008.  J Gastroenterol Hepatol. 2012;27(6):1070-1077.PubMedGoogle ScholarCrossref
19.
Etzioni  DA, Yano  EM, Rubenstein  LV,  et al.  Measuring the quality of colorectal cancer screening: the importance of follow-up.  Dis Colon Rectum. 2006;49(7):1002-1010.PubMedGoogle ScholarCrossref
20.
Morris  S, Baio  G, Kendall  E,  et al.  Socioeconomic variation in uptake of colonoscopy following a positive faecal occult blood test result: a retrospective analysis of the NHS Bowel Cancer Screening Programme.  Br J Cancer. 2012;107(5):765-771.PubMedGoogle ScholarCrossref
21.
Paszat  L, Rabeneck  L, Kiefer  L, Mai  V, Ritvo  P, Sullivan  T.  Endoscopic follow-up of positive fecal occult blood testing in the Ontario FOBT Project.  Can J Gastroenterol. 2007;21(6):379-382.PubMedGoogle ScholarCrossref
22.
Shields  HM, Weiner  MS, Henry  DR,  et al.  Factors that influence the decision to do an adequate evaluation of a patient with a positive stool for occult blood.  Am J Gastroenterol. 2001;96(1):196-203.PubMedGoogle ScholarCrossref
23.
Steele  RJ, Kostourou  I, McClements  P,  et al.  Effect of gender, age and deprivation on key performance indicators in a FOBT-based colorectal screening programme.  J Med Screen. 2010;17(2):68-74.PubMedGoogle ScholarCrossref
24.
Ferrat  E, Le Breton  J, Veerabudun  K,  et al.  Colorectal cancer screening: factors associated with colonoscopy after a positive faecal occult blood test.  Br J Cancer. 2013;109(6):1437-1444.PubMedGoogle ScholarCrossref
25.
Partin  MR, Burgess  DJ, Burgess  JF  Jr, .,  et al.  Organizational predictors of colonoscopy follow-up for positive fecal occult blood test results: an observational study.  Cancer Epidemiol Biomarkers Prev. 2015;24(2):422-434. PubMedGoogle ScholarCrossref
26.
Powell  AA, Nugent  S, Ordin  DL, Noorbaloochi  S, Partin  MR.  Evaluation of a VHA collaborative to improve follow-up after a positive colorectal cancer screening test.  Med Care. 2011;49(10):897-903.PubMedGoogle ScholarCrossref
27.
Correia  A, Rabeneck  L, Baxter  NN,  et al.  Lack of follow-up colonoscopy after positive FOBT in an organized colorectal cancer screening program is associated with modifiable health care practices.  Prev Med. 2015;76:115-122.PubMedGoogle ScholarCrossref
28.
Rabeneck  L, Tinmouth  JM, Paszat  LF,  et al.  Ontario's ColonCancerCheck: results from canada's first province-wide colorectal cancer screening program.  Cancer Epidemiol Biomarkers Prev. 2014;23(3):508-515. PubMedGoogle ScholarCrossref
29.
Rao  SK, Schilling  TF, Sequist  TD.  Challenges in the management of positive fecal occult blood tests.  J Gen Intern Med. 2009;24(3):356-360.PubMedGoogle ScholarCrossref
30.
Carlson  CM, Kirby  KA, Casadei  MA, Partin  MR, Kistler  CE, Walter  LC.  Lack of follow-up after fecal occult blood testing in older adults: inappropriate screening or failure to follow up?  Arch Intern Med. 2011;171(3):249-256.PubMedGoogle ScholarCrossref
31.
Fisher  DA, Jeffreys  A, Coffman  CJ, Fasanella  K.  Barriers to full colon evaluation for a positive fecal occult blood test.  Cancer Epidemiol Biomarkers Prev. 2006;15(6):1232-1235. PubMedGoogle ScholarCrossref
32.
Garman  KS, Jeffreys  A, Coffman  C, Fisher  DA.  Colorectal cancer screening, comorbidity, and follow-up in elderly patients.  Am J Med Sci. 2006;332(4):159-163.PubMedGoogle ScholarCrossref
33.
Miglioretti  DL, Rutter  CM, Bradford  SC,  et al.  Improvement in the diagnostic evaluation of a positive fecal occult blood test in an integrated health care organization.  Med Care. 2008;46(9)(suppl 1):S91-S96.PubMedGoogle ScholarCrossref
34.
Chubak  J, Garcia  MP, Burnett-Hartman  AN,  et al; PROSPR consortium.  Time to colonoscopy after positive fecal blood test in four US health care systems.  Cancer Epidemiol Biomarkers Prev. 2016;25(2):344-350.PubMedGoogle ScholarCrossref
35.
Myers  RE, Turner  B, Weinberg  D,  et al.  Impact of a physician-oriented intervention on follow-up in colorectal cancer screening.  Prev Med. 2004;38(4):375-381.PubMedGoogle ScholarCrossref
36.
Singh  H, Kadiyala  H, Bhagwath  G,  et al.  Using a multifaceted approach to improve the follow-up of positive fecal occult blood test results.  Am J Gastroenterol. 2009;104(4):942-952.PubMedGoogle ScholarCrossref
37.
Taplin  SH, Haggstrom  D, Jacobs  T,  et al.  Implementing colorectal cancer screening in community health centers: addressing cancer health disparities through a regional cancer collaborative.  Med Care. 2008;46(9)(suppl 1):S74-S83.PubMedGoogle ScholarCrossref
38.
Janssen  RM, Takach  O, Nap-Hill  E, Enns  RA.  Time to endoscopy in patients with colorectal cancer: analysis of wait-times.  Can J Gastroenterol Hepatol. 2016;2016:8714587. PubMedGoogle Scholar
39.
Meester  RG, Zauber  AG, Doubeni  CA,  et al.  Consequences of increasing time to colonoscopy examination after positive result from fecal colorectal cancer screening test.  Clin Gastroenterol Hepatol. 2016;14(10):1445-1451.e8. PubMedGoogle ScholarCrossref
40.
Lee  JK, Jensen  CD, Lee  A,  et al.  Development and validation of an algorithm for classifying colonoscopy indication.  Gastrointest Endosc. 2015;81(3):575-582.e4. PubMedGoogle ScholarCrossref
Original Investigation
April 25, 2017

Association Between Time to Colonoscopy After a Positive Fecal Test Result and Risk of Colorectal Cancer and Cancer Stage at Diagnosis

Author Affiliations
  • 1Division of Research, Kaiser Permanente Northern California, Oakland
  • 2Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena
  • 3Department of Family Medicine and Community Health, Perelman School of Medicine, University of Pennsylvania, Philadelphia
  • 4Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York
JAMA. 2017;317(16):1631-1641. doi:10.1001/jama.2017.3634
Key Points

Question  Is time to colonoscopy after a positive fecal immunochemical test (FIT) result associated with an increased risk of colorectal cancer?

Findings  In this cohort study of 70 124 patients with positive FIT results, there was no significant increase in risk of colorectal cancer or advanced-stage disease associated with colonoscopy follow-up within 10 months compared with 8 to 30 days. Follow-up after 10 months was associated with a higher risk of colorectal cancer and advanced-stage disease.

Meaning  Follow-up colonoscopy more than 10 months after a positive FIT result was associated with greater risk of colorectal cancer and more advanced disease at time of diagnosis, but further research is needed to assess whether this relationship is causal.

Abstract

Importance  The fecal immunochemical test (FIT) is commonly used for colorectal cancer screening and positive test results require follow-up colonoscopy. However, follow-up intervals vary, which may result in neoplastic progression.

Objective  To evaluate time to colonoscopy after a positive FIT result and its association with risk of colorectal cancer and advanced-stage disease at diagnosis.

Design, Setting, and Participants  Retrospective cohort study (January 1, 2010-December 31, 2014) within Kaiser Permanente Northern and Southern California. Participants were 70 124 patients aged 50 through 70 years eligible for colorectal cancer screening with a positive FIT result who had a follow-up colonoscopy.

Exposures  Time (days) to colonoscopy after a positive FIT result.

Main Outcomes and Measures  Risk of any colorectal cancer and advanced-stage disease (defined as stage III and IV cancer). Odds ratios (ORs) and 95% CIs were adjusted for patient demographics and baseline risk factors.

Results  Of the 70 124 patients with positive FIT results (median age, 61 years [IQR, 55-67 years]; men, 52.7%), there were 2191 cases of any colorectal cancer and 601 cases of advanced-stage disease diagnosed. Compared with colonoscopy follow-up within 8 to 30 days (n = 27 176), there were no significant differences between follow-up at 2 months (n = 24 644), 3 months (n = 8666), 4 to 6 months (n = 5251), or 7 to 9 months (n = 1335) for risk of any colorectal cancer (cases per 1000 patients: 8-30 days, 30; 2 months, 28; 3 months, 31; 4-6 months, 31; and 7-9 months, 43) or advanced-stage disease (cases per 1000 patients: 8-30 days, 8; 2 months, 7; 3 months, 7; 4-6 months, 9; and 7-9 months, 13). Risks were significantly higher for examinations at 10 to 12 months (n = 748) for any colorectal cancer (OR, 1.48 [95% CI, 1.05-2.08]; 49 cases per 1000 patients) and advanced-stage disease (OR, 1.97 [95% CI, 1.14-3.42]; 19 cases per 1000 patients) and more than 12 months (n = 747) for any colorectal cancer (OR, 2.25 [95% CI, 1.89-2.68]; 76 cases per 1000 patients) and advanced-stage disease (OR, 3.22 [95% CI, 2.44-4.25]; 31 cases per 1000 patients).

Conclusions and Relevance  Among patients with a positive fecal immunochemical test result, compared with follow-up colonoscopy at 8 to 30 days, follow-up after 10 months was associated with a higher risk of colorectal cancer and more advanced-stage disease at the time of diagnosis. Further research is needed to assess whether this relationship is causal.

Introduction

Quiz Ref IDColorectal cancer is the second leading cause of cancer death in the United States.1 Screening reduces mortality through removal of precancerous polyps and treatment of early-stage cancers.2 The US Preventive Services Task Force endorses multiple screening approaches for early detection of colorectal cancer, including fecal immunochemical test (FIT) screening.2 FIT screening is commonly used worldwide3,4 and because of its sensitivity, effectiveness, low cost, and ability to be distributed by mail, it is an increasingly common method for meeting colorectal cancer screening goals in the United States.

Quiz Ref IDA positive FIT result needs to be followed by a complete colon examination, typically with colonoscopy5; however, recommendations for how quickly to complete follow-up differ and lack a strong evidence base.6-8 In practice, there is marked variation in time to follow-up after a positive stool test result, which may result in neoplastic progression. Few studies have evaluated colorectal cancer outcomes associated with variation in time to follow-up. Two studies of military veterans reported no association between longer intervals from a positive test result to colonoscopy and either cancer stage or survival, but small sample sizes limited power.9,10 Because colorectal cancer screening theoretically affects every adult who reaches screening age and adoption of FIT screening worldwide is increasing, there is a need to provide evidence-based follow-up recommendations. The present study tested the hypothesis that longer time to colonoscopy after a positive FIT result is associated with an increased risk of any colorectal cancer and advanced-stage disease at diagnosis.

Methods
Study Population and Oversight

This study was approved by the local institutional review boards and a waiver was granted for obtaining written informed consent from study participants. This was a retrospective cohort study of Kaiser Permanente Northern California and Southern California health plan members. These integrated health care delivery organizations serve approximately 7.5 million members throughout California, and the diverse membership is similar to the region’s census demographics.11-13

Organized Colorectal Cancer Screening Programs

The health plans initiated organized FIT outreach in 2006.14 Each year, health plan members aged 50 to 75 years who are eligible for screening and not up-to-date with screening by other methods are mailed a FIT kit (OC FIT-CHEK, Polymedco). Patients mail completed kits to regional laboratories where they are analyzed using OC-Sensor Diana (Polymedco; positive result, ≥100 ng/mL of hemoglobin [20 µg of hemoglobin per gram of stool]). FIT kits are also distributed in-person to patients not up-to-date at office visits or when receiving a flu shot. Patients with a positive FIT result are referred by their physician or contacted by the gastroenterology department for colonoscopy scheduling.

Study Eligibility Criteria

Members were eligible for the study if they were aged 50 to 75 years and had completed FIT screening between January 1, 2010, and October 31, 2012, for Kaiser Permanente Southern California members and January 1, 2010, and July 31, 2013, for Kaiser Permanente Northern California members. Among those with a positive FIT result, patients were excluded if they had a prior history of colorectal cancer, less than 1 year of membership after FIT screening and no record of a colonoscopy during that period, a more than 3-month gap in membership after screening, less than 1 year of membership prior to screening (to record prior out-of-system endoscopy procedures and diagnoses), a colonoscopy within 10 years or sigmoidoscopy within 5 years before FIT screening, or a colonoscopy or colorectal cancer diagnosis 1 to 7 days after their positive FIT result (because these FITs may represent diagnostic rather than screening tests).

Follow-up Time Intervals and Cancer Outcomes

The exposure was the time elapsed between a positive FIT result and subsequent colonoscopy. Time was examined as a continuous variable and in 7 intervals; the reference group was 8 to 30 days and comparison categories were 2 months (31-60 days), 3 months (61-90 days), 4-6 months (91-180 days), 7-9 months (181-272 days), 10-12 months (273-365 days), and more than 12 months (366-1751 days). The intervals were chosen to evaluate published follow-up recommendations (ie, ≤31 days [European recommendation15] and ≤60 days [Canadian3 and Veterans Health Administration6 recommendations]), to provide calendar month intervals as practical cutoffs (ie, 1, 2, 3, 4-6, 7-9, 10-12, and >12 months), and to balance sample sizes based on outcome distributions.

The primary outcomes were any colorectal adenocarcinoma diagnosed at or within 6 months after the follow-up colonoscopy, cancer by stage, advanced-stage disease, and adenomas with advanced histology (ie, tubulovillous and villous adenomas). The window for the primary outcome was defined as diagnoses at or within 6 months to account for colonoscopies that were repeated due to variables such as poor bowel preparation, incomplete examination or excision, or patient intolerance, among others; however, 96% of diagnoses were within 1 month after the colonoscopy. Adenoma size was not available electronically.

Data Sources

FIT results and dates were obtained from laboratory databases. Colonoscopy procedures were identified using Current Procedural Terminology codes (44388-44394, 44397, 45355, 45378-45392), International Classification of Diseases, Ninth Revision, procedure codes (45.21-45.23, 45.25, 45.42, 45.43, 98.04), and Healthcare Common Procedure Coding System codes (G0105, G0121). Colorectal adenocarcinoma diagnoses and cancer stages were obtained from Kaiser Permanente cancer registries, which report to the Surveillance, Epidemiology, and End Results (SEER) Program and capture more than 99% of cancers diagnosed among members compared with manual review. Advanced-stage cancers were defined as stage III (regional lymph node involvement) or stage IV (distant metastasis) according to the American Joint Committee on Cancer staging system or, for those without such staging, as code 3 (disease in the regional lymph nodes), code 4 (regional disease with direct extension and spread to the regional lymph nodes), or code 7 (distant metastasis) according to the 2013 SEER Program Coding and Staging Manual.16 Adenomas with advanced histology were identified using Systematized Nomenclature of Medicine codes in pathology databases linked to the date of the colonoscopy examination. Validation studies confirmed high levels (>95%) of sensitivity and accuracy for capture and classification of colonoscopy examinations, adenoma diagnoses, histology, and cancers.17

Statistical Analyses

P values for differences in baseline characteristics were derived from χ2 tests. Crude rates and 95% CIs were calculated as cases per 1000 patients who completed a colonoscopy. Risk analyses used multivariable logistic regression models. Odds ratios (ORs) and 95% CIs were adjusted for sex; age at FIT screening (50-54, 55-59, 60-64, 65-69, 70-75 years); self-reported race/ethnicity (non-Hispanic white, Hispanic, black, Asian/Pacific Islander, and other/unknown) because of racial/ethnic differences in colorectal cancer incidence; body mass index (BMI [calculated as weight in kilograms divided by height in meters squared]; <25.0, 25.0-29.9, ≥30, unknown); region (Kaiser Permanente Northern California or Southern California); FIT screening year; completion of previous FIT screening (ever and in the prior year); and in the year before FIT screening, receipt of the flu or pneumonia vaccine, presence of gastrointestinal symptoms (bleeding or blood in stool, unexplained weight loss, abdominal pain, diarrhea, diverticulitis, inflammatory bowel disease, or Lynch syndrome), diagnosis of iron-deficiency anemia or diabetes, smoker status, number of primary care visits (0, 1, 2-3, ≥4), and number of days hospitalized (0-1, 2-3, ≥4). Hypothesis testing was 2-sided with an α of .05. Sensitivity analyses included redefining the reference group to include patients whose examinations were performed after a positive FIT result within 1 to 30 days (to include the earliest examinations, though these have greater risk of being symptom-driven), 8 to 60 days, and 8 to 90 days; excluding follow-up colonoscopies more than 24 months after a positive FIT result; including patients who had less than 1 year of membership prior to FIT screening, or who had a colonoscopy within 10 years or sigmoidoscopy within 5 years prior to FIT screening; and adding an exposure category of 1 to 7 days. To test for effect modification, interaction terms were added to the main model for each covariate and time was included as a continuous variable; likelihood ratio tests generated a P value for each time × covariate interaction. Stratified models are presented when the P value for interaction was less than .10. Point estimates for ORs represent the overall risk estimate for each additional 30-day delay in follow-up compared with follow-up at 8 to 30 days. Analyses were performed with SAS (SAS Institute), version 9.3, and Stata (StataCorp), version 10.1.

Results

Of 1 258 039 patients aged 50 to 75 years who completed FIT screening, 106 520 (8.5%) had a positive FIT result (Figure 1). Of these, 51 patients were excluded for history of colorectal cancer, 2873 for less than 1 year of membership after FIT screening and no record of a colonoscopy during that period, 17 for a membership gap of more than 3 months after screening, 9771 for less than 1 year of membership prior to FIT screening, 10 873 for a colonoscopy within less than 10 years or sigmoidoscopy within less than 5 years before FIT screening, and 1417 for colonoscopy or colorectal cancer diagnosis within 1 to 7 days after their positive FIT. Of the remaining 81 518 patients with a positive FIT result, 70 124 (86.0% and 65.8% of those with a positive FIT result [n = 106 520]) received a follow-up colonoscopy by the end of the study period.

Characteristics of the Cohort

Of the 81 518 eligible patients with a positive FIT result, 33.3% received a colonoscopy within 30 days, 63.6% within 2 months, 74.2% within 3 months, 80.6% within 6 months, and 83.2% within 12 months; completion rates were similar in the total group of 106 520 patients who had a positive FIT result (eFigure 1 in the Supplement). Among the 70 124 patients who received a follow-up colonoscopy (Table 1), the median age was 61 years (interquartile range [IQR], 55-67 years), 52.7% were men, 56.1% were non-Hispanic white, and 42.2% had a BMI of 30 or greater. The median time to colonoscopy was 37 days (IQR, 23-62 days). There were 2191 cases of any colorectal cancer and 601 cases of advanced-stage disease diagnosed (Table 2). Baseline covariates across time-to-colonoscopy exposure groups were typically within a few percentage points (Tables 1 and 2), although even small differences were significant given the large sample size.

Time to Colonoscopy and Risk of Colorectal Cancer Outcomes

Compared with colonoscopy follow-up 8 to 30 days after a positive FIT result, each additional 30-day interval was associated with an average increased risk of approximately 3% for any colorectal cancer (OR, 1.03 [95% CI, 1.03-1.04]; 2191 cases of 70 124 patients = 31 cases per 1000 patients) and advanced-stage disease of approximately 5% (OR, 1.05 [95% CI, 1.04-1.06]; 601 cases of 70 110 patients = 9 cases per 1000 patients); however, the relationships were not linear over time. Compared with patients who received follow-up within 8 to 30 days, there was no significant increase in risk of colorectal cancer outcomes for examinations within 6 months (Figure 2 and Figure 3 [Figures used model 2 from eTable 1 in the Supplement]; and eFigure 2 in the Supplement). For follow-up at 7 to 9 months, there was a higher risk of stage II colorectal cancer (OR, 1.88 [95% CI, 1.09-3.23]; 15 cases of 1292 patients = 12 cases per 1000 patients).

For colonoscopy follow-up at 10 to 12 months, the risk was higher for any colorectal cancer (OR, 1.48 [95% CI, 1.05-2.08]; 37 cases of 748 patients = 49 cases per 1000 patients), advanced-stage disease (OR, 1.97 [95% CI, 1.14-3.42]; 14 cases of 747 patients = 19 cases per 1000 patients), stage II colorectal cancer (OR, 2.39 [95% CI, 1.28-4.46]; 11 cases of 722 patients = 15 cases per 1000 patients), and stage IV colorectal cancer (OR, 2.71 [95% CI, 1.06-6.89]; 5 cases of 716 patients = 7 cases per 1000 patients).

For examinations at more than 12 months, the risk was higher for nearly all colorectal cancer outcomes: advanced adenomas (OR, 1.32 [95% CI, 1.15-1.52]; 247 cases of 2130 patients = 116 cases per 1000 patients), any colorectal cancer (OR, 2.25 [95% CI, 1.89-2.68]; 174 cases of 2304 patients = 76 cases per 1000 patients), advanced-stage disease (OR, 3.22 [95% CI, 2.44-4.25]; 72 cases of 2300 patients = 31 cases per 1000 patients), stage II colorectal cancer (OR, 2.94 [95% CI, 2.05-4.20]; 41 cases of 2171 patients = 19 cases per 1000 patients), stage III colorectal cancer (OR, 3.07 [95% CI, 2.21-4.27]; 49 cases of 2179 patients = 22 cases per 1000 patients), and stage IV colorectal cancer (OR, 3.86 [95% CI, 2.32-6.44]; 23 cases of 2153 patients = 11 cases per 1000 patients).

Compared with no adjustment, accounting for common baseline factors (eg, age, sex, race/ethnicity, comorbidity, and prior FIT screening) moderately reduced the strength of associations (eTable 1, model 1, in the Supplement), but did not change their direction; adjustment for additional factors related to health and health care utilization slightly strengthened the associations (eTable 1, model 2, in the Supplement).

In sensitivity analyses (Table 3), the pattern of increased OR estimates for any colorectal cancer, advanced-stage disease with examinations at 10 to 12 months and more than 12 months after FIT, or both persisted with different reference group definitions and when individuals were excluded if colonoscopy was performed more than 24 months after a positive FIT result (thereby excluding people unlikely to have a cancer, given they had not developed signs or symptoms after extended follow-up). When 20 644 originally excluded patients who had either less than 1 year of membership prior to FIT screening or were up-to-date with screening by prior endoscopy were included, risk was higher only for follow-up at more than 12 months. With 8 to 60 days and 8 to 90 days as the reference group, the risk of any colorectal cancer was also higher in the 7 to 9 months exposure group. The 1 to 7 days exposure group had a higher risk of colorectal cancer outcomes, suggesting that extremely rapid follow-up (within a week) likely represents a high-risk group.

The associations between time to colonoscopy and risk of any colorectal cancer and advanced-stage disease differed somewhat across strata of age, prior FIT screening, and no preventive vaccinations in the year before FIT screening (eTable 2 in Supplement); region was also an effect modifier for advanced-stage disease. However, the differences were small, with the exception of age, and significant associations persisted across all strata. For example, similar increases in risk for advanced-stage disease were found for patients with and without prior FIT screening (OR, 1.05 [95% CI 1.04-1.07] with prior FIT screening vs OR, 1.04 [95% CI 1.02-1.06] without prior FIT screening). Also, stronger associations for both any colorectal cancer and advanced-stage disease were found among older patients rather than younger patients, although significant associations were found for both groups.

Discussion

Quiz Ref IDAmong patients in a community-based setting with positive FIT results, there was no significant increase in risk of overall colorectal cancer or advanced colorectal cancer associated with colonoscopy follow-up within 10 months compared with 8 to 30 days. There was a higher risk of stage II colorectal cancer at 7 to 9 months; of any colorectal cancer, advanced-stage disease, and stage II and IV colorectal cancer at 10 to 12 months; and of advanced adenomas, any colorectal cancer, advanced-stage disease, and stages II-IV colorectal cancer at more than 12 months.

Time intervals between a positive FIT result and colonoscopy follow-up vary widely in practice.18-34 In studies among veterans and within a public health care system, for example, the average and median times to colonoscopy were 103 days among veterans and 174 days within a public health care system.26,34 Longer intervals could increase the chance of neoplastic progression, whereas short intervals may substantially increase patient and clinician burdens without benefiting cancer outcomes. In the current study, nearly 75% of patients with a positive FIT result received a colonoscopy within 90 days. This required rapid communication of positive results to patients and physicians, sufficient colonoscopy access, rapid scheduling, and tracking of examination completion.14 However, even with one of the most rapid follow-up rates reported to date,34 only one-third of patients with a positive FIT result received a follow-up colonoscopy within 30 days.

Guidelines for colonoscopy follow-up vary and lack supporting data. In 2006, a Canadian consensus group recommended colonoscopy follow-up within 2 months of a positive FIT result, although no rationale was provided.7 In 2007, the Veterans Health Administration issued a directive that a colonoscopy be performed within 60 days of a positive FIT result;6 however, a subsequent report found insufficient evidence to support the recommendation.8 Similarly, in 2012, European guidelines recommended colonoscopy within 31 days after referral for a positive FIT result, despite a lack of evidence for effectiveness. Given the lack of supporting evidence for recommendations, and the substantial difficulties for patients and clinicians to rapidly schedule and complete sedated examinations (which require time off from work, a person to accompany the patient home, and skilled personnel),15 current US consensus guidelines offer no recommendation regarding the time interval between a positive FIT result and follow-up colonoscopy.2,5

Prior studies have mainly explored risk factors for different times to follow-up colonoscopy18-25,27,29-32 and methods for improving follow-up,26,33,35-37 rather than the actual consequences of different times to follow-up on cancer outcomes. An analysis of 100 veterans referred for colonoscopy after a positive FIT result reported no association between follow-up time and colorectal cancer stage.10 A study of 231 veterans—which, due to sample-size limitations, primarily evaluated trends rather than specific time intervals—reported that each additional 30-day wait for colonoscopy after a positive FIT result was associated with an increased risk of any adenoma (OR, 1.10 [95% CI, 1.02-1.19]), but did not achieve statistical significance for advanced neoplasia (advanced adenomas or intramucosal carcinoma) or invasive cancers.9 Both studies included single sites with predominantly male populations. A Canadian study of 246 patients with colorectal cancer reported no association between wait-time and node positivity or presence of distant metastases at diagnosis.38 A modeling study reported that, compared with colonoscopy within 2 weeks of a positive FIT result, waiting 12 months might reduce the total years of life gained from screening by an estimated 9%.39 Although the modeling study reported a steady increase in risk between the duration of the delay and screening benefits lost, the current study only found evidence for a higher risk of overall colorectal cancer and advanced disease for colonoscopies performed more than 10 months after a positive FIT result. Quiz Ref IDTherefore, although the time interval from colorectal polyp initiation to colorectal cancer is believed to span years, our study findings raise the possibility that by the time a lesion is detectable by FIT, further lesion progression might occur as soon as 6 to 12 months after a positive FIT result, although confounding remains a possible explanation for these findings.

Study strengths include its large size and number of colorectal cancer outcomes; comprehensive capture of FIT and cancer results; a multi-medical center, community-based, diverse population; validated approaches for capturing pathology data and colonoscopy examinations; histological confirmation of adenomas; validated SEER cancer registries; evaluation of a large number of possible confounding factors; and evaluation of assumptions through sensitivity analyses.

Quiz Ref IDLimitations include the observational design and potential influence of unmeasured confounders, although the large number of patients allowed well-powered evaluations of a large number of possible confounding factors. Increases in risk over time were seen across all strata of assessed potential confounders, including among patients with and without prior screening, comorbidities, and health care–seeking behaviors. Measures of colonoscopy quality were not available for all patients; however, a large-scale chart review in the study population demonstrated cecal intubation rates of 97.7% and adequate to excellent bowel preparations in 92.0% of examinations.40 In addition, adenoma size was not available; thus, advanced adenomas were defined only by advanced histology.

Conclusions

Among patients with a positive fecal immunochemical test result, compared with follow-up colonoscopy at 8 to 30 days, follow-up after 10 months was associated with a higher risk of colorectal cancer and more advanced-stage disease at the time of diagnosis. Further research is needed to assess whether this relationship is causal.

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Article Information

Corresponding Author: Douglas A. Corley, MD, PhD, Kaiser Permanente Division of Research, 2000 Broadway, Oakland, CA 94612 (douglas.corley@kp.org).

Author Contributions: Dr Corley had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Corley, Jensen, Doubeni, Zauber, J.K. Lee, A.T. Lee.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Corley, Jensen, Marks.

Critical revision of the manuscript for important intellectual content: Corley, Jensen, Quinn, Doubeni, Zauber, J.K. Lee, Schottinger, Zhao, Ghai, A.T. Lee, Contreras, Quesenberry, Fireman, Levin.

Statistical analysis: Jensen, J.K. Lee, Marks, Zhao, Quesenberry, Fireman.

Obtained funding: Corley, Jensen, Quinn, Doubeni, Zauber, A.T. Lee, Levin.

Administrative, technical, or material support: Quinn, Schottinger, Marks, Ghai, A.T. Lee.

Supervision: Corley, Quinn, A.T. Lee, Levin.

Other: Contreras.

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Corley reports receiving grant support from Wyeth/Pfizer. No other disclosures were reported.

Funding/Support: This study was conducted within the National Cancer Institute–funded (grant U54 CA163262) Population-based Research Optimizing Screening Through Personalized Regimens consortium, which conducts multisite, coordinated, transdisciplinary research to evaluate and improve cancer-screening processes, and by grant K07 CA212057 from the National Cancer Institute (Dr J.K. Lee).

Role of the Funder/Sponsor: The National Cancer Institute had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit for publication.

References
1.
Centers for Disease Control and Prevention.  Colorectal cancer statistics. https://www.cdc.gov/cancer/colorectal/statistics/index.htm. Accessed March 24, 2017.
2.
Bibbins-Domingo  K, Grossman  DC, Curry  SJ,  et al; US Preventive Services Task Force.  Screening for colorectal cancer: US Preventive Services Task Force Recommendation Statement.  JAMA. 2016;315(23):2564-2575.PubMedGoogle ScholarCrossref
3.
Canadian Task Force on Preventive Health Care, Bacchus  CM, Dunfield  L,  et al.  Recommendations on screening for colorectal cancer in primary care.  CMAJ. 2016;188(5):340-348.PubMedGoogle ScholarCrossref
4.
Stracci  F, Zorzi  M, Grazzini  G.  Colorectal cancer screening: tests, strategies, and perspectives.  Front Public Health. 2014;2:210.PubMedGoogle ScholarCrossref
5.
US Preventive Services Task Force.  Screening for colorectal cancer: US Preventive Services Task Force recommendation statement.  Ann Intern Med. 2008;149(9):627-637.PubMedGoogle ScholarCrossref
6.
Veterans Health Administration.  VHA Directive 2007-004: Colorectal Cancer Screening. Washington, DC: Dept of Veterans Affairs; 2007.
7.
Paterson  WG, Depew  WT, Paré  P,  et al; Canadian Association of Gastroenterology Wait Time Consensus Group.  Canadian consensus on medically acceptable wait times for digestive health care.  Can J Gastroenterol. 2006;20(6):411-423.PubMedGoogle ScholarCrossref
8.
Peterson  K, Carson  S, Humphrey  L, Helfand  M.  Patients with positive screening fecal occult blood tests: evidence brief on the relationship between time delay to colonoscopy and colorectal cancer outcomes. https://www.hsrd.research.va.gov/publications/esp/fecaloccult.pdf. Accessed March 24, 2017.
9.
Gellad  ZF, Almirall  D, Provenzale  D, Fisher  DA.  Time from positive screening fecal occult blood test to colonoscopy and risk of neoplasia.  Dig Dis Sci. 2009;54(11):2497-2502.PubMedGoogle ScholarCrossref
10.
Wattacheril  J, Kramer  JR, Richardson  P,  et al.  Lagtimes in diagnosis and treatment of colorectal cancer: determinants and association with cancer stage and survival.  Aliment Pharmacol Ther. 2008;28(9):1166-1174.PubMedGoogle ScholarCrossref
11.
Gordon  NP.  How does the adult Kaiser Permanente membership in Northern California compare with the larger community?https://www.dor.kaiser.org/external/uploadedFiles/content/research/mhs/_2011_Revised_Site/Documents_Special_Reports/comparison_kaiser_vs_nonKaiser_adults_kpnc(1).pdf. Accessed March 24, 2017.
12.
Koebnick  C, Langer-Gould  AM, Gould  MK,  et al.  Sociodemographic characteristics of members of a large, integrated health care system: comparison with US Census Bureau data.  Perm J. 2012;16(3):37-41.PubMedGoogle ScholarCrossref
13.
Krieger  N.  Overcoming the absence of socioeconomic data in medical records: validation and application of a census-based methodology.  Am J Public Health. 1992;82(5):703-710.PubMedGoogle ScholarCrossref
14.
Levin  TR, Jamieson  L, Burley  DA, Reyes  J, Oehrli  M, Caldwell  C.  Organized colorectal cancer screening in integrated health care systems.  Epidemiol Rev. 2011;33(1):101-110.PubMedGoogle ScholarCrossref
15.
Valori  R, Rey  JF, Atkin  WS,  et al.  European guidelines for quality assurance in colorectal cancer screening and diagnosis: first edition—quality assurance in endoscopy in colorectal cancer screening and diagnosis.  Endoscopy. 2012;44(suppl 3):SE88-105. PubMedGoogle ScholarCrossref
16.
National Cancer Institute.  SEER program coding and staging manual. https://seer.cancer.gov/archive/manuals/2013/SPCSM_2013_maindoc.pdf. Accessed March 10, 2017.
17.
Corley  DA, Jensen  CD, Marks  AR,  et al.  Variation of adenoma prevalence by age, sex, race, and colon location in a large population: implications for screening and quality programs.  Clin Gastroenterol Hepatol. 2013;11(2):172-180. PubMedGoogle ScholarCrossref
18.
Choi  KS, Lee  HY, Jun  JK, Shin  A, Park  EC.  Adherence to follow-up after a positive fecal occult blood test in an organized colorectal cancer screening program in Korea, 2004-2008.  J Gastroenterol Hepatol. 2012;27(6):1070-1077.PubMedGoogle ScholarCrossref
19.
Etzioni  DA, Yano  EM, Rubenstein  LV,  et al.  Measuring the quality of colorectal cancer screening: the importance of follow-up.  Dis Colon Rectum. 2006;49(7):1002-1010.PubMedGoogle ScholarCrossref
20.
Morris  S, Baio  G, Kendall  E,  et al.  Socioeconomic variation in uptake of colonoscopy following a positive faecal occult blood test result: a retrospective analysis of the NHS Bowel Cancer Screening Programme.  Br J Cancer. 2012;107(5):765-771.PubMedGoogle ScholarCrossref
21.
Paszat  L, Rabeneck  L, Kiefer  L, Mai  V, Ritvo  P, Sullivan  T.  Endoscopic follow-up of positive fecal occult blood testing in the Ontario FOBT Project.  Can J Gastroenterol. 2007;21(6):379-382.PubMedGoogle ScholarCrossref
22.
Shields  HM, Weiner  MS, Henry  DR,  et al.  Factors that influence the decision to do an adequate evaluation of a patient with a positive stool for occult blood.  Am J Gastroenterol. 2001;96(1):196-203.PubMedGoogle ScholarCrossref
23.
Steele  RJ, Kostourou  I, McClements  P,  et al.  Effect of gender, age and deprivation on key performance indicators in a FOBT-based colorectal screening programme.  J Med Screen. 2010;17(2):68-74.PubMedGoogle ScholarCrossref
24.
Ferrat  E, Le Breton  J, Veerabudun  K,  et al.  Colorectal cancer screening: factors associated with colonoscopy after a positive faecal occult blood test.  Br J Cancer. 2013;109(6):1437-1444.PubMedGoogle ScholarCrossref
25.
Partin  MR, Burgess  DJ, Burgess  JF  Jr, .,  et al.  Organizational predictors of colonoscopy follow-up for positive fecal occult blood test results: an observational study.  Cancer Epidemiol Biomarkers Prev. 2015;24(2):422-434. PubMedGoogle ScholarCrossref
26.
Powell  AA, Nugent  S, Ordin  DL, Noorbaloochi  S, Partin  MR.  Evaluation of a VHA collaborative to improve follow-up after a positive colorectal cancer screening test.  Med Care. 2011;49(10):897-903.PubMedGoogle ScholarCrossref
27.
Correia  A, Rabeneck  L, Baxter  NN,  et al.  Lack of follow-up colonoscopy after positive FOBT in an organized colorectal cancer screening program is associated with modifiable health care practices.  Prev Med. 2015;76:115-122.PubMedGoogle ScholarCrossref
28.
Rabeneck  L, Tinmouth  JM, Paszat  LF,  et al.  Ontario's ColonCancerCheck: results from canada's first province-wide colorectal cancer screening program.  Cancer Epidemiol Biomarkers Prev. 2014;23(3):508-515. PubMedGoogle ScholarCrossref
29.
Rao  SK, Schilling  TF, Sequist  TD.  Challenges in the management of positive fecal occult blood tests.  J Gen Intern Med. 2009;24(3):356-360.PubMedGoogle ScholarCrossref
30.
Carlson  CM, Kirby  KA, Casadei  MA, Partin  MR, Kistler  CE, Walter  LC.  Lack of follow-up after fecal occult blood testing in older adults: inappropriate screening or failure to follow up?  Arch Intern Med. 2011;171(3):249-256.PubMedGoogle ScholarCrossref
31.
Fisher  DA, Jeffreys  A, Coffman  CJ, Fasanella  K.  Barriers to full colon evaluation for a positive fecal occult blood test.  Cancer Epidemiol Biomarkers Prev. 2006;15(6):1232-1235. PubMedGoogle ScholarCrossref
32.
Garman  KS, Jeffreys  A, Coffman  C, Fisher  DA.  Colorectal cancer screening, comorbidity, and follow-up in elderly patients.  Am J Med Sci. 2006;332(4):159-163.PubMedGoogle ScholarCrossref
33.
Miglioretti  DL, Rutter  CM, Bradford  SC,  et al.  Improvement in the diagnostic evaluation of a positive fecal occult blood test in an integrated health care organization.  Med Care. 2008;46(9)(suppl 1):S91-S96.PubMedGoogle ScholarCrossref
34.
Chubak  J, Garcia  MP, Burnett-Hartman  AN,  et al; PROSPR consortium.  Time to colonoscopy after positive fecal blood test in four US health care systems.  Cancer Epidemiol Biomarkers Prev. 2016;25(2):344-350.PubMedGoogle ScholarCrossref
35.
Myers  RE, Turner  B, Weinberg  D,  et al.  Impact of a physician-oriented intervention on follow-up in colorectal cancer screening.  Prev Med. 2004;38(4):375-381.PubMedGoogle ScholarCrossref
36.
Singh  H, Kadiyala  H, Bhagwath  G,  et al.  Using a multifaceted approach to improve the follow-up of positive fecal occult blood test results.  Am J Gastroenterol. 2009;104(4):942-952.PubMedGoogle ScholarCrossref
37.
Taplin  SH, Haggstrom  D, Jacobs  T,  et al.  Implementing colorectal cancer screening in community health centers: addressing cancer health disparities through a regional cancer collaborative.  Med Care. 2008;46(9)(suppl 1):S74-S83.PubMedGoogle ScholarCrossref
38.
Janssen  RM, Takach  O, Nap-Hill  E, Enns  RA.  Time to endoscopy in patients with colorectal cancer: analysis of wait-times.  Can J Gastroenterol Hepatol. 2016;2016:8714587. PubMedGoogle Scholar
39.
Meester  RG, Zauber  AG, Doubeni  CA,  et al.  Consequences of increasing time to colonoscopy examination after positive result from fecal colorectal cancer screening test.  Clin Gastroenterol Hepatol. 2016;14(10):1445-1451.e8. PubMedGoogle ScholarCrossref
40.
Lee  JK, Jensen  CD, Lee  A,  et al.  Development and validation of an algorithm for classifying colonoscopy indication.  Gastrointest Endosc. 2015;81(3):575-582.e4. PubMedGoogle ScholarCrossref
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