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• W3135786345 abstract "See “Time to colonoscopy after abnormal stool-based screening and risk for colorectal cancer incidence and mortality,” by San Miguel Y, Demb J, Martinez ME, et al, on page 1997. See “Time to colonoscopy after abnormal stool-based screening and risk for colorectal cancer incidence and mortality,” by San Miguel Y, Demb J, Martinez ME, et al, on page 1997. Colorectal cancer (CRC) is a leading cause of cancer mortality in the United States and worldwide. Since the early 1990s, screening has been shown to contribute substantially to the reduction observed in CRC mortality.1Lin J.S. Piper A.M. Perdue L.A. et al.Screening for colorectal cancer: updated evidence report and systemic review for the US Preventive Task Force.JAMA. 2016; 315: 2576-2594Crossref PubMed Scopus (374) Google Scholar However, although recommended,2Robertson D.J. Lee J.K. Boland C.R. et al.Recommendations on fecal immunochemical testing to screen for colorectal neoplasia. A consensus statement by the US Multi-Society Task Force on Colorectal Cancer.Gastroenterology. 2017; 152: 1217-1237.e3Abstract Full Text Full Text PDF PubMed Scopus (133) Google Scholar screening has been underused. A model-based approach concluded that about 50% of CRC deaths in the United States could be attributable to nonuse of screening.3Reinier G.S. Meester MSc Doubeni C.A. et al.Colorectal cancer deaths attributable to nonuse of screening in the united states.Ann Epidemiol. 2015; 25: 208-213.elCrossref PubMed Scopus (55) Google Scholar In the United States, the rates of CRC screening increased to 60% in 2010, remained steady for a few years, and subsequently increased again to 70.5% in 20184Sabatino S.A. Thompson T.D. White M.C. et al.Centers for Disease Control and Prevention. Cancer Screening Test Receipt-United States, 2018.MMWR Morbid Mortal Wkly Rep. 2021; 70 (1445–1441): 29-35Crossref PubMed Google Scholar nearing the 80% target.5Inadomi J.M. Issaka R.B. Green B.B. What multilevel interventions do we need to increase the colorectal cancer screening rate to 80%?.Clin Gastroenterol Hepatol. 2021; 19: 633-645Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar The 2-step approach, a fecal test followed by a colonoscopy for a positive result, is endorsed in population-based programs. As neither randomized trials in the 1990s nor subsequent research established the recommended time interval between a positive result and a diagnostic colonoscopy, practices vary. Simulation models6Meester R.G. Zauber A.G. Doubeni C.A. et al.Consequences of increasing time to colonoscopy examination after positive result from fecal colorectal screening test.Clin Gastroenterol Hepatol. 2016; 14: 1445-2451.e8Abstract Full Text Full Text PDF PubMed Scopus (50) Google Scholar have been developed in recent years, and data from several observational studies have accumulated,7Corley D.A. Jensen C.D. Quinn V.P. et al.Association between time to colonoscopy after a positive fecal test result and risk of colorectal cancer and cancer stage at diagnosis.JAMA. 2017; 317: 1631-1641Crossref PubMed Scopus (120) Google Scholar, 8Flugelman A.A. Stein N. Segol O. et al.Delayed colonoscopy following a positive fecal test result and cancer mortality.JNCI Cancer Spectrum. 2019; 3: pkz024Crossref PubMed Google Scholar, 9Zorzi M. Hassan C. Capodaglio G. et al.Colonoscopy later than 270 days in a fecal immunochemical test-based population screening program is associated with higher prevalence of colorectal cancer.Endoscopy. 2020; 52: 871-876Crossref PubMed Scopus (10) Google Scholar including the research by San Miguel et al10San Miguel Y. Demb J. Martinez M.E. et al.Time to colonoscopy after abnormal stool-based screening and risk for colorectal cancer incidence and mortality.Gastroenterology. 2021; 160: 1997-2005Abstract Full Text Full Text PDF Scopus (2) Google Scholar in this issue of Gastroenterology. San Miguel et al provide new data regarding the association of the timing of a diagnostic colonoscopy with outcomes. This national retrospective cohort study is set in the Veterans Affairs (VA) health care system, using their comprehensive electronic records data. Patients with colonoscopies within 30 days of abnormal fecal tests were excluded from the cohort, owing to the high likelihood of them being diagnostic and therefore not indicated for screening. Only 3% of the study population were female, reflecting the VA demographics, yet they constituted 5500 patients. From a population of 3,702,445 VA patients, 204,733 had a positive fecal occult blood test or fecal immunochemical test result, 6906 were diagnosed with CRC, 2057 harbored advanced disease and 1709 died from CRC. The authors examined 3 primary outcomes—incident CRC, fatal CRC, and stage of CRC at presentation—between October 1, 1999, and December 31, 2015. This study is the first originating from a US population-based national program to examine these outcomes over a prolonged 24-month follow-up period. Using the 1- to 3-month follow-up as a reference, the study compared 3-month intervals of delayed colonoscopy, up to 24 months, and also >24 months delay. For CRC incidence, the 4- to 6-month and 7- to 9-month delay groups fared significantly better than the reference group. Risk was increased with colonoscopic delay beyond 12 months, compared with the reference. For the 2 other outcomes—fatal CRC and stage of CRC at presentation—there was no evidence of significant changes in these outcomes during the first-year delay, although these outcomes worsened starting as late as 16–19 months. The risks of the worse outcomes were 1.5- to 1.7-fold of the reference values. Risks for all outcomes decreased beyond 24 months. Simulation modeling predicted an expected gradual stepwise increase of grave outcomes with time.6Meester R.G. Zauber A.G. Doubeni C.A. et al.Consequences of increasing time to colonoscopy examination after positive result from fecal colorectal screening test.Clin Gastroenterol Hepatol. 2016; 14: 1445-2451.e8Abstract Full Text Full Text PDF PubMed Scopus (50) Google Scholar In contrast, observation demonstrated a U-shaped relation8Flugelman A.A. Stein N. Segol O. et al.Delayed colonoscopy following a positive fecal test result and cancer mortality.JNCI Cancer Spectrum. 2019; 3: pkz024Crossref PubMed Google Scholar between time and more severe outcome, which was concentrated in first 3-month and in delayed groups. The current study is in line with previously published large observational studies.7Corley D.A. Jensen C.D. Quinn V.P. et al.Association between time to colonoscopy after a positive fecal test result and risk of colorectal cancer and cancer stage at diagnosis.JAMA. 2017; 317: 1631-1641Crossref PubMed Scopus (120) Google Scholar,8Flugelman A.A. Stein N. Segol O. et al.Delayed colonoscopy following a positive fecal test result and cancer mortality.JNCI Cancer Spectrum. 2019; 3: pkz024Crossref PubMed Google Scholar The period up to 3 months plausibly represents a diverse population with positive fecal results, including asymptomatic average-risk individuals mixed with symptomatic patients, undergoing urgent colonoscopies, apparently not altering their outcome. The 4–9 months mostly entails the actual average risk patients, with true early detection, and consequently with the best outcomes. The data for the period beyond 12 months reflected the natural course after a positive fecal test in screening programs. Previous observational studies either excluded patients with colonoscopies within 7 days of the positive test,7Corley D.A. Jensen C.D. Quinn V.P. et al.Association between time to colonoscopy after a positive fecal test result and risk of colorectal cancer and cancer stage at diagnosis.JAMA. 2017; 317: 1631-1641Crossref PubMed Scopus (120) Google Scholar assuming a rapid diagnostic workup of symptomatic patients, or did not exclude at all,8Flugelman A.A. Stein N. Segol O. et al.Delayed colonoscopy following a positive fecal test result and cancer mortality.JNCI Cancer Spectrum. 2019; 3: pkz024Crossref PubMed Google Scholar to mirror an actual real-life situation. Similar to these former reports, the current study cannot inform us for how long it is safe to wait before a work-up colonoscopy should be performed. Applying sensitivity analyses could facilitate estimating outcomes under different assumptions. Information regarding the level of positivity of the fecal test (the number of fields for fecal occult blood testing or hemoglobin concentration for fecal immunochemical testing) that may enable further risk stratification was not available in the VA electronic health records data system. This study supports the concept of a safe window in which benefit may be achieved before manifestation of a grave outcome, consistent with the natural history of tumor progression. However, the challenge of selecting those who might wait and those who require immediate diagnostic work-up is still unresolved. Possible explanations for the lower risk of severe outcomes for the interval beyond 24 months include survivor time bias and non-neoplastic bleeding at the index fecal test. The various mechanisms underlying worse outcomes warrant tailored intervention approaches.11Dougherty M. Crockett S. Brenner T.A. et al.Interventions to improve initial colorectal (CRC) screening uptake: a systemic review and meta-analysis of randomized controlled trials.Gastroenterology. 2018; 154 (6(Suppl 1):S770)PubMed Google Scholar,12Doubeni C.A. Fedewa S.A. Levin T.R. et al.Modifiable failures in the colorectal screening process and their association with risk of death.Gastroenterology. 2019; 156: 63-74.e6Abstract Full Text Full Text PDF PubMed Scopus (36) Google Scholar Symptomatic patients of the first period may have escaped timely screening for earlier detection, while still asymptomatic. The higher than expected grave outcomes are probably attributable to nonuse of screening3Reinier G.S. Meester MSc Doubeni C.A. et al.Colorectal cancer deaths attributable to nonuse of screening in the united states.Ann Epidemiol. 2015; 25: 208-213.elCrossref PubMed Scopus (55) Google Scholar,12Doubeni C.A. Fedewa S.A. Levin T.R. et al.Modifiable failures in the colorectal screening process and their association with risk of death.Gastroenterology. 2019; 156: 63-74.e6Abstract Full Text Full Text PDF PubMed Scopus (36) Google Scholar; thus, the patients would have benefited from increased rates of screening.1Lin J.S. Piper A.M. Perdue L.A. et al.Screening for colorectal cancer: updated evidence report and systemic review for the US Preventive Task Force.JAMA. 2016; 315: 2576-2594Crossref PubMed Scopus (374) Google Scholar Because screening uptake has improved since the study period (1999–2015), better outcomes are expected in future studies. To address the needs of patients who delay the diagnostic colonoscopies, policy makers and screening authorities should focus on providing a sufficient follow-up infrastructure and interventions at all levels of the screening process. These policies should aim to address barriers and increase rates of patients receiving high-quality follow-up colonoscopy within the safe time period.5Inadomi J.M. Issaka R.B. Green B.B. What multilevel interventions do we need to increase the colorectal cancer screening rate to 80%?.Clin Gastroenterol Hepatol. 2021; 19: 633-645Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar Importantly, as time elapses, contact with patients may be lost. CRC screening programs should also focus on identifying screening and colonoscopy indications and on encouraging symptomatic patients to inform their practitioners and receive appropriate diagnostic colonoscopies instead of fecal tests. The authors also emphasized the relevance of possible implications of the COVID-19 pandemic on screening, including enhanced reliance on noninvasive modalities, which necessitate further research.13Shaukat A. Church T. Colorectal CANCER SCREENING in the USA in the Wake of COVID-19.Lancet Gastroenterol Hepatol. 2020; 5: 726-727Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar,14Rouillard S. Liu V.X. Corley D.A. COVID-19 and long-term planning for procedure-based specialties during extended mitigation and suppression strategies.Gastroenterology. 2021; 160: P4-P9Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar The authors should be congratulated for completing this large study and adding information for establishing recommendations. More information regarding parameters such as demographics, gastrointestinal symptoms, anemia, level of test positivity and indications for colonoscopy should be collated and adjusted for in future studies. Additional screening programs should aim to clarify shortcomings and collate data to establish solid evidence for national and international guidance for CRC screening, to optimize outcomes of this potentially preventable disease." @default.
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• W3135786345 title "In CRC Screening, Timing Is Almost Everything" @default.
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