AGA Clinical Practice Update on Appropriate and Tailored Polypectomy: Expert Review.

DESCRIPTION: In this Clinical Practice Update (CPU), we provide guidance on the appropriate use of different polypectomy techniques. We focus on polyps <2 cm in size that are most commonly encountered by the practicing endoscopist, including use of classification systems to characterize polyps and various polypectomy methods. We review characteristics of polyps that require complex polypectomy techniques and provide guidance on which types of polyps require more advanced management by a therapeutic endoscopist or surgeon. This CPU does not provide a detailed review of complex polypectomy techniques, such as endoscopic submucosal dissection, which should only be performed by endoscopists with advanced training. METHODS: This expert review was commissioned and approved by the American Gastroenterological Association (AGA) Institute CPU Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership, and underwent internal peer review by the CPU Committee and external peer review through standard procedures of Clinical Gastroenterology and Hepatology. These Best Practice Advice statements were drawn from a review of the published literature and from expert opinion. Because systematic reviews were not performed, these Best Practice Advice statements do not carry formal ratings regarding the quality of evidence or strength of the presented considerations. BEST PRACTICE ADVICE 1: A structured visual assessment using high-definition white light and/or electronic chromoendoscopy and with photodocumentation should be conducted for all polyps found during routine colonoscopy. Closely inspect colorectal polyps for features of submucosally invasive cancer. BEST PRACTICE ADVICE 2: Use cold snare polypectomy for polyps <10 mm in size. Cold forceps polypectomy can alternatively be used for 1- to 3-mm polyps where cold snare polypectomy is technically difficult. BEST PRACTICE ADVICE 3: Do not use hot forceps polypectomy. BEST PRACTICE ADVICE 4: Clinicians should be familiar with various techniques, such as cold and hot snare polypectomy and endoscopic mucosal resection, to ensure effective, safe, and optimal resection of intermediate-size polyps (10-19 mm). BEST PRACTICE ADVICE 5: Consider using lifting agents or underwater endoscopic mucosal resection for removal of sessile polyps 10-19 mm in size. BEST PRACTICE ADVICE 6: Serrated polyps should be resected using cold resection techniques. Submucosal injection may be helpful for polyps >10 mm if margins cannot be well delineated. BEST PRACTICE ADVICE 7: Use hot snare polypectomy to remove pedunculated lesions >10 mm in size. BEST PRACTICE ADVICE 8: Do not routinely use clips to close resection sites for polyps <20 mm. BEST PRACTICE ADVICE 9: Refer patients with polyps to endoscopic referral centers in the context of size ≥20 mm, challenging polypectomy location, or recurrent polyp at a prior polypectomy site. BEST PRACTICE ADVICE 10: Tattoo lesions that may need future localization at endoscopy or surgery. Tattoos should be placed in a location that will not interfere with subsequent attempts at endoscopic resection. BEST PRACTICE ADVICE 11: Refer patients with nonpedunculated polyps with clear evidence of submucosally invasive cancer for surgical evaluation. BEST PRACTICE ADVICE 12: Understand the endoscopy suite's electrosurgical generator settings appropriate for polypectomy or postpolypectomy thermal techniques.

Impact of withdrawal time on adenoma detection rate: results from a prospective multicenter trial.

BACKGROUND AND AIMS: Performing a high-quality colonoscopy is critical for optimizing the adenoma detection rate (ADR). Colonoscopy withdrawal time (a surrogate measure) of ≥6 minutes is recommended; however, a threshold of a high-quality withdrawal and its impact on ADR are not known. METHODS: We examined withdrawal time (excluding polyp resection and bowel cleaning time) of subjects undergoing screening and/or surveillance colonoscopy in a prospective, multicenter, randomized controlled trial. We examined the relationship of withdrawal time in 1-minute increments on ADR and reported odds ratio (OR) with 95% confidence intervals. Linear regression analysis was performed to assess the maximal inspection time threshold that impacts the ADR. RESULTS: A total of 1142 subjects (age, 62.3 ± 8.9 years; 80.5% men) underwent screening (45.9%) or surveillance (53.6%) colonoscopy. The screening group had a median withdrawal time of 9.0 minutes (interquartile range [IQR], 3.3) with an ADR of 49.6%, whereas the surveillance group had a median withdrawal time of 9.3 minutes (IQR, 4.3) with an ADR of 63.9%. ADR correspondingly increased for a withdrawal time of 6 minutes to 13 minutes, beyond which ADR did not increase (50.4% vs 76.6%, P < .01). For every 1-minute increase in withdrawal time, there was 6% higher odds of detecting an additional subject with an adenoma (OR, 1.06; 95% confidence interval, 1.02-1.10; P = .004). CONCLUSIONS: Results from this multicenter, randomized controlled trial underscore the importance of a high-quality examination and efforts required to achieve this with an incremental yield in ADR based on withdrawal time. (Clinical trial registration number: NCT03952611.).

Tailoring Surveillance Colonoscopy in Patients With Advanced Adenomas.

BACKGROUND & AIMS: Patients with advanced colorectal adenomas (AAs) are directed to undergo intensive surveillance. However, the benefit derived from surveillance may be outweighed by the risk of death from non-colorectal cancer (CRC) causes, leading to uncertainty on how best to individualize follow-up. The aim of this study was to derive a risk prediction model and risk index that estimate and stratify the risk for non-CRC cancer mortality (NCM) subsequent to diagnosis and removal of AA. METHODS: We conducted a retrospective cohort study of veterans ≥40 years old who had colonoscopy for diagnostic or screening indications at 13 Veterans Affairs Medical Centers between 2002 and 2009 and had 1 or more AAs. The primary outcome was NCM using a fixed follow-up time period of 5 years. Logistic regression using the lasso technique was used to identify factors independently associated with NCM, and an index based on points from regression coefficients was constructed to estimate risk of 5-year NCM. RESULTS: We identified 2943 veterans with AA (mean age [standard deviation] 63 [8.6] years, 98% male, 74% white), with an overall 5-year mortality of 16.7%, which was nearly all due to NCM (16.6%). Age, comorbidity burden, specific comorbid conditions, and hospitalization within the preceding year were independently associated with NCM. The risk prediction model had a goodness of fit (calibration) P value of .41 and c-statistic (discrimination) of 0.74 (95% confidence interval, 0.71-0.76). On the basis of comparable 5-year risks of NCM, the scores comprised 3 risk categories: low (score of 0-1), intermediate (score of 2-4), and high (score of ≥5), in which NCM occurred in 6.5%, 14.1%, and 33.2%, respectively. CONCLUSIONS: We derived a risk prediction model that identifies veterans with advanced adenomas who are at high risk of NCM within 5 years, and who are thus unlikely to benefit from further surveillance.

High-Definition Colonoscopy Compared With Cuff- and Cap-Assisted Colonoscopy: Results From a Multicenter, Prospective, Randomized Controlled Trial.

BACKGROUND AND AIMS: Mucosal exposure devices including distal attachments such as the cuff and cap have shown variable results in improving adenoma detection rate (ADR) compared with high-definition white light colonoscopy (HDWLE). METHODS: We performed a prospective, multicenter randomized controlled trial in patients undergoing screening or surveillance colonoscopy comparing HDWLE to 2 different types of distal attachments: cuff (CF) (Endocuff Vision) or cap (CP) (Reveal). The primary outcome was ADR. Secondary outcomes included adenomas per colonoscopy, advanced adenoma and sessile serrated lesion detection rate, right-sided ADR, withdrawal time, and adverse events. Continuous variables were compared using Student's t test and categorical variables were compared using chi-square or Fisher's exact test using statistical software Stata version16. A P value <.05 was considered significant. RESULTS: A total of 1203 subjects were randomized to either HDWLE (n = 384; mean 62 years of age; 81.3% males), CF (n = 379; mean 62.7 years of age; 79.9% males) or CP (n = 379; mean age 62.1 years of age; 80.5% males). No significant differences were found among 3 groups for ADR (57.3%, 59.1%, and 55.7%; P = .6), adenomas per colonoscopy (1.4 ± 1.9, 1.6 ± 2.4, and 1.4 ± 2; P = .3), advanced adenoma (7.6%, 9.2%, and 8.2%; P = .7), sessile serrated lesion (6.8%, 6.3%, and 5.5%; P = .8), or right ADR (48.2%, 49.3%, and 46.2%; P = .7). The number of polyps per colonoscopy were significantly higher in the CF group compared with HDWLE and CP group (2.7 ± 3.4, 2.3 ± 2.5, and 2.2 ± 2.3; P = .013). In a multivariable model, after adjusting for age, sex, body mass index, withdrawal time, and Boston Bowel Preparation Scale score, there was no impact of device type on the primary outcome of ADR (P = .77). In screening patients, CF resulted in more neoplasms per colonoscopy (CF: 1.7 ± 2.6, HDWLE: 1.3 ± 1.7, and CP: 1.2 ± 1.8; P = .047) with a shorter withdrawal time. CONCLUSIONS: Results from this multicenter randomized controlled trial do not show any significant benefit of using either distal attachment devices (CF or CP) over HDWLE, at least in high-detector endoscopists. The Endocuff may have an advantage in the screening population. (ClinicalTrials.gov, Number: NCT03952611).

Adenoma Detection Rate (ADR) Irrespective of Indication Is Comparable to Screening ADR: Implications for Quality Monitoring.

BACKGROUND & AIMS: Adenoma detection rate (ADR) is a key measure of colonoscopy quality. However, efficient measurement of ADR can be challenging because many colonoscopies are performed for non-screening purposes. Measuring ADR without being restricted to screening indication may likely facilitate more widespread implementation of quality monitoring. We hypothesized that the ADR for all colonoscopies, irrespective of the indication, would be equivalent to the ADR for screening colonoscopies. METHODS: We reviewed consecutive colonoscopies at two Veterans Affairs centers performed by 21 endoscopists over 6 months in 2015. We calculated the ADR for screening exams, non-screening (surveillance and diagnostic) exams, and all exams (irrespective of indication), correcting for within-endoscopist correlation. We then performed simulation modeling to calculate the ADRs under 16 hypothetical scenarios of various indication distributions. We simulated 100,000 trials with 3,000 participants, randomly assigned indication (screening, surveillance, diagnostic, and FIT+) from a multinomial distribution, randomly drew adenoma using the observed ADRs per indication, and calculated 95% confidence intervals of the mean differences in ADR of screening and non-screening indications. RESULTS: Among 2628 colonoscopies performed by 21 gastroenterologists, the indication was screening in 28.9%, surveillance in 48.2% and diagnostic in 22.9%. There was no significant difference in the ADR, 50% (95%CI: 45-56%) for all colonoscopies vs 49% (95%CI: 43-56%) for screening exams (p=.55). ADRs were 56% for surveillance and 38% for diagnostic exams. In our simulation modeling, only one out of 16 scenarios (screening 10%, surveillance 70%, diagnostic 10% and FIT+ 10%) resulted in a significant difference between the calculated ADRs for screening and non-screening indications. CONCLUSIONS: In our study, the overall ADR computed from all colonoscopies was not significantly different than the conventional ADR based on screening colonoscopies. Assessing ADR for colonoscopy irrespective of indication may be adequate for quality monitoring, and could facilitate the implementation of quality measurement and reporting. Future prospective studies should evaluate the validity of using overall ADR for quality reporting in other jurisdictions before adopting this method in clinical practice.

ACG Clinical Guidelines: Colorectal Cancer Screening 2021.

Colorectal cancer (CRC) is the third most common cancer in men and women in the United States. CRC screening efforts are directed toward removal of adenomas and sessile serrated lesions and detection of early-stage CRC. The purpose of this article is to update the 2009 American College of Gastroenterology CRC screening guidelines. The guideline is framed around several key questions. We conducted a comprehensive literature search to include studies through October 2020. The inclusion criteria were studies of any design with men and women age 40 years and older. Detailed recommendations for CRC screening in average-risk individuals and those with a family history of CRC are discussed. We also provide recommendations on the role of aspirin for chemoprevention, quality indicators for colonoscopy, approaches to organized CRC screening and improving adherence to CRC screening. CRC screening must be optimized to allow effective and sustained reduction of CRC incidence and mortality. This can be accomplished by achieving high rates of adherence, quality monitoring and improvement, following evidence-based guidelines, and removing barriers through the spectrum of care from noninvasive screening tests to screening and diagnostic colonoscopy. The development of cost-effective, highly accurate, noninvasive modalities associated with improved overall adherence to the screening process is also a desirable goal.

Prevalence of Advanced Colorectal Neoplasia in Veterans: Effects of Age, Sex, and Race/Ethnicity.

GOAL: We sought to quantify the independent effects of age, sex, and race/ethnicity on risk of colorectal cancer (CRC) and advanced neoplasia (AN) in Veterans. STUDY: We conducted a retrospective, cross-sectional study of Veterans aged 40 to 80 years who had diagnostic or screening colonoscopy between 2002 and 2009 from 1 of 14 Veterans Affairs Medical Centers. Natural language processing identified the most advanced finding and location (proximal, distal). Logistic regression was used to examine the adjusted, independent effects of age, sex, and race, both overall and in screening and diagnostic subgroups. RESULTS: Among 90,598 Veterans [mean (SD) age 61.7 (9.4) y, 5.2% (n=4673) were women], CRC and AN prevalence was 1.3% (n=1171) and 8.9% (n=8081), respectively. Adjusted CRC risk was higher for diagnostic versus screening colonoscopy [odds ratio (OR)=3.79; 95% confidence interval (CI), 3.19-4.50], increased with age, was numerically (but not statistically) higher for men overall (OR=1.53; 95% CI, 0.97-2.39) and in the screening subgroup (OR=2.24; 95% CI, 0.71-7.05), and was higher overall for Blacks and Hispanics, but not in screening. AN prevalence increased with age, and was present in 9.2% of men and 3.9% of women [adjusted OR=1.90; 95% CI, 1.60-2.25]. AN risk was 11% higher in Blacks than in Whites overall (OR=1.11; 95% CI, 1.04-1.20), was no different in screening, and was lower in Hispanics (OR=0.74; 95% CI, 0.55-0.98). Women had more proximal CRC (63% vs. 39% for men; P=0.03), but there was no difference in proximal AN (38.3% for both genders). CONCLUSIONS: Age and race were associated with AN and CRC prevalence. Blacks had a higher overall prevalence of both CRC and AN, but not among screenings. Men had increased risk for AN, while women had a higher proportion of proximal CRC. These findings may be used to tailor when and how Veterans are screened for CRC.

Cecal retroflexion is infrequently performed in routine practice and the retroflexed view is of poor quality.

BACKGROUND: As right colon polyps are challenging to detect, a retroflexed view of right colon (RV) may be useful. However, cecal retroflexion (CR) without a RV to the hepatic flexure (HF) is inadequate. We aimed to determine the frequency of CR and quality of the RV in routine practice. METHODS: This prospective observational study performed at an academic medical center assessed colonoscopy inspection technique of endoscopists who had performed ≥ 100 annual screening colonoscopies. We video recorded ≥ 28 screening/surveillance colonoscopies per endoscopist and randomly evaluated 7 videos per endoscopist. Six gastroenterologists blindly reviewed the videos to determine if CR was performed and HF withdrawal time (cecum to HF time, excluding ileal/polypectomy time). RESULTS: Reviewers assessed 119 colonoscopies performed by 17 endoscopists. The median HF withdrawal time was 3 min and 46 s. CR was performed in 31% of colonoscopies. CR frequency varied between endoscopists with 9 never performing CR and 2 performing CR in all colonoscopies. When performed, nearly half (43%) of RVs did not extend to the HF with median RV duration of 16 s (IQR 9-30 s). Three polyps were identified in the RV (polyp detection rate of 8.1%), all identified prior to a forward view. CONCLUSIONS: CR is performed infrequently in routine practice. When CR is performed, the RV is of low quality with a very short inspection duration and insufficient ascending colon examination. Further education is required to educate endoscopists in optimal technique to improve overall colonoscopy quality.

Colonoscopy-Naïve Raters Can Be Trained to Assess Colonoscopy Quality.

The ability of a colonoscopist to detect colon polyps is commonly measured by the adenoma detection rate (ADR). The outcome of colonoscopy varies based on ADR, and the relationship between decreasing provider ADR and the increased risk of subsequent fatal colorectal cancer has been clearly established.1 Despite the importance of provider ADR, it is of limited value at lower provider volumes due to imprecise measurements. We have previously shown that ratings of colonoscopy inspection quality (CIQ) from video-taped colonoscopies by experts highly correlate with provider ADR, and can provide colonoscopists with specific techniques in need of remediation.2 It is unclear, however, whether these video-based evaluations are a feasible method of assessing colonoscopy quality due to a reliance upon expert evaluations. The primary aim of this study was to determine whether video-based assessments of colonoscopy inspection quality by colonoscopy-naïve raters (novice raters) correlate with assessments by expert raters and with established colonoscopy quality metrics.

Video-Based Assessments of Colonoscopy Inspection Quality Correlate With Quality Metrics and Highlight Areas for Improvement.

BACKGROUND & AIMS: Adenoma detection rate (ADR) and serrated polyp detection rate (SDR) vary significantly among colonoscopists. Colonoscopy inspection quality (CIQ) is the quality with which a colonoscopist inspects for polyps and may explain some of this variation. We aimed to determine the relationship between CIQ and historical ADRs and SDRs in a cohort of colonoscopists and assess whether there is variation in CIQ components (fold examination, cleaning, and luminal distension) among colonoscopists with similar ADRs and SDRs. METHODS: We conducted a prospective observational study to assess CIQ among 17 high-volume colonoscopists at an academic medical center. Over 6 weeks, we video-recorded >28 colonoscopies per colonoscopist and randomly selected 7 colonoscopies per colonoscopist for evaluation. Six raters graded CIQ using an established scale, with a maximum whole colon score of 75. RESULTS: We evaluated 119 colonoscopies. The median whole-colon CIQ score was 50.1/75. Whole-colon CIQ score (r=0.71; P<.01) and component scores (fold examination r=0.74; cleaning r=0.67; distension r=0.77; all P<.01) correlated with ADR. Proximal colon CIQ score (r=0.67; P<.01) and component scores (fold examination r=0.71; cleaning r=0.62; distension r=0.65; all P<.05) correlated with SDR. CIQ component scores differed significantly between colonoscopists with similar ADRs and SDRs for most of the CIQ skills. CONCLUSION: In a prospective observational study, we found CIQ and CIQ components to correlate with ADR and SDR. Colonoscopists with similar ADRs and SDRs differ in their performance of the 3 CIQ components-specific, actionable feedback might improve colonoscopy technique.

Comparing adenoma and polyp miss rates for total underwater colonoscopy versus standard CO2: a randomized controlled trial using a tandem colonoscopy approach.

BACKGROUND AND AIMS: Although water exchange may improve adenoma detection compared with CO2, it is unclear whether water is a better medium to fill the lumen during withdrawal and visualize the mucosa. Total underwater colonoscopy (TUC) involves the use of water exchange with the air valve off during insertion followed by the inspection of the mucosa under water. Our goal was to compare miss rates for TUC with standard CO2 for polyps and adenomas using a tandem colonoscopy design. METHODS: We randomized participants to undergo tandem colonoscopies using TUC or CO2 first. In TUC, water exchange was performed during insertion, and withdrawal was performed under water. For the CO2 colonoscopy, both insertion and withdrawal were performed with CO2. The main outcomes were miss rates for polyps and adenomas for the first examination calculated as the number of additional polyps/adenomas detected during the second examination divided by the total number of polyps/adenomas detected for both examinations. Inspection times were calculated by subtracting the time for polypectomy, and care was taken to keep the times equal for both examinations. RESULTS: A total of 121 participants were randomized with 61 having CO2 first. The overall miss rate for polyps was higher for the TUC-first group (81/237; 34%) compared with the CO2-first cohort (57/264; 22%) (P = .002). In addition, the overall miss rate for all adenomas was higher for the TUC-first group (52/146; 36%) compared with the CO2 group (37/159; 23%) (P = .025). However, 1 of the 3 endoscopists had higher polyp/adenoma miss rates for CO2, but these were not statistically significant differences. The insertion time was longer for TUC than for CO2. After adjusting for times, participant characteristics, and bowel preparation, the miss rate for polyps was higher for TUC than for CO2. CONCLUSIONS: We found that TUC had an overall higher polyp and adenoma miss rate than colonoscopy performed with CO2, and TUC took longer to perform. However, TUC may benefit some endoscopists, an issue that requires further study. (Clinical trial registration number: NCT03231917.).

Defining adenoma detection rate benchmarks in average-risk male veterans.

BACKGROUND AND AIMS: Veterans have higher prevalence of colorectal neoplasia than non-veterans; however, it is not known whether specific Veterans Affairs (VA) adenoma detection rate (ADR) benchmarks are required. We compared ADRs of a group of endoscopists for colonoscopies performed at a VA center with their ADRs at a non-VA academic medical center. METHODS: This was a retrospective review of screening colonoscopies performed by endoscopists who practice at the Indianapolis VA and Indiana University (IU). Patients were average-risk men aged 50 years or older. ADR, proximal ADR, advanced ADR, and adenomas per colonoscopy were compared between IU and the VA groups. RESULTS: Six endoscopists performed screening colonoscopies at both locations during the study period (470 at IU vs 608 at the VA). The overall ADR was not significantly different between IU and the VA (58% vs 61%; P = .21). Advanced neoplasia detection rate (13% vs 17%; P = .46), proximal ADR (46% vs 47%; P = .31), and adenomas per colonoscopy (1.59 vs 1.84; P = .24) were not significantly different. There were no significant differences in cecal intubation rate (100% vs 99%; P = .13) or withdrawal time (10.9 vs 11.1 min; P = .28). In regression analysis, there was significant correlation between the attending-specific ADRs at IU and the VA (P = .041, r2 = 0.69). CONCLUSIONS: In this study of average-risk men undergoing screening colonoscopies by the same group of endoscopists, the ADRs of VA and non-VA colonoscopies were not significantly different. This suggests that a VA-specific ADR target is not required for endoscopists with high ADRs.

Does Increased Adenoma Detection Reduce the Risk of Colorectal Cancer, and How Good Do We Need to Be?

PURPOSE OF REVIEW: Colorectal cancer (CRC) is largely preventable with colonoscopy and other screening modalities. However, the effectiveness of screening and surveillance depends on the quality of the colonoscopy exam. Adenoma detection rate (ADR) is the best-validated metric by which we measure individual physicians' performance. RECENT FINDINGS: Recent evidence suggests that ADR benchmarks may be inappropriately low. There is proof that improving ADR leads to significant reductions in post-colonoscopy CRC (PCCRC). Two studies have demonstrated that when a colonoscopy is performed by physicians with higher ADRs, patients are less likely to have advanced adenomas on surveillance and less likely to develop or die from PCCRC. Finally, there is at least some evidence that higher ADRs do not lead to more cumulative surveillance exams. The ADR is a useful outcome measure that can provide individual endoscopists and their patients with information about the likelihood of developing PCCRC. To achieve the lowest possible PCCRC rate, we should be striving for higher ADRs. While strategies and innovations may help a bit in improving ADRs, our efforts should focus on ensuring a complete mucosal exam for each patient. Behavioral psychology theories may provide useful frameworks for studying motivating factors that drive a careful exam.

Colonoscopy and Colorectal Cancer Mortality in the Veterans Affairs Health Care System: A Case-Control Study.

Background: Colonoscopy is widely used in the Veterans Affairs (VA) health care system for colorectal cancer (CRC) prevention, but its effect on CRC mortality is unknown. Objective: To determine whether colonoscopy is associated with decreased CRC mortality in veterans and whether its effect differs by anatomical location of CRC. Design: Case-control study. Setting: VA-Medicare administrative data. Participants: Case patients were veterans aged 52 years or older who were diagnosed with CRC between 2002 and 2008 and died of the disease by the end of 2010. Case patients were matched to 4 control patients without prior CRC on the basis of age, sex, and facility. Conditional logistic regression was performed to calculate odds ratios (ORs) for exposure to colonoscopy, with adjustment for race, Charlson Comorbidity Index score, selected chronic conditions, nonsteroidal anti-inflammatory drug use, and family history of CRC. Measurements: Exposure to colonoscopy was determined from 1997 to 6 months before CRC diagnosis in case patients and to a corresponding date in control patients. Subgroup analysis was performed for patients who had undergone screening colonoscopy. Results: A total of 4964 case patients and 19 856 control patients were identified. Case patients were significantly less likely to have undergone any colonoscopy (OR, 0.39 [95% CI, 0.35 to 0.43]). Colonoscopy was associated with reduced mortality for left-sided cancer (OR, 0.28 [CI, 0.24 to 0.32]) and right-sided cancer (OR, 0.54 [CI, 0.47 to 0.63]). The results were similar for patients who had undergone screening colonoscopy (overall OR, 0.30 [CI, 0.24 to 0.38]). Sensitivity analyses that varied the interval between CRC diagnosis and colonoscopy exposure did not affect the primary findings. Limitation: Unmeasured confounding. Conclusion: In this study using national VA-Medicare data, colonoscopy was associated with significant reductions in CRC mortality among veterans and was associated with greater benefit for left-sided cancer than right-sided cancer. Primary Funding Source: U.S. Department of Veterans Affairs.