Comparative Effectiveness and Cost-Effectiveness of Colorectal Cancer Screening With Blood-Based Biomarkers (Liquid Biopsy) vs Fecal Tests or Colonoscopy.

BACKGROUND & AIMS: Colorectal cancer (CRC) screening is highly effective but underused. Blood-based biomarkers (liquid biopsy) could improve screening participation. METHODS: Using our established Markov model, screening every 3 years with a blood-based test that meets minimum Centers for Medicare & Medicaid Services' thresholds (CMSmin) (CRC sensitivity 74%, specificity 90%) was compared with established alternatives. Test attributes were varied in sensitivity analyses. RESULTS: CMSmin reduced CRC incidence by 40% and CRC mortality by 52% vs no screening. These reductions were less profound than the 68%-79% and 73%-81%, respectively, achieved with multi-target stool DNA (Cologuard; Exact Sciences) every 3 years, annual fecal immunochemical testing (FIT), or colonoscopy every 10 years. Assuming the same cost as multi-target stool DNA, CMSmin cost $28,500/quality-adjusted life-year gained vs no screening, but FIT, colonoscopy, and multi-target stool DNA were less costly and more effective. CMSmin would match FIT's clinical outcomes if it achieved 1.4- to 1.8-fold FIT's participation rate. Advanced precancerous lesion (APL) sensitivity was a key determinant of a test's effectiveness. A paradigm-changing blood-based test (sensitivity >90% for CRC and 80% for APL; 90% specificity; cost ≤$120-$140) would be cost-effective vs FIT at comparable participation. CONCLUSIONS: CMSmin could contribute to CRC control by achieving screening in those who will not use established methods. Substituting blood-based testing for established effective CRC screening methods will require higher CRC and APL sensitivities that deliver programmatic benefits matching those of FIT. High APL sensitivity, which can result in CRC prevention, should be a top priority for screening test developers. APL detection should not be penalized by a definition of test specificity that focuses on CRC only.

Effectiveness and Cost-Effectiveness of Colorectal Cancer Screening With a Blood Test That Meets the Centers for Medicare & Medicaid Services Coverage Decision.

BACKGROUND & AIMS: A blood-based colorectal cancer (CRC) screening test may increase screening participation. However, blood tests may be less effective than current guideline-endorsed options. The Centers for Medicare & Medicaid Services (CMS) covers blood tests with sensitivity of at least 74% for detection of CRC and specificity of at least 90%. In this study, we investigate whether a blood test that meets these criteria is cost-effective. METHODS: Three microsimulation models for CRC (MISCAN-Colon, CRC-SPIN, and SimCRC) were used to estimate the effectiveness and cost-effectiveness of triennial blood-based screening (from ages 45 to 75 years) compared to no screening, annual fecal immunochemical testing (FIT), triennial stool DNA testing combined with an FIT assay, and colonoscopy screening every 10 years. The CMS coverage criteria were used as performance characteristics of the hypothetical blood test. We varied screening ages, test performance characteristics, and screening uptake in a sensitivity analysis. RESULTS: Without screening, the models predicted 77-88 CRC cases and 32-36 CRC deaths per 1000 individuals, costing $5.3-$5.8 million. Compared to no screening, blood-based screening was cost-effective, with an additional cost of $25,600-$43,700 per quality-adjusted life-year gained (QALYG). However, compared to FIT, triennial stool DNA testing combined with FIT, and colonoscopy, blood-based screening was not cost-effective, with both a decrease in QALYG and an increase in costs. FIT remained more effective (+5-24 QALYG) and less costly (-$3.2 to -$3.5 million) than blood-based screening even when uptake of blood-based screening was 20 percentage points higher than uptake of FIT. CONCLUSION: Even with higher screening uptake, triennial blood-based screening, with the CMS-specified minimum performance sensitivity of 74% and specificity of 90%, was not projected to be cost-effective compared with established strategies for colorectal cancer screening.

Analysis of Breast Milk Samples in Lactating Women After Undergoing Botulinum Toxin Injections for Facial Rejuvenation: A Pilot Study.

Abstract Background: There are little data on the risk to a breastfeeding infant after facial botulinum toxin injections to the mother. Objective: To detect the presence of botulinum toxin in breast milk from lactating subjects treated with facial botulinum toxin injections, as measured by enzyme-linked immunosorbent assay (ELISA). Methods: For this pilot study, lactating women were injected with standardized facial botulinum toxin type A (BTXA) (range 40-92 U). Collected breast milk samples over 5 days were analyzed for the presence of botulinum toxin. Exclusion criteria included (1) lactating women still using their breast milk for their infant, (2) muscular disorders, (3) any medication that could interfere with neuromuscular function, (4) uncontrolled systemic disease, (5) pregnant, and (6) neuromodulator injection in the past 90 days. Results: Four lactating women were recruited. Eight samples had no BTXA detected, whereas 8 of the 16 total had detectible amounts, which were well below the reported lethal oral dose for an infant. Conclusion: Although the exclusion of lactating women from receiving cosmetic botulinum toxin injections is out of an abundance of caution to the theoretical risk to the infant, this study helps support the notion that facial botulinum toxin injections do not warrant an interruption in breastfeeding. Further studies with larger sample sizes are needed.

T cell lymphoma and secondary primary malignancy risk after commercial CAR T cell therapy.

We report a T cell lymphoma (TCL) occurring 3 months after anti-CD19 chimeric antigen receptor (CAR) T cell immunotherapy for non-Hodgkin B cell lymphoma. The TCL was diagnosed from a thoracic lymph node upon surgery for lung cancer. The TCL exhibited CD8+ cytotoxic phenotype and a JAK3 variant, while the CAR transgene was very low. The T cell clone was identified at low levels in the blood before CAR T infusion and in lung cancer. To assess the overall risk of secondary primary malignancy after commercial CAR T (CD19, BCMA), we analyzed 449 patients treated at the University of Pennsylvania. At a median follow-up of 10.3 months, 16 patients (3.6%) had a secondary primary malignancy. The median onset time was 26.4 and 9.7 months for solid and hematological malignancies, respectively. The projected 5-year cumulative incidence is 15.2% for solid and 2.3% for hematological malignancies. Overall, one case of TCL was observed, suggesting a low risk of TCL after CAR T.

Colon Polyp Surveillance: Separating the Wheat From the Chaff.

One goal of colorectal cancer (CRC) screening is to prevent CRC incidence by removing precancerous colonic polyps, which are detected in up to 50% of screening examinations. Yet, the lifetime risk of CRC is 3.9%-4.3%, so it is clear that most of these individuals with polyps would not develop CRC in their lifetime. It is, therefore, a challenge to determine which individuals with polyps will benefit from follow-up, and at what intervals. There is some evidence that individuals with advanced polyps, based on size and histology, benefit from intensive surveillance. However, a large proportion of individuals will have small polyps without advanced histologic features (ie, "nonadvanced"), where the benefits of surveillance are uncertain and controversial. Demand for surveillance will further increase as more polyps are detected due to increased screening uptake, recent United States recommendations to expand screening to younger individuals, and emergence of polyp detection technology. We review the current understanding and clinical implications of the natural history, biology, and outcomes associated with various categories of colon polyps based on size, histology, and number. Our aims are to highlight key knowledge gaps, specifically focusing on certain categories of polyps that may not be associated with future CRC risk, and to provide insights to inform research priorities and potential management strategies. Optimization of CRC prevention programs based on updated knowledge about the future risks associated with various colon polyps is essential to ensure cost-effective screening and surveillance, wise use of resources, and inform efforts to personalize recommendations.

Impact of Eliminating Cost-Sharing by Medicare Beneficiaries for Follow-Up Colonoscopy After a Positive Stool-based Colorectal Cancer Screening Test.

Medicare coverage of a follow-up colonoscopy after a positive stool-based colorectal cancer screening test with no patient cost-sharing started January 2, 2023, which may favorably affect screening behavior. This analysis estimated the clinical and economic effects of increased colorectal cancer screening participation potentially resulting from this policy change in Medicare beneficiaries. The validated Colorectal Cancer and Adenoma Incidence & Mortality (CRC-AIM) model simulated three guideline-endorsed colorectal cancer screening strategies for average-risk individuals (colonoscopy every 10 years, annual fecal immunochemical test, triennial multitarget stool DNA) from ages 65-75 years. The base-case scenario assumed 0% coinsurance for initial screening and follow-up colonoscopy, real-world screening test use (colonoscopy = 45.3%, stool-based test = 24.4%, unscreened = 30.3%), and real-world follow-up colonoscopy rates. Comparative scenarios assumed an increase in the overall screening rate from 0% to 15% (5% increments) and an increase in the follow-up colonoscopy rate from 0% to 15% (5% increments). The base-case scenario resulted in 128 life-years gained (LYG)/1,000 individuals versus no screening and total screening and treatment costs of $7,938/person. The changes resulted in an increase of up to 26 LYG/1,000 individuals and a decrease in total screening and treatment costs by as much as $128/person. Follow-up colonoscopy at $0 coinsurance became cost-saving with any increase in either overall screening or follow-up colonoscopy. Policies that remove cost barriers to completing colorectal cancer screening may increase rates of screening participation, potentially improving economic and clinical outcomes. SIGNIFICANCE: A follow-up colonoscopy after a positive stool-based colorectal cancer screening test is necessary to complete the full screening process. Policies that remove cost barriers to completing colorectal cancer screening may lead to increases in overall participation rates and use of follow-up colonoscopy, improving clinical and economic outcomes.

Multitarget Stool RNA Test for Colorectal Cancer Screening.

Importance: Noninvasive tests for colorectal cancer screening must include sensitive detection of colorectal cancer and precancerous lesions. These tests must be validated for the intended-use population, which includes average-risk individuals 45 years or older. Objective: To evaluate the sensitivity and specificity of a noninvasive, multitarget stool RNA (mt-sRNA) test (ColoSense) test compared with results from a colonoscopy. Design, Setting, and Participants: This phase 3 clinical trial (CRC-PREVENT) was a blinded, prospective, cross-sectional study to support a premarket approval application for a class III medical device. A total of 8920 participants were identified online using social media platforms and enrolled from June 2021 to June 2022 using a decentralized nurse call center. All participants completed the mt-sRNA test, which incorporated a commercially available fecal immunochemical test (FIT), concentration of 8 RNA transcripts, and participant-reported smoking status. Stool samples were collected prior to participants completing a colonoscopy at their local endoscopy center. The mt-sRNA test results (positive or negative) were compared with index lesions observed on colonoscopy. Over the course of 12 months, individuals 45 years and older were enrolled in the clinical trial using the decentralized recruitment strategy. Participants were enrolled from 49 US states and obtained colonoscopies at more than 3800 different endoscopy centers. Main Outcomes and Measures: The primary outcomes included the sensitivity of the mt-sRNA test for detecting colorectal cancer and advanced adenomas and the specificity for no lesions on colonoscopy. Results: The mean (range) age of participants was 55 (45-90) years, with 4% self-identified as Asian, 11% as Black, and 7% as Hispanic. Of the 8920 eligible participants, 36 (0.40%) had colorectal cancer and 606 (6.8%) had advanced adenomas. The mt-sRNA test sensitivity for detecting colorectal cancer was 94%, sensitivity for detecting advanced adenomas was 46%, and specificity for no lesions on colonoscopy was 88%. The mt-sRNA test showed significant improvement in sensitivity for colorectal cancer (94% vs 78%; McNemar P = .01) and advanced adenomas (46% vs 29%; McNemar P < .001) compared with results of the FIT. Conclusions and Relevance: In individuals 45 years and older, the mt-sRNA test showed high sensitivity for colorectal neoplasia (colorectal cancer and advanced adenoma) with significant improvement in sensitivity relative to the FIT. Specificity for no lesions on colonoscopy was comparable to existing molecular diagnostic tests. Trial Registration: ClinicalTrials.gov Identifier: NCT04739722.

The Risk of Colorectal Polyps after Weight Loss Therapy Versus Obesity: A Propensity-Matched Nationwide Cohort Study.

BACKGROUND: A fundamental understanding of the impact of bariatric surgery (BRS) on mechanisms of colorectal carcinogenesis is limited. For instance, studies report a reduced risk of colorectal cancer in females but not in males after BRS. We examined whether this sex-specific difference existed at the earlier polyp development stage. METHODS: This retrospective cohort study included 281,417 adults from the 2012-2020 MarketScan database. We compared polyps rates on colonoscopy in four groups: post- vs. pre-BRS (treatment) to post- vs. pre-severe obesity (SO) diagnosis (control). We focused our main analysis on a propensity-matched sample that yielded a balanced distribution of covariates in our four groups (n = 9680 adults, 21.9% males). We also adjusted for important covariates. RESULTS: Metabolic syndrome parameters improved after bariatric surgery and worsened after severe obesity diagnosis (p < 0.05). The rate of polyps was 46.7% at a median of 0.5 years pre-BRS and 47.9% at a median of 0.6 years pre-SO diagnosis. The polyps rate was 45.4% at a median (range) of 3.2 (1.0-8.5) years post-BRS. Conversely, 53.8% of adults had polyps at 3.0 (1.0-8.6) years post-SO. There was no change in the risk of colorectal polyps in males or females post- vs. pre-BRS. However, the risk of polyps was higher in males (OR = 1.32, 95% CI: 1.02-1.70) and females (OR = 1.29, 95% CI: 1.13-1.47) post- vs. pre-SO. When compared to the control group (SO), the odds ratios for colorectal polyps were lower for males and females after bariatric surgery (OR = 0.63, 95% CI: 0.44-0.90, and OR = 0.79, 95% CI: 0.66-0.96, respectively). CONCLUSIONS: Obesity is associated with an increased risk of colorectal polyps, an effect that is ameliorated after bariatric surgery. These data are relevant for studies investigating colorectal carcinogenesis mechanisms.

Comparison of Simulated Outcomes Between Stool- and Blood-Based Colorectal Cancer Screening Tests.

The Centers for Medicare & Medicaid Services (CMS) recommend covering blood-based tests meeting proposed minimum performance thresholds for colorectal cancer (CRC) screening. Outcomes were compared between currently available stool-based screening tests and a hypothetical blood-based test meeting CMS minimum thresholds. Using the Colorectal Cancer and Adenoma Incidence and Mortality Microsimulation Model (CRC-AIM), outcomes were simulated for average-risk individuals screened between ages 45 and 75 years with triennial multitarget stool DNA (mt-sDNA), annual fecal immunochemical test (FIT), and annual fecal occult blood test (FOBT). Per CMS guidance, blood-based CRC screening was modeled triennially, with 74% CRC sensitivity and 90% specificity. Although not specified by CMS, adenoma sensitivity was set between 10% and 20%. Published adenoma and CRC sensitivity and specificity were used for stool-based tests. Adherence was set at (1) 100%, (2) 30%-70%, in 10% increments, and (3) real-world rates for stool-based tests (mt-sDNA = 65.6%; FIT = 42.6%; FOBT = 34.4%). Assuming perfect adherence, a blood-based test produced ≥19 lower life-years gained (LYG) than stool-based strategies. At the best-case scenario for blood-based tests (100% adherence and 20% adenoma sensitivity), mt-sDNA at real-world adherence achieved more LYG (287.2 vs. 297.1, respectively) with 14% fewer colonoscopies. At 100% blood-based test adherence and real-world mt-sDNA and FIT adherence, the blood-based test would require advanced adenoma sensitivity of 30% to reach the LYG of mt-sDNA (297.1) and ∼15% sensitivity to reach the LYG of FIT (258.9). This model suggests that blood-based tests with CMS minimally acceptable CRC sensitivity and low advanced adenoma sensitivity will frequently yield inferior outcomes to stool-based testing across a wide range of adherence assumptions.

Baseline Features and Reasons for Nonparticipation in the Colonoscopy Versus Fecal Immunochemical Test in Reducing Mortality From Colorectal Cancer (CONFIRM) Study, a Colorectal Cancer Screening Trial.

Importance: The Colonoscopy Versus Fecal Immunochemical Test in Reducing Mortality From Colorectal Cancer (CONFIRM) randomized clinical trial sought to recruit 50 000 adults into a study comparing colorectal cancer (CRC) mortality outcomes after randomization to either an annual fecal immunochemical test (FIT) or colonoscopy. Objective: To (1) describe study participant characteristics and (2) examine who declined participation because of a preference for colonoscopy or stool testing (ie, fecal occult blood test [FOBT]/FIT) and assess that preference's association with geographic and temporal factors. Design, Setting, and Participants: This cross-sectional study within CONFIRM, which completed enrollment through 46 Department of Veterans Affairs medical centers between May 22, 2012, and December 1, 2017, with follow-up planned through 2028, comprised veterans aged 50 to 75 years with an average CRC risk and due for screening. Data were analyzed between March 7 and December 5, 2022. Exposure: Case report forms were used to capture enrolled participant data and reasons for declining participation among otherwise eligible individuals. Main Outcomes and Measures: Descriptive statistics were used to characterize the cohort overall and by intervention. Among individuals declining participation, logistic regression was used to compare preference for FOBT/FIT or colonoscopy by recruitment region and year. Results: A total of 50 126 participants were recruited (mean [SD] age, 59.1 [6.9] years; 46 618 [93.0%] male and 3508 [7.0%] female). The cohort was racially and ethnically diverse, with 748 (1.5%) identifying as Asian, 12 021 (24.0%) as Black, 415 (0.8%) as Native American or Alaska Native, 34 629 (69.1%) as White, and 1877 (3.7%) as other race, including multiracial; and 5734 (11.4%) as having Hispanic ethnicity. Of the 11 109 eligible individuals who declined participation (18.0%), 4824 (43.4%) declined due to a stated preference for a specific screening test, with FOBT/FIT being the most preferred method (2820 [58.5%]) vs colonoscopy (1958 [40.6%]; P < .001) or other screening tests (46 [1.0%] P < .001). Preference for FOBT/FIT was strongest in the West (963 of 1472 [65.4%]) and modest elsewhere, ranging from 199 of 371 (53.6%) in the Northeast to 884 of 1543 (57.3%) in the Midwest (P = .001). Adjusting for region, the preference for FOBT/FIT increased by 19% per recruitment year (odds ratio, 1.19; 95% CI, 1.14-1.25). Conclusions and Relevance: In this cross-sectional analysis of veterans choosing nonenrollment in the CONFIRM study, those who declined participation more often preferred FOBT or FIT over colonoscopy. This preference increased over time and was strongest in the western US and may provide insight into trends in CRC screening preferences.

At What Age Should We Stop Colorectal Cancer Screening? When Is Enough, Enough?

There is strong evidence that colorectal cancer screening can reduce both colorectal cancer incidence and mortality. Guidelines recommend screening for individuals age 45 to 75 years, but are less certain about the benefits after age 75 years. Dalmat and colleagues provide evidence that individuals with a prior negative colonoscopy 10 years or more prior to reaching age 76 to 85 years, had a low risk of colorectal cancer, and would be less likely to benefit from further screening. It is important to note that this study population did not include individuals with a family history of colon cancer or a personal history of having high-risk adenomas. These data suggest that a negative colonoscopy can be an effective risk-stratification tool when discussing further screening with elderly patients. See related article by Dalmat et al., p. 37.

Third Asia-Pacific consensus recommendations on colorectal cancer screening and postpolypectomy surveillance.

The Asia-Pacific region has the largest number of cases of colorectal cancer (CRC) and one of the highest levels of mortality due to this condition in the world. Since the publishing of two consensus recommendations in 2008 and 2015, significant advancements have been made in our knowledge of epidemiology, pathology and the natural history of the adenoma-carcinoma progression. Based on the most updated epidemiological and clinical studies in this region, considering literature from international studies, and adopting the modified Delphi process, the Asia-Pacific Working Group on Colorectal Cancer Screening has updated and revised their recommendations on (1) screening methods and preferred strategies; (2) age for starting and terminating screening for CRC; (3) screening for individuals with a family history of CRC or advanced adenoma; (4) surveillance for those with adenomas; (5) screening and surveillance for sessile serrated lesions and (6) quality assurance of screening programmes. Thirteen countries/regions in the Asia-Pacific region were represented in this exercise. International advisors from North America and Europe were invited to participate.

AGA White Paper: Challenges and Gaps in Innovation for the Performance of Colonoscopy for Screening and Surveillance of Colorectal Cancer.

In 2018, the American Gastroenterological Association's Center for GI Innovation and Technology convened a consensus conference, entitled "Colorectal Cancer Screening and Surveillance: Role of Emerging Technology and Innovation to Improve Outcomes." The conference participants, which included more than 60 experts in colorectal cancer, considered recent improvements in colorectal cancer screening rates and polyp detection, persistent barriers to colonoscopy uptake, and opportunities for performance improvement and innovation. This white paper originates from that conference. It aims to summarize current patient- and physician-centered gaps and challenges in colonoscopy, diagnostic and therapeutic challenges affecting colonoscopy uptake, and the potential use of emerging technologies and quality metrics to improve patient outcomes.

Colorectal Cancer Risk Is Impacted by Sex and Type of Surgery After Bariatric Surgery.

PURPOSE: Sex differences exist in the associations between obesity and the risk of colorectal cancer (CRC). However, limited data exist on how sex affects CRC risk after bariatric surgery. MATERIALS AND METHODS: This retrospective cohort study used the 2012-2020 MarketScan database. We employed a propensity-score-matched analysis and precise coding to define CRC in this nationwide US study. Adjusted hazards ratio (HR) assessed CRC risk ≥ 6 months. In a restricted analysis, logistic regression with adjusted odds ratios (OR) examined CRC risk ≥ 3 years. RESULTS: Our sample included 327,734 controls with severe obesity and 88,630 patients with Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (VSG). The odds of cessation of diabetes mellitus medications, a surrogate for diabetes remission, were higher post-surgery vs. controls, especially in RYGB and males. In females, CRC risk decreased post-RYGB compared to controls (HR = 0.40, 95%CI: 0.18-0.87, p = 0.02). However, VSG was not associated with lower CRC risk in females. Paradoxically, in males compared to controls, CRC risk trended toward an almost significant increase, especially after 3 years or more from surgery (OR = 2.18, 95%CI: 0.97-4.89, p = 0.06). Males had a higher risk of CRC, particularly rectosigmoid cancer, than females after bariatric surgery (HR = 2.69, 95% CI: 1.35-5.38, p < 0.001). Furthermore, diabetes remission was not associated with a lower CRC risk post-surgery. CONCLUSION: Our data suggest an increased risk of CRC in males compared to females after bariatric surgery. Compared to controls, there was a decrease in CRC risk in females' post-RYGB but not VSG. Mechanistic studies are needed to explain these differences.

Cost-Effectiveness of Waiving Coinsurance for Follow-Up Colonoscopy after a Positive Stool-Based Colorectal Screening Test in a Medicare Population.

Commercial insurance covers a follow-up colonoscopy after a positive colorectal cancer-screening test with no patient cost-sharing. Instituting a similar policy for Medicare beneficiaries may increase screening adherence and improve outcomes. The cost-effectiveness of stool-based colorectal cancer screening was compared across adherence scenarios that assumed Medicare coinsurance status quo (20% for follow-up colonoscopy) or waived coinsurance. The CRC-AIM model simulated previously unscreened eligible Medicare beneficiaries undergoing stool-based colorectal cancer screening at age 65 for 10 years. Medicare costs, colorectal cancer cases, colorectal cancer-related deaths, life-years gained (LYG), and quality-adjusted life-years (QALY) were estimated versus no screening. Scenario 1 (S1) assumed 20% coinsurance for follow-up colonoscopy. Scenario 2 (S2) assumed waived coinsurance without adherence changes. Scenarios 3-7 (S3-S7) assumed that waiving coinsurance increased real-world stool-based screening and/or follow-up colonoscopy adherence by 5% or 10%. Sensitivity analyses assumed 1%-4% increased adherence. Cost-effectiveness threshold was ≤$100,000/QALY. Waiving coinsurance without adherence changes (S2) did not affect outcomes versus S1. S3-S7 versus S1 over 10 years estimated up to 3.6 fewer colorectal cancer cases/1,000 individuals, up to 2.1 fewer colorectal cancer deaths, up to 20.7 more LYG, and had comparable total costs per-patient (≤$6,478 vs. $6,449, respectively) as reduced colorectal cancer medical costs offset increased screening and colonoscopy costs. In sensitivity analyses, any increase in adherence after waiving coinsurance was cost-effective and increased LYG. In simulated Medicare beneficiaries, waiving coinsurance for follow-up colonoscopy after a positive stool-based test improved outcomes and was cost-effective when assumed to modestly increase colorectal cancer screening and/or follow-up colonoscopy adherence. PREVENTION RELEVANCE: Follow-up colonoscopy after a positive stool-based test is necessary to complete the colorectal cancer-screening process. This analysis demonstrated that in a simulated Medicare population, waiving coinsurance for a follow-up colonoscopy improved estimated outcomes and was cost-effective when it was assumed that waiving the coinsurance modestly increased screening adherence. See related Spotlight, p. 641.

Longitudinal assessment of colonoscopy adverse events in the prospective Cooperative Studies Program no. 380 colorectal cancer screening and surveillance cohort.

BACKGROUND AND AIMS: Data are limited regarding colonoscopy risk during long-term, programmatic colorectal cancer screening and follow-up. We aimed to describe adverse events during follow-up in a colonoscopy screening program after the baseline examination and examine factors associated with increased risk. METHODS: Cooperative Studies Program no. 380 includes 3121 asymptomatic veterans aged 50 to 75 years who underwent screening colonoscopy between 1994 and 1997. Periprocedure adverse events requiring significant intervention were defined as major events (other events were minor) and were tracked during follow-up for at least 10 years. Multivariable odds ratios (ORs) were calculated for factors associated with risk of follow-up adverse events. RESULTS: Of 3727 follow-up examinations in 1983 participants, adverse events occurred in 105 examinations (2.8%) in 93 individuals, including 22 major and 87 minor events (examinations may have had >1 event). Incidence of major events (per 1000 examinations) remained relatively stable over time, with 6.1 events at examination 2, 4.8 at examination 3, and 7.2 at examination 4. Examinations with major events included 1 perforation, 3 GI bleeds requiring intervention, and 17 cardiopulmonary events. History of prior colonoscopic adverse events was associated with increased risk of events (major or minor) during follow-up (OR, 2.7; 95% confidence interval, 1.6-4.6). CONCLUSIONS: Long-term programmatic screening and surveillance was safe, as major events were rare during follow-up. However, serious cardiopulmonary events were the most common major events. These results highlight the need for detailed assessments of comorbid conditions during routine clinical practice, which could help inform individual decisions regarding the utility of ongoing colonoscopy follow-up.