The Effect of Nationwide Organized Cancer Screening Programs on Gastric Cancer Mortality: A Synthetic Control Study.

BACKGROUND & AIMS: Nationwide organized gastric cancer (GC) screening programs have been running for decades in South Korea and Japan. This study conducted a quasi-experimental analysis to assess the population impact of these programs on GC mortality. METHODS: We used the flexible synthetic control method (SCM) to estimate the effect of the screening programs on age-standardized GC mortality and other upper gastrointestinal (UGI) diseases (esophageal cancer and peptic ulcer) among people aged ≥40 years. World Health Organization mortality data and country-level covariates from the World Bank and the Global Burden of Diseases study were used for the analyses. We compared postintervention trends in outcome with the counterfactual trend of the synthetic control and estimated average postintervention rate ratios (RRs) with associated 95% confidence intervals (CIs). A series of sensitivity analyses were conducted. RESULTS: The preintervention fits were acceptable for the analyses of South Korea and Japan's GC mortality but poor for Japan's other UGI disease mortality. The average postintervention RRs were 0.83 (95% CI, 0.71-0.96) for GC mortality and 0.72 (95% CI, 0.57-0.90) for other UGI disease mortality in South Korea. The RR reached 0.59 by the 15th year after the initiation of nationwide screening. For Japan, the average RRs were 0.97 (95% CI, 0.88-1.07) for GC mortality and 0.93 (95% CI, 0.68-1.28) for other UGI disease mortality. Sensitivity analysis reveals the result for Japan may potentially be biased. CONCLUSIONS: South Korea's nationwide GC screening has apparent benefits, whereas the Japanese program's effectiveness is uncertain. The experiences of South Korea and Japan could serve as a reference for other countries.

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.

Combining Colonoscopy With Fecal Immunochemical Test Can Improve Current Familial Colorectal Cancer Colonoscopy Surveillance: A Modelling Study.

BACKGROUND & AIMS: The authors assessed whether familial colorectal cancer (FCRC) surveillance in individuals without hereditary CRC can be optimized METHODS: The Adenoma and Serrated Pathway to Colorectal Cancer-FCRC model simulates CRC development in individuals with a family history of CRC at 2-fold and 4-fold increased CRC risk compared with the general population. The authors simulated a strategy without surveillance, the current Dutch guideline (5-yearly colonoscopy between ages 45 and 75 years), and the following 3 sets of alternative strategies: colonoscopy surveillance, surveillance combining colonoscopy and fecal immunochemical test (FIT), and FIT-based surveillance. Each set included a range of strategies differing in age range and test interval. The optimal strategy was defined as the strategy with highest quality-adjusted life-years (QALYs) satisfying all of the following criteria: in the (near-)efficiency area of the cost-effectiveness frontier and compared with current surveillance; noninferior effectiveness; no substantial increase in colonoscopy burden; and not more expensive. RESULTS: The optimal strategy was 10-yearly colonoscopy with 2-yearly FIT between colonoscopies from ages 40 to 80 years for both 2-fold and 4-fold increased CRC risk. At 2-fold risk, this strategy prevented 0.8 more CRC deaths, gained 15.8 more QALYs at 731 fewer colonoscopies, and saved €98,000 over the lifetime of 1000 individuals compared with current surveillance. At 4-fold risk, figures were 2.1 more CRC deaths prevented, 37.0 more QALYs gained at 567 fewer colonoscopies, and €127,000 lower costs. Current surveillance was not (near-)efficient. CONCLUSIONS: FIT could play an important role in FCRC surveillance. Surveillance with 10-yearly colonoscopy and 2-yearly FIT between colonoscopies from ages 40 to 80 years increased QALYs and reduced colonoscopy burden and costs compared with current FCRC surveillance.

Incidence and Prediction of Unrelated Mortality After Successful Endoscopic Eradication Therapy for Barrett's Neoplasia.

BACKGROUND & AIMS: Follow-up (FU) strategies after endoscopic eradication therapy (EET) for Barrett's neoplasia do not consider the risk of mortality from causes other than esophageal adenocarcinoma (EAC). We aimed to evaluate this risk during long-term FU, and to assess whether the Charlson Comorbidity Index (CCI) can predict mortality. METHODS: We included all patients with successful EET from the nationwide Barrett registry in the Netherlands. Data were merged with National Statistics for accurate mortality data. We evaluated annual mortality rates (AMRs, per 1000 person-years) and standardized mortality ratio for other-cause mortality. Performance of the CCI was evaluated by discrimination and calibration. RESULTS: We included 1154 patients with a mean age of 64 years (±9). During median 59 months (p25-p75 37-91; total 6375 person-years), 154 patients (13%) died from other causes than EAC (AMR, 24.1; 95% CI, 20.5-28.2), most commonly non-EAC cancers (n = 58), cardiovascular (n = 31), or pulmonary diseases (n = 26). Four patients died from recurrent EAC (AMR, 0.5; 95% CI, 0.1-1.4). Compared with the general Dutch population, mortality was significantly increased for patients in the lowest 3 age quartiles (ie, age <71 years). Validation of CCI in our population showed good discrimination (Concordance statistic, 0.78; 95% CI, 0.72-0.84) and fair calibration. CONCLUSION: The other-cause mortality risk after successful EET was more than 40 times higher (48; 95% CI, 15-99) than the risk of EAC-related mortality. Our findings reveal that younger post-EET patients exhibit a significantly reduced life expectancy when compared with the general population. Furthermore, they emphasize the strong predictive ability of CCI for long-term mortality after EET. This straightforward scoring system can inform decisions regarding personalized FU, including appropriate cessation timing. (NL7039).

The Ethics of Cancer Screening Based on Race and Ethnicity.

Racial and ethnic disparities in incidence and mortality are well documented for many types of cancer. As a result, there is understandable policy and clinical interest in race- and ethnicity-based clinical screening guidelines to address cancer health disparities. Despite the theoretical benefits, such proposals do not typically address associated ethical considerations. Using the examples of gastric cancer and esophageal adenocarcinoma, which have demonstrated disparities according to race and ethnicity, this article examines relevant ethical arguments in considering screening based on race and ethnicity.Race- and ethnicity-based clinical preventive care services have the potential to improve the balance of harms and benefits of screening. As a result, programs focused on high-risk racial or ethnic groups could offer a practical alternative to screening the general population, in which the screening yield may be too low to demonstrate sufficient effectiveness. However, designing screening according to socially based categorizations such as race or ethnicity is controversial and has the potential for intersectional stigma related to social identity or other structurally mediated environmental factors. Other ethical considerations include miscategorization, unintended negative effects on health disparities, disregard for underlying risk factors, and the psychological costs of being assigned higher risk.Given the ethical considerations, the practical application of race and ethnicity in cancer screening is most relevant in multicultural countries if and only if alternative proxies are not available. Even in those instances, policymakers and clinicians should carefully address the ethical considerations within the historical and cultural context of the intended population. Further research on alternative proxies, such as social determinants of health and culturally based characteristics, could provide more adequate factors for risk stratification.

Prevalence of neoplasia at colonoscopy among testicular cancer survivors treated with platinum-based chemotherapy.

Testicular cancer survivors (TCS) treated with platinum-based chemotherapy have an increased risk of colorectal cancer (CRC). We determined the yield of colonoscopy in TCS to assess its potential in reducing CRC incidence and mortality. We conducted a colonoscopy screening study among TCS in four Dutch hospitals to assess the yield of colorectal neoplasia. Neoplasia was defined as adenomas, serrated polyps (SPs), advanced adenomas (AAs: ≥10 mm diameter, high-grade dysplasia or ≥25% villous component), advanced serrated polyps (ASPs: ≥10 mm diameter or dysplasia) or CRC. Advanced neoplasia (AN) was defined as AA, ASP or CRC. Colonoscopy yield was compared to average-risk American males who underwent screening colonoscopy (n = 24,193) using a propensity score matched analysis, adjusted for age, smoking status, alcohol consumption and body mass index. A total of 137 TCS underwent colonoscopy. Median age was 50 years among TCS (IQR 43-57) vs 55 years (IQR 51-62) among American controls. A total of 126 TCS were matched to 602 controls. The prevalence of AN was higher in TCS than in controls (8.7% vs 1.7%; P = .0002). Nonadvanced adenomas and SPs were detected in 45.2% of TCS vs 5.5% of controls (P < .0001). No lesions were detected in 46.0% of TCS vs 92.9% of controls (P < .0001). TCS treated with platinum-based chemotherapy have a higher prevalence of neoplasia and AN than matched controls. These results support our hypothesis that platinum-based chemotherapy increases the risk of colorectal neoplasia in TCS. Cost-effectiveness studies are warranted to ascertain the threshold of AN prevalence that justifies the recommendation of colonoscopy for TCS.

Risk of COVID-19 death for people with a pre-existing cancer diagnosis prior to COVID-19-vaccination: A systematic review and meta-analysis.

While previous reviews found a positive association between pre-existing cancer diagnosis and COVID-19-related death, most early studies did not distinguish long-term cancer survivors from those recently diagnosed/treated, nor adjust for important confounders including age. We aimed to consolidate higher-quality evidence on risk of COVID-19-related death for people with recent/active cancer (compared to people without) in the pre-COVID-19-vaccination period. We searched the WHO COVID-19 Global Research Database (20 December 2021), and Medline and Embase (10 May 2023). We included studies adjusting for age and sex, and providing details of cancer status. Risk-of-bias assessment was based on the Newcastle-Ottawa Scale. Pooled adjusted odds or risk ratios (aORs, aRRs) or hazard ratios (aHRs) and 95% confidence intervals (95% CIs) were calculated using generic inverse-variance random-effects models. Random-effects meta-regressions were used to assess associations between effect estimates and time since cancer diagnosis/treatment. Of 23 773 unique title/abstract records, 39 studies were eligible for inclusion (2 low, 17 moderate, 20 high risk of bias). Risk of COVID-19-related death was higher for people with active or recently diagnosed/treated cancer (general population: aOR = 1.48, 95% CI: 1.36-1.61, I2 = 0; people with COVID-19: aOR = 1.58, 95% CI: 1.41-1.77, I2 = 0.58; inpatients with COVID-19: aOR = 1.66, 95% CI: 1.34-2.06, I2 = 0.98). Risks were more elevated for lung (general population: aOR = 3.4, 95% CI: 2.4-4.7) and hematological cancers (general population: aOR = 2.13, 95% CI: 1.68-2.68, I2 = 0.43), and for metastatic cancers. Meta-regression suggested risk of COVID-19-related death decreased with time since diagnosis/treatment, for example, for any/solid cancers, fitted aOR = 1.55 (95% CI: 1.37-1.75) at 1 year and aOR = 0.98 (95% CI: 0.80-1.20) at 5 years post-cancer diagnosis/treatment. In conclusion, before COVID-19-vaccination, risk of COVID-19-related death was higher for people with recent cancer, with risk depending on cancer type and time since diagnosis/treatment.

The Natural Disease Course of Pancreatic Cyst-Associated Neoplasia, Dysplasia, and Ductal Adenocarcinoma: Results of a Microsimulation Model.

BACKGROUND & AIMS: Estimates on the progression of precursor lesions to pancreatic cancer (PC) are scarce. We used microsimulation modeling to gain insight into the natural disease course of PC and its precursors. This information is pivotal to explore the efficacy of PC screening. METHODS: A Microsimulation Screening Analysis model was developed in which pancreatic intraepithelial neoplasms and cysts can evolve from low-grade dysplasia (LGD) to high-grade dysplasia (HGD) to PC. The model was calibrated to Dutch PC incidence data and Japanese precursor prevalence data (autopsy cases without PC) and provides estimates of PC progression (precursor lesion onset and stage duration). RESULTS: Mean LGD state durations of cysts and pancreatic intraepithelial neoplasms were 15.8 years and 17.1 years, respectively. Mean HGD state duration was 5.8 years. For lesions that progress to PC, the mean duration was 4.8-4.9 years for LGD lesions and 4.0-4.1 years for HGD lesions. In 13.7% of individuals who developed PC, the HGD state lasted less than 1 year. The probability that an individual at age 50 years developed PC in the next 20 years was estimated to be 1.8% in the presence of any cyst and 6.1% in case of an LGD mucinous cyst. This 20-year PC risk was estimated to be 5.1% for individuals with an LGD pancreatic intraepithelial neoplasm. CONCLUSIONS: Mean duration of HGD lesions before development of PC was estimated to be 4.0 years. This implies a window of opportunity for screening, presuming the availability of a reliable diagnostic test. The probability that an LGD cyst will progress to cancer was predicted to be low.

Risk of Recurrence in Screen-Detected vs Non-Screen-Detected Colorectal Cancer Patients.

BACKGROUND AND AIMS: Patients with screen-detected colorectal cancer (CRC) have a better stage-specific overall survival than non-screen-detected CRC. Currently, it is unknown if recurrence rates differ between screen-detected and non-screen-detected CRCs, and whether this could explain the observed difference in overall survival. Therefore, we aimed to assess the disease-free survival (DFS) rates in screen-detected and non-screen-detected CRCs and if recurrence affects overall survival. METHODS: Dutch CRC (stage I-III) patients, diagnosed by screening or not in the first 6 months of 2015, were included from the Netherlands Cancer Registry. DFS and survival data were retrieved and analyzed by Kaplan-Meier method. The association between mode of detection and recurrence and overall survival was evaluated with a Cox regression model. RESULTS: A total of 3725 CRC patients were included, 2073 (55.7%) non-screen detected and 1652 (44.3%) screen detected. Three-year DFS was significantly higher in screen-detected CRC compared with non-screen-detected CRC (87.8% vs 77.2%; P < .001). Stage-specific DFS rates for screen-detected vs non-screen-detected CRC were 94.7% vs 92.3% for stage I (P = .45), 84.3% vs 81.4% for stage II (P = .17), and 77.9% vs 66.7% for stage III (P < .001), respectively. Detection by screening was independently associated with a lower risk of recurrence (hazard ratio, 0.67; 95% confidence interval, 0.55-0.81; P < .001) when adjusted for age, sex, tumor location, stage and treatment. Recurrence independently predicted overall survival (hazard ratio, 15.90; 95% confidence interval, 13.28-19.04; P < .001). CONCLUSION: DFS was significantly better in screen-detected compared with non-screen-detected CRCs independent of age, sex, tumor location, stage and treatment, and was associated with an overall survival benefit.

Global Progression Rates of Precursor Lesions for Gastric Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND AND AIMS: Whether gastric cancer (GC) precursor lesions progress to invasive cancer at similar rates globally remains unknown. We conducted a systematic review and meta-analysis to determine the progression of precursor lesions to GC in countries with low versus medium/high incidence. METHODS: We searched relevant databases for studies reporting the progression of endoscopically confirmed precursor lesions to GC. Studies were stratified by low (<6 per 100,000) or medium/high (≥6 per 100,000) GC incidence countries. Random-effects models were used to estimate the progression rates of atrophic gastritis (AG), intestinal metaplasia (IM), and dysplasia to GC per 1,000 person-years. RESULTS: Among the 5,829 studies identified, 44 met our inclusion criteria. The global pooled estimates of the progression rate per 1,000 person-years were 2.09 (95% CI 1.46-2.99), 2.89 (2.03-4.11) and 10.09 (5.23-19.49) for AG, IM, and dysplasia respectively. The estimated progression rates per 1,000 person-years for low versus medium/high GC incidence countries, respectively, were 0.97 (0.86-1.10) vs. 2.47 (1.70-2.99) for AG (p<0.01); 2.37 (1.43-3.92) vs. 3.47 (2.13-5.65) for IM (p=0.29); and 5.51 (2.92-10.39) vs. 14.80 (5.87-37.28) for dysplasia (p=0.08). There were no differences for progression of AG between groups when high quality studies were compared. CONCLUSION: Similar progression rates of IM and dysplasia were observed among low and medium/high GC incidence countries. This suggests that the potential benefits of surveillance for these lesions in low-risk regions may be comparable to those of population-wide interventions in high-risk regions. Further prospective studies are needed to confirm these findings and inform global screening and surveillance guidelines.

Prevalence of Gastric Precursor Lesions in Countries With Differential Gastric Cancer Burden: A Systematic Review and Meta-analysis.

BACKGROUND & AIMS: The prevalence of precursor lesions for gastric cancer (GC) and the differential burden between countries of varying GC risk is not well-understood. We conducted a systematic review and meta-analysis to estimate the global prevalence of precursor lesions. METHODS: We estimated the prevalence of atrophic gastritis (AG), gastric intestinal metaplasia (IM), and dysplasia in regions with low, medium, and high GC incidence. Because IM is an advanced manifestation of AG, we assessed the prevalence of less advanced precursors, regardless of the presence of more advanced lesions. Prevalence was sub-stratified by Helicobacter pylori infection, symptomatology, and period (<2000, 2000-2010, and >2010). RESULTS: Among the 582 articles that underwent full-text review, 166 studies met inclusion criteria. The global prevalence estimates of AG, IM, and dysplasia were 25.4%, 16.2%, and 2.0%, respectively, on the basis of 126 studies that reported the prevalence of less advanced precursors, regardless of the presence of more advanced lesions. The prevalence of all precursor lesions was higher in high and medium compared with low GC incidence countries (P < .01). Prevalence of AG and IM was significantly higher among H pylori-infected individuals (P < .01) but not statistically different between symptomatic and asymptomatic individuals (P > .17). All precursors demonstrated a secular decrease in prevalence over time. CONCLUSIONS: Gastric precursor lesions have differences in prevalence in regions with differential GC incidence and are associated with H pylori infection. Because of the substantial prevalence of precursor lesions in both symptomatic and asymptomatic individuals, symptomatic evaluation may not be sufficient to identify individuals at risk. These estimates provide important insights for tailoring GC prevention strategies.

Randomized Trial of Facilitated Adherence to Screening Colonoscopy vs Sequential Fecal-Based Blood Test.

BACKGROUND & AIMS: Colorectal cancer (CRC) screening guidelines include screening colonoscopy and sequential high-sensitivity fecal occult blood testing (HSgFOBT), with expectation of similar effectiveness based on the assumption of similar high adherence. However, adherence to screening colonoscopy compared with sequential HSgFOBT has not been reported. In this randomized clinical trial, we assessed adherence and pathology findings for a single screening colonoscopy vs sequential and nonsequential HSgFOBTs. METHODS: Participants aged 40-69 years were enrolled at 3 centers representing different clinical settings. Participants were randomized into a single screening colonoscopy arm vs sequential HSgFOBT arm composed of 4-7 rounds. Initial adherence to screening colonoscopy and sequential adherence to HSgFOBT, follow-up colonoscopy for positive HSgFOBT tests, crossover to colonoscopy, and detection of advanced neoplasia or large serrated lesions (ADN-SERs) were measured. RESULTS: There were 3523 participants included in the trial; 1761 and 1762 participants were randomized to the screening colonoscopy and HSgFOBT arms, respectively. Adherence was 1473 (83.6%) for the screening colonoscopy arm vs 1288 (73.1%) for the HSgFOBT arm after 1 round (relative risk [RR], 1.14; 95% CI, 1.10-1.19; P ≤ .001), but only 674 (38.3%) over 4 sequential HSgFOBT rounds (RR, 2.19; 95% CI, 2.05-2.33). Overall adherence to any screening increased to 1558 (88.5%) in the screening colonoscopy arm during the entire study period and 1493 (84.7%) in the HSgFOBT arm (RR, 1.04; 95% CI, 1.02-1.07). Four hundred thirty-six participants (24.7%) crossed over to screening colonoscopy during the first 4 rounds. ADN-SERs were detected in 121 of the 1473 participants (8.2%) in the colonoscopy arm who were adherent to protocol in the first 12 months of the study, whereas detection of ADN-SERs among those who were not sequentially adherent (n = 709) to HSgFOBT was subpar (0.6%) (RR, 14.72; 95% CI, 5.46-39.67) compared with those who were sequentially adherent (3.3%) (n = 647) (RR, 2.52; 95% CI, 1.61-3.98) to HSgFOBT in the first 4 rounds. When including colonoscopies from HSgFOBT patients who were never positive yet crossed over (n = 1483), 5.5% of ADN-SERs were detected (RR, 1.50; 95% CI, 1.15-1.96) in the first 4 rounds. CONCLUSIONS: Observed adherence to sequential rounds of HSgFOBT was suboptimal compared with a single screening colonoscopy. Detection of ADN-SERs was inferior when nonsequential HSgFOBT adherence was compared with sequential adherence. However, the greatest number of ADN-SERs was detected among those who crossed over to colonoscopy and opted to receive a colonoscopy. The effectiveness of an HSgFOBT screening program may be enhanced if crossover to screening colonoscopy is permitted. CLINICALTRIALS: gov, Number: NCT00102011.

Projected Colorectal Cancer Incidence and Mortality Based on Observed Adherence to Colonoscopy and Sequential Stool-Based Screening.

INTRODUCTION: Modeling supporting recommendations for colonoscopy and stool-based colorectal cancer (CRC) screening tests assumes 100% sequential participant adherence. The impact of observed adherence on the long-term effectiveness of screening is unknown. We evaluated the effectiveness of a program of screening colonoscopy every 10 years vs annual high-sensitivity guaiac-based fecal occult blood testing (HSgFOBT) using observed sequential adherence data. METHODS: The MIcrosimulation SCreening ANalysis (MISCAN) model used observed sequential screening adherence, HSgFOBT positivity, and diagnostic colonoscopy adherence in HSgFOBT-positive individuals from the National Colonoscopy Study (single-screening colonoscopy vs ≥4 HSgFOBT sequential rounds). We compared CRC incidence and mortality over 15 years with no screening or 10 yearly screening colonoscopy vs annual HSgFOBT with 100% and differential observed adherence from the trial. RESULTS: Without screening, simulated incidence and mortality over 15 years were 20.9 (95% probability interval 15.8-26.9) and 6.9 (5.0-9.2) per 1,000 participants, respectively. In the case of 100% adherence, only screening colonoscopy was predicted to result in lower incidence; however, both tests lowered simulated mortality to a similar level (2.1 [1.6-2.9] for screening colonoscopy and 2.5 [1.8-3.4] for HSgFOBT). Observed adherence for screening colonoscopy (83.6%) was higher than observed sequential HSgFOBT adherence (73.1% first round; 49.1% by round 4), resulting in lower simulated incidence and mortality for screening colonoscopy (14.4 [10.8-18.5] and 2.9 [2.1-3.9], respectively) than HSgFOBT (20.8 [15.8-28.1] and 3.9 [2.9-5.4], respectively), despite a 91% adherence to diagnostic colonoscopy with FOBT positivity. The relative risk of CRC mortality for screening colonoscopy vs HSgFOBT was 0.75 (95% probability interval 0.68-0.80). Findings were similar in sensitivity analyses with alternative assumptions for repeat colonoscopy, test performance, risk, age, and projection horizon. DISCUSSION: Where sequential adherence to stool-based screening is suboptimal and colonoscopy is accessible and acceptable-as observed in the national colonoscopy study, microsimulation, comparative effectiveness, screening recommendations.

Risk factors for advanced colorectal neoplasia and colorectal cancer detected at surveillance: a nationwide study in the modern era.

AIM: Recommendations for surveillance after colonoscopy are based on risk factors for metachronous advanced colorectal neoplasia (AN) and colorectal cancer (CRC). The value of these risk factors remains unclear in populations enriched by individuals with a positive faecal immunochemical test and were investigated in a modern setting. METHODS AND RESULTS: This population-based cohort study included all individuals in the Netherlands of ≥55 years old with a first adenoma diagnosis in 2015. A total of 22,471 patients were included. Data were retrieved from the Dutch Nationwide Pathology Databank (Palga). Primary outcomes were metachronous AN and CRC. Patient and polyp characteristics were evaluated by multivariable Cox regression analyses. During follow-up, 2416 (10.8%) patients were diagnosed with AN, of which 557 (2.5% from the total population) were CRC. Adenomas with high-grade dysplasia (hazard ratio [HR] 1.60, 95% confidence interval [CI] 1.40-1.83), villous histology (HR 1.91, 95% CI 1.59-2.28), size ≥10 mm (HR 1.12, 95% CI 1.02-1.23), proximal location (HR 1.12, 95% CI 1.02-1.23), two or more adenomas (HR 1.28, 95% CI 1.16-1.41), and serrated polyps ≥10 mm (HR 1.67, 95% CI 1.42-1.97) were independent risk factors for metachronous AN. In contrast, only adenomas with high-grade dysplasia (HR 2.49, 95% CI 1.92-3.24) were an independent risk factor for metachronous CRC. CONCLUSIONS: Risk factors for metachronous AN and CRC were identified for populations with access to a faecal immunochemical test (FIT)-based screening programme. If only risk factors for metachronous CRC are considered, a reduction in criteria for surveillance seems reasonable.

Differences in treatment of stage I colorectal cancers: a population-based study of colorectal cancers detected within and outside of a screening program.

BACKGROUND: Screen-detected colorectal cancers (CRCs) are often treated less invasively than stage-matched non-screen-detected CRCs, but the reasons for this are not fully understood. This study evaluated the treatment of stage I CRCs detected within and outside of the screening program in the Netherlands. METHODS : Data from the Netherlands Cancer Registry for all stage I CRCs diagnosed between January 1, 2008 and December 31, 2020 were analyzed, comparing patient, tumor, and treatment characteristics of screen-detected and non-screen-detected stage I CRCs. Multivariable logistic regression was used to assess the association between treatment (local excision only vs. surgical oncologic resection) and patient and tumor characteristics, stratified for T stage and tumor location. RESULTS: Screen-detected stage I CRCs were relatively more often T1 than T2 compared with non-screen-detected stage I CRCs (66.9 % vs. 53.3 %; P < 0.001). When only T1 tumors were considered, both screen-detected colon and rectal cancers were more often treated with local excision only than non-screen-detected T1 cancers (odds ratio [OR] 2.19, 95 %CI 1.93-2.49; and OR 1.29, 95 %CI 1.05-1.59, respectively), adjusted for sex, tumor location, lymphovascular invasion (LVI) status, and tumor differentiation. CONCLUSIONS : Less invasive treatment of screen-detected stage I CRC is partly explained by the higher rate of T1 cancers compared with non-screen-detected stage I CRCs. T1 stage I screen-detected CRCs were also more likely to undergo less invasive treatment than non-screen-detected CRCs, adjusted for risk factors such as LVI and tumor differentiation. Future research should investigate whether the choice of local excision was related to unidentified cancer-related factors or the expertise of the endoscopists.

Oncologic outcomes of screen-detected and non-screen-detected T1 colorectal cancers.

BACKGROUND: The incidence of T1 colorectal cancer (CRC) has increased with the implementation of CRC screening programs. It is unknown whether the outcomes and risk models for T1 CRC based on non-screen-detected patients can be extrapolated to screen-detected T1 CRC. This study aimed to compare the stage distribution and oncologic outcomes of T1 CRC patients within and outside the screening program. METHODS: Data from T1 CRC patients diagnosed between 2014 and 2017 were collected from 12 hospitals in the Netherlands. The presence of lymph node metastasis (LNM) at diagnosis was compared between screen-detected and non-screen-detected patients using multivariable logistic regression. Cox proportional hazard regression was used to analyze differences in the time to recurrence (TTR), metastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival. Additionally, the performance of conventional risk factors for LNM was evaluated across the groups. RESULTS: 1803 patients were included (1114 [62%] screen-detected), with median follow-up of 51 months (interquartile range 30). The proportion of LNM did not significantly differ between screen- and non-screen-detected patients (12.6% vs. 8.9%; odds ratio 1.41; 95%CI 0.89-2.23); a prediction model for LNM performed equally in both groups. The 3- and 5-year TTR, MFS, and CSS were similar for patients within and outside the screening program. However, overall survival was significantly longer in screen-detected T1 CRC patients (adjusted hazard ratio 0.51; 95%CI 0.38-0.68). CONCLUSIONS: Screen-detected and non-screen-detected T1 CRCs have similar stage distributions and oncologic outcomes and can therefore be treated equally. However, screen-detected T1 CRC patients exhibit a lower rate of non-CRC-related mortality, resulting in longer overall survival.

A digital intake tool to avert outpatient visits in a FIT-based colorectal cancer screening population: study protocol of a multicentre, prospective non-randomized trial - the DIT-trial.

BACKGROUND: Currently all participants of the Dutch colorectal cancer (CRC) screening program with a positive faecal immunochemical test (FIT) are seen at the outpatient clinic to assess their health status, receive information on colonoscopy and CRC risk, and provide informed consent. However, for many patients this information could probably also safely be exchanged in an online setting, in order to reduce the burden for patients, healthcare system, and environment. In this study we will evaluate if a face-to-face pre-colonoscopy consultation can be replaced by a Digital Intake Tool (DIT) in a CRC screening population. METHODS: This is a prospective multicentre single-arm, non-randomized study with a non-inferiority design. The DIT will triage a total of 1000 participants and inform them about CRC risk, colonoscopy, sedation, and provide bowel preparation instructions. Participants identified as high-risk (i.e., red-triaged) will be contacted by phone or scheduled for an appointment at the outpatient clinic. The primary outcome measure will be adequate bowel preparation rate, defined as the proportion of participants with a Boston Bowel Preparation (BBPS) score ≥ 6. To compare our primary outcome, we will use colonoscopy data from 1000 FIT positive participants who visited the outpatient clinic for pre-colonoscopy consultation. Secondary outcomes will include participation rate, colonoscopy adherence rate, patient experience in terms of satisfaction and anxiety, knowledge transfer, number of outpatient visits that can be averted by the DIT, and cost-effectiveness of the tool. Ethical approval was obtained from the Medical Ethical Committee of the Erasmus Medical Center (MEC-2021-0098). DISCUSSION: This study aims to assess if a face-to-face pre-colonoscopy consultation can be replaced by an eHealth assessment and education tool in a FIT-based CRC screening program. In case favourable results are established, the intervention evaluated in this study could significantly impact CRC screening programs, benefiting both patients and healthcare systems on a (inter)national scale. Additionally, it would enable more personalized care as the DIT can be easily customized and made feasible in other languages, thereby enhancing healthcare accessibility. TRIAL REGISTRATION: Dutch Trial Register: NL9315 , date of registration: March 8th, 2021.

Impact of delayed screening invitations on screen-detected and interval cancers in the Dutch colorectal cancer screening programme: individual-level data analysis.

OBJECTIVE: To assess the impact of delayed invitation on screen-detected and interval colorectal cancers (CRC) within a faecal immunochemical testing (FIT)-based CRC screening programme. DESIGN: All individuals that participated in 2017 and 2018 with a negative FIT and were eligible for CRC screening in 2019 and 2020 were included using individual-level data. Multivariable logistic regression analyses were used to assess the association between either the different time periods (ie, 'before', 'during' and 'after' the first COVID-19 wave) or the invitation interval on screen-detected and interval CRCs. RESULTS: Positive predictive value for advanced neoplasia (AN) was slightly lower during (OR=0.91) and after (OR=0.95) the first COVID-19 wave, but no significant difference was observed for the different invitation intervals. Out of all individuals that previously tested negative, 84 (0.004%) had an interval CRC beyond the 24 months since their last invitation. The time period of invitation as well as the extended invitation interval was not associated with detection rates for AN and interval CRC rate. CONCLUSION: The impact of the first COVID-19 wave on screening yield was modest. A very small proportion of the FIT negatives had an interval CRC possibly due to an extended interval, which potentially could have been prevented if they had received the invitation earlier. Nonetheless, no increase in interval CRC rate was observed, indicating that an extended invitation interval up to 30 months had no negative impact on the performance of the CRC screening programme and a modest extension of the invitation interval seems an appropriate intervention.

Faecal occult blood loss accurately predicts future detection of colorectal cancer. A prognostic model.

OBJECTIVES: To examine the prognostic potential of repeated faecal haemoglobin (F-Hb) concentration measurements in faecal immunochemical test (FIT)-based screening for colorectal cancer (CRC). DESIGN: Prognostic model. SETTING: Dutch biennial FIT-based screening programme during 2014-2018. PARTICIPANTS: 265 881 participants completing three rounds of FIT, with negative test results (F-Hb <47 µg Hb/g faeces) in rounds 1 and 2. INTERVENTIONS: Colonoscopy follow-up in participants with a positive FIT (F-Hb ≥47 µg Hb/g faeces). MAIN OUTCOMES: We evaluated prognostic models for detecting advanced neoplasia (AN) and CRC in round 3, with as predictors, participant age, sex, F-Hb in rounds 1 and 2, and categories/combinations/non-linear transformations of F-Hb. Primary evaluation criteria included: risk prediction accuracy (calibration), discrimination of participants with versus without AN or CRC (optimism-adjusted C-statistics, range 0.5-1.0), the degree of risk stratification and C-statistics in external validation. RESULTS: Among study participants, 8806 (3.3%) had a positive FIT result, 3254 (1.2%) had AN detected and 557 (0.2%) had cancer. F-Hb concentrations in rounds 1 and 2 were the strongest outcome predictors, with adjusted ORs of up to 9.4 (95% CI 7.5 to 11.7) for the highest F-Hb category. Risk predictions matched the observed risk for most participants (calibration intercept -0.008 to -0.099; slope 0.982-0.998), and discriminated participants with versus without AN or CRC with C-statistics of 0.78 (95% CI 0.77 to 0.79) and 0.73 (95% CI 0.71 to 0.75), respectively. The predicted risk ranged from 0.4% to 36.7% for AN and from 0.0% to 5.5% for CRC across participants. In external validation, the model retained similar discrimination accuracy for AN (C-statistic 0.77, 95% CI 0.66 to 0.87) and CRC (C-statistic 0.78, 95% CI 0.66 to 0.91). CONCLUSION: Participants at lower versus higher risk of future AN or CRC can be accurately identified based on their age, sex and particularly, prior F-Hb concentrations. Risk stratification should be considered based on this information.

The impact of pancreatic cancer screening on life expectancy: A systematic review of modeling studies.

Evidence supporting the effectiveness of pancreatic cancer (PC) screening is scant. Most clinical studies concern small populations with short follow-up durations. Mathematical models are useful to estimate long-term effects of PC screening using short-term indicators. This systematic review aims to evaluate the impact of PC screening on life expectancy (LE) in model-based studies. Therefore, we searched four databases (Embase, Medline, Web-of-science, Cochrane) until 30 May 2022 to identify model-based studies evaluating the impact of PC screening on LE in different risk populations. Two authors independently screened identified papers, extracted data and assessed the methodological quality of studies. A descriptive analysis was performed and the impact of screening strategies on LE of different risk groups was reported. Our search resulted in 419 studies, of which eight met the eligibility criteria (mathematical model, PC screening, LE). Reported relative risks (RR) for PC varied from 1 to 70. In higher risk individuals (RR > 5), annual screening (by imaging with 56% sensitivity for HGD/early stage PC) predicted to increase LE of screened individuals by 20 to 260 days. In the general population, one-time PC screening was estimated to decrease LE (2-110 days), depending on the test characteristics and treatment mortality risk. In conclusion, although the models use different and sometimes outdated or unrealistic assumptions, it seems that PC screening in high-risk populations improves LE, and that this gain increases with a higher PC risk. Updated model studies, with data from large clinical trials are necessary to predict the long-term effect of PC screening more accurately.