Early-Onset Colorectal Cancer Patients Do Not Require Shorter Intervals for Post-Surgical Surveillance Colonoscopy.

BACKGROUND: Early-onset colorectal cancer (EO-CRC), diagnosed before age 50, is rising in incidence worldwide. Although post-surgical colonoscopy surveillance strategies exist, appropriate intervals in EO-CRC remain elusive, as long-term surveillance outcomes remain scant. We sought to compare findings of surveillance colonoscopies of EO-CRC to average onset colorectal cancer (AO-CRC) patients to help define surveillance outcomes in these groups. METHODS: Single institution retrospective chart review identified EO-CRC and AO-CRC patients with colonoscopy and no evidence of disease. Surveillance intervals and time to development of advanced neoplasia (CRC and advanced polyps (adenoma/sessile serrated)) were examined. For each group, three serial surveillance colonoscopies were evaluated. Statistical analyses were performed utilizing log-ranked Kaplan-Meier method and Cox proportional hazards. RESULTS: A total of 1259 CRC patients were identified, with 612 and 647 patients in the EO-CRC and AO-CRC groups, respectively. Compared to AO-CRC patients, EO-CRC patients had a 29% decreased risk of developing advanced neoplasia from time of initial surgery to first surveillance colonoscopy (HR=0.71, 95% CI 0.52 - 1.0). Average follow-up time from surgical resection to first surveillance colonoscopy was 12.6 months for both cohorts. Overall surveillance findings differed between cohorts (p=0.003), and EO-CRC were found to have less advanced neoplasia compared to AO-CRC counterparts (12.4% vs 16.0%, respectively). Subsequent colonoscopies found that while EO-CRC patients returned for follow-up surveillance colonoscopy earlier than AO-CRC patients, the EO-CRC cohort did not have more advanced neoplasia nor non-advanced adenomas. CONCLUSIONS: EO-CRC patients do not have an increased risk of advanced neoplasia compared to AO-CRC patients and therefore do not require more frequent colonoscopy surveillance than current guidelines recommend.

CLINICOPATHOLOGICAL CHARACTERISTICS AND RISK FACTORS OF YOUNG-ONSET GASTRIC CARCINOMA: A SYSTEMATIC REVIEW AND META-ANALYSIS.

BACKGROUND: The characteristics of gastric carcinoma in young individuals differ from older individuals. We conducted a systematic review and meta-analysis to explore the clinicopathological features and risk factors associated with young-onset (<50 years) gastric carcinoma. METHODS: We searched for studies published between January 1, 1990, and September 1, 2023, on patients with young-onset gastric carcinoma in PubMed, EMBASE, Web of Science, and MEDLINE to explore clinicopathological characteristics among this specific patient group. Extracted information included the proportion of patients with symptoms or family history of gastric cancer, tumor location, and histological features such as Lauren or WHO histological classification and degree of differentiation. Additional analyses were conducted on risk factors such as a positive family history, Helicobacter pylori (H. pylori) infection, or high-risk nutritional or behavioral factors. The estimates were derived using random or fixed-effect models and included subgroup analyses based on different sex and age groups. This study was registered in PROSPERO (CRD42023466131). RESULTS: We identified 5,696 records, 1,292 were included in the quality assessment stage. Finally, 84 studies from 18 countries or regions including 89,447 patients with young-onset gastric carcinoma were included. Young-onset gastric carcinoma has slight female predominance (53.7%, 95%CI: 51.6-55.7%), with most having symptoms (87.0%, 95%CI: 82.4-91.7%). Family history was reported in 12.1% (95%CI: 9.5-14.7%). H. pylori infection was detected in 60.0% of cases (95%CI: 47.1-72.8%). The majority of these carcinomas were in the non-cardia region (89.6%, 95%CI:82.4-96.8%), exhibiting Lauren diffuse-type histology (71.1%, 95%CI: 66.8-75.3%) and poor/undifferentiated features (81.9%, 95%CI: 79.7-84.2%). A positive family history of gastric cancer was the most important risk factor associated with the development of gastric carcinoma in young individuals (pooled odds ratios [OR] 4.0, 95% CI: 2.8-5.2), followed by H. pylori infection (OR 2.3; 95% CI: 1.4-3.2) and dietary and other lifestyle risk factors. CONCLUSION: Young-onset gastric carcinoma exhibits specific clinicopathological characteristics, with positive family history being the most important risk factor. The majority of patients were symptomatic at diagnosis. These findings could help to inform future strategies for the early detection of gastric carcinoma among young individuals.

Global burden of young-onset gastric cancer: a systematic trend analysis of the global burden of disease study 2019.

BACKGROUND: While gastric cancer is generally declining globally, the temporal trend of young-onset (< 40 years) gastric cancer remains uncertain. We performed this analysis to determine the temporal trends of young-onset gastric cancer compared to late-onset cancer (≥ 40 years). METHODS: We extracted cross-sectional data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. The burden of gastric cancer from 1990 to 2019 was assessed through indicators including incidence and mortality rates, which were classified at global, national, and regional levels, and according to socio-demographic indexes (SDI) and age or sex groups. Joinpoint regression analysis was used to identify specific years with significant changes. The correlation between AAPC with countries' average SDI was tested by Pearson's Test. RESULTS: The global incidence rate of young-onset gastric cancer decreased from 2.20 (per 100,000) in 1990 to 1.65 in 2019 (AAPC: - 0.95; 95% confidence interval [CI] - 1.25 to - 0.65; P < 0.001). Late-onset cancer incidence also decreased from 59.53 (per 100,000) in 1990 to 41.26 in 2019 (AAPC: - 1.23; 95% CI - 1.39 to - 1.06, P < 0.001). Despite an overall decreasing trend, the incidence rate of young-onset cancer demonstrated a significant increase from 2015 to 2019 (annual percentage change [APC]: 1.39; 95% CI 0.06 to 2.74; P = 0.041), whereas no upward trend was observed in late-onset cancer. Mortality rates of young- and late-onset cancer both exhibited a significant decline during this period (AAPC: - 1.82; 95% CI - 2.15 to - 1.56; P < 0.001 and AAPC: - 1.69, 95% CI - 1.79 to - 1.59; P < 0.001). The male-to-female rate ratio for incidence and mortality in both age groups have been increasing since 1990. While countries with high SDI have had a greater decline in the incidence of late-onset gastric cancer (slope of AAPC change: - 0.20, P = 0.004), it was not observed in young-onset cancer (slope of AAPC change: - 0.11, P = 0.13). CONCLUSIONS: The global incidence and mortality rates of both young- and late-onset gastric cancer have decreased since 1990. However, the incidence rate of young-onset cancer has demonstrated a small but significant upward trend since 2015. There was disparity in the decline in young-onset gastric cancer among male and high SDI countries. These findings could help to inform future strategies in preventing gastric cancer in younger individuals.

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.

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.

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.

Projected long-term effects of colorectal cancer screening disruptions following the COVID-19 pandemic.

The aftermath of the initial phase of the COVID-19 pandemic may contribute to the widening of disparities in colorectal cancer (CRC) outcomes due to differential disruptions to CRC screening. This comparative microsimulation analysis uses two CISNET CRC models to simulate the impact of ongoing screening disruptions induced by the COVID-19 pandemic on long-term CRC outcomes. We evaluate three channels through which screening was disrupted: delays in screening, regimen switching, and screening discontinuation. The impact of these disruptions on long-term CRC outcomes was measured by the number of life-years lost due to CRC screening disruptions compared to a scenario without any disruptions. While short-term delays in screening of 3-18 months are predicted to result in minor life-years loss, discontinuing screening could result in much more significant reductions in the expected benefits of screening. These results demonstrate that unequal recovery of screening following the pandemic can widen disparities in CRC outcomes and emphasize the importance of ensuring equitable recovery to screening following the pandemic.

Factors associated with detection of hereditary diffuse gastric cancer on endoscopy in individuals with germline CDH1 mutations.

BACKGROUND AND AIMS: Individuals with germline pathogenic CDH1 variants have a high risk of hereditary diffuse gastric cancer. The sensitivity of EGD in detecting signet ring cell carcinoma (SRCC) in this population is low. We aimed to identify endoscopic findings and biopsy practices associated with detection of SRCC. METHODS: This retrospective cohort included individuals with a germline pathogenic/likely pathogenic CDH1 variant undergoing at least 1 EGD at Memorial Sloan Kettering Cancer Center between January 1, 2006, and March 25, 2022. The primary outcome was detection of SRCC on EGD. Findings on gastrectomy were also assessed. The study included periods before and after implementation of the Cambridge protocol for endoscopic surveillance, allowing for assessment of a spectrum of biopsy practices. RESULTS: Ninety-eight CDH1 patients underwent at least 1 EGD at our institution. SRCC was detected in 20 (20%) individuals on EGD overall and in 50 (86%) of the 58 patients undergoing gastrectomy. Most SRCC foci were detected in the gastric cardia/fundus (EGD, 50%; gastrectomy, 62%) and body/transition zone (EGD, 60%; gastrectomy, 62%). Biopsy results of gastric pale mucosal areas were associated with detection of SRCC (P < .01). The total number of biopsy samples taken on EGD was associated with increased detection of SRCC (P = .01), with 43% detected when ≥40 samples were taken. CONCLUSIONS: Targeted biopsy sampling of gastric pale mucosal areas and increasing number of biopsy samples taken on EGD were associated with detection of SRCC. SRCC foci were mostly detected in the proximal stomach, supporting updated endoscopic surveillance guidelines. Further studies are needed to refine endoscopic protocols to improve SRCC detection in this high-risk population.

Critical Appraisal of Decision Models Used for the Economic Evaluation of Bladder Cancer Screening and Diagnosis: A Systematic Review.

BACKGROUND AND OBJECTIVE: Bladder cancer is common among current and former smokers. High bladder cancer mortality may be decreased through early diagnosis and screening. The aim of this study was to appraise decision models used for the economic evaluation of bladder cancer screening and diagnosis, and to summarise the main outcomes of these models. METHODS: MEDLINE via PubMed, Embase, EconLit and Web of Science databases was systematically searched from January 2006 to May 2022 for modelling studies that assessed the cost effectiveness of bladder cancer screening and diagnostic interventions. Articles were appraised according to Patient, Intervention, Comparator and Outcome (PICO) characteristics, modelling methods, model structures and data sources. The quality of the studies was also appraised using the Philips checklist by two independent reviewers. RESULTS: Searches identified 3082 potentially relevant studies, which resulted in 18 articles that met our inclusion criteria. Four of these articles were on bladder cancer screening, and the remaining 14 were diagnostic or surveillance interventions. Two of the four screening models were individual-level simulations. All screening models (n = 4, with three on a high-risk population and one on a general population) concluded that screening is either cost saving or cost effective with cost-effectiveness ratios lower than $53,000/life-years saved. Disease prevalence was a strong determinant of cost effectiveness. Diagnostic models (n = 14) assessed multiple interventions; white light cystoscopy was the most common intervention and was considered cost effective in all studies (n = 4). Screening models relied largely on published evidence generalised from other countries and did not report the validation of their predictions to external data. Almost all diagnostic models (n = 13 out of 14) had a time horizon of 5 years or less and most of the models (n = 11) did not incorporate health-related utilities. In both screening and diagnostic models, epidemiological inputs were based on expert elicitation, assumptions or international evidence of uncertain generalisability. In modelling disease, seven models did not use a standard classification system to define cancer states, others used risk-based, numerical or a Tumour, Node, Metastasis classification. Despite including certain components of disease onset or progression, no models included a complete and coherent model of the natural history of bladder cancer (i.e. simulating the progression of asymptomatic primary bladder cancer from cancer onset, i.e. in the absence of treatment). CONCLUSIONS: The variation in natural history model structures and the lack of data for model parameterisation suggest that research in bladder cancer early detection and screening is at an early stage of development. Appropriate characterisation and analysis of uncertainty in bladder cancer models should be considered a priority.

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.

Impact and Recovery from COVID-19-Related Disruptions in Colorectal Cancer Screening and Care in the US: A Scenario Analysis.

BACKGROUND: Many colorectal cancer-related procedures were suspended during the COVID-19 pandemic. In this study, we predict the impact of resulting delays in screening (colonoscopy, FIT, and sigmoidoscopy) and diagnosis on colorectal cancer-related outcomes, and compare different recovery scenarios. METHODS: Using the MISCAN-Colon model, we simulated the US population and evaluated different impact and recovery scenarios. Scenarios were defined by the duration and severity of the disruption (percentage of eligible adults affected), the length of delays, and the duration of the recovery. During recovery (6, 12 or 24 months), capacity was increased to catch up missed procedures. Primary outcomes were excess colorectal cancer cases and -related deaths, and additional colonoscopies required during recovery. RESULTS: With a 24-month recovery, the model predicted that the US population would develop 7,210 (0.18%) excess colorectal cancer cases during 2020-2040, and 6,950 (0.65%) excess colorectal cancer-related deaths, and require 108,500 (8.6%) additional colonoscopies per recovery month, compared with a no-disruption scenario. Shorter recovery periods of 6 and 12 months, respectively, decreased excess colorectal cancer-related deaths to 4,190 (0.39%) and 4,580 (0.43%), at the expense of 260,200-590,100 (20.7%-47.0%) additional colonoscopies per month. CONCLUSIONS: The COVID-19 pandemic will likely cause more than 4,000 excess colorectal cancer-related deaths in the US, which could increase to more than 7,000 if recovery periods are longer. IMPACT: Our results highlight that catching-up colorectal cancer-related services within 12 months provides a good balance between required resources and mitigation of the impact of the disruption on colorectal cancer-related deaths.

Unequal Recovery in Colorectal Cancer Screening Following the COVID-19 Pandemic: A Comparative Microsimulation Analysis.

The aftermath of the initial phase of the COVID-19 pandemic may contribute to the widening of disparities in access to colorectal cancer (CRC) screening due to differential disruptions to CRC screening. This comparative microsimulation analysis uses two CISNET CRC models to simulate the impact of ongoing screening disruptions induced by the COVID-19 pandemic on long-term CRC outcomes. We evaluate three channels through which screening was disrupted: delays in screening, regimen switching, and screening discontinuation. The impact of these disruptions on long-term colorectal cancer (CRC) outcomes was measured by the number of Life-years lost due to CRC screening disruptions compared to a scenario without any disruptions. While short-term delays in screening of 3-18 months are predicted to result in minor life-years loss, discontinuing screening could result in much more significant reductions in the expected benefits of screening. These results demonstrate that unequal recovery of screening following the pandemic can widen disparities in colorectal cancer outcomes and emphasize the importance of ensuring equitable recovery to screening following the pandemic.