Effectiveness of Colonoscopy Screening vs Sigmoidoscopy Screening in Colorectal Cancer.

Importance: Randomized clinical screening trials have shown that sigmoidoscopy screening reduces colorectal cancer (CRC) incidence and mortality. Colonoscopy has largely replaced sigmoidoscopy for CRC screening, but long-term results from randomized trials on colonoscopy screening are still lacking. Objective: To estimate the additional screening benefit of colonoscopy compared with sigmoidoscopy. Design, Setting, and Participants: This comparative effectiveness simulation study pooled data on 358 204 men and women randomly assigned to sigmoidoscopy screening or usual care in 4 randomized sigmoidoscopy screening trials conducted in Norway, Italy, the US, and UK with inclusion periods in the years 1993 to 2001. The primary analysis of the study was conducted from January 19 to December 30, 2021. Intervention: Invitation to endoscopic screening. Main Outcomes and Measures: Primary outcomes were CRC incidence and mortality. Using pooled 15-year follow-up data, colonoscopy screening effectiveness was estimated assuming that the efficacy of colonoscopy in the proximal colon was similar to that observed in the distal colon in the sigmoidoscopy screening trials. The simulation model was validated using data from Norwegian participants in a colonoscopy screening trial. Results: This analysis included 358 204 individuals (181 971 women [51%]) aged 55 to 64 years at inclusion with a median follow-up time ranging from 15 to 17 years. Compared with usual care, colonoscopy prevented an estimated 50 (95% CI, 42-58) CRC cases per 100 000 person-years, corresponding to 30% incidence reduction (rate ratio, 0.70 [95% CI, 0.66-0.75]), and prevented an estimated 15 (95% CI, 11-19) CRC deaths per 100 000 person-years, corresponding to 32% mortality reduction (rate ratio, 0.68 [95% CI, 0.61-0.76]). The additional benefit of colonoscopy screening compared with sigmoidoscopy was 12 (95% CI, 10-14) fewer CRC cases and 4 (95% CI, 3-5) fewer CRC deaths per 100 000 person-years, corresponding to percentage point reductions of 6.9 (95% CI, 6.0-7.9) for CRC incidence and 7.6 (95% CI, 5.7-9.6) for CRC mortality. The number needed to switch from sigmoidoscopy to colonoscopy screening was 560 (95% CI, 486-661) to prevent 1 CRC case and 1611 (95% CI, 1275-2188) to prevent 1 CRC death. Conclusions and Relevance: The findings of this comparative effectiveness study assessing long-term follow-up after CRC screening suggest that there was an additional preventive effect on CRC incidence and mortality associated with colonoscopy screening compared with sigmoidoscopy screening, but the additional preventive effect was less than what was achieved by introducing sigmoidoscopy screening where no screening existed. The results probably represent the upper limit of what may be achieved with colonoscopy screening compared with sigmoidoscopy screening.

Roadmap to improve the organized cancer screening programs - The case of colorectal cancer screening in Montenegro.

BACKGROUND: Implementation of organized cancer screening programs comes with many challenges and barriers, which may inhibit the achievement of the screening activities' desired benefits. In this paper we outline a plan for improving the colorectal cancer (CRC) screening system in Montenegro. METHODS: We formulated a roadmap, which was generally defined as a country-specific strategic plan to improve cancer screening programs. The roadmap development was an iterative, step-by-step process. First, we described the current screening program, then identified and described key barriers, and finally proposed actions to overcome them. Multiple sources of information (e.g., documents, expert opinions) were collected and processed by local and international stakeholders. RESULTS: The CRC screening program was implemented between 2013-2019 by gradually increasing the invitation of the target population. Key barriers of the implementation were defined: 1) Lack of colonoscopy capacity in the northern part of the country; 2) Inadequate information technology systems; 3) Inadequate public promotion of screening. The defined actions were related to overcoming lack of available resources (e.g., financial, human and technological), to improve the policy environment and the knowledge, and to facilitate information sharing. CONCLUSION: The collaboration between local stakeholders of CRC screening and researchers experienced in planning and evaluating screening programs resulted in the first comprehensive description of CRC screening in Montenegro, detailed understanding of key barriers that emerged during implementation and a carefully designed list of actions. The implementation of these actions and the evaluation of whether barriers were solved will be captured in the upcoming period by maintaining this collaboration.

SIED-GISCOR recommendations for colonoscopy in screening programs: Part I - Diagnostic.

The implementation of FIT programs reduces incidence and mortality from CRC in the screened subjects. The ultimate efficacy for CRC morbidity and mortality prevention in a FIT program depends on the colonoscopy in FIT+ subjects that has the task of detecting and removing these advanced lesions. Recently, there has been growing evidence on factors that influence the quality of colonoscopy specifically withing organized FIT programs, prompting to dedicated interventions in order to maximize the benefit/harm ratio of post-FIT colonoscopy. This document focuses on the diagnostic phase of colonoscopy, providing indications on how to standardise colonoscopy in FIT+ subjects, regarding timing of examination, management of antithrombotic therapy, bowel preparation, competence and sedation.

Profiling small RNAs in fecal immunochemical tests: is it possible?

Fecal microRNAs represent promising molecules with potential clinical interest as non-invasive diagnostic and prognostic biomarkers. Colorectal cancer (CRC) screening based on the fecal immunochemical test (FIT) is an effective tool for prevention of cancer development. However, due to the poor sensitivity of FIT especially for premalignant lesions, there is a need for implementation of complementary tests. Improving the identification of individuals who would benefit from further investigation with colonoscopy using molecular analysis, such as miRNA profiling of FIT samples, would be ideal due to their widespread use. In the present study, we assessed the feasibility of applying small RNA sequencing to measure human miRNAs in FIT leftover buffer in samples from two European screening populations. We showed robust detection of miRNAs with profiles similar to those obtained from specimens sampled using the established protocol of RNA stabilizing buffers, or in long-term archived samples. Detected miRNAs exhibited differential abundances for CRC, advanced adenoma, and control samples that were consistent for FIT and RNA-stabilizing buffers. Interestingly, the sequencing data also allowed for concomitant evaluation of small RNA-based microbial profiles. We demonstrated that it is possible to explore the human miRNome in FIT leftover samples across populations and envision that the analysis of small RNA biomarkers can complement the FIT in large scale screening settings.

Rationale for organized Colorectal cancer screening programs.

Colorectal cancer (CRC) is a major health problem and it is expected that the number of persons diagnosed with CRC and CRC-related deaths will continue to increase. However, recent years have shown reductions in CRC incidence and mortality particularly among individuals aged 50 years and older which can be attributed to screening, improvements in patients' management, closer adherence to treatment guideline recommendations and a higher utilization of curative surgery, chemotherapy and radiotherapy. The International Agency for Research on Cancer has concluded that there has been sufficient evidence that biennially screening using a stool-test or once-only endoscopy screening reduces CRC-related mortality. In Europe, between 2008 and 2018, nine countries have successfully implemented a population-based organized program and another six are in the roll-out phase. Population-based organized programs show higher screening participation rates and lower lack of compliance to follow-up testing after a positive screen test compared to opportunistic screening. Moreover, organized programs aim to provide high quality screening thereby reducing the risk of the harms of screening, including over-screening, and complications of screening, and poor follow-up of those who test positive. We describe how population-based organized CRC screening programs are preferred, since they reflect a more appropriate utilization of available resources, reduce inequities in access, and can integrate interventions addressing barriers to screening at the individual and health system levels.

Testing behavioral economics messages to increase non-responders' participation in organized colorectal cancer-screening programs: A randomized controlled trial.

This study aimed to evaluate the impact of behavioral economic-inspired messages on participation in colorectal cancer (CRC) screening programs. We conducted a randomized-controlled trial involving 11,505 non-responders to the CRC screening programs in Florence, Rome, and Turin in 2020. Participants aged 54-70 years were randomly assigned to four conditions. Individuals in the control conditions received a standard invitation letter while the three intervention groups included an additional paragraph featuring either i. normative feedback [F] message (giving feedback that invited subjects did not participate); ii. Minority norm [MN] message (only a minority did not participate); iii. F+ MN message (combining both messages). The primary outcome was the screening participation rate 90 days after the invitation was completed. A multivariate analysis was conducted adjusting for gender, age and birthplace. Overall, screening participation rates were 5.3% in the control condition, 7.0% in the F, 8.2% in the MN, and 7.4% in the F + MN arms (p = 0.002). Invited subjects in the MN arm were more likely to participate (adjusted Odds Ratio[aOR] = 1.38; 95% Confidence Interval [95%CI,1.13-1.68]), particularly those aged 54-59 years (aOR = 1.52; 95%CI:1.16-1.98), and 60-64 (aOR = 1.57; 95%CI:1.62-; 95%CI: 1.06-2.48). Additionally, individuals aged 60-64 invited in F and F + MN arms demonstrated a higher likelihood of participation (aOR for F arm = 1.60; 95%CI: 1.06-2.41; aOR for F + MN arm = 1.99; 95%CI: 1.35-2.92). The inclusion of MN and/or F messages in the invitation letter increased participation among previous non-responders <65 years. Behavioral economics is a promising area of interest for enhancing CRC screening participation. TRIAL REGISTRATION: ISRCTN registration number: ISRCTN11841256.

An efficient strategy for evaluating new non-invasive screening tests for colorectal cancer: the guiding principles.

OBJECTIVE: New screening tests for colorectal cancer (CRC) are rapidly emerging. Conducting trials with mortality reduction as the end point supporting their adoption is challenging. We re-examined the principles underlying evaluation of new non-invasive tests in view of technological developments and identification of new biomarkers. DESIGN: A formal consensus approach involving a multidisciplinary expert panel revised eight previously established principles. RESULTS: Twelve newly stated principles emerged. Effectiveness of a new test can be evaluated by comparison with a proven comparator non-invasive test. The faecal immunochemical test is now considered the appropriate comparator, while colonoscopy remains the diagnostic standard. For a new test to be able to meet differing screening goals and regulatory requirements, flexibility to adjust its positivity threshold is desirable. A rigorous and efficient four-phased approach is proposed, commencing with small studies assessing the test's ability to discriminate between CRC and non-cancer states (phase I), followed by prospective estimation of accuracy across the continuum of neoplastic lesions in neoplasia-enriched populations (phase II). If these show promise, a provisional test positivity threshold is set before evaluation in typical screening populations. Phase III prospective studies determine single round intention-to-screen programme outcomes and confirm the test positivity threshold. Phase IV studies involve evaluation over repeated screening rounds with monitoring for missed lesions. Phases III and IV findings will provide the real-world data required to model test impact on CRC mortality and incidence. CONCLUSION: New non-invasive tests can be efficiently evaluated by a rigorous phased comparative approach, generating data from unbiased populations that inform predictions of their health impact.

A Fecal MicroRNA Signature by Small RNA Sequencing Accurately Distinguishes Colorectal Cancers: Results From a Multicenter Study.

BACKGROUND & AIMS: Fecal tests currently used for colorectal cancer (CRC) screening show limited accuracy in detecting early tumors or precancerous lesions. In this respect, we comprehensively evaluated stool microRNA (miRNA) profiles as biomarkers for noninvasive CRC diagnosis. METHODS: A total of 1273 small RNA sequencing experiments were performed in multiple biospecimens. In a cross-sectional study, miRNA profiles were investigated in fecal samples from an Italian and a Czech cohort (155 CRCs, 87 adenomas, 96 other intestinal diseases, 141 colonoscopy-negative controls). A predictive miRNA signature for cancer detection was defined by a machine learning strategy and tested in additional fecal samples from 141 CRC patients and 80 healthy volunteers. miRNA profiles were compared with those of 132 tumors/adenomas paired with adjacent mucosa, 210 plasma extracellular vesicle samples, and 185 fecal immunochemical test leftover samples. RESULTS: Twenty-five miRNAs showed altered levels in the stool of CRC patients in both cohorts (adjusted P < .05). A 5-miRNA signature, including miR-149-3p, miR-607-5p, miR-1246, miR-4488, and miR-6777-5p, distinguished patients from control individuals (area under the curve [AUC], 0.86; 95% confidence interval [CI], 0.79-0.94) and was validated in an independent cohort (AUC, 0.96; 95% CI, 0.92-1.00). The signature classified control individuals from patients with low-/high-stage tumors and advanced adenomas (AUC, 0.82; 95% CI, 0.71-0.97). Tissue miRNA profiles mirrored those of stool samples, and fecal profiles of different gastrointestinal diseases highlighted miRNAs specifically dysregulated in CRC. miRNA profiles in fecal immunochemical test leftover samples showed good correlation with those of stool collected in preservative buffer, and their alterations could be detected in adenoma or CRC patients. CONCLUSIONS: Our comprehensive fecal miRNome analysis identified a signature accurately discriminating cancer aimed at improving noninvasive diagnosis and screening strategies.

Risk prediction for advanced neoplasia using longitudinal adherence measures to fecal immunochemical test-based colorectal cancer screening programs.

BACKGROUND: Patterns of longitudinal adherence may predict advanced neoplasia (AN) detection in subsequent rounds of colorectal cancer (CRC) screening. However, after more than five rounds, it is important to obtain a simplified measure. The aim was to determine the best simplified measure of longitudinal adherence to predict AN detection in CRC screening. METHODS: Individuals with four invitations from a Dutch Fecal immunochemical testing (FIT-)based pilot study and two Italian FIT-based CRC screening programs were included. We calculated AN detection in the fourth round, stratified by prior adherence. Five simplified measures were compared to full information (permutations) using chi-squared goodness-of-fit: adherence previous invitation, consistency, frequency, frequency + adherence previous invitation, and proportion of invitations covered. RESULTS: AN detection in the fourth round was highly dependent on prior adherence behavior. For inconsistent adherence, detection in the fourth round was strongly dependent on frequency and time since last participation. The performance of the simplified measures to capture this variation differed considerably. 'Adherence previous invitation' scored worst in predicting AN detection. 'Frequency+adherence previous invitation' had lowest chi-squared goodness-of-fit. DISCUSSION: The simplified measure 'frequency+adherence previous invitation' is the best measure to reflect patterns of longitudinal adherence and could be used to emphasize to individuals the importance of CRC screening.

Overcoming barriers: Modelling the effect of potential future changes of organized breast cancer screening in Italy.

OBJECTIVES: Organized breast cancer screening may not achieve its full potential due to organizational and cultural barriers. In Italy, two identified barriers were low attendance in Southern Italy and, in Italy as a whole, underscreening and overscreening in parts of the eligible population. The objective of this study was to identify potential changes to overcome these barriers and to quantify their costs and effects. METHODS: To assess the impact of potential measures to improve breast cancer screening in Italy, we performed an evaluation of costs and effects for increasing adherence for Southern Italy and harmonizing screening intervals (biennial screening) for the whole of Italy, using an online tool (EU-TOPIA evaluation tool) based on the MIcrosimulation SCreening ANalysis (MISCAN) model. RESULTS: Increasing adherence in Southern Italy through investing in mobile screening units has an acceptable cost-effectiveness ratio of €9531 per quality-adjusted life year gained. Harmonizing the screening interval by investing in measures to reduce opportunistic screening and simultaneously investing in mobile screening units to reduce underscreening is predicted to gain 1% fewer life-years, while saving 19% of total screening costs compared to the current situation. CONCLUSIONS: Increasing adherence in Southern Italy and harmonizing the screening interval could result in substantial improvements at acceptable costs, or in the same benefits at lower costs. This example illustrates a systematic approach that can be easily applied to other European countries, as the online tools can be used by stakeholders to quantify effects and costs of a broad range of specific barriers, and ways to overcome them.

The impact of the COVID-19 pandemic on Italian population-based cancer screening activities and test coverage: Results from national cross-sectional repeated surveys in 2020.

Background: In Italy, regions have the mandate to implement population-based screening programs for breast, cervical, and colorectal cancer. From March to May 2020, a severe lockdown was imposed due to the COVID-19 pandemic by the Italian Ministry of Health, with the suspension of screening programs. This paper describes the impact of the pandemic on Italian screening activities and test coverage in 2020 overall and by socioeconomic characteristics. Methods: The regional number of subjects invited and of screening tests performed in 2020 were compared with those in 2019. Invitation and examination coverage were also calculated. PASSI surveillance system, through telephone interviews, collects information about screening test uptake by test provider (public screening and private opportunistic). Test coverage and test uptake in the last year were computed by educational attainment, perceived economic difficulties, and citizenship. Results: A reduction of subjects invited and tests performed, with differences between periods and geographical macro areas, was observed in 2020 vs. 2019. The reduction in examination coverage was larger than that in invitation coverage for all screening programs. From the second half of 2020, the trend for test coverage showed a decrease in all the macro areas for all the screening programs. Compared with the pre-pandemic period, there was a greater difference according to the level of education in the odds of having had a test last year vs. never having been screened or not being up to date with screening tests. Conclusions: The lockdown and the ongoing COVID-19 emergency caused an important delay in screening activities. This increased the preexisting individual and geographical inequalities in access. The opportunistic screening did not mitigate the impact of the pandemic. Funding: This study was partially supported by Italian Ministry of Health - Ricerca Corrente Annual Program 2023 and by the Emilian Region DGR 839/22.

15-Year Benefits of Sigmoidoscopy Screening on Colorectal Cancer Incidence and Mortality : A Pooled Analysis of Randomized Trials.

BACKGROUND: The effectiveness of screening for colorectal cancer (CRC) by sex and age in randomized trials is uncertain. OBJECTIVE: To evaluate the 15-year effect of sigmoidoscopy screening on CRC incidence and mortality. DESIGN: Pooled analysis of 4 large-scale randomized trials of sigmoidoscopy screening. SETTING: Norway, the United States, the United Kingdom, and Italy. PARTICIPANTS: Women and men aged 55 to 64 years at enrollment. INTERVENTION: Sigmoidoscopy screening. MEASUREMENTS: Primary end points were cumulative incidence rate ratio (IRR) and mortality rate ratio (MRR) and rate differences after 15 years of follow-up comparing screening versus usual care in intention-to-treat analyses. Stratified analyses were done by sex, cancer site, and age at screening. RESULTS: Analyses comprised 274 952 persons (50.7% women), 137 493 in the screening and 137 459 in the usual care group. Screening attendance was 58% to 84%. After 15 years, the rate difference for CRC incidence was 0.51 cases (95% CI, 0.40 to 0.63 cases) per 100 persons and the IRR was 0.79 (CI, 0.75 to 0.83). The rate difference for CRC mortality was 0.13 deaths (CI, 0.07 to 0.19 deaths) per 100 persons, and the MRR was 0.80 (CI, 0.72 to 0.88). Women had less benefit from screening than men for CRC incidence (IRR for women, 0.84 [CI, 0.77 to 0.91]; IRR for men, 0.75 [CI, 0.70 to 0.81]; P = 0.032 for difference) and mortality (MRR for women, 0.91 [CI, 0.77 to 1.17]; MRR for men, 0.73 [CI, 0.64 to 0.83]; P = 0.025 for difference). There was no statistically significant difference in screening effect between persons aged 55 to 59 years and those aged 60 to 64 years. LIMITATION: Data from the U.K. trial were less granular because of privacy regulations. CONCLUSION: This pooled analysis of all large randomized trials of sigmoidoscopy screening demonstrates a significant and sustained effect of sigmoidoscopy on CRC incidence and mortality for 15 years. PRIMARY FUNDING SOURCE: Health Fund of South-East Norway.

Promoting healthy lifestyle habits among participants in cancer screening programs: Results of the randomized controlled Sti.Vi study.

Background: Unhealthy diets, physical inactivity, alcohol and tobacco consumption are among the leading risk factors for non-communicable diseases. It is estimated that around 40% of cancers could be prevented by adopting healthy lifestyles. Design and methods: The Stili di Vita (Sti.Vi) study was a randomized study for assessing the impact of healthy lifestyle interventions on anthropometric measures, metabolic parameters, and health outcomes among participants of cancer screening programs in Turin (Italy). Eligible women aged 50-54 years, invited to biennial mammography screening, and 58-years-old men and women, invited to a once-only sigmoidoscopy for colorectal cancer (CRC) screening were randomly allocated to Diet group (DG), Physical Activity group (PAG), Physical Activity plus Diet group (PADG), or control group (CG). Physical and eating habits, metabolic and anthropometric measurements, repeatedly collected, were the study outcomes. The active intervention, offered to participants assigned to the DG, PAG, and PADG arms, consisted of a basic module and an advanced module. The effect of the interventions was estimated through logistic regression or a difference in differences approach. A multiple imputation procedure was implemented to deal with missing values and q-values have been calculated in the presence of multiple hypothesis testing. Results: Out of the 8442 screened attendees, 1270 signed informed consent, while 1125 participants accomplished the baseline visit. Participants were equally distributed across the four treatments as following: 273 (24.3%) in DG, 288 (25.6%) in the PAG, 283 (25.1%) in PADG, and 281 (25%) in the CG. Participants assigned to DG or PADG increased their consumption of whole grains (OR = 1.77, 95% CI: 1.20-2.60 and OR = 1.55, 95% CI: 1.06-2.27, respectively) and legumes (OR = 1.77, 95% CI: 1.12-2.79 and OR = 2.24, 95% CI: 1.41-3.57, respectively), with respect to CG. The participants randomized to DG reduced processed meat and increased fruit consumption (OR = 2.57, 95% CI: 1.76-3.76 and OR = 2.38, 95% CI: 1.12-5.06, respectively). The effects were more evident in the CRC screening subgroup. No relevant difference was observed between PAG and CG. No impact was observed on physical activity habits. Conclusions: Our findings suggest that active interventions can increase awareness and induce diet changes. However, participation rate and compliance to the courses was quite low, innovative strategies to enhance participants' retention are needed, with the ultimate goal of increasing awareness and inducing positive lifestyle changes.

Guidance for setting international standards on reporting longitudinal adherence to stool-based colorectal cancer screening.

Longitudinal adherence to colorectal cancer (CRC) screening is reported using different summarizing measures, which hampers international comparison. We provide evidence to guide recommendations on which longitudinal adherence measure to report. Using adherence data over four stool-based CRC screening rounds in three countries, we calculated six summarizing adherence measures; adherence over all rounds, adherence per round, rescreening, full programme adherence (yes/no), regularity (never/inconsistent/consistent screenees) and number of times participated. For each measure, we calculated the accuracy in capturing the observed adherence patterns. Using the ASCCA model, we predicted screening effectiveness when using summarizing measures as model input versus the observed adherence patterns. Adherence over all rounds in the Italian, Spanish and Dutch cohorts was 64.9%, 42.8% and 61.5%, respectively, and the proportion of consistent screenees was 50.9%, 26.3% and 45.7%. Number of times participated and regularity were most accurate and resulted in similar model-predicted screening effectiveness as simulating the observed adherence patterns of Italy, Spain and the Netherlands (mortality reductions: 24.4%, 16.9% and 23.5%). Adherence over all rounds and adherence per round were least accurate. Screening effectiveness was overestimated when using adherence over all rounds (mortality reductions: 26.8%, 19.4% and 25.7%) and adherence per round (mortality reductions: 26.8%, 19.5% and 25.9%). To conclude, number of times participated and regularity were most accurate and resulted in similar model-predicted screening effectiveness as using the observed adherence patterns. However they require longitudinal data. To facilitate international comparison of CRC screening programme performance, consensus on an accurate adherence measure to report should be reached.

Overall and stage-specific survival of patients with screen-detected colorectal cancer in European countries: A population-based study in 9 countries.

Background: An increasing proportion of colorectal cancers (CRCs) are detected through screening due to the availability of organised population-based programmes. We aimed to analyse survival probabilities of patients with screen-detected CRC in European countries. Methods: Data from CRC patients were obtained from 16 population-based cancer registries in nine European countries. We included patients with cancer diagnosed from the year organised CRC screening programmes were introduced until the most recent year with available data at the time of analysis, whose ages at diagnosis fell into the age groups targeted by screening. Patients were followed up with regards to vital status until 2016-2020 across the various countries. Overall and CRC-specific survival were analysed by mode of detection and stage at diagnosis for all countries combined and for each country separately using the Kaplan-Meier method. Findings: We included data from 228 134 patients, of whom 134 597 (aged 60-69 years at diagnosis targeted by screening in all countries) were considered in analyses for all countries combined. 22·3% (38 080/134 597) of patients had cancer detected through screening. Most screen-detected cancers were found at stages I-II (65·6% [12 772/19 469 included in stage-specific analyses]), while the majority of non-screen-detected cancers were found at stages III-IV (56·4% [31 882/56 543 included in stage-specific analyses]). Five-year overall and CRC-specific survival rates for patients with screen-detected cancer were 83·4% (95% CI 82·9-83·9) and 89·2% (88·8-89·7), respectively; for patients with non-screen-detected cancer, they were much lower (57·5% [57·2-57·8] and 65·7% [65·4-66·1], respectively). The favourable survival of patients with screen-detected cancer was also seen within each stage - five-year overall survival rates for patients with screen-detected stage I, II, III, and IV cancers were 92.4% (95% CI 91·6-93·1), 87·9% (86·6-89·1), 80·7% (79·3-82·0), and 32·3 (29·4-35·2), respectively. These patterns were also consistently seen for each individual country. Interpretation: Patients with cancer diagnosed at screening have a very favourable prognosis. In the rare case of detection of advanced stage cancer, survival probabilities are still much higher than those commonly reported for all patients regardless of mode of detection. Although these results cannot be taken to quantify screening effects, they provide useful and encouraging information for patients with screen-detected CRC and their physicians. Funding: This study was supported in part by grants from the German Federal Ministry of Education and Research and the German Cancer Aid.

Screening colonoscopy similarly prevented distal and proximal colorectal cancer: a prospective study among 55-69-year-olds.

OBJECTIVES: We aimed to evaluate the effectiveness of screening colonoscopy in reducing incidence of distal vs. proximal colorectal cancer (CRC) in persons aged 55-69 years. STUDY DESIGN AND SETTING: Using observational data from a German claims database (German Pharmacoepidemiological Research Database), we emulated a target trial with two arms: Colonoscopy screening vs. no-screening at baseline. Adjusted cumulative incidence of total, distal, and proximal CRC over 11 years of follow-up was estimated in 55-69-year-olds at an average CRC risk and without colonoscopy, polypectomy, or fecal occult blood test before baseline. RESULTS: Overall, 307,158 persons were included (screening arm: 198,389 and control arm: 117,399). The adjusted 11-year risk of any CRC was 1.62% in the screening group and 2.38% in the no-screening group resulting in a relative risk of 0.68 (95% CI: 0.63-0.73). The relative risk was 0.67 for distal CRC (95% CI: 0.62-0.73) and 0.70 (95% CI: 0.63-0.79) for proximal CRC. The cumulative incidence curves of the groups crossed after 6.7 (distal CRC) and 5.0 years (proximal CRC). CONCLUSION: Our results suggest that colonoscopy is effective in preventing distal and proximal CRC. Unlike previous studies not using a target trial approach, we found no relevant difference in the effectiveness by location.

Proportion and stage distribution of screen-detected and non-screen-detected colorectal cancer in nine European countries: an international, population-based study.

BACKGROUND: The effects of recently implemented colorectal cancer screening programmes in Europe on colorectal cancer mortality will take several years to be fully known. We aimed to analyse the characteristics and parameters of screening programmes, proportions of colorectal cancers detected through screening, and stage distribution in screen-detected and non-screen-detected colorectal cancers to provide a timely assessment of the potential effects of screening programmes in several European countries. METHODS: We conducted this population-based study in nine European countries for which data on mode of detection were available (Belgium, Denmark, England, France, Italy, Ireland, the Netherlands, Slovenia, and Spain). Data from 16 population-based cancer registries were included. Patients were included if they were diagnosed with colorectal cancer from the year that organised colorectal cancer screening programmes were implemented in each country until the latest year with available data at the time of analysis, and if their age at diagnosis fell within the age groups targeted by the programmes. Data collected included sex, age at diagnosis, date of diagnosis, topography, morphology, clinical and pathological TNM information based on the edition in place at time of diagnosis, and mode of detection (ie, screen detected or non-screen detected). If stage information was not available, patients were not included in stage-specific analyses. The primary outcome was proportion and stage distribution of screen-detected versus non-screen detected colorectal cancers. FINDINGS: 228 667 colorectal cancer cases were included in the analyses. Proportions of screen-detected cancers varied widely across countries and regions. The highest proportions (40-60%) were found in Slovenia and the Basque Country in Spain, where FIT-based programmes were fully rolled out, and participation rates were higher than 50%. A similar proportion of screen-detected cancers was also found for the Netherlands in 2015, where participation was over 70%, even though the programme had not yet been fully rolled out to all age groups. In most other countries and regions, proportions of screen-detected cancers were below 30%. Compared with non-screen-detected cancers, screen-detected cancers were much more often found in the distal colon (range 34·5-51·1% screen detected vs 26·4-35·7% non-screen detected) and less often in the proximal colon (19·5-29·9% screen detected vs 24·9-32·8% non-screen detected) p≤0·02 for each country, more often at stage I (35·7-52·7% screen detected vs 13·2-24·9% non-screen detected), and less often at stage IV (5·8-12·5% screen detected vs 22·5-31·9% non-screen detected) p<0·0001 for each country. INTERPRETATION: The proportion of colorectal cancer cases detected by screening varied widely between countries. However, in all countries, screen-detected cancers had a more favourable stage distribution than cancers detected otherwise. There is still much need and scope for improving early detection of cancer across all segments of the colorectum, and particularly in the proximal colon and rectum. FUNDING: Deutsche Krebshilfe.

Cancer screening programmes in Italy during the COVID-19 pandemic: an update of a nationwide survey on activity volumes and delayed diagnoses.

INTRODUCTION: In Italy, regional governments are in charge of implementing cervical, breast and colorectal cancer screening programmes. The 2020 Coronavirus pandemic led to a national lockdown and the temporary suspension of several non-urgent healthcare activities, including cancer screening. This paper aims to describe the results of a national survey carried out by the National Centre for Screening Monitoring (ONS) on cervical, breast and colorectal cancer screening activities in 2020. MATERIALS AND METHODS: A national survey was conducted by ONS in 2020 to assess: the number of screening invitations by Region; the volumes of screening tests and the attitude to attend the screening programme compared to 2019; the number of delayed diagnoses of malignant or pre-malignant lesions caused by the slowing down of screening programmes, based on the average Region-specific screening detection rate for cervical, breast and colorectal cancers. RESULTS: Screening tests for breast, colorectal and cervical cancer decreased by 37.6%, 45.5% and 43.4% in 2020 compared with 2019. In 2020 the estimated numbers of undiagnosed lesions are: 3,324 breast cancers, 1,299 colorectal cancers, 7,474 colorectal advanced adenomas and 2,782 CIN2 or more severe cervical lesions. Participation in cancer screening programmes decreased by 15%, 15% and 20%, for cervical, breast and CRC screening, respectively. DISCUSSION AND CONCLUSIONS: An urgent call to action is needed to prevent further delays and to limit the impact of the pandemic on cancer diagnosis and prevention.