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.

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.

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.

Factors associated with interval colorectal cancer after negative FIT: Results of two screening rounds in the Dutch FIT-based CRC screening program.

The interval colorectal cancer (CRC) rate after negative fecal immunochemical testing (FIT) is an important quality indicator of CRC screening programs. We analyzed the outcomes of two rounds of the FIT-based CRC screening program in the Netherlands, using data from individuals who participated in FIT-screening from 2014 to 2017. Data of individuals with one prior negative FIT (first round) or two prior negative FITs (first and second round) were included. Outcomes included the incidence of interval CRC in FIT-negative participants (<47 µg Hb/g feces [µg/g]), FIT-sensitivity, and the probability of detecting an interval CRC by fecal hemoglobin concentration (f-Hb). FIT-sensitivity was estimated using the detection method and the proportional incidence method (based on expected CRC incidence). Logistic regression analysis was performed to estimate whether f-Hb affects probability of detecting interval CRC, adjusted for sex- and age-differences. Incidence of interval CRC was 10.4 per 10 000 participants after the first and 9.6 after the second screening round. FIT-sensitivity based on the detection method was 84.4% (95%CI 83.8-85.0) in the first and 73.5% (95% CI 71.8-75.2) in the second screening round. The proportional incidence method resulted in a FIT-sensitivity of 76.4% (95%CI 73.3-79.6) in the first and 79.1% (95%CI 73.7-85.3) in the second screening round. After one negative FIT, participants with f-Hb just below the cut-off (>40-46.9 µg/g) had a higher probability of detecting an interval CRC (OR 16.9; 95%CI: 14.0-20.4) than had participants with unmeasurable f-Hb (0-2.6 µg/g). After two screening rounds, the odds ratio for interval CRC was 12.0 (95%CI: 7.8-17.6) for participants with f-Hb just below the cut-off compared with participants with unmeasurable f-Hb. After both screening rounds, the Dutch CRC screening program had a low incidence of interval CRC and an associated high FIT-sensitivity. Our findings suggest there is a potential for further optimizing CRC screening programs with the use of risk-stratified CRC screening based on prior f-Hb.

Initial Impact of National CRC Screening on Incidence and Advanced Colorectal Cancer.

BACKGROUND AND AIMS: Screening for colorectal cancer (CRC) aims to decrease CRC incidence and mortality. Biennial fecal immunochemical test screening started in the Netherlands in 2014 for individuals 55-75 years of age. This study investigated the effect of screening on stage-specific incidence, with focus on stage III and IV CRC. METHODS: Inhabitants diagnosed with CRC in 2009-2018 were included. CRC incidence per stage, year, and detection method (ie, screen-detected vs clinically detected) was evaluated. Patient, tumor, and treatment characteristics, and survival of patients with stage III and IV CRC, were compared according to the detection method. RESULTS: Included were 140,649 CRCs in 136,882 patients. An initial peak of stage I-III CRC diagnoses after initiation of screening was followed by a continuous decrease within screening-eligible ages. Total CRC incidence remained higher than before screening, although stage II and IV CRC incidence decreased below prescreening levels. Screen-detected CRCs were significantly more frequently located in the left-sided colon (stage III; 43.7% vs 30.9%; stage IV: 45.1% vs 36.1%), and the primary tumor resection rate was higher (stage III colon: 99.8% vs 99.0%, rectum: 97.3% vs 89.7%; stage IV colon: 65.4% vs 56.6%, rectum: 47.3% vs 33.5%). Patients with screen-detected stage IV CRC had significantly more often single-organ metastases (74.5% vs 57.0%; P < .001) and more frequently received treatment with curative intent (colon: 41.3% vs 27.4%; rectum: 33.8% vs 24.6%). Overall survival significantly improved for patients with screen-detected CRCs (stage III: P < .001; stage IV: P < .001). CONCLUSIONS: Five years after the start of a nationwide CRC screening program, a decrease in stage II and IV CRC incidence was observed. Patients with screen-detected stage III and stage IV CRC had less extensive disease and improved survival compared with those with clinically detected CRC.

Interval post-colonoscopy colorectal cancer following a negative colonoscopy in a fecal immunochemical test-based screening program.

BACKGROUND: In the Dutch colorectal (CRC) screening program, fecal immunochemical test (FIT)-positive individuals are referred for colonoscopy. If no relevant findings are detected at colonoscopy, individuals are reinvited for FIT screening after 10 years. We aimed to assess CRC risk after a negative colonoscopy in FIT-positive individuals. METHODS: In this cross-sectional cohort study, data were extracted from the Dutch national screening information system. Participants with a positive FIT followed by a negative colonoscopy between 2014 and 2018 were included. A negative colonoscopy was defined as a colonoscopy during which no more than one nonvillous, nonproximal adenoma < 10 mm or serrated polyp < 10 mm was found. The main outcome was interval post-colonoscopy CRC (iPCCRC) risk. iPCCRC risk was reviewed against the risk of interval CRC after a negative FIT (FIT IC) with a 2-year screening interval. RESULTS: 35 052 FIT-positive participants had a negative colonoscopy and 24 iPCCRCs were diagnosed, resulting in an iPCCRC risk of 6.85 (95 %CI 4.60-10.19) per 10 000 individuals after a median follow-up of 1.4 years. After 2.5 years of follow-up, age-adjusted iPCCRC risk was approximately equal to FIT IC risk at 2 years. CONCLUSION: Risk of iPCCRC within a FIT-based CRC screening program was low during the first years after colonos-copy but, after 2.5 years, was the same as the risk in FIT-negative individuals at 2 years, when they are reinvited for screening. Colonoscopy quality may therefore require further improvement and FIT screening interval may need to be reduced after negative colonoscopy.

Advanced serrated polyps as a target of screening: detection rate and positive predictive value within a fecal immunochemical test-based colorectal cancer screening population.

BACKGROUND : Advanced serrated polyps (ASPs) have a comparable risk to advanced adenomas for progression to colorectal cancer (CRC). The yield of most CRC screening programs, however, is based on advanced adenomas and CRC only. We assessed the ASP detection rate, and positive predictive value (PPV) including ASPs in a fecal immunochemical test (FIT)-based screening program. METHODS : We analyzed the findings of follow-up colonoscopies of FIT-positive screenees in the Dutch CRC screening program from 2014 until 2020. Data were retrieved from the national screening and pathology database. An ASP was defined as any serrated polyp of ≥ 10 mm, sessile serrated lesion with dysplasia, or traditional serrated adenoma. The ASP detection rate was defined as the proportion of colonoscopies with ≥ 1 ASP. PPV was originally defined as the proportion of individuals with a CRC or advanced adenoma. The updated PPV definition included CRCs, advanced adenomas, and/or ASPs. RESULTS : 322 882 colonoscopies were included in the analyses. The overall detection rate of ASPs was 5.9 %. ASPs were detected more often in women than men (6.3 % vs. 5.6 %; P < 0.001). ASP detection rates in individuals aged 55-59, 60-64, 65-69, and 70 + were 5.2 %, 6.1 %, 6.1 %, and 5.9 %, respectively (P < 0.001). The PPV for CRCs and advanced adenomas was 41.1 % and increased to 43.8 % when including ASPs. The PPV increase was larger in women than in men (3.2 vs. 2.4 percentage points). CONCLUSIONS : 5.9 % of FIT-positive screenees had ASPs, but half of these were detected in combination with a CRC or advanced adenoma. Therefore, including ASPs results in a small increase in the yield of FIT-based screening.

Personalized colorectal cancer screening: study protocol of a mixed-methods study on the effectiveness of tailored intervals based on prior f-Hb concentration in a fit-based colorectal cancer screening program (PERFECT-FIT).

BACKGROUND: In 2014, the national population-based colorectal cancer (CRC) screening program was implemented in the Netherlands. Biennial fecal immunochemical testing (FIT) for hemoglobin (Hb) is used at a cut-off of 47 µg Hb per gram feces. The CRC screening program successfully started, with high participation rates and yield of screening. Now that the program has reached a steady state, there is potential to further optimize the program. Previous studies showed that prior fecal Hb (f-Hb) concentrations just below the FIT cut-off are associated with a higher risk for detection of advanced neoplasia (AN) at subsequent screening rounds. We aim to achieve a better balance between the harms and benefits of CRC screening by offering participants tailored invitation intervals based on prior f-Hb concentrations after negative FIT. METHODS: This mixed-methods study will be performed within the Dutch national CRC screening program and will consist of: (1) a randomized controlled trial (RCT), (2) focus group studies, and (3) decision modelling. The primary outcome is the yield of AN per screened individual in personalized screening vs. uniform screening. Secondary outcomes are perspectives on, acceptability of and adherence to personalized screening, as well as long-term outcomes of personalized vs. uniform screening. The RCT will include 20,000 participants of the Dutch CRC screening program; 10,000 in the intervention and 10,000 in the control arm. The intervention arm will receive a personalized screening interval based on the prior f-Hb concentration (1, 2 or 3 years). The control arm will receive a screening interval according to current practice (2 years). The focus group studies are designed to understand individuals' perspectives on and acceptability of personalized CRC screening. Results of the RCT will be incorporated into the MISCAN-Colon model to determine long-term benefits, harms, and costs of personalized vs. uniform CRC screening. DISCUSSION: The aim of this study is to evaluate the yield, feasibility, acceptability and (cost-) effectiveness of personalized CRC screening through tailored invitation intervals based on prior f-Hb concentrations. This knowledge may be of guidance for health policy makers and may provide evidence for implementing personalized CRC screening in The Netherlands and/or other countries using FIT as screening modality. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05423886, June 21, 2022, https://clinicaltrials.gov/ct2/show/NCT05423886.

Somatic hits in mismatch repair genes in colorectal cancer among non-seminoma testicular cancer survivors.

BACKGROUND: Non-seminoma testicular cancer survivors (TCS) have an increased risk of developing colorectal cancer (CRC) when they have been treated with platinum-based chemotherapy. Previously we demonstrated that among Hodgkin lymphoma survivors (HLS) there is enrichment of rare mismatch repair (MMR) deficient (MMRd) CRCs with somatic hits in MMR genes. We speculate that this phenomenon could also occur among other cancer survivors. We therefore aim to determine the MMR status and its underlying mechanism in CRC among TCS (TCS-CRC). METHODS: Thirty TCS-CRC, identified through the Dutch pathology registry, were analysed for MMR proteins by immunohistochemistry. Next-generation sequencing was performed in MMRd CRCs without MLH1 promoter hypermethylation (n = 4). Data were compared with a male cohort with primary CRC (P-CRC, n = 629). RESULTS: MMRd was found in 17% of TCS-CRCs vs. 9% in P-CRC (p = 0.13). MMRd was more often caused by somatic double or single hit in MMR genes by mutation or loss of heterozygosity in TCS-CRCs (3/30 (10%) vs. 11/629 (2%) in P-CRCs (p < 0.01)). CONCLUSIONS: MMRd CRCs with somatic double or single hit are more frequent in this small cohort of TCS compared with P-CRC. Exposure to anticancer treatments appears to be associated with the development of these rare MMRd CRC among cancer survivors.

Personalised colorectal cancer screening strategies: Information needs of the target population.

Prior faecal Hemoglobin (f-Hb) concentrations of a negative fecal immunochemical test (FIT) can be used for risk stratification in colorectal cancer (CRC) screening. Individuals with higher f-Hb concentrations may benefit from a shorter screening interval (1 year), whereas individuals with undetectable f-Hb concentrations could benefit from a longer screening interval (3 year). Individuals' views on personalised CRC screening and information needed to make a well-informed decision is unknown. We conducted three semi-structured focus groups among individuals eligible for CRC screening (i.e. men and women aged 55 to 75) in the Netherlands. Thematic analysis was used to analyse participants' information need on personalised CRC screening strategies. Fourteen individuals took part. The majority were positive about CRC screening and indicated that they would participate in personalised CRC screening. The rationale for a longer interval among those at lowest risk was, however, unclear for many. The preferred information on individual risk was variable: ranging from full information to only information on the personalised strategy without mentioning the risk. It was not possible to address everyone's need with a single approach. Additional communications, e.g. public media campaigns, billboards, videos on social media, were also suggested as necessary. This study showed that preferences on receiving information on individual CRC risk varied substantially and no consensus was reached. Introducing a personalised screening programme will require careful communication, particularly around the rationale for the strategy, and a layered approach to deliver information.

Advanced-stage CRC incidence patterns following the phased implementation of the CRC screening programme in the Netherlands.

BACKGROUND AND AIMS: From 2014, the Dutch colorectal cancer (CRC) faecal immunochemical testing-based screening programme was gradually rolled out by birth cohort. We evaluated changes in advanced-stage CRC incidence by timing of invitation to further strengthen the evidence for the effectiveness of CRC screening. METHODS: Data on advanced-stage CRC incidence in the period 2010-2019 by invitation cohort were collected through the Netherlands Cancer Registry. Crude rates of advanced-stage CRC incidence and cumulative advanced-stage CRC incidence were calculated. Observed advanced-stage CRC incidence and cumulative advanced-stage CRC incidence were compared with expected advanced-stage CRC incidence and cumulative advanced-stage CRC incidence by invitation cohort using trend lines extrapolating data prior to the introduction of screening. RESULTS: For the invitation cohort that was first invited for screening in 2014, advanced-stage CRC incidence increased before the introduction of screening from 94.1 to 124.7 per 100,000 individuals in the period 2010-2013. In 2014, the observed increase was higher than in preceding years, to 184.9 per 100,000 individuals. Hereafter, a decrease in incidence was observed to levels below expected incidence based on trends before the introduction of screening. A similar pattern was observed for invitation cohorts in subsequent years, coinciding with the first invitation to the screening programme. In 2019, the observed incidence for all invitation cohorts remained below expected incidence. The cumulative advanced-stage CRC incidence in the 2014-2016 invitation cohorts was significantly lower than the expected cumulative CRC incidence in the period 2010-2019. CONCLUSIONS: In the period 2014-2019, an increase in advanced-stage CRC incidence was observed for all invitation cohorts first invited for screening, followed by a decrease below expected incidence, following the pattern of the phased implementation. The cumulative advanced-stage CRC incidence in invitation cohorts invited for screening multiple times was lower than expected based on trends from the pre-screening era. These findings support a causal relationship between the introduction of the Dutch screening programme and a decrease in advanced-stage CRC incidence.

Concurrent participation in breast, cervical, and colorectal cancer screening in the Netherlands.

BACKGROUND: Many European countries offer organised population-based breast, cervical, and colorectal cancer screening programmes. Around age 55 and 60, Dutch women are invited to all three screening programmes. We examined the extent to which participation concurs and identified factors influencing concurrent participation. MATERIALS AND METHODS: Individual level data from breast, cervical, and colorectal cancer screening invitations between 2017 and 2019 were extracted from the Dutch screening registry. The percentages of women participating in all three, two, one, or none of the programmes around age 55 and 60, and before subsequent round invitation were determined. Multivariate ordinal regression analyses were performed to estimate whether population density, socio-economic status (SES) per postal code area, and time between the three invitations (<3, 3-6, >6 months) were associated with concurrent participation. RESULTS: Data from 332,484 women were analysed. At age 55, 53.7% participated in all three programmes, 22.1% in two, 11.7% in one, and 12.6% did not participate at all. At age 60, a similar participation pattern was observed. Women living in areas with higher population density were less likely (odds ratios 0.75-0.94) and women in higher SES groups were more likely (odds ratios 1.12-1.60) to participate in more screening programmes, although this positive association was smaller for the highest SES group. No substantial association was found between concurrent participation and timing of invitations. CONCLUSIONS: More than half of Dutch women participated in all three screening programmes and around 12% did not participate in any. Concurrent participation was lower in cities and lower SES groups.

Modelling optimal use of temporarily restricted colonoscopy capacity in a FIT-based CRC screening program: Application during the COVID-19 pandemic.

OBJECTIVE: The COVID-19 pandemic forced colorectal cancer (CRC) screening programs to downscale their colonoscopy capacity. In this study, we assessed strategies to deal with temporary restricted colonoscopy capacity in a FIT-based CRC screening program while aiming to retain the maximum possible preventive effect of the screening program. DESIGN: We simulated the Dutch national CRC screening program inviting individuals between ages 55 and 75 for biennial FIT using the MISCAN-Colon model including the 3-month disruption in the first half of 2020 due to the COVID-19 pandemic. For the second half of 2020 and 2021, we simulated three different strategies for the total target population: 1) increasing the FIT cut-off, 2) skipping one screening for specific screening ages, and 3) extending the screening interval. We estimated the impact on required colonoscopy capacity in 2020-2021 and life years (LYs) lost in the long-term. RESULTS: Increasing the FIT cut-off, skipping screening ages and extending the screening interval resulted in a maximum reduction of 25,100 (-17.0%), 16,100(-10.9%) and 19,000 (-12.9%) colonoscopies, respectively. Modelling an increased FIT cut-off, the number of LYs lost ranged between 1,400 and 4,400. Skipping just a single screening age resulted in approximately 2,700 LYs lost and this was doubled in case of skipping two screening ages. Extending the screening interval up to 34 months had the smallest impact on LYs lost (up to 1,100 LYs lost). CONCLUSION: This modelling study shows that to anticipate on restricted colonoscopy capacity, temporarily extending the screening interval retains the maximum possible preventive effect of the CRC screening program.

Colorectal cancer incidence, mortality, tumour characteristics, and treatment before and after introduction of the faecal immunochemical testing-based screening programme in the Netherlands: a population-based study.

BACKGROUND: In 2014, a population-based colorectal cancer (CRC) screening programme was stepwise implemented in the Netherlands comprising faecal immunochemical testing once every 2 years, with a cutoff value for positivity of 47 µg haemoglobin per g faeces. We aimed to assess CRC incidence, mortality, tumour characteristics, and treatment before and after introduction of this screening programme. METHODS: We did a retrospective, observational, population-based study in the Netherlands and gathered CRC incidence data from the Netherlands Cancer Registry from Jan 1, 2010, to Dec 31, 2019, in people aged 55 years or older. Patients with a CRC diagnosis between Jan 1, 2014, and Dec 31, 2018, in the Netherlands Cancer Registry were linked with the nationwide registry of histopathology and cytopathology (PALGA) to identify mode of detection (ie, screening-detected vs clinically detected). We calculated age-standardised CRC incidence rates and used data from Statistics Netherlands to calculate CRC-related mortality in 2010-19. We compared localisation, stage distribution, and treatment of screening-detected CRCs with clinically detected CRCs diagnosed in 2014-18 in patients aged 55-75 years. FINDINGS: Between Jan 1, 2010, and Dec 31, 2019, 125 215 CRCs were diagnosed in individuals aged 55 years or older and were included in the analyses for CRC incidence. Before the introduction of the screening programme, the age-standardised CRC incidence rate was 214·3 per 100 000 population in 2013 in people aged 55 years or older. After the introduction of the screening programme, this rate initially increased to 259·2 per 100 000 population in 2015, and subsequently decreased to 181·5 per 100 000 population in 2019. Age-standardised incidence rates for advanced CRCs (stage III and IV) were 117·0 per 100 000 population in 2013 and increased to 122·8 per 100 000 population in 2015; this rate then decreased to 94·7 per 100 000 population in 2018. Age-standardised CRC mortality decreased from 87·5 deaths per 100 000 population in 2010 to 64·8 per 100 000 population in 2019. Compared with clinically detected CRCs, screening-detected CRCs were more likely to be located in the left side of the colon (48·6% vs 35·2%) and to be detected at an early stage (I or II; 66·7% vs 46·2%). Screening-detected CRCs were more likely to be treated by local excision compared with clinically detected CRCs, and this finding persisted when stage I CRCs were analysed separately. INTERPRETATION: After introduction of this national screening programme, a decrease in overall and advanced-stage CRC incidence was observed. In view of this observation, together with the observed shift to detection at earlier stages and more screening-detected CRCs being treated by local excision, we might cautiously conclude that, in the long-term, faecal immunochemical testing-based screening could ultimately lead to a decrease in CRC-related morbidity and mortality. FUNDING: None.

Survival in Patients with Neuroendocrine Tumours of the Small Intestine: Nomogram Validation and Predictors of Survival.

Neuroendocrine tumours of the small intestine (SI-NETs) are rare and heterogeneous. There is an unmet need for prognostication of disease course and to aid treatment strategies. A previously developed nomogram based on clinical and tumour characteristics aims to predict disease-specific survival (DSS) in patients with a SI-NET. We aimed to validate the nomogram and identify predictors of survival. Four hundred patients with a grade 1 or 2 SI-NET were included, between January 2000 and June 2016. Predicted 5- and 10-year survival was compared to actual DSS. Multivariable analysis identified predictors for actual DSS. We found that in low-, medium- and high-risk groups 5-year nomogram DSS vs. actual DSS was 0.86 vs. 0.82 (p < 0.001), 0.52 vs. 0.71 (p < 0.001) and 0.26 vs. 0.53 (p < 0.001), respectively. Ten-year nomogram DSS vs. actual DSS was 0.68 vs. 0.69 (p < 0.001), 0.40 vs. 0.50 (p < 0.001) and 0.20 vs. 0.35 (p < 0.001), respectively. Age, WHO-performance score of 2, Ki-67 index ≥10, unknown primary tumour, CgA > 6x ULN and elevated liver tests were identified as independent predictors for a worse DSS. This shows that the nomogram was able to differentiate, but underestimated DSS for patients with a SI-NET. Improvement of prognostication incorporating new emerging biomarkers is necessary to adequately estimate survival.