Colorectal Cancer Stage Distribution at First and Repeat Fecal Immunochemical Test Screening.

BACKGROUND & AIMS: For colorectal cancer (CRC) screening to be effective, it is important that screen-detected cancers are found at an early stage. Studies on stage distribution of screen-detected CRC at repeat screening of large population-based fecal immunochemical test (FIT)-based screening programs and the impact of FIT cut-off values on staging currently are lacking. METHODS: We obtained data for FIT-positive participants (FIT cut-off, 47 µg hemoglobin/g feces) at their first or second (ie, repeat) screening from the Dutch National Screening Database from 2014 to 2018. Tumor characteristics were acquired through linkage with The Netherlands Cancer Registry. We compared stage at diagnosis (I-II vs III-IV) of CRCs detected at a first or second screening. In addition, we analyzed the hypothetical yield and stage distribution of CRC for different FIT cut-off values up to 250 µg hemoglobin/g feces. RESULTS: At the first and second screenings, respectively, 15,755 and 3304 CRCs were detected. CRCs detected at the first or second screening were equally likely to be stages I to II (66.5% vs 67.7%; relative risk, 1.02; 95% CI, 1.00-1.05). A hypothetical increase of the FIT cut-off value from 47 µg to 250 µg resulted in a reduction of detected CRCs by 88.3% and 79.0% at the first or second screening, respectively. Even then, the majority of detected CRCs (63%-64%) still would be diagnosed at stages I to II. CONCLUSIONS: FIT-based screening is effective in downstaging CRC, and also at repeat screening. Increasingly, the FIT cut-off level has a limited impact on the stage distribution of detected CRCs, although it greatly affects CRC detection and thus is important to keep low.

Colonoscopy-Related Mortality in a Fecal Immunochemical Test-Based Colorectal Cancer Screening Program.

BACKGROUND & AIMS: Many countries have introduced colorectal cancer (CRC) screening programs with fecal immunochemical tests (FITs), and follow-up colonoscopies for individuals with a positive FIT result. In order to make an informed decision to participate, individuals must be informed about the benefits and harms of FIT-based screening and subsequent colonoscopy. Colonoscopy-related fatal complications in FIT-based screening are understudied. We aimed to estimate the colonoscopy-related mortality in a national FIT-based CRC screening program. METHODS: Colonoscopy-related mortality within 30 days after colonoscopy was assessed by analysis of data from national endoscopy complication databases in the Netherlands, determining the excess 30-day rate of death in FIT-positive individuals undergoing colonoscopy vs FIT-negative individuals (based on data from the national screening database), and determining the rate of likely colonoscopy-related deaths based on registered causes of death by the Statistics Netherlands. RESULTS: Between October 2013 and December 2017, 172,797 participants underwent colonoscopy after a positive result from a FIT in the Dutch national CRC screening program; 13,848 participants received a diagnosis of CRC. The reported fatal complication rate was 0.23 per 10,000 FIT-positive participants (or 1 per 43,199; 95% CI, 0.090 - 0.60) undergoing colonoscopy, whereas this was 0.91 per 10,000 FIT-positive participants (or 1 per 10,961; 95% CI, 0.44 - 1.38) according to the excess death rate. Likely colonoscopy-related causes of death were reported in 0.86 per 10,000 FIT-positive participants (or 1 per 11,236; 95% CI, 0.48 - 1.63) who underwent colonoscopy, of which 50% considered cardiovascular events. CONCLUSIONS: Colonoscopy-related mortality within the Dutch FIT-based CRC screening program was estimated to range from 0.23 to 0.91 per 10,000 FIT-positive participants undergoing colonoscopy. These findings indicate underreporting of fatal complications in registries and a noteworthy incidence of fatal cardiovascular adverse events that requires further investigation. Nevertheless, the harm of FIT-based CRC screening is vastly outweighed by the benefits.

The second round of the Dutch colorectal cancer screening program: Impact of an increased fecal immunochemical test cut-off level on yield of screening.

The Dutch colorectal cancer (CRC) screening program started in 2014, inviting the target population biennially to perform a fecal immunochemical test (FIT). We obtained prospectively collected data from the national screening information-system to present the results of the second round (2016) and evaluate the impact of increasing the FIT cut-off halfway through the first round from 15 to 47 µg Hb/g feces on outcomes in the second round. Second round screening was done with a 47 µg Hb/g feces FIT cut-off. Participants were classified based on first round participation status as either FIT (15,47) or FIT (47,47) participants, and previous nonparticipants. In total, 348,891 (75.9%) out of 459,740 invitees participated in the second round. Participation rates were 93.4% among previous participants and 21.0% among previous non-participants. FIT(47,47) participants had a significantly higher detection rate of AN (15.3 vs. 10.4 per 1,000 participants) compared to FIT(15,47) participants in the second round, while their cumulative detection rate of AN over two rounds was significantly lower (45.6 vs. 52.6 per 1,000 participants). Our results showed that participation in the Dutch CRC screening program was consistently high and that second round detection rates depended on the first round FIT cut-off. The cumulative detection over two rounds was higher among FIT(15,47) participants. These findings suggest that a substantial part of, but not all the missed findings in the first round due to the increased FIT cut-off were detected in the subsequent round.

HCV antigen instead of RNA testing to diagnose acute HCV in patients treated in the Dutch Acute HCV in HIV Study.

INTRODUCTION: Affordable and sensitive screening methods for acute hepatitis C (HCV) are necessary to successfully intervene in the current HCV epidemic among HIV-positive men having sex with men. HCV core antigen (Ag) testing has been proven effective in diagnosing chronic HCV-infected patients at low costs. We studied the characteristics of HCV Ag testing in acute HCV-infected HIV-positive patients. Methods Plasma samples were selected from acutely HCV genotype 1-infected patients treated with peginterferon, ribavirin and boceprevir in the Dutch Acute HCV in HIV Study. The control group consisted of HIV-positive patients with a newly raised alanine aminotransferase (ALT) (>41 U/L) in whom HCV RNA was undetectable and who were tested for HCV Ag. Spearman correlation coefficient between HCV RNA and HCV Ag was calculated together with the sensitivity and specificity of HCV Ag testing at acute HCV diagnosis. RESULTS AND DISCUSSION: Upon acute HCV diagnosis, HCV Ag was identified in 39 out of 44 patients with detectable HCV RNA levels. In all 23 control patients without detectable HCV RNA in plasma, HCV Ag was undetectable as well. This resulted in a sensitivity and specificity of HCV Ag of respectively 89% (95% CI 75-96) and 100% (95% CI 82-100). The correlation between HCV Ag and HCV RNA was 0.97 (p < 0.001) upon diagnosis. CONCLUSION: The data presented in this study suggest that HCV Ag testing is a sensitive and specific method that can be used in diagnosing AHCV in HIV-infected patients.