Fecal Immunochemical Tests Detect Screening Participants with Multiple Advanced Adenomas Better than T1 Colorectal Cancers.

BACKGROUND: Fecal immunochemical tests (FITs) are widely used for colorectal cancer (CRC) screening. The detection of early-stage cancer and advanced adenoma (AA), the most important premalignant lesion, is highly relevant to reducing CRC-related deaths. We aimed to assess sensitivity for the detection of CRC and AA stratified by tumor stage; number; size; histology of AA; and by location, age, sex, and body mass index (BMI). METHODS: Participants of screening colonoscopy (n = 2043) and newly diagnosed CRC patients (n = 184) provided a stool sample before bowel preparation or CRC surgery. Fecal hemoglobin concentration was determined in parallel by nine different quantitative FITs among 94 CRC patients, 200 AA cases, and 300 participants free of advanced neoplasm. Sensitivities were calculated at original cutoffs and at adjusted cutoffs, yielding 93% specificity among all FITs. RESULTS: At adjusted cutoffs, UICC stage I cancers yielded consistently lower sensitivities (range: 62-68%) compared to stage II-IV cancers (range: 73-89%). An even stronger gradient was observed according to T status, with substantially lower sensitivities for T1 (range: 39-57%) than for T2-T4 cancers (range: 71-100%). Sensitivities for the detection of participants with multiple AAs ranged from 55% to 64% and were by up to 25% points higher than sensitivities for T1 cancers. CONCLUSIONS: FITs detect stage I cancers and especially T1 cancers at substantially lower sensitivities than more advanced cancer stages. Participants with multiple AAs were detected with slightly lower sensitivities than stage I cancers and with even higher sensitivities than T1 cancers. Further research should focus on improving the detection of early-stage cancers.

The Effects of Differing Invitation Models on the Uptake of Immunological Fecal Occult Blood Testing.

BACKGROUND: Participation rates in colorectal cancer screening in Germany are low. We therefore investigated the effectiveness of different invitation models for immunological stool blood tests (fecal immunological tests, FITs). METHODS: A randomized controlled trial in 50- to 54-year-old clients of the health insurance provider AOK Baden-Wuerttemberg. A total of 17 532 insured persons were randomized to receive: (A) an invitation letter including a FIT (n = 5850); (B) an invitation letter including an option to request a FIT (n = 5844); or (C) an invitation letter only (n = 5838; control group, routine practice). Reminder letters were sent to half the members of groups A and B, selected at random, after 4 weeks. The primary endpoint was the use of a FIT within 1 year of the date of the invitation letter. IRRID: RR2-10.2196/16413. Registration: DRKS00011858. RESULTS: The invitation letter with a FIT enclosed (A) increased usage from 10% to 29.7% compared with the control group (+19.7% points, p < 0.0001; men: +19.4%, women: +18.8%). The invitation letter with a FIT request option (B) increased usage from 10% to 27.7% (+17.7% points, p < 0.0001; men: +17.7%, women: +17.4%). Reminders increased usage in group A by 7.5% points and in group B by 8.5% points. Participation among women was higher than among men in all groups. The FIT positivity rate was 6.9%. A subsequent colonoscopy was reported for 64.3% of FIT-positive participants, and advanced neoplasia was found in 21.3% of these cases. CONCLUSION: Letters of invitation that include a FIT and those that offer low-threshold access to a FIT achieve strong, comparable increases in the usage of FIT in the context of colorectal cancer screening.

Effect of Various Invitation Schemes on the Use of Fecal Immunochemical Tests for Colorectal Cancer Screening: Protocol for a Randomized Controlled Trial.

BACKGROUND: Fecal occult blood testing has been offered for many years in the German health care system, but participation rates have been notoriously low. OBJECTIVE: The aim of this study is to evaluate the effect of various personal invitation schemes on the use of fecal immunochemical tests (FITs) in persons aged 50-54 years. METHODS: This study consists of a three-armed randomized controlled trial: (1) arm A: an invitation letter from a health insurance plan including a FIT test kit, (2) arm B: an invitation letter from a health insurance plan including an offer to receive a free FIT test kit by mail upon easy-to-handle request (ie, by internet, fax, or reply mail), and (3) arm C: an information letter on an existing colonoscopy offer (ie, control). Within arms A and B, a random selection of 50% of the study population will receive reminder letters, the effects of which are to be evaluated in a substudy. RESULTS: A total of 17,532 persons aged 50-54 years in a statutory health insurance plan in the southwest of Germany-AOK Baden-Wuerttemberg-were sent an initial invitation, and 5825 reminder letters were sent out. The primary end point is FIT usage within 1 year from receipt of invitation or information letter. The main secondary end points include gender-specific FIT usage within 1 year, rates of positive test results, rates of colonoscopies following a positive test result, and detection rates of advanced neoplasms. The study was launched in September 2017. Data collection and workup were completed in fall 2019. CONCLUSIONS: This randomized controlled trial will provide important empirical evidence for enhancing colorectal cancer screening offers in the German health care system. TRIAL REGISTRATION: German Clinical Trials Register (DRKS) DRKS00011858; https://bit.ly/2UBTIdt. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/16413.

Effect of Imperfect Compliance With Instructions for Fecal Sample Collection on Diagnostic Performance of 9 Fecal Immunochemical Tests.

BACKGROUND & AIMS: Fecal immunochemical tests (FITs) measure hemoglobin in stool to identify individuals at risk for colorectal cancer (CRC). However, there are many different FITs, with different instructions for fecal sample collection. In routine practice, participants do not always follow these instructions exactly. We assessed the effects of violations of fecal sampling instructions on the diagnostic performance of 9 quantitative FITs. METHODS: We obtained stool samples from 76 patients with CRC scheduled for surgery at 4 hospitals in Germany and 100 participants without advanced neoplasms who participated in a prospective colonoscopy screening program. We filled fecal sample tubes according to the manufacturers' instructions or with 3 violations that are likely to occur in routine practice. The diagnostic performance was assessed for a total of 6336 FIT samples (176 participants × 9 FITs × 4 sampling methods). RESULTS: Sample collection instructions varied widely among FITs but included 3 key components: multiple insertions of the sampling rod into stool, a visual check of rod for complete filling with stool, and once-only insertion of the stool-filled rod into the tube. Violation of the first 2 components (inserting the rod into the stool sample only 1 time or not visually checking the rod for complete filling) reduced levels of hemoglobin measured. However, the effect on diagnostic performance was generally small. Violation of the third component (insertion of more stool into the tube than recommended) increased levels of hemoglobin measured in samples and identified more patients with CRC (increase of median sensitivity by almost 10% units) at a small loss of specificity (decrease of median specificity by 2% units), and produced the highest area under the curve for detection of CRC cases for 6 FITs. CONCLUSIONS: Violations of fecal sampling instructions can lead to non-negligible variations in fecal hemoglobin measurements. The limited adverse effects on diagnostic performance indicate the robustness of FITs. The potential for increasing diagnostic performance by collecting more stool material should be followed up in further research.