A variety of fecal immunochemical tests (FITs) for hemoglobin (Hb) are used in colorectal cancer screening. It is unclear to what extent differences in reported sensitivities and specificities reflect true heterogeneity in test performance or differences in study populations or varying pre-analytical conditions. We directly compared the sensitivity and specificity values with which 9 quantitative (laboratory-based and point-of-care) FITs detected advanced neoplasms (AN) in a single colorectal cancer screening study. Pre-colonoscopy stool samples were obtained from participants of screening colonoscopy in Germany from 2005 through 2010 and frozen at -80°C until analysis. The stool samples were thawed, homogenized, and used for 9 different quantitative FITs in parallel. Colonoscopy and histology reports were collected from all participants and evaluated by 2 independent, trained research assistants who were blinded to the test results. Comparative evaluations of diagnostic performance for AN were made at preset manufacturers' thresholds (range, 2.0-17.0 μg Hb/g feces), at a uniform threshold (15 μg Hb/g feces), and at adjusted thresholds yielding defined levels of specificity (99%, 97%, and 93%). Of the 1667 participants who fulfilled the inclusion criteria, all cases with AN (n = 216) and 300 randomly selected individuals without AN were included in the analysis. Sensitivities and specificities for AN varied widely when we used the preset thresholds (21.8%-46.3% and 85.7%-97.7%, respectively) or the uniform threshold (16.2%-34.3% and 94.0%-98.0%, respectively). Adjusting thresholds to yield a specificity of 99%, 97%, or 93% resulted in almost equal sensitivities for detection of AN (14.4%-18.5%, 21.3%-23.6%, and 30.1%-35.2%, respectively) and almost equal positivity rates (2.8%-3.4%, 5.8%-6.1%, and 10.1%-10.9%, respectively). Apparent heterogeneity in diagnostic performance of quantitative FITs can be overcome to a large extent by adjusting thresholds to yield defined levels of specificity or positivity rates. Rather than simply using thresholds recommended by the manufacturer, screening programs should choose thresholds based on intended levels of specificity and manageable positivity rates.

Objective: Plasma protein biomarkers could be an efficient alternative for population-based screening for early detection of colorectal cancer (CRC). The objective of this study was to evaluate and validate plasma proteins individually and as a signature for early detection of CRC. Methods: In a three-stage design, proteins were measured firstly by liquid chromatography/multiple reaction monitoring-mass spectrometry (LC/MRM-MS) and later by proximity extension assay (PEA) in a discovery set consisting of 96 newly diagnosed CRC cases and 94 controls free of neoplasms at screening colonoscopy. Two algorithms (one for each measurement method) were derived by Lasso regression and .632+ bootstrap based on 11 proteins that were included in both the LC/MRM-MS and PEA measurements. Additionally, another algorithm was constructed from the same eleven biomarkers plus amphireglin, the most promising protein marker in the PEA measurements that had not been available from the LC/MRM-MS measurements. Lastly the three prediction signatures were validated with PEA in independent samples of participants of screening colonoscopy (CRC (n = 56), advanced adenoma (n = 101), and participants free of neoplasm (n = 102)). Results: The same four proteins were included in all three prediction signatures; mannan binding lectin serine protease 1, osteopontin, serum paraoxonase lactonase 3 and transferrin receptor protein 1, and the third prediction signature additionally included amphiregulin. In the independent validation set from a true screening setting, the five-marker blood-based signature including AREG presented areas under the curves of 0.82 (95% CI, 0.74–0.89), 0.86 (95% CI, 0.77–0.92) and 0.76 (95% CI, 0.64–0.86) for all, early and late stages CRC, respectively. Conclusion: Two different measurement methods consistently identified four protein markers and an algorithm additionally including amphiregulin, a marker measured by PEA only, showed promising performance for detecting early stage CRC in an independent validation in a true screening setting. These proteins may be potential candidates for blood-based tests for early detection of CRC.

Personal invitations for fecal occult blood tests (nowadays mostly fecal immunochemical tests) are increasingly used to raise their usage for colorectal cancer screening. However, there is a large heterogeneity in applied invitation schemes. We aimed to review evidence for the effectiveness of various invitation schemes. The main outcome was the fecal occult blood test usage rate. A systematic search was performed in Medline and Web of Science (up to 9 July 2020). Randomized controlled trials or cluster-randomized controlled trials were eligible, which reported on general invitations for fecal occult blood test-based colorectal cancer screening sent to the general population at average colorectal cancer risk. (PROSPERO 2020 CRD42020169409). Overall, 34 studies were included. Invitations with an attached, i.e., mailed fecal occult blood test consistently increased test usage by 4–19.7% points, compared to other methods of test provision. Likewise, the introduction of advance notification consistently led to a higher usage rate, with an increase of 3.3–10.8% points. Reminders showed positive but varying effects by method. With an increase of 8.5–15.8% points, letter or email reminders were more effective than reminders by phone call or text message (0.6–6.5% points). Inconsistent results were found for financial incentives ((−8.4)–20% points) and for added or changed invitation material ((−3.5)–11.8% points). With 3.5–24.7% points, the strongest increases in use were achieved by multifaceted invitation, implementing multiple components. Any invitation scheme was superior over no invitation. Advance notification, mailing of fecal occult blood test, and reminders were consistently shown to have major, complementary potential to increase participation in fecal occult blood test-based colorectal cancer screening settings.

The success of a colonoscopy in detecting and removing pre-cancerous and cancerous lesions depends heavily on the quality of bowel preparation. Despite efforts, 20–44% of colonoscopy participants have an inadequate bowel preparation. We aimed to assess and compare risk factors for inadequate bowel preparation and for the presence of advanced colorectal neoplasms in routine screening practice. In this cross-sectional study, among 8125 participants of screening colonoscopy in Germany with a comprehensive assessment of sociodemographic factors, lifestyle and medical history, we examined factors associated with inadequate bowel preparation and with findings of advanced neoplasms using adjusted log-binomial regression models. Among the identified risk factors assessed, three factors were identified that were significantly associated with inadequate bowel preparation: age ≥ 70 years (adjusted prevalence ratios, aPR, 1.50 95%CI 1.31–1.71), smoking (aPR 1.29 95%CI 1.11–1.50) and abdominal symptoms (aPR 1.14 95%CI 1.02–1.27). The same risk factors were also associated with the prevalence of advanced neoplasms in our study (aPR 1.72, 1.62 and 1.44, respectively). The risk factors associated with inadequate bowel preparation in this study were also associated with a higher risk for advanced neoplasms. Inadequate bowel preparation for colonoscopy might lead to missed colorectal cancer (CRC) precursors and the late diagnosis of CRC. People at high risk of advanced neoplasms are in particular need of enhanced bowel preparation.