Cause of Death, Mortality and Occult Blood in Colorectal Cancer Screening

Fecal hemoglobin (f-Hb) detected by the guaiac fecal occult blood test (gFOBT) may be associated with mortality and cause of death in colorectal cancer (CRC) screening participants. We investigated this association in a randomly selected population of 20,694 participants followed for 33 years. We followed participants from the start of the Hemoccult-II CRC trial in 1985–1986 until December 2018. Data on mortality, cause of death and covariates were retrieved using Danish national registers. We conducted multivariable Cox regressions with time-varying exposure, reporting results as crude and adjusted hazard ratios (aHRs). We identified 1766 patients with at least one positive gFOBT, 946 of whom died in the study period. Most gFOBT-positive participants (93.23%) died of diseases unrelated to CRC and showed higher non-CRC mortality than gFOBT-negative participants (aHR: 1.20, 95% CI 1.10–1.30). Positive gFOBT participants displayed a modest increase in all-cause (aHR: 1.28, 95% CI: 1.18–1.38), CRC (aHR: 4.07, 95% CI: 3.00–5.56), cardiovascular (aHR: 1.22, 95% CI: 1.07–1.39) and endocrine and hematological mortality (aHR: 1.58, 95% CI: 1.19–2.10). In conclusion, we observed an association between positive gFOBT, cause of death and mortality. The presence of f-Hb in the gFOBT might indicate the presence of systemic diseases.

Change in Colorectal Cancer Tests Submitted for Reimbursement in Switzerland 2012–2018: Evidence from Claims Data of a Large Insurance

Objectives: Guidelines recommend colorectal cancer (CRC) screening by fecal occult blood test (FOBT) or colonoscopy. In 2013, Switzerland introduced reimbursement of CRC screening by mandatory health insurance for 50-69-years-olds, after they met their deductible. We hypothesized that the 2013 reimbursement policy increased testing rate.Methods: In claims data from a Swiss insurance, we determined yearly CRC testing rate among 50-75-year-olds (2012–2018) and the association with socio-demographic, insurance-, and health-related covariates with multivariate-adjusted logistic regression models. We tested for interaction of age (50–69/70–75) on testing rate over time.Results: Among insurees (2012:355′683; 2018:348′526), yearly CRC testing rate increased from 2012 to 2018 (overall: 8.1–9.9%; colonoscopy: 5.0–7.6%; FOBT: 3.1–2.3%). Odds ratio (OR) were higher for 70–75-year-olds (2012: 1.16, 95%CI 1.13–1.20; 2018: 1.05, 95%CI 1.02–1.08). Deductible interacted with changes in testing rate over time (p < 0.001). The increase in testing rate was proportionally higher among 50-69-years-olds than 70-75-year-olds over the years.Conclusions: CRC testing rate in Switzerland increased from 2012 to 2018, particularly among 50-69-years-olds, the target population of the 2013 law. Future studies should explore the effect of encouraging FOBT or waiving deductible.

Multi-dimensional fragmentomic assay for ultrasensitive early detection of colorectal advanced adenoma and adenocarcinoma

Previous studies on liquid biopsy-based early detection of advanced colorectal adenoma (advCRA) or adenocarcinoma (CRC) were limited by low sensitivity. We performed a prospective study to establish an integrated model using fragmentomic profiles of plasma cell-free DNA (cfDNA) for accurately and cost-effectively detecting early-stage CRC and advCRA. The training cohort enrolled 310 participants, including 149 early-stage CRC patients, 46 advCRA patients and 115 healthy controls. Plasma cfDNA samples were prepared for whole-genome sequencing. An ensemble stacked model differentiating healthy controls from advCRA/early-stage CRC patients was trained using five machine learning models and five cfDNA fragmentomic features based on the training cohort. The model was subsequently validated using an independent test cohort (N = 311; including 149 early-stage CRC, 46 advCRA and 116 healthy controls). Our model showed an area under the curve (AUC) of 0.988 for differentiating advCRA/early-stage CRC patients from healthy individuals in an independent test cohort. The model performed even better for identifying early-stage CRC (AUC 0.990) compared to advCRA (AUC 0.982). At 94.8% specificity, the sensitivities for detecting advCRA and early-stage CRC reached 95.7% and 98.0% (0: 94.1%; I: 98.5%), respectively. Promisingly, the detection sensitivity has reached 100% and 97.6% in early-stage CRC patients with negative fecal occult or CEA blood test results, respectively. Finally, our model maintained promising performances (AUC: 0.982, 94.4% sensitivity at 94.8% specificity) even when sequencing depth was down-sampled to 1X. Our integrated predictive model demonstrated an unprecedented detection sensitivity for advCRA and early-stage CRC, shedding light on more accurate noninvasive CRC screening in clinical practice.

Colorectal Cancer Screening: Have We Addressed Concerns and Needs of the Target Population?

Despite the recognized benefits of colorectal cancer (CRC) screening, uptake is still suboptimal in many countries. In addressing this issue, one important element that has not received sufficient attention is population preference. Our review provides a comprehensive summary of the up-to-date evidence relative to this topic. Four OVID databases were searched: Ovid MEDLINE® ALL, Biological Abstracts, CAB Abstracts, and Global Health. Among the 742 articles generated, 154 full texts were selected for a more thorough evaluation based on predefined inclusion criteria. Finally, 83 studies were included in our review. The general population preferred either colonoscopy as the most accurate test, or fecal occult blood test (FOBT) as the least invasive for CRC screening. The emerging blood test (SEPT9) and capsule colonoscopy (nanopill), with the potential to overcome the pitfalls of the available techniques, were also favored. Gender, age, race, screening experience, education and beliefs, the perceived risk of CRC, insurance, and health status influence one’s test preference. To improve uptake, CRC screening programs should consider offering test alternatives and tailoring the content and delivery of screening information to the public’s preferences. Other logistical measures in terms of the types of bowel preparation, gender of endoscopist, stool collection device, and reward for participants can also be useful.

Factors affecting the follow-up time after a positive result in the fecal occult blood test

In 2010, Taiwan included the fecal occult blood test (FOBT) under preventive health insurance services. For patients whose test positive, receiving follow-ups is paramount. This study investigated factors affecting the follow-up time of these patients. This retrospective study used data from the colorectal cancer screening archives. The study period was from 2010 to 2013, and the subjects were 50–75-year-old persons who tested positive for FOBT. The t test, one-way ANOVA, and multiple regression were performed to address the differences in the mean tracking period between variables such as the population’s demographic characteristics. The mean follow-up time for the 98,482 participants whose screening results were positive exhibited significant differences (p < 0.001) according to medical unit region and classification, age, screening location, family history, examination method, and diagnosis. The model predicting the mean follow-up time predicted a period of 10.079 days longer for those whose hospital was on an offshore island than that of those whose hospital was in the eastern regions. The follow-up time was 1.257 days shorter for people who were inpatients than those who were outpatients and was 8.902 days longer for people who underwent double contrast barium enema plus flexible sigmoidoscopy than those who underwent other examination methods. Patients with a family history of colorectal cancer and those whose examination results indicated cancer had a follow-up time of 2.562 and 2.476 days shorter than those who did not know their family history and those with other results, respectively. Factors affecting the follow-up time of people whose FOBT results were positive consisted of the location and classification of the follow-up institution, age, screening location, family history, examination method, and diagnosis. This provides valuable references for improving the cancer screening program.