ABSTRACT
BACKGROUND & AIM: Patients with screen-detected colorectal cancer (CRC) have a better stage-specific overall survival than non-screen detected CRC. Currently, it is unknown if recurrence rates differ between screen- and non-screen detected CRCs, and whether this could explain the observed difference in overall survival. Therefore, we aimed to assess the disease-free survival (DFS) rates in screen-detected and non-screen detected CRCs and if recurrence affects overall survival. METHODS: Dutch CRC (stage I-III) patients, diagnosed by screening or not in the first six months of 2015, were included from the Netherlands Cancer Registry. DFS and survival data were retrieved and analyzed by Kaplan Meier method. The association between mode of detection and recurrence and overall survivall was evaluated with a Cox-regression model. RESULTS: A total of 3725 CRC patients were included, 2073 (55.7%) non-screen-detected and 1652 (44.3%) screen-detected CRCs. Three-year DFS was significantly higher in screen-detected CRC compared to non-screen-detected CRC (87.8% versus 77.2.%, p<0.001). Stage-specific DFS rates for screen-detected vs. non-screen-detected CRC were 94.7% vs. 92.3% for stage I (p=0.45), 84.3% vs. 81.4% for stage II (p=0.17) and 77.9% vs 66.7% for stage III (p<0.001), respectively. Detection by screening was independently associated with a lower risk of recurrence (HR 0.67; CI 0.55 - 0.81, p<0.001) when adjusted for age, gender, tumor location, stage and treatment. Recurrence independently predicted overall survival (HR 15.90; CI 13.28-19.04, p<0.001). CONCLUSION: Disease-free survival was significantly better in screen-detected compared to non-screen-detected CRCs independent of age, gender, tumor location, stage and treatment, and was associated with an overall survival benefit.
ABSTRACT
BACKGROUND: Many screening programs for colorectal cancer (CRC) use the fecal immunochemical test (FIT) to triage individuals for colonoscopy. Although these programs reduce CRC incidence and CRC-related mortality, the detection of advanced precursor lesions (advanced adenomas and advanced serrated polyps) by FIT could be improved. As an alternative for FIT, the antibody-based multitargetFIT (mtFIT) has been proposed. The mtFIT measures three protein markers: hemoglobin, calprotectin, and serpin family F member 2. In a retrospective diagnostic accuracy study in a large colonoscopy-controlled series (n = 1284), mtFIT showed increased sensitivity for advanced neoplasia (AN), at equal specificity, compared to FIT (42.9% versus 37.3%; p = 0.025). This increase was mainly due to a higher sensitivity of mtFIT for advanced adenomas (37.8% versus 28.1% for FIT; p = 0.006). The present mtFIT study aims to prospectively validate these findings in the context of the Dutch national CRC screening program. METHOD: The mtFIT study is a cross-sectional intervention study with a paired design. Eligible subjects for the Dutch FIT-based national CRC screening program are invited to perform mtFIT in addition to FIT. Samples are collected at home, from the same bowel movement, and are shipped to a central laboratory by postal mail. If either one or both tests are positive, participants are referred for colonoscopy. Detailed colonoscopy and pathology data are centrally stored in a national screening database (ScreenIT; Topicus, Deventer, the Netherlands) that is managed by the screening organization, and will be retrieved for this study. We aim to determine the relative sensitivity for AN, comprising of CRC, advanced adenomas and advanced serrated polyps, of mtFIT compared to FIT at an equal positivity rate. Additionally, we will use the Adenoma and Serrated Pathway to Colorectal CAncer model to predict lifetime health effects and costs for programmatic mtFIT- versus FIT-based screening. The target sample size is 13,131 participants. DISCUSSION: The outcome of this study will inform on the comparative clinical utility of mtFIT versus FIT in the Dutch national CRC screening program and is an important step forward in the development of a new non-invasive stool test for CRC screening. TRIAL REGISTRATION: Clinicaltrials.gov ; NCT05314309, registered April 6th 2022, first inclusions March 25th 2022 https://clinicaltrials.gov/ct2/results?cond=&term=NCT05314309&cntry=&state=&city=&dist =.