Fecal Immunochemical Test Screening and Risk of Colorectal Cancer Death

Abstract

Importance: The fecal immunochemical test (FIT) is widely used for colorectal cancer (CRC) screening, but evidence of its effectiveness is limited.

Objective: To evaluate whether FIT screening is associated with a lower risk of dying from CRC overall, according to cancer location, and within demographic groups.

Design, setting, and participants: This nested case-control study in a cohort of screening-eligible people was conducted in 2 large, integrated health systems of racially, ethnically, and socioeconomically diverse members with long-term programs of mailed FIT screening outreach. Eligible participants included people aged 52 to 85 years who died from colorectal adenocarcinoma between 2011 and 2017 (cases); cases were matched in a 1:8 ratio based on age, sex, health-plan membership duration, and geographic area to randomly selected persons who were alive and CRC-free on case's diagnosis date (controls). Data analysis was conducted from January 2002 to December 2017.

Exposures: Completing 1 or more FIT screenings in the 5-year period prior to the CRC diagnosis date among cases or the corresponding date among controls; in secondary analyses, 2- to 10-year intervals were evaluated.

Main outcomes and measures: The primary study outcome was CRC death overall and by tumor location. Secondary analyses were performed to assess CRC death by race and ethnicity.

Results: From a cohort of 2 127 128 people, a total of 10 711 participants (3529 aged 60-69 years [32.9%]; 5587 male [52.1%] and 5124 female [47.8%]; 1254 non-Hispanic Asian [11.7%]; 973 non-Hispanic Black [9.1%]; 1929 Hispanic or Latino [18.0%]; 6345 non-Hispanic White [59.2%]) was identified, including 1103 cases and 9608 controls. Among controls during the 10-year period prior to the reference date, 6101 (63.5%) completed 1 or more FITs with a cumulative 12.6% positivity rate (768 controls), of whom 610 (79.4%) had a colonoscopy within 1 year. During the 5-year period, 494 cases (44.8%) and 5345 controls (55.6%) completed 1 or more FITs. In regression analysis, completing 1 or more FIT screening was associated with a 33% lower risk of death from CRC (adjusted odds ratio [aOR], 0.67; 95% CI, 0.59-0.76) and 42% lower risk in the left colon and rectum (aOR, 0.58; 95% CI, 0.48-0.71). There was no association with right colon cancers (aOR, 0.83; 95% CI, 0.69-1.01) but the difference in the estimates between the right colon and left colon or rectum was statistically significant (P = .01). FIT screening was associated with lower CRC mortality risk among non-Hispanic Asian (aOR, 0.37; 95% CI, 0.23-0.59), non-Hispanic Black (aOR, 0.58; 95% CI, 0.39-0.85) and non-Hispanic White individuals (aOR, 0.70; 95% CI, 0.57-0.86) (P for homogeneity = .04 for homogeneity).

Conclusions and relevance: In this nested case-control study, completing FIT was associated with a lower risk of overall death from CRC, particularly in the left colon, and the associations were observed across racial and ethnic groups. These findings support the use of FIT in population-based screening strategies.

Figure.. Flow of the Study

Selection criteria at reference date included being aged 52 to 85 y during 2011 to 2017, 5 or more years prior enrollment in the health plan, and no prior gastrointestinal cancers, colectomy, inflammatory bowe disease, or genetic colorectal cancer syndromes in the 10 years prior to cohort entry. ^aThe date of colorectal cancer diagnosis was set as the reference and if unknown, the death date was used (32 participants). ^bMatching was based on age, sex, health plan membership duration, and geographic region in a 1:8 ratio of case to control persons. Geographic regions were determined based on the medical center or facility in which a person received most of their care or were assigned for care by the health plan. ^cThe location was defined using the splenic flexure such that cancers that form in the colon proximal to the splenic flexure were classified as right colon cancers and those distal were left colon and rectum.