Clinical Question

Does screening with colonoscopy result in an increased diagnosis of colorectal cancer and a larger reduction in mortality compared with the sequential use of fecal immunochemical testing (FIT)?

Evidence-Based Answer

No trials have directly compared colonoscopy and sequential FIT. The U.S. Preventive Services Task Force (USPSTF) estimates that, over a lifetime, using colonoscopy compared with FIT may avert one additional death for every approximately 500 people screened starting at 50 years of age. (Strength of Recommendation [SOR]: C, estimate from modeling projections.) There are conflicting mortality data for colonoscopy. Several cohort studies found a 68% reduced mortality compared with no screening (SOR: B, two cohort studies with long follow-up periods.); however, a recent large European randomized controlled trial (RCT) found no colorectal cancer–specific mortality reduction from colonoscopy when using an intention-to-treat analysis. (SOR: B, single large RCT.) FIT reduced colorectal cancer– specific mortality by 16% to 62% compared with no screening. (SOR: B, older RCTs and one large cohort study.)

Evidence Summary

EFFECTIVENESS OF COLONOSCOPY

A pragmatic randomized trial performed between 2009 and 2014 found that screening colonoscopy compared with no screening reduced the risk of colorectal cancer but not colorectal cancer–specific mortality (when using an intention-to-treat analysis).¹ A total of 84,585 adults (55 to 64 years of age) from Poland, Norway, and Sweden who had never been screened were randomized in a 1: 2 ratio to have a colonoscopy or no screening (which is not the standard of care). The patients who were not screened were not eligible for screening during the intervention or follow-up periods. People with a history of colon cancer were excluded. The primary outcomes were colorectal cancer and death from colorectal cancer. Participants who were invited to undergo screening colonoscopy using an intention-to-treat analysis had a 10-year relative risk reduction of colorectal cancer 18% lower than the usual care group (0.98% and 1.2%, respectively; relative risk [RR] = 0.82; 95% CI, 0.70 to 0.93; number needed to screen [NNS] = 455) but no significant difference in death from colorectal cancer (RR = 0.90; 95% CI, 0.64 to 1.16). Using a per-protocol analysis, the 10-year relative risk of colon cancer was 31% lower in the screening group than in the usual care group (1.22% vs. 0.84%; RR = 0.69; 95% CI, 0.55 to 0.83; NNS = 263), and colorectal cancer–specific mortality was 50% lower (0.15% vs. 0.30%, respectively; RR = 0.50; 95% CI, 0.27 to 0.77; NNS = 667). This per-protocol analysis found one fewer colorectal cancer–related death for every 667 people screened with colonoscopy over 10 years compared with no screening. (SOR: B, single RCT.)

Two prospective cohort studies of colonoscopy screening found reductions in colorectal cancer rates and mortality compared with no screening.^2,3 The first study compared screening with colonoscopy or flexible sigmoidoscopy in 88,902 patients (women 30 to 55 years of age; men 40 to 75 years of age) who were followed for up to 22 years. All patients were U.S. health care professionals who answered biennial questionnaires reporting completion of sigmoidoscopy or colonoscopy. Primary outcomes were colorectal cancer incidence and colorectal cancer mortality. Compared with no endoscopy, both endoscopy methods resulted in fewer colon cancer diagnoses, with colonoscopy (hazard ratio [HR] = 0.44; 95% CI, 0.38 to 0.52) having lower colorectal cancer incidence than sigmoidoscopy (HR = 0.60; 95% CI, 0.53 to 0.68). Compared with no endoscopy, death from colon cancer was reduced after colonoscopy (HR = 0.32; 95% CI, 0.24 to 0.45) and sigmoidoscopy (HR = 0.59; 95% CI, 0.45 to 0.76).

A prospective cohort of Medicare beneficiaries 70 to 79 years of age (n = 1,355,692) found that participants 70 to 74 years of age who had a colonoscopy between 2004 and 2012 had a lower eight-year risk of colorectal cancer diagnosis: 2.19% compared with 2.62% in the no-screening arm (absolute risk reduction = −0.42%; 95% CI, −0.24 to −0.63; NNS = 239 to avoid one colorectal cancer diagnosis). No difference was found among participants who were 75 to 79 years of age. The mortality data were not specific to colorectal cancer.

EFFECTIVENESS OF FECAL IMMUNOCHEMICAL TESTING

A large cohort study and a smaller meta-analysis of RCTs found that screening with FIT reduced cancer mortality compared with no screening.^4,5 A 2015 prospective cohort study compared screened residents of Taiwan who were 50 to 69 years of age (n = 1,160,895), defined as those who underwent one to three rounds of FIT, and unscreened individuals (n = 4,256,804). Primary outcomes included a diagnosis of colorectal cancer and deaths from colorectal cancer by five years after the study onset. Screening with FIT resulted in a 62% lower colorectal cancer mortality for screened participants compared with unscreened participants (0.014% vs. 0.036%; RR = 0.38; 95% CI, 0.35 to 0.42; NNS = 4,545). The 21.4% of the population who received FIT had a 10% mortality reduction from colorectal cancer after adjustments for self-selection bias (RR = 0.90; 95% CI, 0.84 to 0.95). Not all participants with a positive FIT result underwent colonoscopy, which may have biased the apparent benefit of screening.

The smaller meta-analysis reviewed four RCTs (n = 327,043) that compared fecal occult blood testing (guaiac or immunochemical) and no screening. The studies, originating in the 1990s, followed patients 45 to 75 years of age for 8.5 to 18.4 years. The meta-analysis used intention-to-treat methods and found a 16% reduction in colorectal cancer mortality (RR = 0.84; 95% CI, 0.78 to 0.90). The noncompliance rates ranged from 33% to 46% for the first screening and 22% and 40% for at least one round of screening. Adjusting the analysis for compliance yielded a 25% reduction in colorectal cancer mortality (RR = 0.75; 95% CI, 0.66 to 0.84).

ESTIMATE OF RELATIVE EFFECTIVENESS

The USPSTF used modeling from FIT and colonoscopy test characteristics available in 2021 (including the data presented in this review) to estimate colorectal cancer cases and deaths avoided from having FIT annually and colonoscopy every 10 years.⁶ They calculated that using colonoscopy compared with FIT would avoid one death for every approximately 500 people screened over a lifetime, starting at 50 years of age. This calculation was based on 25 vs. 27 deaths being averted per 1,000 people screened with FIT and colonoscopy, respectively, over a lifetime. The models incorporated assumptions about follow-up that potentially made the projections imprecise. Similarly, USPSTF authors calculated that 11 additional cases of colorectal cancer would be averted (47 vs. 58) per 1,000 patients screened over a lifetime.

Recommendations From Others

The USPSTF, American Cancer Society, and American Academy of Family Physicians have endorsed colorectal cancer screening with 10-year colonoscopy and annual FIT, stating that the choice of modality should be based on shared decision-making. Screening should be the focus regardless of which method a patient chooses.^7–9 A 2021 focused update to the 2017 U.S. Multi-Society Task Force on Colorectal Cancer (comprised of proceduralists who perform endoscopy) recommends screening colonoscopy every 10 years or FIT annually beginning at 45 years of age.¹⁰