COLONPREV
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Clinical Question
In asymptomatic adults age 50-69, is fecal immunochemical testing (FIT) every 2 years noninferior to colonoscopy in terms of reduction of colorectal cancer mortality?
Bottom Line
An interim analysis in 2012 determined that baseline fecal immunochemical testing (FIT) is noninferior to baseline colonoscopy in terms of detecting colorectal cancer.
Major Points
FIT every 1-2 years is the predominant method of colorectal cancer screening in Europe, whereas colonoscopy every 10 years is the predominant screening method in the United States. There is a substantial difference in both cost and patient compliance between these methods, yet there is no conclusive evidence as to which is more effective at reducing mortality.
The ongoing COLONPREV study aims to ascertain differences in the prevention of death from colorectal cancer by screening with FIT vs. colonoscopy. Ten-year outcomes will be reported in 2021, but in the meantime, interim results have been published. Inviting patients to biennial FIT screening resulted in 39% higher participation and resulted in the same detection rate of colorectal cancer compared to colonoscopy (0.1% in each arm), after only the first FIT (of five). Over the course of ten years, the trade-off between any additional colorectal cancers that will be detected by FIT versus the additional adenomas already removed by colonoscopy will be quantifiable in terms of mortality difference.
Guidelines
US Preventive Services Task Force (2013) Screening Average Risk Asymptomatic Patients, Age 50-75:
- FIT every 1 to 2 years is recommended, with follow-up for any positive FIT with colonoscopy.
- Colonoscopy every 10 years is an acceptable alternative for screening.
- American Cancer Society, US Multi Society Task Force, and American College of Radiology, 2008
Screening Average Risk Asymptomatic Patients, Age 50+:
- Flexible sigmoidoscopy every 5 years, or
- Colonoscopy every 10 years, or
- Double-contrast barium enema every 5 years, or
- CT colonography (virtual colonoscopy) every 5 years, or
- Yearly guaiac-based fecal occult blood test (gFOBT), or
- Yearly fecal immunochemical test (FIT), or
- Stool DNA test (sDNA) every 3 years
Design
- Multicenter randomized, controlled noninferiority trial
- N=53,302
- FIT, every 2 years (n=26,703)
- Colonoscopy, one time (n=26,599)
- Setting: 15 centers in Spain
- Enrollment: June 2009 to June 2011
- Follow-up: Ten-year follow-up will be complete in June 2021
- Analysis: Intention-to-screen and as-screened
- Primary outcome: Reduction in rate of death from colorectal cancer at 10 years
Population
Inclusion Criteria
- Adult men and women ages 50-69
- Asymptomatic
Exclusion Criteria
- Personal history of colorectal cancer, adenoma, or IBD
- Family history of hereditary or familiar colorectal cancer
- Severe coexisting illness
- Recently screened for colorectal cancer (FOBT within 2 years or sigmoid/colonoscopy within 5 years)
Baseline Characteristics
Mean age: 59.2 years Female: 53.9%
Interventions
Subjects were randomized to receive an invitation for:
- FIT testing every 2 years, or
- One-time colonoscopy
Subjects could accept the invited screening method or crossover between groups.
Any positive FIT test was to be followed up with colonoscopy.
Reduction in CRC death would be assessed 10 years after onset of screening modality.
Outcomes
Comparisons are colonoscopy group vs. FIT.
Primary Outcome
- Risk reduction in colorectal cancer deaths
- Analysis expected to be performed in 2021, after 10 years of follow-up
Secondary Outcomes
- Detection of colorectal cancer
- Intention-to-screen: 0.1% vs. 0.1% (P=0.99)
- As-screened: 0.5% vs. 0.3% (P=0.09)
- Detection of advanced adenomas
- Intention-to-screen: 1.9% vs. 0.9% (OR 2.30; CI 1.97-2.56, P<0.001)
- As-screened: 9.7% vs. 2.4% (OR 4.32; CI 3.69-5.07, P<0.001)
- Detection of non-advanced adenomas
- Intention-to-screen: 4.2% vs. 0.4% (OR 9.80; CI 8.10-11.85, P<0.001)
- As-screened: 22.1% vs. 1.1% (OR 25.98; CI 21.27-31.74, P<0.001)
- Participation rate
- 24.9% vs. 34.2% (OR 0.63; CI 0.60-0.65, P<0.001)
- Patient crossover between groups
- 1628 vs. 106 (OR 16.8; CI 13.9-20.2, P<0.001)
Subgroup Analysis
Colorectal cancer detection in the two groups had no significant difference when stratified by tumor location (proximal vs. distal colon).
Adverse Events
- Major complications (bleeding, hypotension, bradycardia, or perforation)
- 0.5% vs. 0.1% (OR 4.81; CI 2.26- 10.20, P<0.001)
Criticisms
- Mortality data is not currently available as the data collection period is still underway
- The generalizability of this study is somewhat limited due to mail-based invitation for screening, which may differ from invitations stemming from physician-patient relationships. However, the as-screened analysis does provide data on colorectal cancer detection per procedure performed.
- It is unclear how to interpret the difference in detecting non-advanced adenomas which, unlike advanced adenomas, do not elevate CRC risk enough to warrant escalation of screening regimen.
Funding
Funded by Instituto de Salud Carlos III, Asociación Española contra el Cáncer, FEDER funds, and Agència de Gestió d’Ajuts Universitaris de Recerca.
Further Reading
Meissner HI, Breen N, Klabunde CN, Vernon SW. Patterns of colorectal cancer screening uptake among men and women in the United States. Cancer Epidemiol Biomarkers Prev 2006; 15: 389–394.
Segnan N, Senore C, Andreoni B, et al., Comparing attendance and detection rate of colonoscopy with sigmoidoscopy and FIT for colorectal cancer screening. Gastroenterology 2007;132(7):2304-2312.
Johnson CD, Chen MH, Toledano AY, et al., Accuracy of CT colonography for detection of large adenomas and cancers. N Engl J Med. 2008;359:1207-17.