What is the role of the Fecal Immunochemical Test (FIT) in screening for colorectal cancer?

Fecal Immunochemical Test (FIT) for Colorectal Cancer Screening

FIT is an essential, highly effective noninvasive screening tool for colorectal cancer that should be performed annually, with a sensitivity of approximately 79% for cancer detection and superior adherence compared to other stool-based tests. 1

Test Performance Characteristics

Cancer Detection

• FIT demonstrates pooled sensitivity of 79% (95% CI, 69-86%) for colorectal cancer with specificity of 94% (95% CI, 92-95%) 1, 2
• When using colonoscopy as the reference standard, one-time FIT screening achieves 77% sensitivity for cancer 2
• The FDA-cleared OC FIT CHEK demonstrated 74% sensitivity and 96% specificity in a large US study of 9,989 individuals 1, 2
• FIT achieves 100% sensitivity for cancer in some studies, though this varies by brand and cut-off value 1, 3

Advanced Adenoma Detection

• FIT has significantly lower sensitivity for advanced adenomas, ranging from 22-40% depending on test parameters 1, 2
• Sensitivity can be adjusted by modifying hemoglobin cut-off values: decreasing OC-Sensor FIT cut-off from 20 to 10 μg/g increases sensitivity from 29% to 35%, but decreases specificity from 97% to 93% 2
• This trade-off between sensitivity and specificity allows programs to adjust based on available colonoscopy resources 1

Critical Limitation: Sessile Serrated Polyps

• FIT has poor sensitivity (approximately 5-12%) for sessile serrated adenomas/polyps (SSA/Ps), a major limitation given their role in interval cancers 2, 4, 5
• At standard cut-offs, FIT detected large SSA/Ps with only 10.5-18.4% sensitivity compared to 20.9-32.4% for advanced adenomas 5
• Patients with large SSA/Ps were significantly less likely to have positive FIT results than those with advanced adenomas (OR 0.30-0.44) 5

Comparative Effectiveness

FIT vs Guaiac-Based FOBT (gFOBT)

• FIT substantially outperforms gFOBT with approximately twice the sensitivity for cancer detection (79% vs 30-65%) 2, 4
• FIT demonstrates superior adherence (RR 1.16,95% CI 1.03-1.30) and advanced neoplasia detection (RR 2.28,95% CI 1.68-3.10) compared to gFOBT 1
• Direct comparison studies show FIT sensitivity of 84.6% vs gFOBT at 30.8% for cancer 2, 4
• FIT achieved 100% cancer sensitivity vs 61.5% for Hemoccult SENSA in one randomized trial, despite lower participation 1, 3

FIT vs Colonoscopy

• While colonoscopy detects more advanced neoplasia per screening round (RR 3.21,95% CI 2.38-4.32), FIT achieves superior participation rates (RR 1.49,95% CI 1.25-1.79) 1
• In the ColonPrev study, participation was higher with FIT (40.7%) vs colonoscopy (24.6%), with no difference in cancer detection (0.4% each) 1
• Advanced neoplasia detection was superior with colonoscopy (1.3%) vs single FIT (0.8%), but repeated annual FIT testing narrows this gap over time 1
• Sequential testing (offering colonoscopy first, then FIT to those who decline) improves overall participation by 19-25% 1

FIT vs FIT-DNA Testing

• FIT-DNA (Cologuard) has higher single-time cancer sensitivity (92%) but substantially lower specificity (86.6% vs 96% for FIT alone) 1
• Annual FIT is more cost-effective than FIT-DNA every 3 years, with FIT-DNA costing approximately 10 times more ($500-600 vs $20) 1
• The decreased specificity of FIT-DNA (only 83% in patients >65 years) results in more false positives and unnecessary colonoscopies 1

Practical Implementation

Testing Frequency and Format

• FIT must be performed annually to maintain programmatic effectiveness 1, 6
• Single-sample FITs have higher patient uptake than multi-sample tests 1
• Quantitative FIT assays allow adjustment of positivity thresholds to balance sensitivity and specificity based on colonoscopy capacity 1, 2

Patient Advantages

• Requires only 1-2 stool samples vs 3 for gFOBT, improving compliance 4, 7
• No dietary restrictions required, unlike gFOBT 4, 7
• Not affected by vitamin C supplements or upper GI bleeding (globin degraded by digestive enzymes) 4
• Detects human globin specifically, reducing false positives from dietary sources 4

Follow-Up Requirements

• Any positive FIT result requires diagnostic colonoscopy, not repeat FIT testing 4, 6
• High-quality FIT programs require timely diagnostic follow-up after abnormal results 6
• Annual patient participation must be maintained for programmatic success 6

Common Pitfalls to Avoid

• Never perform in-clinic FOBT during digital rectal examination for screening—sensitivity is <10% and this approach is not recommended 4
• Do not use FIT as the sole screening strategy for patients at high risk for serrated lesions given its poor sensitivity for SSA/Ps 2, 5
• Avoid single-sample testing when multi-sample options are available, as sensitivity is lower 4
• Do not repeat FIT testing after a positive result—proceed directly to colonoscopy 4
• Ensure only superior FIT formats are used in screening programs; brand and cut-off values significantly affect performance 1, 6

Role in Screening Strategy

FIT serves as an essential element of the colorectal cancer screening armamentarium and is commonly the test of choice in programmatic screening 1. It represents an excellent second choice in sequential testing approaches where colonoscopy is offered first, and should be included when offering multiple screening options to patients 1. The US Multi-Society Task Force on Colorectal Cancer considers FIT a cornerstone of effective screening programs, particularly given its superior adherence compared to other modalities 1.