BLUE-C
Clinical Validation of An Optimized Multi-Target Stool DNA (Mt-sDNA 2.0) Test, for Colorectal Cancer Screening (BLUE-C)
Phase observationalN = 20,176NCT04144738
- Population
- Asymptomatic adults aged 40 years or older undergoing screening colonoscopy (20,176 participants). Funded by Exact Sciences.
- Design
- Prospective study of a next-generation multitarget stool DNA test (DNA molecular markers plus hemoglobin) in asymptomatic adults aged 40 years or older undergoing screening colonoscopy, with a commercially available FIT as comparator. Primary outcomes: sensitivity for colorectal cancer and specificity for advanced neoplasia. Secondary: sensitivity for advanced precancerous lesions, specificity for nonneoplastic findings or negative colonoscopy, and comparison with FIT. Of 20,176 participants, 98 had colorectal cancer, 2,144 advanced precancerous lesions, 6,973 nonadvanced adenomas and 10,961 nonneoplastic findings or a negative colonoscopy. The FDA summary describes a prospective, cross-sectional, multicenter pivotal study of 26,758 participants at 186 US sites.
- Primary endpoint
- Sensitivity for colorectal cancer, Specificity for advanced neoplasia
- Arms
- Next-generation multitarget stool DNA test (experimental, n = 20,176): Stool DNA markers plus hemoglobin (Cologuard Plus)
- FIT (control, n = 20,176): Commercially available fecal immunochemical test
- People
- Imperiale TF
Δ Sensitivity for colorectal cancer+26.6 pointsΔ Sensitivity for advanced precancerous lesions+20.1 pointsΔ Specificity for advanced neoplasia−4.2 pointsΔ Specificity for nonneoplastic findings or negative colonoscopy−3 points
Show the numbers
| Endpoint | Analysis | Next-generation multitarget stool DNA test | FIT | Effect |
|---|---|---|---|---|
| Sensitivity for colorectal cancerParticipants with colorectal cancer (98 of 20,176)Proportion of participants with colorectal cancer on colonoscopy whose test was positive | primaryImperiale 2024 | 93.9% (87.1–97.7%) | 67.3% (57.1–76.5%) | P<0.001Paired comparison in the same participants. The FDA summary, whose primary population excludes participants under 45 and those with a first-degree relative with colorectal cancer, reports 95.3% (95% CI 88.4 to 98.7). |
| Sensitivity for advanced precancerous lesionsParticipants with advanced precancerous lesions (2,144 of 20,176)Proportion of participants with an advanced precancerous lesion on colonoscopy whose test was positive | primaryImperiale 2024 | 43.4% (41.3–45.6%) | 23.3% (21.5–25.2%) | P<0.001Secondary outcome. |
| Specificity for advanced neoplasiaParticipants without advanced neoplasiaProportion of participants without colorectal cancer or advanced precancerous lesions on colonoscopy whose test was negative | primaryImperiale 2024 | 90.6% (90.1–91.0%) | 94.8% (94.4–95.1%) | P<0.001Lower for the stool DNA test than for FIT: more false-positive results. |
| Specificity for nonneoplastic findings or negative colonoscopyParticipants with nonneoplastic findings or a negative colonoscopy (10,961)Proportion of participants with nonneoplastic findings or a negative colonoscopy whose test was negative | primaryImperiale 2024 | 92.7% (92.2–93.1%) | 95.7% (95.3–96.1%) | Secondary outcome; the abstract gives no P value for this comparison. |
| Endpoint | Analysis | Next-generation multitarget stool DNA test | FIT | Effect |
|---|---|---|---|---|
| Sensitivity for colorectal cancerParticipants with colorectal cancer (98 of 20,176)Proportion of participants with colorectal cancer on colonoscopy whose test was positive | primaryImperiale 2024 | 93.9% (87.1–97.7%) | 67.3% (57.1–76.5%) | P<0.001Paired comparison in the same participants. The FDA summary, whose primary population excludes participants under 45 and those with a first-degree relative with colorectal cancer, reports 95.3% (95% CI 88.4 to 98.7). |
| Sensitivity for advanced precancerous lesionsParticipants with advanced precancerous lesions (2,144 of 20,176)Proportion of participants with an advanced precancerous lesion on colonoscopy whose test was positive | primaryImperiale 2024 | 43.4% (41.3–45.6%) | 23.3% (21.5–25.2%) | P<0.001Secondary outcome. |
| Specificity for advanced neoplasiaParticipants without advanced neoplasiaProportion of participants without colorectal cancer or advanced precancerous lesions on colonoscopy whose test was negative | primaryImperiale 2024 | 90.6% (90.1–91.0%) | 94.8% (94.4–95.1%) | P<0.001Lower for the stool DNA test than for FIT: more false-positive results. |
| Specificity for nonneoplastic findings or negative colonoscopyParticipants with nonneoplastic findings or a negative colonoscopy (10,961)Proportion of participants with nonneoplastic findings or a negative colonoscopy whose test was negative | primaryImperiale 2024 | 92.7% (92.2–93.1%) | 95.7% (95.3–96.1%) | Secondary outcome; the abstract gives no P value for this comparison. |