DeeP-C

In the pivotal DeeP-Ca study of multitarget stool DNA (mt-sDNA) vs fecal immunochemical test (FITb), 9989 evaluable and asymptomatic participants with average colorectal cancer (CRC) risk aged 50-84 years provided a stool sample and underwent colonoscopy with mt-sDNA and FITb tests performed on each sample.1

The mt-sDNA test demonstrated significantly greater sensitivity vs FIT for CRC (92.3% vs 73.8%, respectively; P=0.002) and for advanced precancerous lesions (42.4% vs 23.8%, respectively; P<0.001).

The overall sensitivity of mt-sDNA was 87% (vs 95% for FITb) among average-risk individuals with nonadvanced or negative findings on colonoscopy and 90% (vs 96% for FITb) in clean colonoscopy.1

Extrapolation of results from the pivotal study to a hypothetical population of 10,000 persons at average risk for CRC showed that of 1611 individuals (16.1%) who would have a positive mt-sDNA result, only 3.7% would have CRC detected by colonoscopy.

DeeP-C Informational Download

Additional information on the mt-sDNA pivotal study, DeeP-C

mt-sDNA Pivotal Study Download

Greater sensitivity for CRC1
mt-sDNA: 92.3%
FITb: 73.8%

Greater sensitivity for precancerous lesions1
mt-sDNA: 42.4%
FITb: 23.8%

Greater sensitivity for both colorectal cancer and high-grade dysplasia
mt-sDNA: 83.7%
FITb: 63.5%

mt-sDNA PIVOTAL STUDY DESIGN1,2

The prospective, cross-sectional, multicenter pivotal study evaluated the performance of mt-sDNA vs FITb

Asymptomatic adults between the ages of 50 and 84 who were considered to be at the average risk for CRC and who were scheduled to undergo screening colonoscopy

Participants provided single stool sample
Laboratory performed mt-sDNA and FITb on each stool sample
Paticipants also underwent screening colonoscopyc (reference standard)

Primary outcome

  1. Ability of the mt-sDNA test to detect CRC (i.e. adenocarcinoma)
    1. Disease stage determined by the AJCC staging system

Secondary outcome

  1. Ability of the mt-sDNA test to detect advanced precancerous lesionsd
  2. Comparison of mt-sDNA vs commercially available FITb performance in the detection of both CRC and advanced precancerous lesions

mt-sDNA PROVIDED GREATER SENSITIVITY VS FITb ACROSS CRC STAGES AND HIGHER-RISK PRECANCEROUS LESIONS1-3

The image shows a clustered bar graph of mt-sDNA and FIT sensitivity values across CRC stages and for high-risk precancerous lesions. For all categories, mt-sDNA shows greater sensitivity.
  • mt-sDNA demonstrated superior sensitivity when compared to a commercially available FITb for detecting CRC and advanced adenomas1
  • The sensitivity of mt-sDNA for CRC of any stage was 92% (positive results in 60 of 65 cancer cases) versus 74% for FITb (positive results in 48 of 65 cancer cases)1
  • mt-sDNA can detect proximal colon cancers with 90% sensitivity (vs 67% for FIT)1

SPECIFICITY OF mt-sDNA VS FIT1,b

The image shows mt-sDNA vs. FIT specificity values on a forest-plot-like visual. The overall specificity of mt-sDNA was about 87% versus about 95% for FIT among average-risk individuals with nonadvanced adenomas, non-neoplastic findings, and negative colonoscopy results.
  • The overall specificity of mt-sDNA was 87% (vs 95% for FITb) among average-risk individuals with nonadvanced or negative findings on colonoscopy and 90% in clean colonoscopy1
  • Of 9167 patients with nonadvanced adenomas, nonneoplastic findings, and negative results on colonoscopy, 1231 (13.4%) tested falsely positive with mt-sDNA1
  • Of 4457 patients with totally negative results on colonoscopy, 455 (10.2%) tested falsely positive with mt-sDNA1
  • The overall specificity of mt-sDNA was 90% (vs 96.4% in for FITb) among average-risk individuals with negative findings on colonoscopy1
  • mt-sDNA specificity was 94% among participants younger than 65 years of age and 87% among those 65 years of age or older (P<0.001)1
  • The Act Now study evaluated the specificity of mt-sDNA in individuals aged 45-49 years4

EXTRAPOLATION OF STUDY RESULTS TO HYPOTHETICAL POPULATION AT AVERAGE RISK OF CRC1,b,h

The image shows two donut charts depicting positive and negative mt-sDNA results based on extrapolation to a hypothetical population of ten thousand participants at average risk of colorectal cancer. A main takeaway from the graphic is that 99.94% of people with negative mt-sDNA results will not have colorectal cancer on colonoscopy.
  • An extrapolation of the pivotal study results to a hypothetical reference population of 10,000 participants at average risk for CRC undergoing screening with mt-sDNA or FIT was conducted
  • 83.9% of patients would have screened negative using mt-sDNA, and 16.1% would have screened positive1
  • Of the negative patients, 99.94% would have accurately screened negative for CRC, leaving 0.06% (or 5 patients out of 10,000) that would have had a CRC missed1
  • Of the positive patients, only 3.7% would have been diagnosed with CRC, 19.9% would have had advanced precancerous lesions, 30.9% would have had nonadvanced adenomas, and 45.4% would have had no findings on diagnostic colonoscopy1
The image shows two donut charts depicting the positive and negative FIT results based on extrapolation to a hypothetical population of ten thousand participants at average risk of colorectal cancer. A main takeaway from the graphic is that 99.82% of people with a negative FIT result would not have colorectal cancer on colonoscopy.
  • 93.04% of patients would have screened negative using FIT and 6.9% would have screened positive1
  • Of the negative patients, 99.82% would have accurately screened negative for CRC, leaving 0.18% (or 17 patients out of 10,000) that would have had a CRC missed1
  • Of the positive patients, only 6.9% would have been diagnosed with CRC, 25.9% would have had advanced precancerous lesions, 31.6% would have had nonadvanced adenomas, and 35.6% would have had no findings on diagnostic colonoscopy1

Learn more about the full Indications/Contraindications for the mt-sDNA test. Please see complete prescribing information for the Cologuard® test in the Cologuard Clinician Brochure.

FIT: fecal immunochemical test; mt-sDNA: multitarget stool DNA.

Related Topics

Footnotes

  1. Multitarget colorectal cancer screening test for the Detection of Colorectal Advanced Adenomatous Polyps and Cancer (DeeP-C Study).
  2. OC FIT-CHEK, Polymedco, Inc.
  3. Done within 90 days of providing informed consent.
  4. Advanced adenoma defined as: colorectal adenoma or sessile serrated adenoma/polyp ≥1.0 cm in diameter, or adenoma with high grade dysplasia ≥25% villous component, of any size.
  5. Cologuard® test sensitivity, per stage of cancer: I: 90% (n=29); II: 100% (n=21); III: 90% (n=10); IV: 75% (n=4).
  6. Statistic calculated using data from the pivotal study and reported within the Ahlquist review article.
  7. P value is for the trend.
  8. Protocol specified the detection of CRC and advanced precancerous lesionsc as positive findings and the detection of nonadvanced adenomas as negative findings.
  9. All patients with positive results on FIT or mt-sDNA should be referred for follow-up colonoscopy.
  10. Advanced precancerous lesions were defined as: adenoma with carcinoma in situ/high-grade dysplasia, any size; adenoma, villous growth pattern (≥25%), any size; adenoma ≥1.0 cm in size; or serrated lesion, ≥1.0 cm in size.

List of definitions

AJCC: American Joint Committee on Cancer; CRC: colorectal cancer; FIT: fecal immunochemical test; mt-sDNA: multitarget stool DNA.


References

  1. Imperiale TF, Ransohoff DF, Itzkowitz SH, et al. Multitarget stool DNA testing for colorectal-cancer screening. N Engl J Med. 2014;370(14):1287-1297.
  2. Cologuard Clinician Brochure. Exact Sciences Corporation. Madison, WI.
  3. Ahlquist DA. Multi-target stool DNA test: a new high bar for noninvasive screening. Dig Dis Sci. 2015;60:623-633.
  4. Imperiale TF, Kisiel JB, Itzkowitz SH, et al. Specificity of the multi-target stool DNA test for colorectal cancer screening in average-risk 45-49 year-olds: a cross-sectional study. Cancer Prev Res (Phila). 2021;14(4):489-496.