Act Now

The Act Now study was a prospective, cross-sectional, multicenter study of individuals aged 45-49 years at average risk for colorectal cancer (CRC).1 The primary outcome measure was to determine the specificity of the mt-sDNA test for advanced colorectal neoplasia using colonoscopy as the reference standard.

A total of 983 participants were enrolled from 31 sites across the US from November 2018 to June 2019. The mt-sDNA test demonstrated high specificity (95.2%) in this population.1

The primary aim of the Act Now prospective, cross-sectional, multicenter study was to quantify the specificity of the mt-sDNA test1

mt-sDNA demonstrated 95.2% specificity for advanced colorectal neoplasia when using colonoscopy as the reference standard (in average-risk patients, age 45-49)1

mt-sDNA specificity was 96.3% in those with negative results on colonoscopy (in average-risk patients, age 45-49)1

ACT NOW STUDY DESIGN1,a

Image summarizes the Act Now study design in three text boxes. The study design starts with participants completing the mt-sDNA screening test, then moves to participants completing a screening colonoscopy within 60 days of enrollment. After that, outcomes are assessed by comparing mt-sDNA test results with colonoscopy results.

Participant Disposition1

The image summarizes participant disposition. Of the 983 participants who provided written informed consent, 107 could not be evaluated. Of the 876 who submitted stool samples and underwent colonoscopy, 15 had their mt-sDNA tests excluded, and 19 had their colonoscopies excluded. Of the 842 included in the intent-to-screen population, 26 submitted stool samples after 72 hours and were thus excluded. 816 were included in the evaluable cohort.
  • The evaluable cohort included 816 individuals, and the mean age was 47.8 years and included 47.7% women1
  • 84% of the enrolled participants were White1
  • Participants in the enrolled, intent-to-screen, and evaluable cohorts were similar in age, sex, and race/ethnicity

mt-sDNA DEMONSTRATES HIGH SPECIFICITY IN INDIVIDUALS AGED 45-49 YEARS1

Overall Findings1,b
Total CRC APL Nonadvanced neoplasia Negative Findings
n(%)c 816 0 (0.0%) 49 (6.0%) 253 (31.0%) 514 (63.0%)
mt-sDNA positive 53 0 16 18 19
Most advanced finding Colonoscopy (n=816) mt-sDNA (n=816)d
n Positive results, n Specificity, % (95% CI)
All nonadvanced, non-neoplastice findings, and negative results on colonoscopy 767 37 95.2 (93.4-96.6)
Negative results on colonoscopy 514 19 96.3 (94.3-97.8)
  • Specificity did not differ by sex (94.9% male vs 95.4% female; P=0.75) or race (94.5% White vs 98.9% Black or African American; P=0.36 across all races)1
  • The specificity is higher (fewer false positives) in the 45–49-year-old population1 than in those 50 years and older in the DeeP-C study (87%)2
  • The higher specificity in this younger age group is in line with the expected lower prevalence of any colorectal neoplasia, lesions that cause bleeding, and lower background methylation in stool samples3
  • Limitations of the Act Now studyf include possible selection bias, most participants were White individuals, and CRC screening adherence in this cohort is not well defined1
  • The incidence and mortality of CRC in adults <50 years is increasing, making it more critical to detect CRC and precancerous lesions at early stages4

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. Standard deviation=19.4 days.
  2. Findings identified during colonoscopy.
  3. Also indicated as prevalence, used in positive predictive (PPV) and negative predictive (NPV) values.
  4. The evaluable cohort included only participants with a usable mt-sDNA and complete colonoscopy. Participants with stool samples received outside of the 72-hour mt-sDNA processing window, incomplete/not reportable colonoscopies, and other major protocol violations (inclusion/exclusion criteria not met) were excluded.
  5. Non-neoplastic findings=hyperplastic polyps, lymphoid aggregates, others.
  6. Evaluation of a Multi-target Stool DNA (mt-sDNA) Test, Cologuard®, for Colorectal Cancer Screening in Individuals Aged 45-49 and at Average Risk for Development of Colorectal Cancer (Act Now Study).

List of definitions

APL: advanced precancerous lesion; CRC: colorectal cancer; mt-sDNA: multitarget stool DNA; PPV: positive predictive value; NPV: negative predictive value.


Footnotes

  1. 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. 2021;14(4):489-496.
  2. 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.
  3. Ahlquist DA. Multi-target stool DNA test: a new high bar for noninvasive screening. Dig Dis Sci. 2015;60:623-633.
  4. Wolf AMD, Fontham ETH, Church TR, et al. Colorectal cancer screening for average-risk adults: 2018 guideline update from the American Cancer Society. CA Cancer J Clin. 2018;68(4):250-281.