Inclusion Criteria:

All Participants:

• Participant understands the study procedures and can provide informed consent to participate in the study and authorization for release of relevant personally identifiable information (PII).
• Participant is willing to provide all specimen(s) as requested.  CRC Screening Population (Cohort 1):
• Participant is at least age 40 years.
• Participant is due for a screening colonoscopy, or a follow-up colonoscopy for a positive non-invasive CRC screening test, per standard-of-care within 180 days of enrollment.  Advanced Neoplasia Population (Cohort 2):
• Participant is at least age 18 years.
• Participant has a diagnosis of CRC (any stage) confirmed with a tissue biopsy, or has a colorectal lesion estimated to be at least 10 mm in size suspicious for CRC or APL on a pre-enrollment colonoscopy, sigmoidoscopy, or computed tomography (CT) colonography.
• At the time of enrollment, the residual lesion in the colon is estimated to be at least 10 mm in size as to require additional therapeutic intervention.  Increased Risk/Surveillance Population (Cohort 3):
• Participant is at least age 18 years.
• Participant is due for a surveillance colonoscopy per healthcare provider’s advice within 60 days of enrollment.
• Participant has at least one of the following:
  • Diagnosis of a relevant familial (hereditary) cancer syndrome or other polyposis syndrome, such as Familial adenomatous polyposis (FAP or Gardner’s), Hereditary nonpolyposis colorectal cancer syndrome (HNPCC or Lynch), Peutz-Jeghers, MYH-Associated Polyposis (MAP), Turcot’s (or Crail’s), Cowden’s, Juvenile  Polyposis, Cronkhite-Canada, Neurofibromatosis, or Serrated Polyposis,
  • Diagnosis or personal history of inflammatory bowel disease (IBD) including chronic ulcerative colitis and/or Crohn’s disease
  • At least one first-degree relative diagnosed with CRC
  • Personal history of colorectal lesions requiring a repeat colonoscopy ≤6 years following their most recent colonoscopy.
  • Has experienced overt rectal bleeding (e.g., hematochezia, melena) within the previous 30 days. 

 Exclusion Criteria:

All Participants:

• Any previous cancer diagnosis (with the exceptions of basal cell or squamous cell skin cancers) or cancer-related treatment (e.g., chemotherapy, immunotherapy, radiation, and/or surgery) within the past 5 years. (Note for Cohort 2: “previous cancer diagnosis” refers to diagnosis prior to their current condition.)
• Participant has any condition that in the opinion of the Investigator should preclude participation in the study.
• Participant has enrolled in any other Exact Sciences study within the past year or has previously enrolled in this study.

CRC Screening Population (Cohort 1):

• Participant has symptoms or signs that require immediate, or near-term, referral for diagnostic or therapeutic colonoscopy.
• Participant has a personal history of CRC or APL.
• Participant has a personal diagnosis, personal history, firstdegree family history of a relevant familial (hereditary) cancer syndrome or other polyposis syndrome, such as Familial adenomatous polyposis (FAP or Gardner’s), Hereditary nonpolyposis colorectal cancer syndrome (HNPCC or Lynch), Peutz-Jeghers, MYH-Associated Polyposis (MAP), Turcot’s (or Crail’s), Cowden’s, Juvenile Polyposis, Cronkhite-Canada, Neurofibromatosis, or Serrated Polyposis.
• Participant has a diagnosis or personal history of inflammatory bowel disease (IBD) including chronic ulcerative colitis and/or Crohn’s disease.

Advanced Neoplasia Population (Cohort 2):

• Less than 7 days between pre-enrollment colonoscopy, sigmoidoscopy, or CT colonography and enrollment.

Increased Risk/Surveillance Population (Cohort 3):

• There are no additional exclusion criteria for Cohort 3

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 4/08/2025. Questions regarding updates should be directed to the study team contact.