The proposed study is a multicenter parallel group clinical trial that will include 821 evaluable patients per group who will be randomly assigned to either high definition white light colonoscopy (HDWLC) with targeted biopsies plus 2 random biopsies in 4 segments to assess for inflammation (limited biopsy strategy) or HDWLC with targeted biopsies plus 4 biopsies every 10 cm throughout the colon, at a minimum in all segments of the colon known to have been affected by IBD at any time, regardless of the extent of disease (random biopsy strategy). Participants will be followed until total proctocolectomy or the end of the study period to determine whether the two methods of surveillance colonoscopy are associated with detection of dysplasia or sessile serrated adenoma at follow-up colonoscopy. Follow-up via chart review may continue for up to 15 years from enrollment.

To maximize the yield of surveillance colonoscopy, minimize risk to patients, and deliver cost-effective care, it is imperative to resolve whether random biopsies are warranted for patients with long standing Inflammatory Bowel Disease (IBD) undergoing dysplasia and colorectal cancer (CRC) surveillance with high-definition white light colonoscopy (HDWLC). For this protocol, dysplasia surveillance refers to the process of identifying precancerous dysplasia, sessile serrated adenoma (SSA) or CRC. This protocol describes a pragmatic, multicenter randomized trial of patients with IBD undergoing dysplasia surveillance with HDWLC, the most common type of surveillance colonoscopy performed in the US, to definitively answer this question.

The primary objective of the study is to determine if HDWLC using a limited biopsy strategy is non-inferior to HDWLC using a random biopsy strategy to detect dysplasia or sessile serrated adenoma (SSA) in patients with IBD.

Secondary objectives include:

1. Determine if HDWLC using a limited biopsy strategy is superior to HDWLC with a random biopsy strategy to detect one or more dysplastic or SSA lesion in patients with IBD
2. Determine whether the number of targeted biopsies differs based on the number of random biopsies obtained.

Inclusion Criteria:

• Diagnosis of left-sided (greater than 15 cm of disease but not beyond the splenic flexure) or extensive (extending beyond the splenic flexure) ulcerative colitis or IBD-U or colonic Crohn's disease involving at least 1/3 of the colon (defined as 2 segments of the remaining colon; segments include right colon, transverse colon, left colon and rectum).

• Disease duration must meet one of the following criteria:

  1. onset of symptoms of IBD at least 8 years prior
  2. diagnosis of IBD at least 8 years prior
  3. diagnosis of IBD for any duration if other risk factors for colon cancer are present including: concomitant diagnosis of primary sclerosing cholangitis, personal history of dysplasia, sessile serrated adenoma or right sided hyperplastic polyps greater than 10mm in diameter, or a family history of colon cancer in a first degree relative or two second degree relatives.

• Scheduled to undergo colonoscopy as part of routine care

• At least one indication for the index colonoscopy must be to perform dysplasia surveillance.

Exclusion Criteria:

• Any condition that the endoscopist feels is a contraindication to random biopsies

• History of visible (high or low grade) dysplasia not completely removed

• History of sessile serrated adenoma not completely removed

• History of colorectal cancer

• Any condition for which the endoscopist feels that pancolonic contrast or virtual chromoendoscopy is mandatory

• Less than 2 segments of the remaining colon have ever been involved with IBD

• Colonoscopy* in the last 11 months unless the colonoscopy:

  1. was determined by the endoscopist to be insufficient for dysplasia surveillance and,
  2. did not include a diagnosis of dysplasia or sessile serrated adenoma. *Does not include sigmoidoscopy

• Inability to provide informed consent

The endoscopist will not be informed of the biopsy strategy until he/she is ready to insert the scope. Participants will not be informed of the randomization until the colonoscopy is completed.