Optimal Surveillance Strategy After Positive FIT and Negative Colonoscopy

From Uncertainty to Evidence: A Randomized Controlled Trial for Optimal Surveillance in High-Risk Colonoscopy-Negative Individuals After Positive FIT

Individuals with high fecal hemoglobin concentrations detected by fecal immunochemical testing (FIT) but negative findings on high-quality colonoscopy represent a clinically challenging population. Although colonoscopy is considered the gold standard diagnostic procedure, previous studies suggest that these individuals may still have an elevated long-term risk of colorectal cancer.

This randomized controlled trial aims to determine the optimal surveillance strategy for this high-risk group by comparing two approaches: repeat FIT testing after two years versus direct colonoscopy after two years.

Study Overview

• Status: Enrolling by invitation
• Conditions: Colo-rectal Cancer; Advanced Colorectal Cancer; Fecal Immunochemical Test
• Intervention / Treatment: Diagnostic test: Colonoscopy Surveillance

Detailed Description

In colorectal cancer screening programs based on fecal immunochemical testing (FIT), a subgroup of individuals presents with strongly positive FIT results but negative findings on subsequent high-quality colonoscopy. Despite the absence of detected adenomas or cancer, these individuals may remain at increased risk of colorectal cancer.

Currently, there is no consensus guideline regarding the optimal follow-up strategy for this population. Some clinicians recommend repeat colonoscopy, while others prefer non-invasive monitoring using FIT.

This pragmatic randomized controlled trial will compare two surveillance strategies:

Repeat FIT testing two years after enrollment

Direct colonoscopy two years after enrollment

The primary objective is to compare the detection rate of advanced colorectal neoplasia (ACN) between the two strategies. The results of this study may help establish evidence-based surveillance guidelines for this high-risk population.

• Study Type: Observational
• Enrollment (Estimated): 1274

Contacts and Locations

Study Locations

• Taiwan
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

Gastroenterology outpatient clinic at National Taiwan University Hospital and Cancer Hospital

Description

Inclusion Criteria:

• Age 45-74 years
• Quantitative FIT result with fecal hemoglobin ≥100 µg/g within the past two years
• Negative high-quality colonoscopy following the positive FIT result
• Ability to provide written informed consent

Exclusion Criteria:

• History of colorectal cancer
• Inflammatory bowel disease
• Known hereditary colorectal cancer syndrome
• Life expectancy less than five years
• Inability or unwillingness to undergo colonoscopy

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
FIT Surveillance; Participants will undergo repeat fecal immunochemical testing two years after enrollment. Colonoscopy will only be recommended if the repeat FIT result is positive.	Diagnostic test: Colonoscopy Surveillance; Participants will undergo direct colonoscopy two years after enrollment regardless of FIT results.
Colonoscopy Surveillance; Participants will undergo direct colonoscopy two years after enrollment regardless of FIT results.	Diagnostic test: Colonoscopy Surveillance; Participants will undergo direct colonoscopy two years after enrollment regardless of FIT results.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Detection rate of advanced colorectal neoplasia (ACN)	ACN is defined as colorectal cancer or advanced adenoma (adenoma ≥10 mm, villous histology, or high-grade dysplasia).	2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Detection rate of any adenoma	2 years
Detection rate of colorectal cancer	2 years
Screening compliance rate	2 years
Cost-effectiveness comparison between surveillance strategies	2 years

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 10, 2026
• Primary Completion (Estimated): October 31, 2029
• Study Completion (Estimated): October 31, 2029

Study Registration Dates

• First Submitted: March 10, 2026
• First Submitted That Met QC Criteria: March 10, 2026
• First Posted (Actual): March 13, 2026

Study Record Updates

• Last Update Posted (Actual): March 13, 2026
• Last Update Submitted That Met QC Criteria: March 10, 2026
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Colonic Diseases; Colonic Neoplasms
• Other Study ID Numbers: 202508171RINA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No