Optimising Colorectal Cancer Patient Pathways

Optimising Patient Pathways for Earlier Detection of Colorectal Cancer in Secondary Care: Implementation of Multiple FIT Testing

Bowel cancer (colorectal cancer) is the 4th most common cancer in Scotland. Approximately 4,000 cases are diagnosed annually. Cancer-related deaths in Scotland are higher than other UK nations. Improving the early detection of bowel cancer, and therefore survival, is important.

The majority of bowel cancers are diagnosed within secondary-care (colorectal surgery unit). Upon GP referral to secondary-care, patients provide stool samples which are analysed for microscopic blood (FIT; faecal immunohistochemical test). Patients with a single positive result are more likely to have bowel cancer (0.2% risk if no blood detected, but 8.4% if detected). A positive test triggers further investigation, either CT scan or colonoscopy depending on the result. Currently, colonoscopy and radiology services throughout Scotland are under significant pressure causing delays.

Only 2% of patients referred to secondary-care are diagnosed with bowel cancer, and most colonoscopies performed do not yield significant findings. We have shown that performing two repeated FITs upon referral improves cancer pick-up rate (sensitivity) and reduces missed cancers. We successfully implemented this in NHS Lothian and contributed to national guidelines. Optimising allocation of investigations and therefore improving the detection-rate (specificity) may reduce colonoscopy demand, saving vital resources.

NHS Lothian patients referred to secondary-care with symptoms concerning of bowel cancer will be included. ~1,000 included patients will undertake extra FIT tests in study whether changes in stool blood levels over time help better allocate investigations and improve test specificity. With these results, a new secondary-care pathway will be designed. Health economic analysis will determine costs and benefits of implementing a new pathway and the risks of missed cancers. The project also provides infrastructure to collect additional stool and blood samples to develop new tests that improve bowel cancer detection.

Study Overview

• Status: Not yet recruiting
• Conditions: Colorectal Cancer; Significant Bowel Pathology
• Intervention / Treatment: Diagnostic test: Additional FIT testing

Detailed Description

Study design:

This research study will perform multiple FIT testing in a prospective cohort of patients referred through the NHS Lothian CRC USoC/urgent pathway. This pathway is co-ordinated by the Colorectal Surgery team and the Interface Triage Office ('FIT office') situated at the Western General Hospital.

Current standard patient care:

A patient with 'red-flag' lower GI symptoms presenting to their GP is referred to the CRC USoC pathway. Urgent referrals for patients with similar symptoms outwith primary care are also included.

Referrals are sent to the NHS Lothian FIT office. Receipt of referral triggers the postage of 1 FIT collection kit (Minaris Medical Co. Ltd) and information leaflet to the patient. Within a few days, a second FIT collection kit and information leaflet is sent to the patient. The patient is instructed to provide a stool sample for FIT analysis, and to hand the samples into their GP practice. The patient is instructed to leave around 4 days between 1st and 2nd sample collection.

FIT samples are sent from the GP to the UKAS accredited NHS Tayside Blood Sciences laboratory based in Ninewells Hospital (Dundee) where samples are analysed to ISO15189 standards using the HM-JACKarc analyser (Minaris Medical Co. Ltd). Results are automatically transferred from NHS Tayside to the patient's electronic health record within NHS Lothian. The NHS Lothian FIT office monitor referrals and incoming FIT results day-to-day. A follow-up call is made to the patients if 10 days elapse from postage of the FIT kit without upload of a FIT result.

The highest result of the two FITs dictates patient management. Results range from <10 to ≥400 µgHb/g. There are 3 main categories:

1. Highest FIT result <10 µgHb/g: Patient referrals are sent to Consultant Colorectal Surgeons for review - the majority of these patients receive a clinical safety netting letter, however, ~30% undergo CT colonography or colonoscopy.
2. Highest FIT result 10-79 µgHb/g: A CT colonography is requested for the patient by the NHS Lothian FIT office. Results of this are sent to the Duty Consultant Colorectal Surgeon. If the patient is young or presents with rectal bleeding, a colonoscopy is requested instead.
3. Highest FIT result ≥80 µgHb/g: If clinically appropriate (deemed by GP within referral), a colonoscopy is requested for the patient by the NHS Lothian FIT office. Results are sent to the Duty Consultant Colorectal Surgeon.

If patients have two negative results they will receive a standardised letter from the Consultant providing safety netting. Otherwise, patients will subsequently receive correspondence from the relevant department with instructions of their planned investigation e.g. colonoscopy letter and pack from Endoscopy department, or similar information pack from Radiology department. Following investigation, patients are then appropriately managed based on investigative findings by the clinical team.

Implementation of intervention:

The clinical and research teams will monitor the FIT results from USoC and urgent referrals. Patients who have provided 2 FIT samples will be included. Patients with 2 negative results (<10 µgHb/g) will be excluded.

Eligible patients will be contacted by a member of the research team after both FIT results have been returned and a clinical decision of investigation has been made by the clinical team (i.e. CT colonography or colonoscopy). If they are agreeable to take part in the study, they will be sent a research study information pack containing patient information sheets (PIS), additional FIT sample kits with instructions and a consent form with a prepaid envelope for return of consent form. The patient's GP will be sent a letter containing study details, what participation involves and any impact on clinical care.

The research study will deploy additional multiple FIT testing. Participants will be asked to provide a weekly FIT sample for 3 weeks - until they undergo colonic investigation. Patients will be advised to submit their collected stool sample to their GP for delivery to NHS Tayside, as what is carried out within the standard pathway. FIT results will be uploaded to the patient's EHR within NHS Lothian. In order to ensure adequate patient and sample recruitment, participants will be called one week into recruitment to discuss any concerns and encourage sample collection.

The additional 3 FIT results are unlikely to impact clinical care. Results will be monitored by the research team as they are received by the FIT office. Patients will continue with standard clinical care based on their 2 initial FIT results, as detailed above. Collection of samples should not be taken at the time of bowel prep for colonic investigations. There may be a small proportion of cases in which the additional FIT tests (tests 3-5) return a significantly higher FIT value than tests 1-2. This relates to a specific situation in which patients with initial FIT results of <80 µgHb/g return an additional FIT result ≥80 µgHb/g. In the first instance they would have been scheduled a CT colonography as per our USoC/urgent pathway. Upon identifying a result of ≥80 µgHb/g, the research team will contact the relevant clinician to highlight this result, and as per our clinical pathway, recommend a colonoscopy to be performed. Conversely, there will be no de-escalation of pathway management should the additional tests are lower than the initial 2 FIT tests. Patients will not be routinely informed of their additional FIT results unless they are significantly higher than tests 1-2 or if the patient contacts the research team to enquire.

Patients will be included within our study for 10-year follow-up, to allow for data collection purposes (no further intervention will take place), in particular for cancer-related outcomes.

Additional sample collection:

The prospective intervention study represents a unique opportunity to collect samples for potential biomarkers that can aid early detection. Metabolomic analysis of patient faeces and blood serum has shown to improve CRC detection. The results of faecal and plasma short chain fatty acid (SCFA) analysis and plasma lipidomics can be used in combination with traditional FIT analysis to improve overall specificity for CRC. SCFAs are by-products from the gut microbiota digestion of starches and are altered in patients with CRC. These changes are detectable in both faeces and in blood serum. Furthermore, cf- and ct-DNA has been showed to have high sensitivity in the detection of early colorectal cancer.

Symptomatic patients scheduled for colonoscopy will only be included as attendance at endoscopy provides an opportunity for additional sample collection.

Additional faecal and blood samples will be stored at -80°C in a secure location in the Colon Cancer Genetic Group laboratories at the University of Edinburgh (UoE) Institute of Genetics and Cancer (IGC). Gas chromatography will be applied to analyse SCFA/lipid structure and concentration levels within samples, which will take place at the University of Glasgow. cf- and ct-DNA analysis will take place locally at the University of Edinburgh.

Recruitment:

Our study recruitment will take place for 1 year. Recruitment figures are based on pathway data. During 2024, 2,000 symptomatic patients were referred, and had at least one positive FIT result following submission of two FITs. CRC prevalence in this cohort is 0.077%.

There are no study comparators to estimate drop-out over five tests. The RFIT return rate was 64% and 57% for two and three FITs, respectively. Furthermore, in comparison to previous research within the unit (Gerrard et al, 2023), all patients within the proposed study will have a positive FIT and awaiting investigation. Thus, participants may have invested interest in providing more samples. Local data and experience signifies the importance of a patient follow-up call to encourage sample collection, which is incorporated into the research plan.

We anticipate around 25% of patients will not meet study eligibility, answer the phone or participate. A further estimated 25% will not submit additional FIT tests. Therefore, we predict a total of ~1,000 patients to submit five FIT tests over a 1-year period (50% of relevant cohort).

• Study Type: Interventional
• Enrollment (Estimated): 1000
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Edinburgh, United Kingdom
    • NHS Lothian

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients referred to the NHS Lothian USoC CRC pathway or an urgent referral with 'red-flag' symptoms, and with a positive FIT on referral will be included.
• Referred from start date of study, for up to 1 year

Exclusion Criteria:

• Two negative FITs on referral
• Patients referred with a palpable rectal or abdominal mass
• Previous history of CRC or IBD, or under polyp surveillance
• Known to have genetic hereditary condition predisposing patient to increased risk of CRC (e.g. Lynch, FAP, etc).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Additional FIT testing; Additional (3) FITs	Diagnostic test: Additional FIT testing; Additional (3) FIT tests

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathway diagnostic accuracy	Diagnostic accuracy of multiple FIT testing pathway (sensitivity, specificity, NNI)	One year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cost-per diagnosis	Cost per diagnosis within the multiple FIT pathway	1 year
Re-referral rate	Re-referral rate to the service	2 years
Interval CRC rate	Rate of interval CRC following pathway management	2 years

Collaborators and Investigators

• Sponsor: University of Edinburgh

Publications and helpful links

General Publications

• Flahault A, Cadilhac M, Thomas G. Sample size calculation should be performed for design accuracy in diagnostic test studies. J Clin Epidemiol. 2005 Aug;58(8):859-62. doi: 10.1016/j.jclinepi.2004.12.009.
• Lin JS, Perdue LA, Henrikson NB, Bean SI, Blasi PR. Screening for Colorectal Cancer: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force. JAMA. 2021 May 18;325(19):1978-1998. doi: 10.1001/jama.2021.4417.
• Seum T, Frick C, Cardoso R, Bhardwaj M, Hoffmeister M, Brenner H. Potential of pre-diagnostic metabolomics for colorectal cancer risk assessment or early detection. NPJ Precis Oncol. 2024 Oct 27;8(1):244. doi: 10.1038/s41698-024-00732-5.
• Farkas NG, Palyvos L, O'Brien JW, Yu KS, Pigott C, Whyte M, Jourdan I, Rockall T, Fraser CG, Benton SC. The repeat FIT (RFIT) study: Does repeating faecal immunochemical tests provide reassurance and improve colorectal cancer detection? Colorectal Dis. 2024 Sep;26(9):1711-1719. doi: 10.1111/codi.17132. Epub 2024 Aug 13.
• Gerrard AD, Maeda Y, Noble C, Gunn F, Porteous L, Cheesbrough R, Thomson A, Dunlop MG, Din FVN; Edinburgh Colorectal Group. Clinical impact of double-faecal immunochemical testing following implementation into standard triage and investigation of primary care referrals in patients with lower gastrointestinal symptoms. BJS Open. 2025 Sep 8;9(5):zraf098. doi: 10.1093/bjsopen/zraf098.
• Lemmon E, Hanna C, Diernberger K, Paterson HM, Wild SH, Ennis H, Hall PS. Variation in colorectal cancer treatment and outcomes in Scotland: real world evidence from national linked administrative health data. Int J Popul Data Sci. 2024 Feb 20;9(1):2179. doi: 10.23889/ijpds.v6i1.2179. eCollection 2024.
• Farkas N, O'Brien JW, Palyvos L, Maclean W, Benton S, Rockall T, Jourdan I. The increasing burden of the 2-week wait colorectal cancer pathway in a single centre: the impact of faecal immunochemical tests. Ann R Coll Surg Engl. 2024 Apr;106(4):338-343. doi: 10.1308/rcsann.2022.0138. Epub 2023 Jan 23.
• Cubiella J, Salve M, Diaz-Ondina M, Vega P, Alves MT, Iglesias F, Sanchez E, Macia P, Blanco I, Bujanda L, Fernandez-Seara J. Diagnostic accuracy of the faecal immunochemical test for colorectal cancer in symptomatic patients: comparison with NICE and SIGN referral criteria. Colorectal Dis. 2014 Aug;16(8):O273-82. doi: 10.1111/codi.12569.
• Bailey JA, Ibrahim H, Bunce J, Chapman CJ, Morling JR, Simpson JA, Humes DJ, Banerjea A. Quantitative FIT stratification is superior to NICE referral criteria NG12 in a high-risk colorectal cancer population. Tech Coloproctol. 2021 Oct;25(10):1151-1154. doi: 10.1007/s10151-021-02466-z. Epub 2021 Jul 14.
• Pin-Vieito N, Tejido-Sandoval C, de Vicente-Bielza N, Sanchez-Gomez C, Cubiella J. Faecal immunochemical tests safely enhance rational use of resources during the assessment of suspected symptomatic colorectal cancer in primary care: systematic review and meta-analysis. Gut. 2022 May;71(5):950-960. doi: 10.1136/gutjnl-2021-324856. Epub 2021 Jun 9.
• Saw KS, Liu C, Xu W, Varghese C, Parry S, Bissett I. Faecal immunochemical test to triage patients with possible colorectal cancer symptoms: meta-analysis. Br J Surg. 2022 Feb 1;109(2):182-190. doi: 10.1093/bjs/znab411.
• Gerrard AD, Maeda Y, Miller J, Gunn F, Theodoratou E, Noble C, Porteous L, Glancy S, MacLean P, Pattenden R, Dunlop MG, Din FVN; Edinburgh Colorectal Group. Double faecal immunochemical testing in patients with symptoms suspicious of colorectal cancer. Br J Surg. 2023 Mar 30;110(4):471-480. doi: 10.1093/bjs/znad016.
• Cubiella J, Vega P, Salve M, Diaz-Ondina M, Alves MT, Quintero E, Alvarez-Sanchez V, Fernandez-Banares F, Boadas J, Campo R, Bujanda L, Clofent J, Ferrandez A, Torrealba L, Pinol V, Rodriguez-Alcalde D, Hernandez V, Fernandez-Seara J; COLONPREDICT study investigators. Development and external validation of a faecal immunochemical test-based prediction model for colorectal cancer detection in symptomatic patients. BMC Med. 2016 Aug 31;14(1):128. doi: 10.1186/s12916-016-0668-5.
• Perkmann T, Koller T, Perkmann-Nagele N, Ozsvar-Kozma M, Eyre D, Matthews P, Bown A, Stoesser N, Breyer MK, Breyer-Kohansal R, Burghuber OC, Hartl S, Aletaha D, Sieghart D, Quehenberger P, Marculescu R, Mucher P, Radakovics A, Klausberger M, Duerkop M, Holzer B, Hartmann B, Strassl R, Leitner G, Grebien F, Gerner W, Grabherr R, Wagner OF, Binder CJ, Haslacher H. Increasing test specificity without impairing sensitivity: lessons learned from SARS-CoV-2 serology. J Clin Pathol. 2023 Nov;76(11):770-777. doi: 10.1136/jcp-2022-208171. Epub 2022 Aug 30.

Helpful Links

• Cancer Research UK (CRUK). Bowel cancer statistics [Internet]. Cancer Research UK. Published 2024
• National Institute for Health and Care Research. Clinical decision support tools. [Internet]. National Institute for Health and Care Research. Published 2020

Study record dates

Study Major Dates

• Study Start (Estimated): June 30, 2026
• Primary Completion (Estimated): March 22, 2028
• Study Completion (Estimated): March 22, 2037

Study Registration Dates

• First Submitted: February 18, 2026
• First Submitted That Met QC Criteria: February 18, 2026
• First Posted (Actual): February 24, 2026

Study Record Updates

• Last Update Posted (Actual): June 3, 2026
• Last Update Submitted That Met QC Criteria: May 29, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: colorectal cancer; Diagnostic accuracy; qFIT; Multiple testing; Faecal Immunohistochemical Test
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Colorectal Neoplasms
• Other Study ID Numbers: AC26021

Drug and device information, study documents

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