Secondary Care Colorectal Cancer Pathway Review

Official title

A Retrospective Review of the Secondary-care Colorectal Cancer Pathway Within NHS Lothian: An Evaluation of 3 Years of Pathway Performance

Overview

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 pickup rate (sensitivity) and reduces missed cancers. We successfully implemented this in NHS Lothian and contributed to national guidelines. This study will undertake a comprehensive retrospective review of the double-FIT urgent suspicion of bowel cancer pathway within NHS Lothian, from April 2022 (date of pathway inception) to August 2025, including around 25,000 patients that have been managed through the pathway. We will calculate key performance indicators and diagnostic accuracy of the pathway. Health economic analysis will determine cost-per-diagnosis. Risk factors for bowel cancer in this patient cohort will be identified to develop a support tool for primary and secondary-care. These results will be used to develop a future pathway to optimise pathway efficiency and cancer detection.

Detailed description

Design:

This is a retrospective observational cohort data-analysis study of patients managed within the NHS Lothian colorectal cancer (CRC) urgent suspicion of cancer (USoC) pathway and patients referred urgently to the Colorectal department from April 2022 to August 2025. April 2022 corresponds to the start of double FIT testing within the pathway. 5-year follow-up will be included (up to August 2030) to include 5-year cancer outcomes.

Methods:

Patients will be identified from our pathway. Estimated \~25,000 patients will be included. Data will be collected on patient characteristics, past medical and prescribing history, hospital presentations and investigation outcomes, cancer outcomes and mortality data. Linkage to relevant patient datasets will be required.

A service review of the USoC/urgent pathway will focus on key performance indicators such as time to diagnosis and treatment, as well as patient journey pathways (Sankey plots) and re-referral rates.

Furthermore, data will be analysed using standard methods such as odds-ratio multivariate logistic regression to determine any significant associations which enrich for CRC and significant bowel pathology in this patient group. Significant bowel pathology includes advanced adenoma, advanced colorectal neoplasia and inflammatory bowel disease (IBD). Importantly, the modelling will only utilise readily available information from the electronic health record (EHR) such as age, sex, blood haemoglobin, BMI and SIMD to improve pre-test probability by restricting the target population.

Markov models will be formed as part of the health economic analysis, and the financial cost per case detected within the pathway will be calculated. We will explore the impact of waiting times on disease progression and the associated impact on the financial costs of treatment and patient quality of life.

Results from the above analyses will be incorporated into a decision-flow as guidance for referrals to secondary-care.

Sample size calculation:

To perform regression analysis, at a significance level of 0.05, medium size effect and 10 predictors, 170 cases of CRC are required. Our database of \~25,000 patients has approximately 500 cases of CRC. There will be minimal anticipated drop-out. Therefore our required sample size will be achievable.22

Proposed analyses:

Standard summary statistics of the pathway will be reported (means, standard deviations, medians, inter-quartile range). Multivariate logistic regression will be performed to determine risk-factors significant for CRC at different FIT levels. Subgroup analyses will take place within different FIT result thresholds (\<10, 10-79, \>79 µgHb/g) as well as between cancer and non-cancer patients, and for other significant bowel pathology. Long-term outcome data will be analysed, up to 5 years.

Furthermore, a service evaluation of the USoC/urgent pathway will focus on key performance indicators such as time to diagnosis and treatment, as well as patient journey pathways (Sankey plots) and re-referral rates. Markov models will be formed as part of the health economic analysis, and the financial cost per case detected within the pathway will be calculated. We will explore the impact of waiting times on disease progression and the associated impact on the financial costs of treatment and patient quality of life. The rate of interval cancers over long-term follow-up will be calculated.

We do not anticipate a significant amount of missing data. Data entries will be removed due to missing data on an analysis-by-analysis basis.

Interventions

• Diagnostic test Faecal Immunohistochemical test
  Faecal Immunohistochemical test

Primary outcome measures

• Pathway diagnostic accuracy [Time frame: 1 year]

Secondary outcome measures (1)

• Cost per diagnosis [Time frame: 1 year]

Eligibility criteria

Inclusion criteria

Patients managed within the NHS Lothian CRC USoC/urgent pathway (including urgent referrals) due to 'red-flag' symptoms concerning of CRC from April 2022 to August 2025.

Exclusion criteria

• Under the age of 18.
• History of inflammatory bowel disease.
• Under polyp surveillance.
• Previous diagnosis of CRC.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Observational model

Cohort

Study locations

United Kingdom · 1 center

• NHS Lothian — Edinburgh

Publications

• 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 PMID 36041815
• 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 sympt PMID 27580745
• 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. PMID 36785496
• 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. PMID 34907419
• 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. PMID 34108236
• 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. PMID 34263362
• 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. PMID 24456168
• 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. PMID 36688865

Identifiers

NCT: NCT07430527 · AC26020

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗