Delays in Referral from Primary Care Worsen Survival for Patients with Colorectal Cancer: A Retrospective Cohort Study
Open accessAbstract
Background: Delays in referral for patients with colorectal cancer may occur if the presenting symptom is falsely attributed to a benign condition. Aim: To investigate whether delays in referral from primary care are associated with a later stage of cancer at diagnosis and worse prognosis. Design and setting: A national retrospective cohort study in England including adult patients with colorectal cancer identified from the cancer registry with linkage to Clinical Practice Research Datalink, who had been referred following presentation to their GP with a ‘red flag’ or ‘non-specific’ symptom. Method: The hazard ratios (HR) of death were calculated for delays in referral of between 2 weeks and 3 months, and >3 months, compared with referrals within 2 weeks. Results: A total of 4527 (63.5%) patients with colon cancer and 2603 (36.5%) patients with rectal cancer were included in the study. The percentage of patients presenting with red-flag symptoms who experienced a delay of >3 months before referral was 16.9% of those with colon cancer and 13.5% of those with rectal cancer, compared with 35.7% of patients with colon cancer and 42.9% of patients with rectal cancer who presented with non-specific symptoms. Patients referred after 3 months with red-flag symptoms demonstrated a significantly worse prognosis than patients who were referred within 2 weeks (colon cancer: HR 1.53; 95% confidence interval [CI] = 1.29 to 1.81; rectal cancer: HR 1.30; 95% CI = 1.06 to 1.60). This association was not seen for patients presenting with non-specific symptoms. Delays in referral were associated with a significantly higher proportion of late-stage cancers. Conclusion: The first presentation to the GP provides a referral opportunity to identify the underlying cancer, which, if missed, is associated with a later stage in diagnosis and worse survival.
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Poor referral access can hinder patients' opportunity for proper investigations, resulting in patients waiting longer or being sent to an unsuitable specialist.
“Poor referral access can hinder patients’ opportunity for proper investigations, resulting in patients waiting longer or being sent to an unsuitable specialist [48,49].”
From Toward Safer Diagnoses: A SEIPS-Based Narrative Review of Diagnostic Errors (2026) · cites this paper as [49]
The Discussion Summary (page not provided) links delayed primary-care referral for colorectal cancer with later diagnosis and worse prognosis; the Comparison with existing literature section describes investigations after referral and a longer interval for some patients referred late. The paper does not establish that poor referral access prevents proper investigations or leads to referral to an unsuitable specialist. (LLM, conf=0.83)
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References 47 · Cited by 33
Research works printed but not linked: 43
- Coleman MP, Forman D, Bryant H, et al. Cancer survival in Australia, Canada, Denmark, Norway, Sweden, and the UK, 1995-2007 (the International Cancer Benchmarking Partnership): an analysis of population-based cancer registry data. Lancet 2011; 377(9760): 127-138.
- Neal RD, Din NU, Hamilton W, et al. Comparison of cancer diagnostic intervals before and after implementation of NICE guidelines: analysis of data from the UK General Practice Research Database. Br J Cancer 2014; 110(3): 584-592.
- Currie AC, Evans J, Smith NJ, et al. The impact of the two-week wait referral pathway on rectal cancer survival. Colorectal Dis 2012; 14(7): 848-853.
- Zafar A, Mak T, Whinnie S, Chapman MA. The 2-week wait referral system does not improve 5-year colorectal cancer survival. Colorectal Dis 2012; 14(4): e177-e180.
- Sharpe D, Williams RN, Ubhi SS, et al. The 'two-week wait' referral pathway allows prompt treatment but does not improve outcome for patients with oesophago-gastric cancer. Eur J Surg Oncol 2010; 36(10): 977-981.
- Ramos M, Esteva M, Cabeza E, et al. Relationship of diagnostic and therapeutic delay with survival in colorectal cancer: a review. Eur J Cancer 2007; 43(17): 2467-2478.
- Tørring ML, Murchie P, Hamilton W, et al. Evidence of advanced stage colorectal cancer with longer diagnostic intervals: a pooled analysis of seven primary care cohorts comprising 11 720 patients in five countries. Br J Cancer 2017; 117(6): 888-897.
- Astin M, Griffin T, Neal RD, et al. The diagnostic value of symptoms for colorectal cancer in primary care: a systematic review. Br J Gen Pract 2011; DOI: https://doi.org/10.3399/bjgp11X572427. · DOI
- Møller H, Gildea C, Meechan D, et al. Use of the English urgent referral pathway for suspected cancer and mortality in patients with cancer: cohort study. BMJ 2015; 351: h5102.
- Williams T, van Staa T, Puri S, Eaton S. Recent advances in the utility and use of the General Practice Research Database as an example of a UK Primary Care Data resource. Ther Adv Drug Saf 2012; 3(2): 89-99.
- Khan NF, Perera R, Harper S, Rose PW. Adaptation and validation of the Charlson Index for Read/OXMIS coded databases. BMC Fam Pract 2010; 11: 1.
- Crooks CJ, West J, Card TR. A comparison of the recording of comorbidity in primary and secondary care by using the Charlson Index to predict short-term and long-term survival in a routine linked data cohort. BMJ Open 2015; 5(6): e007974.
- Elliss-Brookes L, McPhail S, Ives A, et al. Routes to diagnosis for cancer: determining the patient journey using multiple routine data sets. Br J Cancer 2012; 107(8): 1220-1226.
- Din NU, Ukoumunne OC, Rubin G, et al. Age and gender variations in cancer diagnostic intervals in 15 cancers: analysis of data from the UK Clinical Practice Research Datalink. PLoS One 2015; 10(5): e0127717.
- Renzi C, Lyratzopoulos G, Card T, et al. Do colorectal cancer patients diagnosed as an emergency differ from non-emergency patients in their consultation patterns and symptoms? A longitudinal data-linkage study in England. Br J Cancer 2016; 115(7): 866-875.
- Weller D, Vedsted P, Rubin G, et al. The Aarhus statement: improving design and reporting of studies on early cancer diagnosis. Br J Cancer 2012; 106(7): 1262-1267.
- Lyratzopoulos G, Saunders CL, Abel GA, et al. The relative length of the patient and the primary care interval in patients with 28 common and rarer cancers. Br J Cancer 2015; 112(suppl 1): S35-S40.
- Lyratzopoulos G, Abel GA, McPhail S, et al. Measures of promptness of cancer diagnosis in primary care: secondary analysis of national audit data on patients with 18 common and rarer cancers. Br J Cancer 2013; 108(3): 686-690.
- Bottle A, Tsang C, Parsons C, et al. Association between patient and general practice characteristics and unplanned first-time admissions for cancer: observational study. Br J Cancer 2012; 107(8): 1213-1219.
- Herrett E, Thomas SL, Schoonen WM, et al. Validation and validity of diagnoses in the General Practice Research Database: a systematic review. Br J Clin Pharmacol 2010; 69(1): 4-14.
- Walter FM, Emery JD, Mendonca S, et al. Symptoms and patient factors associated with longer time to diagnosis for colorectal cancer: results from a prospective cohort study. Br J Cancer 2016; 115(5): 533-541.
- Price SJ, Stapley SA, Shephard E, et al. Is omission of free text records a possible source of data loss and bias in Clinical Practice Research Datalink studies? A case-control study. BMJ Open 2016; 6(5): e011664.
- Neal RD, Allgar VL, Ali N, et al. Stage, survival and delays in lung, colorectal, prostate and ovarian cancer: comparison between diagnostic routes. Br J Gen Pract 2007; 57(536): 212-219.
- Ramsay G, MacKay C, Nanthakumaran S, et al. Urgency of referral and its impact on outcome in patients with colorectal cancer. Colorectal Dis 2012; 14(7): e375-e377.
- Neal RD, Tharmanathan P, France B, et al. Is increased time to diagnosis and treatment in symptomatic cancer associated with poorer outcomes? Systematic review. Br J Cancer 2015; 112(suppl 1): S92-S107.
- Iversen LH, Antonsen S, Laurberg S, Lautrup MD. Therapeutic delay reduces survival of rectal cancer but not of colonic cancer. Br J Surg 2009; 96(10): 1183-1189.
- Tørring ML, Frydenberg M, Hamilton W, et al. Diagnostic interval and mortality in colorectal cancer: U-shaped association demonstrated for three different datasets. J Clin Epidemiol 2012; 65(6): 669-678.
- Redaniel MT, Martin RM, Ridd MJ, et al. Diagnostic intervals and its association with breast, prostate, lung and colorectal cancer survival in England: historical cohort study using the Clinical Practice Research Datalink. PLoS One 2015; 10(5): e0126608.
- Stapley S, Peters TJ, Sharp D, Hamilton W. The mortality of colorectal cancer in relation to the initial symptom at presentation to primary care and to the duration of symptoms: a cohort study using medical records. Br J Cancer 2006; 95(10): 1321-1325.
- Thompson MR, Asiimwe A, Flashman K, Tsavellas G. Is earlier referral and investigation of bowel cancer patients presenting with rectal bleeding associated with better survival? Colorectal Dis 2011; 13(11): 1242-1248.
- Singh H, Shu E, Demers A, et al. Trends in time to diagnosis of colon cancer and impact on clinical outcomes. Can J Gastroenterol 2012; 26(12): 877-880.
- Van Hout AM, de Wit NJ, Rutten FH, Peeters PH. Determinants of patient's and doctor's delay in diagnosis and treatment of colorectal cancer. Eur J Gastroenterol Hepatol 2011; 23(11): 1056-1063.
- Terhaar sive Droste JS, Oort FA, van der Hulst RW, et al. Does delay in diagnosing colorectal cancer in symptomatic patients affect tumor stage and survival? A population-based observational study. BMC Cancer 2010; 10: 332.
- Guzman Laura KP, Bolibar Ribas I, Alepuz MT. Impact on patient care time and tumor stage of a program for fast diagnosis and treatment of colorectal cancer. Rev Esp Engerm Dig 2011; 103(1): 13-19.
- Pruitt SL, Harzke AJ, Davidson NO, Schootman M. Do diagnostic and treatment delays for colorectal cancer increase risk of death? Cancer Causes Control 2013; 24(5): 961-977.
- Murchie P, Raja EA, Brewster DH, et al. Time from first presentation in primary care to treatment of symptomatic colorectal cancer: effect on disease stage and survival. Br J Cancer 2014; 111(3): 461-469.
- Jones R, Latinovic R, Charlton J, Gulliford MC. Alarm symptoms in early diagnosis of cancer in primary care: cohort study using General Practice Research Database. BMJ 2007; 334(7602): 1040.
- Alexiusdottir KK, Möller PH, Snaebjornsson P, et al. Association of symptoms of colon cancer patients with tumor location and TNM tumor stage. Scand J Gastroenterol 2012; 47(7): 795-801.
- Korsgaard M, Pedersen L, Sørensen HT, Laurberg S. Reported symptoms, diagnostic delay and stage of colorectal cancer: a population-based study in Denmark. Colorectal Dis 2006; 8(8): 688-695. British Journal of General Practice, July 2020 e470
- Dregan A, Møller H, Charlton J, Gulliford MC. Are alarm symptoms predictive of cancer survival?: population-based cohort study. Br J Gen Pract 2013; DOI: https://doi.org/10.3399/bjgp13X675197. · DOI
- Ben-Ishay O, Peled Z, Othman A, et al. Clinical presentation predicts the outcome of patients with colon cancer. World J Gastrointest Surg 2013; 5(4): 104-109.
- Barrett J, Jiwa M, Rose P, Hamilton W. Pathways to the diagnosis of colorectal cancer: an observational study in three UK cities. Fam Pract 2006; 23(1): 15-19.
- Cancer Research UK. National Cancer Diagnosis Audit. http://www. cancerresearchuk.org/health-professional/early-diagnosis-activities/national- cancer-diagnosis-audit (accessed 22 May 2020). e471 British Journal of General Practice, July 2020
- Authors
- Arhi, C. S., Burns, E. M., Bottle, A., Bouras, G., Aylin, P., Ziprin, P., & Darzi, A.
- Affiliations
- Imperial College London (GB)
- Venue
- British Journal of General Practice
- Published
- 2020-06-15
- Volume
- 70
- Issue
- 696
- Pages
- e463-e471
- ISSN
- 0960-1643 (ISSN-L)
- 1478-5242
- PMC
- PMC7299547
- OpenAlex
- W3035085994
- Cited by
- 33
- References
- 47
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 10 · 2023: 3 · 2022: 5 · 2021: 6
- FWCI
- 1.26
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- British Journal of General Practice (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Spiral (Imperial College London) (submittedVersion)
- Funders
- National Institute for Health and Care Research (NF-SI-0510-10186, NF-SI-0617-10038)
- Topics
- Health Sciences › Medicine › Oncology › Colorectal Cancer Screening and Detection
- Social Sciences › Business, Management and Accounting › Organizational Behavior and Human Resource Management › Healthcare Systems and Technology
- Health Sciences › Medicine › Oncology › Colorectal Cancer Surgical Treatments
- Keywords
- colorectal cancer, late referral, primary care, red flag symptoms, colon cancer, rectal cancer, cancer stage at diagnosis, survival, prognosis, non-specific symptoms, general practice
- MeSH terms
- Adult, England, Humans, Primary Health Care, Referral and Consultation, Retrospective Studies, Colorectal Neoplasms
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