Skip to main content

Main menu

  • HOME
  • ONLINE FIRST
  • CURRENT ISSUE
  • ALL ISSUES
  • AUTHORS & REVIEWERS
  • SUBSCRIBE
  • RESOURCES
    • About BJGP
    • Conference
    • Advertising
    • BJGP Life
    • eLetters
    • Librarian information
    • Alerts
    • Resilience
    • Video
    • Audio
    • COVID-19 Clinical Solutions
  • RCGP
    • BJGP for RCGP members
    • BJGP Open
    • RCGP eLearning
    • InnovAIT Journal
    • Jobs and careers
    • RCGP e-Portfolio

User menu

  • Subscriptions
  • Alerts
  • Log in

Search

  • Advanced search
British Journal of General Practice
  • RCGP
    • BJGP for RCGP members
    • BJGP Open
    • RCGP eLearning
    • InnovAIT Journal
    • Jobs and careers
    • RCGP e-Portfolio
  • Subscriptions
  • Alerts
  • Log in
  • Follow bjgp on Twitter
  • Visit bjgp on Facebook
  • Blog
  • Listen to BJGP podcast
Advertisement
British Journal of General Practice

Advanced Search

  • HOME
  • ONLINE FIRST
  • CURRENT ISSUE
  • ALL ISSUES
  • AUTHORS & REVIEWERS
  • SUBSCRIBE
  • RESOURCES
    • About BJGP
    • Conference
    • Advertising
    • BJGP Life
    • eLetters
    • Librarian information
    • Alerts
    • Resilience
    • Video
    • Audio
    • COVID-19 Clinical Solutions
Editorials

The elusive diagnosis of cancer: testing times

Brian D Nicholson, Rafael Perera and Matthew J Thompson
British Journal of General Practice 2018; 68 (676): 510-511. DOI: https://doi.org/10.3399/bjgp18X699461
Brian D Nicholson
Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK.
Roles: Clinical Researcher
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Rafael Perera
Nuffield Department of Primary Care Health Sciences, University of Oxford; NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust Oxford, UK.
Roles: Professor of Medical Statistics
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Matthew J Thompson
Department of Family Medicine, University of Washington, US.
Roles: Professor of Family Medicine
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Info
  • eLetters
  • PDF
Loading

This article has a correction. Please see:

  • Correction - April 01, 2019

In this issue of the BJGP, Just and colleagues question PSA testing in men with lower urinary tract symptoms (LUTS).1 Like others, they propose that the majority of cancers detected will be indolent and unrelated to the LUTS, basing their judgement on PSA screening trial data and general population LUTS surveys.2 Danish primary care data, not included by Just and colleagues, indicates that indolent prostate cancer detection increases as PSA testing increases without a corresponding change in advanced disease detection or mortality.3 Over half of UK hospitals now use multiparametric-MRI to protect men from the harms of unnecessary biopsy and treatment for indolent prostate cancer.4 The important question Just and colleagues raise is not which test should be performed once a patient is referred for suspected prostate cancer, but rather should patients with non-specific symptoms be tested in primary care and are there harms of testing them?

The myriad of urgent referral pathways, complex referral criteria, and regional variations in test and specialist access have created a complex bureaucracy for UK cancer diagnosis that has favoured patients with ‘alarm’ symptoms. Within this context, cancers with non-specific symptom signatures such as myeloma and pancreatic cancer have become associated with longer intervals between presentation and diagnosis, they are less likely to be diagnosed via urgent GP referral and more likely to be diagnosed as an emergency.5,6

But general practice is dominated by common non-specific cancer symptoms such as LUTS, abdominal pain, back pain, and fatigue. Like cancer, these symptoms increase in incidence with age and comorbidity. Our conundrum as specialist generalists has always been how to efficiently differentiate benign or self-limiting causes from more serious diseases, such as cancer, without subjecting patients to the harms of unnecessary testing or overburdening secondary care. Given the high prevalence of non-specific symptoms and the low prevalence of cancer in primary care, different approaches are necessary for patients with these symptoms.

RULING OUT CANCER NOT RULING IN CANCER

As GPs we are familiar with using tests to triage patients into further cancer investigation rather than away from it. Low haemoglobin, for example, rules-in patients for urgent colorectal investigation but a normal haemoglobin does not rule it out.7 Raised platelets are of interest to rule-in patients for investigation across a number of cancers, but normal platelets do not rule-out cancer.8 There are surprisingly few simple triage tests or test combinations that GPs can use to rule out cancer and avoid the need for further investigation, but the evidence is building.

The combination of normal inflammatory marker (ESR or plasma viscosity) and normal haemoglobin confidently rules-out myeloma in patients tested in primary care without necessitating the GP to think myeloma when requesting the test.9 Faecal immunochemical testing (FIT) shows promise as a rule-out test for colorectal cancer in patients with non-specific abdominal symptoms, but access to FIT (a cheap and simple test) remains patchy in the UK, its suggested use as both a rule-in and rule-out test is confusing,10 and the optimum analytical threshold to minimise false negatives in primary care is unclear.11

Transferring testing strategies from settings with higher (secondary care) or lower (screening) cancer prevalence should be avoided as this leads to inaccurate predictions of test performance.12 In cancer screening, for example, testing is calibrated to minimise referrals for false positive results rather than minimising false negatives. Continued analysis of primary care data should focus on identifying clusters of symptomatic and at-risk patients for whom a cancer rule-out strategy could be confidently employed. It is unlikely, though, that currently available laboratory tests will advance GPs’ rule-out ability significantly enough, and uncertainty for many cancers will remain.

EXPLAINING SYMPTOMS NOT JUST RULING IN CANCER

There is limited but increasing evidence for a move away from linear pathways to rule-in individual cancers, to more sophisticated multidisciplinary diagnostic centres (MDCs) equipped to explain the cause of non-specific symptoms. As complex healthcare interventions, MDCs intend to avoid multiple cancer site specific referrals for a heterogeneous group of patients. Reports from Danish MDCs show that cancer is diagnosed following 11% to 21% of referrals, exceeding the 8% achieved by the UK’s 2-week-wait referral pathways, and serious other disease is diagnosed in 22% to 34% of patients.13

A range of MDC models are under evaluation in the UK, some with stringent pre-referral triage testing (akin to the Danish MDCs), others with an MDC triage step following referral and prior to investigation, and some with up-front imaging then triage. MDCs have the potential to be a step beyond ‘one-stop-shop’ clinics as multiple assessments and investigations may occur in series over time and across multiple body sites, and serious or non-serious disease may be diagnosed.14 MDCs that retain responsibility for the patient until their symptoms are explained and managed are distinct from GP direct access (cancer) testing which leaves these actions to the GP.15

After years of investment in cancer site-specific urgent referral pathways, this change in thinking appeals to generalists and specialists interested in explaining symptom causation and frustrated with subspecialist silos restricted to one cancer site. But for these MDCs to function, their positioning must become established within local healthcare systems, and test access and patient flow must be liberated to allow cross-speciality referrals and shared multidisciplinary clinical responsibility. Ongoing evaluation of the optimal constellation of patient characteristics, symptoms, and pre-referral triage testing will facilitate adoption by ensuring that MDCs only accept patients who will benefit from intense investigation. One might also ask whether MDCs are filling a gap that GPs themselves could fill (given greater test access and more resources such as longer consultation times) by managing the diagnostic uncertainty inherent in primary care.

REASSURINGLY NORMAL?

Overuse of diagnostic testing occurs when the potential harms of testing outweigh the potential benefits. This overuse is regarded as a driver of overdiagnosis in primary care, but is difficult to quantify.16 In the LUTS example, more testing led to more men being diagnosed with indolent prostate cancer and more men being given the all clear. Unlike screening, a negative test in the presence of burdensome symptoms may be reassuring and reduce future primary care attendances. The counter to this is that a diagnosed cancer (that may otherwise have not caused problems) may lead to unnecessary treatment, further testing, and the psychological consequences of being given a disease label.17 We don’t fully understand how these trade-offs play out in populations of symptomatic patients.

The bureaucracy that surrounds cancer diagnosis in the UK is unfamiliar to US family physicians (FPs). For cancers without a screening programme, FPs do not refer into cancer pathways but for a long time have had relatively liberal access to cancer investigations (particularly imaging), limited mainly by healthcare insurance coverage. In the largely fee-for-service model, subspecialists in the US have incentives to see patients and investigate. However, diagnostic delays of patients with symptomatic cancer still occur. International comparisons between health systems with differing models of test access could help us to better understand where the line between over- and under-investigation lies, especially in relation to the many incidentally detected findings that modern imaging tests reveal when testing primary care patients with non- specific symptoms.

GETTING THE BALANCE RIGHT

You might ask, then, where does a GP’s expertise in clinical reasoning and diagnosis fit into a healthcare system being slowly reconfigured into a tangled web of algorithmic guidelines including known risk factors and clinical features? Clearly, testing or referring every patient presenting with non-specific symptoms is not appropriate and we should feel justified to tolerate risk to differing extents. Without tests to hand, our clinical judgement (sometimes even a reassuring gut feeling) will mean we don’t test, we watch-and-wait, or we test then monitor in primary care. These patients require appropriate and robust safety netting but, as pressures of time and workload increase in primary care, GPs report selecting patients perceived to be at higher risk for closer follow-up.18 When safety netting patients with non-specific symptoms we should be mindful to discuss the implications of our chosen testing strategy including, as Just and colleagues1 point out, the potential for overdiagnosis.

Notes

Funding

Brian D Nicholson is funded by a National Institute for Health Research (NIHR) Doctoral Research Fellowship (DRF-2015-08-18). Rafael Perera is supported by the NIHR Oxford Biomedical Research Centre. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health. Matthew J Thompson receives funding from the multi-institutional CanTest Research Collaborative funded by a Cancer Research UK Population Research Catalyst award (C8640/A23385).

Provenance

Commissioned; externally peer reviewed.

Competing interest

The authors have declared no competing interests.

  • © British Journal of General Practice 2018

REFERENCES

  1. 1.↵
    1. Just J,
    2. Osgun F,
    3. Knight C
    (2018) Br J Gen Pract, Lower urinary tract symptoms and prostate cancer: is PSA testing in men with symptoms wise? DOI: https://doi.org/10.3399/bjgp/18X699689.
  2. 2.↵
    1. Ostero IJJ,
    2. Brodersen J
    (2018) Do men with lower urinary tract symptoms have an increased risk of advanced prostate cancer? BMJ 361:k1202.
    OpenUrlFREE Full Text
  3. 3.↵
    1. Hjertholm P,
    2. Fenger-Gron M,
    3. Vestergaard M,
    4. et al.
    (2015) Variation in general practice prostate-specific antigen testing and prostate cancer outcomes: an ecological study. Int J Cancer 136(2):435–442.
    OpenUrlPubMed
  4. 4.↵
    1. Roland M,
    2. Neal D,
    3. Buckley R
    (2018) What should doctors say to men asking for a PSA test? BMJ 362:k3702.
    OpenUrlFREE Full Text
  5. 5.↵
    1. Koo MM,
    2. Hamilton W,
    3. Walter FM,
    4. et al.
    (2018) Symptom signatures and diagnostic timeliness in cancer patients: a review of current evidence. Neoplasia 20(2):165–174.
    OpenUrlCrossRefPubMed
  6. 6.↵
    1. Zhou Y,
    2. Mendonca SC,
    3. Abel GA,
    4. et al.
    (2018) Variation in ‘fast-track’ referrals for suspected cancer by patient characteristic and cancer diagnosis: evidence from 670 000 patients with cancers of 35 different sites. Br J Cancer 118(1):24–31.
    OpenUrl
  7. 7.↵
    1. Hamilton W,
    2. Lancashire R,
    3. Sharp D,
    4. et al.
    (2008) The importance of anaemia in diagnosing colorectal cancer: a case-control study using electronic primary care records. Br J Cancer 98(2):323–327.
    OpenUrlCrossRefPubMed
  8. 8.↵
    1. Bailey SE,
    2. Ukoumunne OC,
    3. Shephard EA,
    4. Hamilton W
    (2017) Br J Gen Pract, Clinical relevance of thrombocytosis in primary care: a prospective cohort study of cancer incidence using English electronic medical records and cancer registry data. DOI: https://doi.org/10.3399/bjgp17X691109.
  9. 9.↵
    1. Koshiaris C,
    2. Van den Bruel A,
    3. Oke JL,
    4. et al.
    (2018) Early detection of multiple myeloma in primary care using blood tests: a case-control study in primary care. Br J Gen Pract, https://doi.org/10.3399/bjgp18X698357.
  10. 10.↵
    1. von Wagner C,
    2. Stoffel S,
    3. Freeman M,
    4. et al.
    (2018) Attitudes towards faecal immunochemical testing in patients at increased risk of colorectal cancer: an online survey of GPs in England. Br J Gen Pract, https://doi.org/10.3399/bjgp18X699413.
  11. 11.↵
    1. Juul JS,
    2. Hornung N,
    3. Andersen B,
    4. et al.
    (2018) The value of using the faecal immunochemical test in general practice on patients presenting with non-alarm symptoms of colorectal cancer. Br J Cancer 119(4):471–479.
    OpenUrl
  12. 12.↵
    1. Usher-Smith JA,
    2. Sharp SJ,
    3. Griffin SJ
    (2016) The spectrum effect in tests for risk prediction, screening, and diagnosis. BMJ 353:i3139.
    OpenUrlFREE Full Text
  13. 13.↵
    1. Forster AS,
    2. Renzi C,
    3. Lyratzopoulos G
    (2018) Diagnosing cancer in patients with ‘non-alarm’ symptoms: Learning from diagnostic care innovations in Denmark. Cancer Epidemiol 54:101–103.
    OpenUrlCrossRefPubMed
  14. 14.↵
    1. Friedemann Smith C,
    2. Tompson A,
    3. Holtman GA,
    4. et al.
    (2018) General practitioner referrals to one-stop clinics for symptoms that could be indicative of cancer: a systematic review of use and clinical outcomes. Fam Pract doi:10.1093/fampra/cmy069.
    OpenUrlCrossRef
  15. 15.↵
    1. Friedemann Smith C,
    2. Tompson AC,
    3. Jones N,
    4. et al.
    (2018) Br J Gen Pract, Direct access cancer testing in primary care: a systematic review of use and clinical outcomes. DOI: https://doi.org/10.3399/bjgp18X698561.
  16. 16.↵
    1. Kale MS,
    2. Korenstein D
    (2018) Overdiagnosis in primary care: framing the problem and finding solutions. BMJ 362:k2820.
    OpenUrlAbstract/FREE Full Text
  17. 17.↵
    1. Nickel B,
    2. Moynihan R,
    3. Barratt A,
    4. et al.
    (2018) Renaming low risk conditions labelled as cancer. BMJ 362:k3322.
    OpenUrlFREE Full Text
  18. 18.↵
    1. Evans J,
    2. Ziebland S,
    3. MacArtney JI,
    4. et al.
    (2018) Br J Gen Pract, GPs’ understanding and practice of safety netting for potential cancer presentations: a qualitative study in primary care. DOI: https://doi.org/10.3399/bjgp18X696233.
View Abstract
Back to top
Previous ArticleNext Article

In this issue

British Journal of General Practice: 68 (676)
British Journal of General Practice
Vol. 68, Issue 676
November 2018
  • Table of Contents
  • Index by author
Download PDF
Article Alerts
Or,
sign in or create an account with your email address
Email Article

Thank you for recommending British Journal of General Practice.

NOTE: We only request your email address so that the person to whom you are recommending the page knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
The elusive diagnosis of cancer: testing times
(Your Name) has forwarded a page to you from British Journal of General Practice
(Your Name) thought you would like to see this page from British Journal of General Practice.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
The elusive diagnosis of cancer: testing times
Brian D Nicholson, Rafael Perera, Matthew J Thompson
British Journal of General Practice 2018; 68 (676): 510-511. DOI: 10.3399/bjgp18X699461

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
The elusive diagnosis of cancer: testing times
Brian D Nicholson, Rafael Perera, Matthew J Thompson
British Journal of General Practice 2018; 68 (676): 510-511. DOI: 10.3399/bjgp18X699461
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One
  • Mendeley logo Mendeley

Jump to section

  • Top
  • Article
    • RULING OUT CANCER NOT RULING IN CANCER
    • EXPLAINING SYMPTOMS NOT JUST RULING IN CANCER
    • REASSURINGLY NORMAL?
    • GETTING THE BALANCE RIGHT
    • Notes
    • REFERENCES
  • Info
  • eLetters
  • PDF

More in this TOC Section

  • COVID-19 vaccination programme: a central role for primary care
  • Time to reshape our delivery of primary care to vulnerable older adults in social housing?
  • General practice in the years ahead: relationships will matter more than ever
Show more Editorials

Related Articles

Cited By...

Advertisement

BJGP Life

BJGP Open

 

@BJGPjournal's Likes on Twitter

 
 

British Journal of General Practice

NAVIGATE

  • Home
  • Current Issue
  • All Issues
  • Online First
  • Authors & reviewers

RCGP

  • BJGP for RCGP members
  • BJGP Open
  • RCGP eLearning
  • InnovAiT Journal
  • Jobs and careers
  • RCGP e-Portfolio

MY ACCOUNT

  • RCGP members' login
  • Subscriber login
  • Activate subscription
  • Terms and conditions

NEWS AND UPDATES

  • About BJGP
  • Alerts
  • RSS feeds
  • Facebook
  • Twitter

AUTHORS & REVIEWERS

  • Submit an article
  • Writing for BJGP: research
  • Writing for BJGP: other sections
  • BJGP editorial process & policies
  • BJGP ethical guidelines
  • Peer review for BJGP

CUSTOMER SERVICES

  • Advertising
  • Contact subscription agent
  • Copyright
  • Librarian information

CONTRIBUTE

  • BJGP Life
  • eLetters
  • Feedback

CONTACT US

BJGP Journal Office
RCGP
30 Euston Square
London NW1 2FB
Tel: +44 (0)20 3188 7679
Email: journal@rcgp.org.uk

British Journal of General Practice is an editorially-independent publication of the Royal College of General Practitioners
© 2021 British Journal of General Practice

Print ISSN: 0960-1643
Online ISSN: 1478-5242