One in two people in Ireland will develop cancer at some point in their lives, and cancer is now our leading cause of mortality, causing almost one in three deaths in this country.^1,2,3 Survival from cancer has improved considerably in recent decades; by the end of 2020, for the first time, the number of people living after an invasive cancer diagnosis had exceeded 200,000.⁴

Approximately 50% of people with cancer will present with non-specific symptoms of cancer (NSSC), and the majority of these will present first to their GP. GPs need to be aware of the importance of NSSC and develop a strategy for managing patients who present in this way.

The crucial role of the GP in diagnosing cancer early

Diagnosing cancer early is a critical first step in achieving higher survival rates, reducing treatment severity and improving the quality of life of patients.⁵ Research undertaken during the Covid-19 pandemic suggests that, for many cancers, including those of the colorectum and lung, a three-month delay to diagnosis could reduce long-term (10-year) survival by more than 10% in most age groups.⁶

For most cancer patients, general practice is the starting point of their cancer journey. Data from the UK demonstrate that 72% of patients subsequently diagnosed with cancer first present to the GP or have a home visit. The vast majority of these, between 85%⁴ and 94%,⁷ will have at least one recorded symptom. Symptoms of cancer may be:

• Site-specific, and therefore suggestive of a particular tumour type, eg. breast lump, suggestive of breast cancer

• Non-specific (eg. weight loss, appetite loss, fatigue, pain, bloating) and therefore potentially indicative of any of multiple different tumour types.

Evidence from the UK suggests that, compared to patients with site-specific symptoms, cancer patients with non-specific symptoms have a longer diagnostic process, are more likely to present with late-stage disease, are more likely to be diagnosed via emergency presentation and have poorer disease outcomes.⁸

GPs have a key role in diagnosing cancer early. Achieving this in the 50% of cancer patients who present with NSSC symptoms⁹ represents a considerable challenge.

The challenge of NSSC in general practice

Patients with non-specific symptoms possibly indicative of cancer present two key challenges for GPs: appraising the likelihood of cancer in these patients and deciding how to manage these patients.

Appraising the likelihood of cancer in the NSSC patient

Appraising the likelihood of cancer in a patient with non-specific symptoms requires consideration of multiple factors, including disease incidence, the patient’s symptoms, signs and risk factors for cancer, as well as the GP’s own ‘gut instinct’ or clinical intuition.

Disease incidence

While symptoms possibly indicative of cancer are very common in primary care, cancer itself is relatively rare compared to the myriad self-limiting conditions that GPs encounter daily. This presents a challenge for GPs, who need to recognise and act in relation to suspected cancer. 

Approximately 24,300 invasive cancer cases are diagnosed annually in Ireland, the majority via symptomatic services, eg. Symptomatic Breast Disease Clinics, Rapid Access Lung Clinics and other outpatient services, with a relatively small proportion (25% of breast cancers, 32% of cervical cancers and 6% of colorectal cancers) diagnosed via screening.¹⁰ On average, each GP in Ireland can expect to see seven new invasive cancer cases annually, including one new case each of breast and prostate cancer. For each patient diagnosed with cancer, multiple others may require investigation and/or referral for suspected cancer.   

NSSC

There is no universally agreed definition of ‘non-specific symptoms of cancer’. Some European countries (including the UK, Norway and Denmark) have introduced dedicated rapid access referral pathways for patients with suspected cancer who present with NSSC. The ‘Core Referral Criteria’ for England’s NSSC pathway offers a guide as to which non-specific symptoms and signs could indicate cancer and may require further investigation (see Table 1).  

A 2022 systematic review examining NSSC pathways in several European countries found that 11-35% of patients referred to these pathways were diagnosed with cancer. The most commonly diagnosed cancers included haematological (14-30%), gastrointestinal (13-23%) and lung cancers (13%). Weight loss, fatigue, pain and loss of appetite were the most common symptoms prompting referral.¹²

Risk factors for cancer

Cancer can happen to anyone at any age, but certain risk factors increase the likelihood of cancer.  Awareness of these risk factors can assist GPs in identifying patients most at risk of cancer.

Non-modifiable risk factors

Older age is the single greatest risk factor for cancer, with 86% of invasive cancers in Ireland occurring in people aged 50 years and older.¹³

Genetics and family history: while most cancers are sporadic, between 5-10% are caused by inherited pathogenic gene variants.¹⁴

Past medical history: certain medical conditions are associated with increased cancer risk, eg. inflammatory bowel disease and colon cancer.

Socioeconomic deprivation: cancer incidence has been shown to be 7% higher in males and 5% higher in females living in most deprived areas of Ireland compared to those living in the least deprived areas, with a higher incidence of stomach, lung and cervical cancer in people living in most deprived areas.¹⁵

Modifiable risk factors

Approximately one in three (29.3%) invasive cancer cases in Ireland are attributable to 11 modifiable risk factors¹⁶ (see Table 2).

GP ‘gut instinct’

‘Gut instinct’ has been described as the “rapid summing up of multiple verbal and non-verbal patient cues in the context of the GPs’ clinical knowledge and experience”.¹⁷ It is an acknowledged component of clinical decision-making in primary care and a valuable diagnostic tool for cancer with a predictive value of up to 35%.¹⁷ A 2020 study evaluating NSSC pilot pathways in England found that GP ‘clinical suspicion’ was a highly significant predictor of cancer (p = 0.006).  The accuracy of ‘gut feeling’ in predicting a cancer diagnosis increases with increasing GP experience,¹⁸ age and familiarity with the patient.

Both verbal and non-verbal patient cues can trigger a ‘gut instinct’ in the GP. Verbal cues include the symptoms that the patient reports, while non-verbal cues include changes from the patient’s baseline physical appearance, consulting frequency or behaviour, including the way patient sits or speaks during the consultation.

Management patients with NSSC in primary care

Investigations

Deciding which investigation to order for patients with non-specific symptoms represents a challenge for GPs. In England, GPs are requested to undertake a suite of ‘filter function tests’ before referring patients to NSSC pathways – this comprises a useful list for GPs in Ireland to consider.

Referral

There is no dedicated ‘urgent suspected cancer’ referral pathway for patients with NSSC in Ireland. Therefore, GPs must decide whether to refer and where to refer on a case-by-case basis. If you decide to refer the patient, consider carefully which service to refer to – know your local services/pathways. Foster relationships with local hospital-based clinicians and don’t hesitate to phone them for advice.

Safety-netting 

The term ‘safety-netting’ was first coined by Roger Neighbour in 1987 as an in-consultation tool for managing diagnostic uncertainty.¹⁹ He described safety-netting as a process whereby the GP asks themselves three questions: 

• If I’m right what do I expect to happen? 

• How will I know if I am wrong?

• What would I do then?

Effective safety-netting requires clinicians to share these questions with their patients, explaining how the questions relate to their problem.²⁰ A recent literature review of safety-netting in primary care identified the following components:²¹

• Communication of uncertainty to the patient: advise the patient of the need to re-consult eg. if symptoms change or worsen. Ensure your patient understands the safety-netting advice, eg. language/health literacy barriers. It may be useful to send your patient text message reminders to reaffirm the importance of this

• Advice on worrying symptoms and ‘red flags’: this could include a description of ‘red flag’ symptoms to look out for in a patient presenting with non-specific symptoms, eg. a patient presenting with unexplained vague abdominal pain may be warned to be vigilant for rectal bleeding or diarrhoea, and to re-attend if they develop these symptoms

• The likely time course of the illness: persistent or non-resolving symptoms may warrant further investigation or consultation and may in some situations be considered ‘red flags’

• How to seek further medical care: it may not always appropriate for the GP to refer someone immediately with new symptoms or signs. Instead, an initial “watch and wait” strategy may be appropriate. In this case, patients need to be informed of:

– When to contact the GP again

– Why this is important

– How to book a follow-up appointment should their symptoms persist, worsen or change

– It may be advisable to arrange planned follow-up, eg. to monitor their progress or review results of investigations

• Primary care investigations and safety-netting: much of the safety-netting advice around cancer diagnosis focuses on investigations.²⁰ Remind patients to follow up test results and ensure that your practice has robust systems in place to review and act upon results of investigations appropriately. Don’t be overly reassured by negative/normal test results, eg. a ‘normal’ chest x-ray may miss lung cancer in up to 23% of cases.

Conclusion

Up to 50% of people with cancer will present with non-specific symptoms, and the majority of these will present first to their GP. Managing patients presenting with non-specific symptoms possibly indicative of cancer is a challenge for GPs and involves appraising the likelihood of cancer in these patients, deciding whether to undertake investigations or onward referral and engaging in safety-netting.

Further information/resources are available at:

• www.hse/cancerearlydetection

• www.hse.ie/eng/services/list/5/cancer/profinfo/resources/ 

• The HSE National Cancer Control Programme has developed an eLearning Programme on Early Diagnosis of Cancer, approved for 1 external CPD point and available via HSELanD (www.hseland.ie).

References

1. Neal RD, Din NU, Hamilton W, Ukoumunne OC, Carter B, Stapley S, Rubin G (2014). Comparison of cancer diagnostic intervals before and after implementation of NICE guidelines: analysis of data from the UK General Practice Research Database. British journal of cancer, 110(3), 584–592. https://doi.org/10.1038/bjc.2013.791
2. https://www2.hse.ie/conditions/cancer/
3. www.cso.ie
4. www.ncri.ie Annual report 2022
5. National Cancer Strategy 2017-26.  Dept of Health, Ireland. https://assets.gov.ie/9315/6f1592a09583421baa87de3a7e9cb619.pdf
6. https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(20)30392-2/fulltext
7. Swann R, McPhail S, Witt J, Shand B, Abel GA, Hiom S, Rashbass J, Lyratzopoulos G, Rubin G, National Cancer Diagnosis Audit Steering Group (2018). Diagnosing cancer in primary care: results from the National Cancer Diagnosis Audit. The British journal of general practice : the journal of the Royal College of General Practitioners, 68(666), e63–e72. https://doi.org/10.3399/bjgp17X694169
8. https://bmjopen.bmj.com/content/10/1/e033008
9. Neal RD, Din NU, Hamilton W, Ukoumunne OC, Carter B, Stapley S, Rubin G. (2014). Comparison of cancer diagnostic intervals before and after implementation of NICE guidelines: analysis of data from the UK General Practice Research Database. British journal of cancer, 110(3), 584–592. https://doi.org/10.1038/bjc.2013.791
10. https://www.ncri.ie/sites/ncri/files/pubs/Trendsreport_breast_cervical_colorectal_22092022.pdf
11. https://www.england.nhs.uk/publication/cancer-programme-faster-diagnosis-framework/
12. https://bmccancer.biomedcentral.com/articles/10.1186/s12885-022-09535-y
13. www.ncri.ie
14. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8767154/
15. Bambury N, Brennan A, McDevitt J, Walsh PM. (2023) Cancer inequalities in Ireland by deprivation, 2004- 2018: a National Cancer Registry report. NCRI, Cork, Ireland
16. Modifiable risk factors and cancer in Ireland. National Cancer Registry Ireland, 2020
17. Smith et al. Understanding the role of GPs’ gut feelings in diagnosing cancer in primary care: a systematic review and meta-analysis of existing evidence.  e612 British Journal of General Practice, September 2020
18. Donker GA, Wiersma E, van der Hoek L et al. Determinants of general practitioner’s cancer-related gut feelings—a prospective cohort study. BMJ Open 2016;6:e012511. doi:10.1136/bmjopen-2016- 012511
19. Neighbour, R. The Inner Consultation:  how to develop an effective and intuitive consulting style.  2nd edition.  CRC Press, 2015
20. Nicholson et al.  Can safety-netting improve cancer detection in patients with vague symptoms?  BMJ 2016 355
21. Jones et al. Safety netting for primary care: evidence from a literature review.  Br J Gen Pract. 2019 Jan; 69(678): e70–e79