16 January 2023

People presenting to GPs with fatigue in combination with a range of other ‘vague’ symptoms might indicate potential cancer, according to a new UK study.

Whilst fatigue is common, it may be among 20 ‘vague’ symptoms that together point to significant, while still small, cancer risk, depending on age and sex.

Many patients with cancer are diagnosed after presenting with vague symptoms, say Dr Becky White of University College London and colleagues in the British Journal of General Practice.

These symptoms are often “characterised by lack of organ specificity and low positive predictive value for any single cancer type”, they write.

Fatigue is reported by patients before diagnosis for a number of cancers, but its predictive value is low, as it could signal many other conditions.

The team aimed to measure cancer risk in patients with fatigue who present with other ‘vague’ symptoms in the absence of ‘alarm’ symptoms or anaemia.

The research team used UK primary care information and national cancer registries from 2007 to 2015, looking for patients with fatigue and any of 19 other ‘vague’ potential cancer symptoms.

Analysis of 285,382 patients with fatigue showed that 38% of those without alarm symptoms or anaemia had one or more vague symptoms for cancer.

In their analysis, for each of the vague symptoms in addition to fatigue, they estimated the age at which the cancer risk in the next nine months rose above 3%.

For example, the age at which risk exceed 3% is 59 years for males presenting with fatigue and weight loss, and 65 years for males presenting with fatigue and abdominal pain.

In females, risk exceeded 3% for only three symptom combinations: fatigue and weight-loss (at 65 years old), abdominal pain (at 79 years old), and abdominal bloating (at 80 years old).

Cancer risk was very low in younger patients who reported fatigue.

To conclude, the authors write: “In the absence of alarm symptoms or anaemia, fatigue combined with specific vague presenting symptoms, alongside patient age and sex, can guide clinical decisions about referral for suspected cancer.”

Dr White said: “Although tiredness is rarely caused by a life-threatening condition, our findings can help doctors decide in which cases cancer tests are necessary.”


White B, Renzi C, Barclay M, and Lyratzopoulos G (2023) “Underlying cancer risk among patients with fatigue and other vague symptoms: a population-based cohort study in primary care.” British Journal of General Practice, doi: 10.3399/BJGP.2022.0371

Link: https://bjgp.org/content/early/2023/01/09/BJGP.2022.0371

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