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Underlying cancer risk among patients with fatigue and other vague symptoms in primary care: a population-based cohort study

BACKGROUND: Presenting to primary care with fatigue is associated with slightly increased cancer risk, although it is unknown how this varies in the presence of other ‘vague’ symptoms. AIM: To quantify cancer risk in fatigued patients presenting with other ‘vague’ symptoms, in the absence of ‘alarm’ symptoms for cancer DESIGN: Cohort study of patients presenting in UK primary care with new-onset fatigue during 2007-2015, using Clinical Practice Research Datalink data linked to national cancer registration data.. METHODS: We identified fatigue presenters without co-occurring alarm symptoms or anaemia, whom we further characterised for co-occurrence of 19 other ‘vague’ potential cancer symptoms. We calculated sex and age-specific nine-month cancer risk for each fatigue-vague symptom cohort. RESULTS:Of 285,382 patients presenting with new-onset fatigue, 84% (n=239,846) did not have co-occurring alarm symptoms or anaemia. Of these, 38% (n=90,828) presented with at least one of 19 vague symptoms for cancer. Cancer risk exceeded 3% in older men with fatigue combined with any of the vague symptoms studied. The age at which risk exceeded 3% was 59 years for fatigue-weight loss, 65 years for fatigue-abdominal pain, 67 years for fatigue-constipation, and 67 years for fatigue-dyspepsia. For women, risk exceeded 3% only in older patients with fatigue-weight loss (from 65 years), fatigue-abdominal pain (from 79 years), or fatigue-abdominal bloating (from 80 years). CONCLUSIONS: 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.