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

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 patients with fatigue who present with other 'vague' symptoms in the absence of 'alarm' symptoms for cancer.Design and setting 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.Method Patients presenting with fatigue without co-occurring alarm symptoms or anaemia were identified, who were further characterised as having co-occurrence of 19 other 'vague' potential cancer symptoms. Sex-and age-specific 9-month cancer risk for each fatigue- vague symptom cohort were calculated.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 >= 1 of 19 vague symptoms for cancer. Cancer risk exceeded 3% in older males 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-other upper gastrointestinal symptoms. For females, 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).Conclusion 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.