Risk of cancer following primary care presentation with fatigue: a population-based cohort study of a quarter of a million patients.

Background: The management of adults presenting with fatigue presents a diagnostic challenge, particularly regarding possible underlying cancer.

Methods: Using electronic health records, we examined cancer risk in patients presenting to primary care with new-onset fatigue in England during 2007-2013, compared to general population estimates. We examined variation by age, sex, deprivation, and time following presentation.

Findings: Of 250,606 patients presenting with fatigue, 12-month cancer risk exceeded 3% in men aged 65 and over and women aged 80 and over, and 6% in men aged 80 and over. Nearly half (47%) of cancers were diagnosed within 3 months from first fatigue presentation. Site-specific cancer risk was higher than the general population for most cancers studied, with greatest relative increases for leukaemia, pancreatic and brain cancers.

Conclusions: In older patients, new-onset fatigue is associated with cancer risk exceeding current thresholds for urgent specialist referral. Future research should consider how risk is modified by the presence or absence of other signs and symptoms. Excess cancer risk wanes rapidly after 3 months, which could inform the duration of a 'safety-netting' period. Fatigue presentation is not strongly predictive of any single cancer, although certain cancers are over-represented; this knowledge can help prioritise diagnostic strategies.