Abstract
BackgroundThe management of adults presenting with fatigue presents a diagnostic challenge, particularly regarding possible underlying cancer.MethodsUsing 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.FindingsOf 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.ConclusionsIn 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.
Highlights
The management of adults presenting with fatigue presents a diagnostic challenge, regarding possible underlying cancer
The range of cancer sites associated with fatigue and their relative specific risk is not adequately described in current literature, which is dominated by studies focusing on individual cancer sites
Cohort description Of the 278,821 individuals who had a record of fatigue in primary care between 2007 and 2013, 250,606 (90%) had at least one ‘eligible’ record within the patient’s inclusion period, without either a cancer diagnosis or an ‘ineligible’ fatigue record in the previous year (Fig. 1)
Summary
The management of adults presenting with fatigue presents a diagnostic challenge, regarding possible underlying cancer. Cancer patients least likely to be diagnosed following fast-track referral are those with cancers typically characterised by such non-site specific presenting symptoms (e.g. fatigue, weight loss etc.), which have low positive predictive value (PPV) for any single cancer [3]. These patients often experience prolonged intervals before diagnosis [2]. Diagnostic guidelines by the National Institute for Health and Care Excellence (NICE) regarding fatigue recommend urgent 2-week-wait referral only for specific presentations where available evidence shows the positive predictive value (PPV) for specific cancer diagnosis (usually within 12 months) exceeds 3% [12,13,14]. As a relatively common symptom, fatigue can signal a range of other conditions, including but not limited to: self-limiting illnesses (e.g. short-term post-viral fatigue); chronic fatigue syndrome; depression; a range of other diseases (e.g. hypothyroidism, vitamin deficiency, iron deficiency, coeliac disease etc.); and more rarely, autoimmune disease such as lupus or chronic infection such as hepatitis C [5, 18,19,20,21]
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