Intended for healthcare professionals

Practice Uncertainties

When should unexpected weight loss warrant further investigation to exclude cancer?

BMJ 2019; 366 doi: (Published 23 September 2019) Cite this as: BMJ 2019;366:l5271
  1. Brian D Nicholson, clinical researcher1,
  2. Paul Aveyard, professor of behavioural medicine1,
  3. Willie Hamilton, professor of primary care diagnostics2,
  4. F D Richard Hobbs, Nuffield professor of primary care1
  1. 1Nuffield Department of Primary Care Health Sciences, University of Oxford OX2 6GG, UK
  2. 2Medical School, University of Exeter, UK
  1. Correspondence to: B D Nicholson brian.nicholson{at}
  2. This is one of a series of occasional articles that highlight areas of practice where management lacks convincing supporting evidence. The series advisers are Sera Tort, clinical editor, and David Tovey, editor in chief, the Cochrane Library. To suggest a topic for this series, please email us at uncertainties{at}

What you need to know

  • Unexpected weight loss can be associated with cancer, but also with a range of other conditions

  • Weight loss codes in primary care typically represent ≥5% loss within a 6 month period, but there is a lack of evidence on how much weight loss and over what time period increase the likelihood of a cancer diagnosis in primary care

  • Urgently refer people over the age of 60 years with unexpected weight loss for investigations to exclude cancer

  • The optimal diagnostic strategy to detect cancer in patients with weight loss remains unclear

Unexpected weight loss presents a diagnostic challenge in primary care. It is associated with a wide range of benign and serious conditions (box 1).1

Box 1

Differential diagnosis for patients with unexpected weight loss1

  • Cardiovascular—End stage heart failure (cardiac cachexia)

  • Endocrine—Adrenal insufficiency, diabetes, hyperthyroidism

  • Gastrointestinal—Diarrhoea, colitis, malabsorption, mesenteric ischaemia

  • Infection—Chronic infection (such as HIV, tuberculosis)

  • Malignancy—Solid tumours more likely than haematological malignancies

  • Medication—Antidepressants, antiepileptics, anxiolytics, diuretics, laxatives, stimulants

  • Neurological—Dementia, multiple sclerosis, neuromuscular disease, Parkinson’s disease, stroke

  • Psychiatric—Anorexia nervosa, anxiety, bulimia, depression

  • Renal—End stage renal failure (uraemic cachexia)

  • Respiratory—Chronic obstructive pulmonary disease (COPD), interstitial lung disease, vasculitis

  • Rheumatologic—Rheumatoid arthritis

  • Social—Excess alcohol consumption, neglect, use of opiates, poor oral health, poverty, smoking


Weight loss may be missed or misattributed because of several factors (see box 2). Once it is detected, the uncertainty for clinicians is not about whether unexpected weight loss is a symptom of concern, it is about who should be investigated further and who can be spared unnecessary investigation. Specifically, how much weight loss, over how much time, in combination with what other clinical features makes cancer sufficiently likely to warrant urgent investigation?

Box 2

Challenges in detecting weight loss in primary care

Physiological factors

  • Being overweight both increases the risk of cancer and the challenge of detecting weight loss2

  • Gradual decline in muscle mass is expected …

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