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Unexpected weight loss

Unexpected weight loss ( UWL ) is a non-specific symptom and a decrement of 5 % or more ( in the last 6 to 12 months ) of the usual body weight is considered clinically important.


Seen in about 1.5 % of adults in primary care ( BMJ 2020 ) BMJ Best Practice quotes that the prevalence of UWL varies between 7% and 13 % -differences are due to the fact that studies vary in demographics and duration of follow up UWL recorded in primary care is associated with a broad range of cancer sites of early and late stage ( Brian D Nicholson et al 2020 ) Currently NICE threshold for referral for intensive cancer search is 3 % and the risk of undiagnosed cancer in adults with UWL alone is below 1 % National guidelines in several countries encourage early recognition -by acting on symptoms known as red flags or alarm symptoms as rectal bleeding , haemoptysis etc however half of the patients with cancer can present with non-specific symptoms such as UWL that do not point to a specific cancer site.


Poses a diagnostic challenge No formal consensus on definition of UWL or time period No national guidelines or standard practice to guide management UWL can trigger extensive investigations as clinicians fear missing a diagnosis of cancer UWL can cause considerable stress for both the patient and the clinician UWL is associated with decreased functional abilities and increased morbidity and mortality BMJ study reports that the likelihood of cancer in people with UWL is increased in the 3-6 months after the 1st report of unexpected WL compared with people without UWL BJGP reports that people who have lost more weight are more likely to have cancer than those who have lose less.


BMJ Paper – Prioritising primary care patients with unexpected weight loss for cancer investigations : diagnostic accuracy study ( BMJ 2020; 370: m2651 )


A large study involving 63 973 adults Risk of cancer in adults who present to primary care with UWL is < 2 % Males ever smokers aged 50 or older and in patients who have concurrent clinical features – further investigations should be organised as they are at increased risk of cancer Both early and late stage cancers are associated with UWL Greatest risk of cancer is from
○ unknown primary
○ pancreas , GI tract , lung , bowel or renal tract In up to 25 % of patients no diagnosis can be made after extended F/U Features positively associated with cancer in all people with UWL were
○ abdominal pain ○ loss of appetite ○ abdominal mass ○ iron deficiency anaemia
○ jaundice ○ lymphadenopathy ○ chest signs

Dysphagia , haemoptysis and non cardiac chest pain in men &
Back pain , CIBH , dyspepsia and VTE in women
 Role of blood tests in UWL patients to select who needs further investigations is poorly understood and abnormal results may
○ be poor predictor of cancer
○ be predictive across several cancer sites Several abnormal blood results in combination with UWL did show a high positive likelihood ratio values as
○ low albumin
○ raised platelets
○ raised calcium levels
○ raised WCC and raised CRP
Important to note that normal inflammatory markers had the lowest negative likelihood ratios ( negative LR describes how probablity of a disease shifts when it is absent ) In this study cancer was diagnosed in 1.4 % of the patients within 6 months of the index date, majority (97.1 % ) were > 50 or older and 99.3 % were 40 or older Most common cancer were those of lungs , bowel ,gastro-oesophagus and pancreas


 Detailed history Symptoms Ideas concerns and expectations Previous concerns / investigations Medications Psychosocial factors Alcohol / smoking Nutritional status Dementia / depression


Weight / height- BMI Focused physical examination Mental state Compare to previous recorded figures , if no baseline available – change in clothing size , information from relatives Offer bloods – beware that blood tests may not aid in deciding who needs further investigations


Unexplained loss of appetite Several cancers for e.g lung , oesophageal , stomach , pancreatic , bladder or renal . check for additional symptoms signs or findings which may point to a likely site of cancer offer urgent investigation or a suspected cancer pathway referral within 2 weeks.


Unexplained appetite loss 40 and over ever smoked-Lung or mesothelioma Offer an urgent CXR to be performed within 2 weeks



Unexplained appetite loss 40 and over and exposed to asbestos mesothelioma Offer an urgent CXR to be performed within 2 weeks


Unexplained appetite loss with cough or fatigue or SOB or chest pain or weight loss -40 and over lung or mesothelioma-urgent CXR within 2 weeks.


Women -appetite loss or persistent or frequent early satiety – particularly more than 12 times / month especially of over 50-ovarian measure CA125 if > 35-refer US of abdomen and pelvis if CA125 normal or CA125 of > 35 and US normal
○ assess for other clinical causes which may account for her symptoms and investigate if appropriate
○ advise to return if her symptoms become more frequent persistent.


Unexplained weight loss with abdominal pain > 40 colorectal-refer 2 week usc.


Unexplained weight loss without rectal bleeding , 50 and over- colorectal-offer FIT test


Weight loss with unexplained splenomegaly in adults NHL- Consider a 2-week USC Take into account any associated symptoms Referral pathways are different for children and young people Young people aged 16-24 may be referred using either pathway.


Weight loss with unexplained lymphadenopathy in adults –Hodgkin’s lymphoma or non-Hodgkin’s lymphoma. Consider a 2-week USC Take into account any associated symptoms Referral pathways are different for children and young people Young people aged 16-24 may be referred using either pathway.


Weight loss with upper andominal pain or reflux or dyspepsia-55 and over Oesophageal or stomach Offer 2 week urgent direct access upper GI endoscopy


Weight loss with diarrhoea or back pain or abdominal pain or nausea or vomiting or constipation or new onset diabetes , 60 and over pancreatic Consider an urgent direct access CT scan to be done within 
2 weeks or an urgent US scan if CT is not available


Weight loss with raised platelet count or nausea or vomiting , 55 and over oesophageal or stomach Consider non-urgent direct access upper GI endoscopy.


  1. Nicholson B DAveyard PPrice S JHobbs F RKoshiaris CHamilton W et al. Prioritising primary care patients with unexpected weight loss for cancer investigation: diagnostic accuracy study doi:10.1136/bmj.m2651
  2. Weight loss as a predictor of cancer in primary care: a systematic review and meta-analysis
    Brian D NicholsonWilliam HamiltonJack O’SullivanPaul AveyardFD Richard Hobbs
  3. Wallace JI, Schwartz RS. Epidemiology of weight loss in humans with special reference to wasting in the elderly. Int J Cardiol. 2002 Sep;85(1):15-21. doi: 10.1016/s0167-5273(02)00246-2. PMID: 12163206.
  4. Nicholson, B.D., Hamilton, W., Koshiaris, C. et al. The association between unexpected weight loss and cancer diagnosis in primary care: a matched cohort analysis of 65,000 presentations. Br J Cancer 122, 1848–1856 (2020).
  5. Suspected cancer: recognition and referral NICE guideline [NG12]Published:  Last updated:


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