Weight loss and cancer risk

Weight loss is a non-specific symptom posing a diagnostic challenge to clinicians in non-specialist settings such as primary care

• can be associated with several cancer and non-cancer conditions (1)
  • two main diagnostic groupings exist:
    • patients with additional clinical features, such as haemoptysis, which can focus diagnostic efforts; and
    • patients without such a pointer in whom, if cancer is suspected, the clinician must consider several possible sites (2)

Re: weight loss and cancer

• people who have lost more weight are more likely to have cancer than those who have lost less (1)
• weight loss has been previously considered as a feature of advanced cancer only - however evidence relating to weight loss and cancer state diagnosis is conflicting:
  • studies of colorectal, pancreatic, and lung cancer have reported that even people with early-stage cancer may present with weight loss (3,4,5)
  • however, there is data that shows no relationship between weight loss and stage or mortality from colorectal cancer (6)
• weight loss might occur in the period immediately before a diagnosis is established, or be a symptom that occurs well before cancer is manifest

A systematic review was undertaken relating to weight loss and cancer risk (7):

• total of 25 studies were included, with 23 (92%) using primary care records
  • of these, 20 (80%) defined weight loss as a physician’s coding of the symptom; the remainder collected data directly
  • one defined unexplained weight loss using objective measurements
  • positive associations between weight loss and cancer were found for 10 cancer sites:
    • prostate, colorectal, lung, gastro-oesophageal, pancreatic, non-Hodgkin’s lymphoma, ovarian, myeloma, renal tract, and biliary tree
    • sensitivity ranged from 2% to 47%, and specificity from 92% to 99%, across cancer sites
    • positive predictive value for cancer in male and female patients with weight loss for all age groups >= 60 years exceeded the 3% risk threshold that current UK guidance proposes for further investigation
    • risk with weight loss increases when it presents alongside another clinical feature suggesting an individual cancer site, and with increasing age
• the study authors concluded that a primary care clinician's decision to code for weight loss is highly predictive of cancer. For such patients, urgent referral pathways are justified to investigate for cancer across multiple sites

The incidence of cancer associated with weight loss was investigated in a cohort study (8):

• among 157,474 health professionals followed up for a mean of 28 years, recent weight loss of greater than 10.0% of body weight was associated with an increased rate of cancer during the next 12 months vs those without recent weight loss (1362 cancer cases/100 000 person-years vs 869 cancer cases/100 000 person-years, respectively; between-group difference, 493 cases/100 000 person-years) - an approximate 40% increased risk of cancer associated with >10% weight loss versus no weight loss
• recent weight change was calculated from the participant weights that were reported biennially
  • intentionality of weight loss was categorized as high if both physical activity and diet quality increased, medium if only 1 increased, and low if neither increased
• among participants categorized with low intentionality for weight loss, there were 2687 cancer cases/100 000 person-years for those with weight loss of greater than 10.0% of body weight compared with 1220 cancer cases/100 000 person-years for those without recent weight loss (between-group difference, 1467 cases/100 000 person-years [95% CI, 799-2135 cases/100 000 person-years]; P < .001) - an approximate 55% increased risk of cancer associated with >10% weight loss versus no weight loss
• note that in the high intentionality for weight loss group
  • for weight loss greater than 10%, there were 1459 cancer cases/100000 person-years compared with 1007 cancer cases/100 000 person years for those without recent weight loss (between group difference, 452 cases/100 000 person years (adjusted relative risk 1.30 (1.12-1.50))
• cancer of the upper gastrointestinal tract (cancer of the esophagus, stomach, liver, biliary tract, or pancreas) was particularly common among participants with recent weight loss
• study authors concluded:
  • health professionals with weight loss within the prior 2 years had a significantly higher risk of cancer during the subsequent 12 months compared with those without recent weight loss
  • cancer of the upper gastrointestinal tract was particularly common among participants with recent weight loss compared with those without recent weight loss

Reference:

1. Wong CJ. Involuntary weight loss. Med Clin North Am 2014; 98(3): 625–643.
2. Hamilton W. Five misconceptions in cancer diagnosis. BJGP 2009 DOI: https://doi.org/10.3399/bjgp09X420860.
3. Olson SH, Xu Y, Herzog K, et al. Weight loss, diabetes, fatigue, and depression preceding pancreatic cancer. Pancreas 2016; 45(7): 986–991.
4. Ewing M, Naredi P, Zhang C, Månsson J. Identification of patients with non-metastatic colorectal cancer in primary care: a case-control study. Br J Gen Pract 2016; DOI: https://doi.org/10.3399/bjgp16X687985
5. Ades AE, Biswas M, Welton NJ, Hamilton W. Symptom lead time distribution in lung cancer: natural history and prospects for early diagnosis. Int J Epidemiol 2014; 43(6): 1865–1873.
6. Stapley S, Peters TJ, Sharp D, Hamilton W. The mortality of colorectal cancer in relation to the initial symptom at presentation to primary care and to the duration of symptoms: a cohort study using medical records. Br J Cancer 2006; 95(10): 1321–1325.
7. Nicholson BD et al. Weight loss as a predictor of cancer in primary care: a systematic review and meta-analysis. BJGP 2018; 68 (670): e311-e322. DOI: https://doi.org/10.3399/bjgp18X695801
8. Wang Q, Babic A, Rosenthal MH, et al. Cancer Diagnoses After Recent Weight Loss. JAMA. 2024;331(4):318–328.