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Research

Prioritising primary care patients with unexpected weight loss for cancer investigation: diagnostic accuracy study

BMJ 2020; 370 doi: https://doi.org/10.1136/bmj.m2651 (Published 13 August 2020) Cite this as: BMJ 2020;370:m2651

Linked Opinion

When does unexpected weight loss warrant cancer investigation?

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  1. Brian D Nicholson, academic clinical lecturer1,
  2. Paul Aveyard, professor of behavioural medicine1,
  3. Sarah J Price, research fellow2,
  4. FD Richard Hobbs, Nuffield professor of primary care1,
  5. Constantinos Koshiaris, medical statistician1,
  6. Willie Hamilton, professor of primary care diagnostics2
  1. 1Nuffield Department of Primary Care Health Sciences, University of Oxford, Radcliffe Observatory Quarter, Oxford OX2 6GG, UK
  2. 2Medical School, University of Exeter, Exeter, UK
  1. Correspondence to: B D Nicholson brian.nicholson{at}phc.ox.ac.uk (or @briandnicholson on Twitter)
  • Accepted 8 June 2020

Abstract

Objective To quantify the predictive value of unexpected weight loss (WL) for cancer according to patient’s age, sex, smoking status, and concurrent clinical features (symptoms, signs, and abnormal blood test results).

Design Diagnostic accuracy study.

Setting Clinical Practice Research Datalink electronic health records data linked to the National Cancer Registration and Analysis Service in primary care, England.

Participants 63 973 adults (≥18 years) with a code for unexpected WL from 1 January 2000 to 31 December 2012.

Main outcome measures Cancer diagnosis in the six months after the earliest weight loss code (index date). Codes for additional clinical features were identified in the three months before to one month after the index date. Diagnostic accuracy measures included positive and negative likelihood ratios, positive predictive values, and diagnostic odds ratios.

Results Of 63 973 adults with unexpected WL, 37 215 (58.2%) were women, 33 167 (51.8%) were aged 60 years or older, and 16 793 (26.3%) were ever smokers. 908 (1.4%) had a diagnosis of cancer within six months of the index date, of whom 882 (97.1%) were aged 50 years or older. The positive predictive value for cancer was above the 3% threshold recommended by the National Institute for Health and Care Excellence for urgent investigation in male ever smokers aged 50 years or older, but not in women at any age. 10 additional clinical features were associated with cancer in men with unexpected WL, and 11 in women. Positive likelihood ratios in men ranged from 1.86 (95% confidence interval 1.32 to 2.62) for non-cardiac chest pain to 6.10 (3.44 to 10.79) for abdominal mass, and in women from 1.62 (1.15 to 2.29) for back pain to 20.9 (10.7 to 40.9) for jaundice. Abnormal blood test results associated with cancer included low albumin levels (4.67, 4.14 to 5.27) and raised values for platelets (4.57, 3.88 to 5.38), calcium (4.28, 3.05 to 6.02), total white cell count (3.76, 3.30 to 4.28), and C reactive protein (3.59, 3.31 to 3.89). However, no normal blood test result in isolation ruled out cancer. Clinical features co-occurring with unexpected WL were associated with multiple cancer sites.

Conclusion The risk of cancer in adults with unexpected WL presenting to primary care is 2% or less and does not merit investigation under current UK guidelines. However, in male ever smokers aged 50 years or older and in patients with concurrent clinical features, the risk of cancer warrants referral for invasive investigation. Clinical features typically associated with specific cancer sites are markers of several cancer types when they occur with unexpected WL.

Footnotes

  • Contributors: BDN (principal investigator) conceived and oversaw the study, wrote the protocol, developed the code lists for use in the study, conducted the data management, conducted the statistical analysis with guidance from CK, and interpreted the statistical analysis. SJP collated the CPRD code lists for the features of cancer. BDN wrote the first draft of the manuscript. All members of the team were involved in the drafting and commenting on further revisions of the manuscript. All authors read and approved the final manuscript. BDN is the guarantor. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted.

  • Funding: This study received no specific funding. BDN was supported by National Institute for Health Research (NIHR) doctoral research fellowship (DRF-2015-08-18). PA is an NIHR senior investigator and is funded by NIHR Oxford Biomedical Research Centre (BRC) and Applied Research Collaboration (ARC). WH is co-principal investigator of the multi-institutional CanTest Research Collaborative funded by a Cancer Research UK Population Research Catalyst award (C8640/A23385). FDRH acknowledges part funding from the National Institute for Health Research (NIHR) School for Primary Care Research, the NIHR Collaboration for Leadership in Health Research and Care (CLARHC) Oxford, the NIHR Oxford BRC and ARC, and the NIHR Oxford Medtech and In-Vitro Diagnostics Co-operative (MIC). While collating the code lists used in this study, SJP was funded by Cancer Research UK funding (C56843/A21550). The views expressed are those of the authors and not necessarily those of the National Health Service, the NIHR, or the Department of Health.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

  • Ethical approval: The protocol was approved by the Independent Scientific Advisory Committee (ISAC) of the Medicines and Healthcare products Regulatory Agency (MHRA) (ISAC protocol No 16_164A2A). Ethical approval for observational research using the CPRD with approval from ISAC was granted by a National Research Ethics Service committee (Trent Multiresearch Ethics Committee, REC reference No 05/MRE04/87).

  • Data sharing: This study is based on CPRD data and is subject to a full licence agreement, which does not permit data sharing outside of the research team. Code lists are available from the corresponding author.

  • The lead author (BDN) affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

  • Preprint: This manuscript was not registered as a preprint.

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