{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T18:04:16Z","timestamp":1789668256081,"version":"4.0.1"},"reference-count":31,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000272","name":"National Institute for Health and Care Research","doi-asserted-by":"publisher","award":["PR-PRU-NIHR206132"],"award-info":[{"award-number":["PR-PRU-NIHR206132"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["RCCPDF\\100005"],"award-info":[{"award-number":["RCCPDF\\100005"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIHR","award":["ARC OTV"],"award-info":[{"award-number":["ARC OTV"]}]}],"content-domain":{"domain":["www.plosmedicine.org"],"crossmark-restriction":false},"short-container-title":["PLoS Med"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Unexpected weight loss (UWL) is a non-specific cancer symptom. Abnormalities in the most recent blood test contribute to cancer referral decisions in primary care. Interpreting historical changes (trends) in blood tests could enhance discrimination for undiagnosed cancer. We aimed to assess the discrimination of blood test trend for undiagnosed cancer and compare this to that of blood test abnormality in patients presenting to primary care with UWL.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods and findings<\/jats:title>\n                    <jats:p>\n                      We conducted a retrospective cohort study of patients presenting to English primary care with UWL aged \u226518 years between 01\/01\/2000 and 31\/12\/2018 in the Clinical Practice Research Datalink. We extracted all quantitative results for 26 blood tests prior to the date of UWL. Overall and site-specific cancer diagnosis was ascertained using linked National Cancer Registrations Data. Cox models, unadjusted and adjusted for age and sex, estimated cancer risk based on blood test abnormalities (such as low albumin or raised platelets) co-occurring with UWL and joint models assessed trends in each blood test over 1-, 3-, 5-, and 10-year periods prior to UWL. The area under the curve (AUC) was used to assess discrimination, with 95% confidence intervals (CIs). Amongst 275,205 UWL patients, 5.0% (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200913,798) with cancer, the median (interquartile range (IQR)) number of blood tests per person over the 10 years ranged from 2 (IQR [12\u20133]) for 3 types of tests to 4 (IQR [2\u20137]) for 12 types of tests. The median (IQR) time between the first and last blood test per person was 5.2 (IQR [1.5\u20138.2]) years cases and 4.3 (IQR [1.0\u20137.7]) years for those cancer-free. The median time between the last blood test and UWL per person was 0.1 (IQR [0.0\u20130.6]) years for cases and 0.3 (IQR [0.0\u20131.1]) years for those cancer-free. Adjusted blood test abnormalities and trends were more discriminative than the unadjusted equivalent. Adjustment resulted in higher AUCs for trend compared to the equivalent blood test abnormality on 34 occasions, with highest AUC of 0.82 (95% CI [0.81, 0.83]). This included 26 trends for cancer overall, mean cell volume trend for bowel cancer and lymphoma, white blood count and neutrophil trend for lung cancer, and aspartate aminotransferase, red blood cell count, haematocrit, and platelet-to-lymphocyte ratio trend for prostate cancer. A limitation of our modelling strategy is that it did not take into account the bias in who was tested and our trend analysis was also restricted to patients with 2 or more tests in each trend window.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Blood test abnormalities should be interpreted after age and sex adjustment to improve triage for cancer investigation in patients attending primary care with UWL. Evaluating historical trend offers further discrimination after adjustment for some test-cancer combinations.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pmed.1004956","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T17:22:43Z","timestamp":1789665763000},"page":"e1004956","update-policy":"https:\/\/doi.org\/10.1371\/journal.pmed.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Blood test trend versus single threshold abnormality to discriminate cancer from non-cancer in patients with unexpected weight loss: A retrospective cohort study"],"prefix":"10.1371","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0661-7362","authenticated-orcid":true,"given":"Brian D.","family":"Nicholson","sequence":"first","affiliation":[{"name":"University of Oxford","place":["Oxford, United Kingdom"],"department":["Nuffield Department of Primary Care Health Sciences"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1588-3849","authenticated-orcid":true,"given":"Clare R.","family":"Bankhead","sequence":"additional","affiliation":[{"name":"University of Oxford","place":["Oxford, United Kingdom"],"department":["Nuffield Department of Primary Care Health Sciences"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1298-3905","authenticated-orcid":true,"given":"Sufen","family":"Zhu","sequence":"additional","affiliation":[{"name":"University of Oxford","place":["Oxford, United Kingdom"],"department":["Nuffield Department of Primary Care Health Sciences"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason Lee","family":"Oke","sequence":"additional","affiliation":[{"name":"University of Oxford","place":["Oxford, United Kingdom"],"department":["Nuffield Department of Primary Care Health Sciences"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7196-1509","authenticated-orcid":true,"given":"Cynthia","family":"Wright Drakesmith","sequence":"additional","affiliation":[{"name":"University of Oxford","place":["Oxford, United Kingdom"],"department":["Nuffield Department of Primary Care Health Sciences"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"Perera","sequence":"additional","affiliation":[{"name":"University of Oxford","place":["Oxford, United Kingdom"],"department":["Nuffield Department of Primary Care Health Sciences"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7976-7172","authenticated-orcid":true,"given":"Frederick D. Richard","family":"Hobbs","sequence":"additional","affiliation":[{"name":"University of Oxford","place":["Oxford, United Kingdom"],"department":["Nuffield Department of Primary Care Health Sciences"]},{"name":"Oxford Institute of Digital Health","place":["Oxford, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3006-8730","authenticated-orcid":true,"given":"Pradeep S.","family":"Virdee","sequence":"additional","affiliation":[{"name":"University of Oxford","place":["Oxford, United Kingdom"],"department":["Nuffield Department of Primary Care Health Sciences"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,9,17]]},"reference":[{"key":"pmed.1004956.ref001","author":"NICE","year":"2020"},{"key":"pmed.1004956.ref002","article-title":"Blood markers for cancer","volume":"367","author":"J Watson","year":"2019","journal-title":"BMJ"},{"issue":"7","key":"pmed.1004956.ref003","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pmed.1004426","article-title":"Predictive value of abnormal blood tests for detecting cancer in primary care patients with nonspecific abdominal symptoms: a population-based cohort study of 477,870 patients in England","volume":"21","author":"M Rafiq","year":"2024","journal-title":"PLoS Med"},{"key":"pmed.1004956.ref004","article-title":"Prioritising primary care patients with unexpected weight loss for cancer investigation: diagnostic accuracy study (update)","volume":"387","author":"BD Nicholson","year":"2024","journal-title":"BMJ"},{"key":"pmed.1004956.ref005","article-title":"Combining symptoms and blood tests to enhance risk stratification of cancer in patients presenting with unexpected weight loss: a prediction model derivation and validation study using English primary care data","author":"BD Nicholson","year":"2025","journal-title":"Preprints with The Lancet"},{"issue":"1","key":"pmed.1004956.ref006","doi-asserted-by":"crossref","DOI":"10.1136\/bmjopen-2019-033008","article-title":"Cross-sectional study using primary care and cancer registration data to investigate patients with cancer presenting with non-specific symptoms","volume":"10","author":"C Pearson","year":"2020","journal-title":"BMJ Open"},{"issue":"4","key":"pmed.1004956.ref007","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/S1470-2045(12)70041-4","article-title":"Variation in number of general practitioner consultations before hospital referral for cancer: findings from the 2010 National Cancer Patient Experience Survey in England","volume":"13","author":"G Lyratzopoulos","year":"2012","journal-title":"Lancet Oncol"},{"issue":"7","key":"pmed.1004956.ref008","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1038\/bjc.2016.250","article-title":"Do colorectal cancer patients diagnosed as an emergency differ from non-emergency patients in their consultation patterns and symptoms? 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