{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T11:20:20Z","timestamp":1788175220187,"version":"build-2803163510"},"reference-count":25,"publisher":"Walter de Gruyter GmbH","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Cancer screening has been at the forefront of the war against cancer for decades. Yet professional organizations such as the U.S. Preventive Services Task Force (USPSTF) recommend cancer screening for only a handful of cancers (cervical, lung, colon, breast, prostate). Screening for other serious cancers (ovarian, pancreatic, etc.) is not recommended, at least for individuals with low\/moderate risk. The discovery of circulating tumor DNA (ctDNA) as a non-invasive biomarker for diverse cancers prompted many companies to develop screening tests for one or more cancer types. Particularly, one test, known as \u201cthe Galleri test\u201d, marketed by Grail Inc., combined with standard of care, claims to be able to detect simultaneously 40\u201350 cancer types, thus potentially reducing costs. The literature on the clinical effectiveness of this test is currently controversial. Here, we comment on the results of a randomized trial that is currently ongoing in the United\u00a0Kingdom, evaluating the ability of the test to meet its primary clinical endpoint. Analysis of these new data showed that the primary endpoint of the trial, aiming to reduce the incidence of stage III-IV cancer by at least 20\u202f%, was missed. The trial is still ongoing.<\/jats:p>","DOI":"10.1515\/dx-2026-0055","type":"journal-article","created":{"date-parts":[[2026,4,26]],"date-time":"2026-04-26T04:05:16Z","timestamp":1777176316000},"page":"406-409","source":"Crossref","is-referenced-by-count":0,"title":["Failure of the Galleri multi-cancer detection trial to meet its primary endpoint"],"prefix":"10.1515","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1589-820X","authenticated-orcid":false,"given":"Eleftherios P.","family":"Diamandis","sequence":"first","affiliation":[{"name":"Lunenfeld-Tanenbaum Research Institute (LTRI) , Toronto , ON , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2026,4,21]]},"reference":[{"key":"2026083110583465167_j_dx-2026-0055_ref_001","doi-asserted-by":"crossref","unstructured":"Aravanis, AM, Lee, M, Klausner, RD. Next-generation sequencing of circulating tumor DNA for early cancer detection. Cell 2017;168:571\u20134. https:\/\/doi.org\/10.1016\/j.cell.2017.01.030.","DOI":"10.1016\/j.cell.2017.01.030"},{"key":"2026083110583465167_j_dx-2026-0055_ref_002","doi-asserted-by":"crossref","unstructured":"Schrag, D, Beer, TM, McDonnell, CH, Nadauld, L, Dilaveri, CA, Reid, R, et al.. Blood-based tests for multicancer early detection (PATHFINDER): a prospective cohort study. Lancet 2023;402:1251\u201360. https:\/\/doi.org\/10.1016\/s0140-6736(23)01700-2.","DOI":"10.1016\/S0140-6736(23)01700-2"},{"key":"2026083110583465167_j_dx-2026-0055_ref_003","doi-asserted-by":"crossref","unstructured":"Jamshidi, A, Liu, MC, Klein, EA, Venn, O, Hubbell, E, Beausang, JF, et al.. Evaluation of cell-free DNA approaches for multi-cancer early detection. Cancer Cell 2022;40:1537\u201349.e12. https:\/\/doi.org\/10.1016\/j.ccell.2022.10.022.","DOI":"10.1016\/j.ccell.2022.10.022"},{"key":"2026083110583465167_j_dx-2026-0055_ref_004","doi-asserted-by":"crossref","unstructured":"O\u2019Donnell, EK, Kauffman, TL, Asnis, S, Kelly, VA, Matthews, E, Kartsounis, M, et al.. Diagnostic outcomes among patients with positive multi-cancer early detection test results. Cancer Res Commun 2026;6:511\u20135. https:\/\/doi.org\/10.1158\/2767-9764.CRC-25-0723.","DOI":"10.1158\/2767-9764.CRC-25-0723"},{"key":"2026083110583465167_j_dx-2026-0055_ref_005","doi-asserted-by":"crossref","unstructured":"Matrana, M, Shukla, V, Kingsbury, D, Poliak, M, Lipton, J, McMillin, M, et al.. Real-world data and clinical experience from over 100,000\u00a0multi-cancer early detection tests. Nat Commun 2025;16:9625. https:\/\/doi.org\/10.1038\/s41467-025-64094-7.","DOI":"10.1038\/s41467-025-64094-7"},{"key":"2026083110583465167_j_dx-2026-0055_ref_006","doi-asserted-by":"crossref","unstructured":"Kahwati, LC, Avenarius, M, Brouwer, L, Crossnohere, NL, Doubeni, CA, Miller, C, et al.. Multicancer detection tests for screening: a systematic review. Ann Intern Med 2025;178:1591\u2013604. https:\/\/doi.org\/10.7326\/annals-25-01877.","DOI":"10.7326\/ANNALS-25-01877"},{"key":"2026083110583465167_j_dx-2026-0055_ref_007","doi-asserted-by":"crossref","unstructured":"Sasieni, P, Swanton, C, Neal, RD. The National Health Service-Galleri multicancer screening trial: explanation and justification of unique and important design issues. J\u00a0Natl Cancer Inst 2025;118:573\u20138. djaf218. https:\/\/doi.org\/10.1093\/jnci\/djaf218.","DOI":"10.1093\/jnci\/djaf218"},{"key":"2026083110583465167_j_dx-2026-0055_ref_008","doi-asserted-by":"crossref","unstructured":"Diamandis, EP. Cancer biomarkers: can we turn recent failures into success? J\u00a0Natl Cancer Inst 2010;102:1462\u20137. https:\/\/doi.org\/10.1093\/jnci\/djq306.","DOI":"10.1093\/jnci\/djq306"},{"key":"2026083110583465167_j_dx-2026-0055_ref_009","doi-asserted-by":"crossref","unstructured":"Cramer, DW, Bast, RC, Berg, CD, Diamandis, EP, Godwin, AK, Hartge, P, et al.. Ovarian cancer biomarker performance in prostate, lung, colorectal, and ovarian cancer screening trial specimens. Cancer Prev Res 2011;4:365\u201374. https:\/\/doi.org\/10.1158\/1940-6207.capr-10-0195.","DOI":"10.1158\/1940-6207.CAPR-10-0195"},{"key":"2026083110583465167_j_dx-2026-0055_ref_010","doi-asserted-by":"crossref","unstructured":"Fiala, C, Diamandis, EP. Utility of circulating tumor DNA in cancer diagnostics with emphasis on early detection. BMC Med 2018;16:166. https:\/\/doi.org\/10.1186\/s12916-018-1157-9.","DOI":"10.1186\/s12916-018-1157-9"},{"key":"2026083110583465167_j_dx-2026-0055_ref_011","doi-asserted-by":"crossref","unstructured":"Fiala, C, Diamandis, EP. Cell-free DNA analysis in cancer. N\u00a0Engl J Med 2019;380:501. https:\/\/doi.org\/10.1056\/NEJMc1816154.","DOI":"10.1056\/NEJMc1816154"},{"key":"2026083110583465167_j_dx-2026-0055_ref_012","doi-asserted-by":"crossref","unstructured":"Fiala, C, Diamandis, EP. A multi-cancer detection test: focus on the positive predictive value. Ann Oncol 2020;31:1267\u20138. https:\/\/doi.org\/10.1016\/j.annonc.2020.05.028.","DOI":"10.1016\/j.annonc.2020.05.028"},{"key":"2026083110583465167_j_dx-2026-0055_ref_013","doi-asserted-by":"crossref","unstructured":"Robbins, HA. Multicancer early detection tests\u00a0\u2013\u00a0keeping a high bar for evidence of benefit. N\u00a0Engl J Med 2024;391:292\u20134. https:\/\/doi.org\/10.1056\/nejmp2400297.","DOI":"10.1056\/NEJMp2400297"},{"key":"2026083110583465167_j_dx-2026-0055_ref_014","doi-asserted-by":"crossref","unstructured":"McCartney, M, Cohen, D. Galleri promises to detect multiple cancers\u00a0\u2013\u00a0but new evidence casts doubt on this much hyped blood test. BMJ 2024;386:q1706. https:\/\/doi.org\/10.1136\/bmj.q1706.","DOI":"10.1136\/bmj.q1706"},{"key":"2026083110583465167_j_dx-2026-0055_ref_015","doi-asserted-by":"crossref","unstructured":"Gogebakan, KC, Lange, J, Owens, L, Pinderup, A, Gulati, R, Kessler, LG, et al.. Clinical significance of a multicancer screening trial with stage-based end points. JAMA Netw Open 2025;8:e2536247. https:\/\/doi.org\/10.1001\/jamanetworkopen.2025.36247.","DOI":"10.1001\/jamanetworkopen.2025.36247"},{"key":"2026083110583465167_j_dx-2026-0055_ref_016","doi-asserted-by":"crossref","unstructured":"Fiala, C, Diamandis, EP. Can a broad molecular screen based on circulating tumor DNA aid in early cancer detection? J\u00a0Appl Lab Med 2020;5:1372\u20137. https:\/\/doi.org\/10.1093\/jalm\/jfaa138.","DOI":"10.1093\/jalm\/jfaa138"},{"key":"2026083110583465167_j_dx-2026-0055_ref_017","doi-asserted-by":"crossref","unstructured":"Fiala, C, Diamandis, EP. Can grail find the trail to early cancer detection? Clin Chem Lab Med 2019;57:403\u20136. https:\/\/doi.org\/10.1515\/cclm-2018-1249.","DOI":"10.1515\/cclm-2018-1249"},{"key":"2026083110583465167_j_dx-2026-0055_ref_018","unstructured":"GRAIL PATHFINDER 2 results show galleri multi-cancer early detection blood test increased cancer detection more than seven-fold when added to USPSTF A and B recommended screenings [internet]. Grail 2025 [Accessed 2026 Feb 24]. https:\/\/grail.com\/press-releases\/grail-pathfinder-2-results-show-galleri-multi-cancer-early-detection-blood-test-increased-cancer-detection-more-than-seven-fold-when-added-to-uspstf-a-and-b-recommended-screenings\/."},{"key":"2026083110583465167_j_dx-2026-0055_ref_019","unstructured":"Landmark NHS-galleri trial demonstrates a substantial reduction in stage IV cnacer diagnoses, increased stage I and II detection of deadly cancers, and four-fold higher cancer detection rate [internet]. PR Newswire 2026. [cited 2026 Feb 2024]. Available from: https:\/\/www.prnewswire.com\/news-releases\/landmark-nhs-galleri-trial-demonstrates-a-substantial-reduction-in-stage-iv-cancer-diagnoses-increased-stage-i-and-ii-detection-of-deadly-cancers-and-four-fold-higher-cancer-detection-rate-302693013.html."},{"key":"2026083110583465167_j_dx-2026-0055_ref_020","doi-asserted-by":"crossref","unstructured":"Fernandez-Uriarte, A, Pons-Belda, OD, Diamandis, EP. Cancer screening companies are rapidly proliferating: are they ready for business? Cancer Epidemiol Biomarkers Prev 2022;31:1146\u201350. https:\/\/doi.org\/10.1158\/1055-9965.epi-22-0102.","DOI":"10.1158\/1055-9965.EPI-22-0102"},{"key":"2026083110583465167_j_dx-2026-0055_ref_021","doi-asserted-by":"crossref","unstructured":"Papanastasiou, AP, Chatanaka, MK, Diamandis, EP. Comparison of\u00a0liquid biopsy-based technologies for cancer screening. Crit Rev Clin Lab Sci 2025:1\u201312. https:\/\/doi.org\/10.1080\/10408363.2025.2606357.","DOI":"10.1080\/10408363.2025.2606357"},{"key":"2026083110583465167_j_dx-2026-0055_ref_022","doi-asserted-by":"crossref","unstructured":"Diamandis, EP, Li, M. The side effects of translational omics: overtesting, overdiagnosis, overtreatment. Clin Chem Lab Med 2016;54:389\u201396. https:\/\/doi.org\/10.1515\/cclm-2015-0762.","DOI":"10.1515\/cclm-2015-0762"},{"key":"2026083110583465167_j_dx-2026-0055_ref_023","unstructured":"Wilson, JMG, Jungner, G. Principles and practice of screening for disease. Geneva, Switzerland: World Health Organization; 1968."},{"key":"2026083110583465167_j_dx-2026-0055_ref_024","doi-asserted-by":"crossref","unstructured":"Bretthauer, M, Wieszczy, P, L\u00f8berg, M, Kaminski, MF, Werner, TF, Helsingen, LM, et al.. Estimated lifetime gained with cancer screening tests: a meta-analysis of randomized clinical trials. JAMA Intern Med 2023;183:1196\u2013203. https:\/\/doi.org\/10.1001\/jamainternmed.2023.3798.","DOI":"10.1001\/jamainternmed.2023.3798"},{"key":"2026083110583465167_j_dx-2026-0055_ref_025","doi-asserted-by":"crossref","unstructured":"Chatanaka, MK, Yousef, GM, Diamandis, EP. The unholy grail of cancer\u00a0screening: or is it just about the benjamins? Clin Chem Lab Med 2024;63:499\u2013506. https:\/\/doi.org\/10.1515\/cclm-2025-0531. Erratum in: Clin Chem Lab Med. 2025;63:1888.","DOI":"10.1515\/cclm-2024-1013"}],"container-title":["Diagnosis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.degruyterbrill.com\/document\/doi\/10.1515\/dx-2026-0055\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.degruyterbrill.com\/document\/doi\/10.1515\/dx-2026-0055\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T11:01:24Z","timestamp":1788174084000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.degruyterbrill.com\/document\/doi\/10.1515\/dx-2026-0055\/html"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,21]]},"references-count":25,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,9,2]]},"published-print":{"date-parts":[[2026,9,1]]}},"alternative-id":["10.1515\/dx-2026-0055"],"URL":"https:\/\/doi.org\/10.1515\/dx-2026-0055","relation":{},"ISSN":["2194-8011","2194-802X"],"issn-type":[{"value":"2194-8011","type":"print"},{"value":"2194-802X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,21]]}}}