{"id":"early-detection-roadmap","name":"Early detection roadmap: organ screening → blood tests for many cancers","route":"/roadmaps/early-detection-roadmap/","eras":[{"era":"1943-2011","title":"Organ-specific screening proven","description":"Pap smear (1943), mammography (1970s-80s RCTs), colonoscopy/FIT, PSA (contested), low-dose CT for lung (NLST 2011). Each reduces mortality in its cancer; together they cover under half of cancer deaths.","status":"historic","refs":[{"id":"mammography","kind":"technology","name":"Mammography & tomosynthesis","route":"/technologies/mammography/","status":"standard-of-care","tldr":"Low-dose breast X-ray used for screening. Newer 3D versions find more cancers with fewer false alarms."},{"id":"ct","kind":"technology","name":"CT (computed tomography)","route":"/technologies/ct/","status":"standard-of-care","tldr":"A CT scan is a fast 3D X-ray that shows the size and shape of tumours and whether they have spread."}],"trials":[],"papers":[]},{"era":"2014-2021","title":"cfDNA and methylation science","description":"CCGA study (GRAIL) shows methylation classifiers detect >50 cancers with ~0.5% false positives and predict tissue of origin; Galleri launched as an LDT (2021); Cologuard and Epi proColon establish stool and blood DNA screening.","status":"historic","refs":[{"id":"methylation-profiling","kind":"technology","name":"DNA methylation profiling","route":"/technologies/methylation-profiling/","status":"established","tldr":"Reading chemical tags on DNA that reveal a cell's identity, used to classify brain tumours and to detect cancer in blood."},{"id":"galleri","kind":"drug","name":"Galleri","route":"/drugs/galleri/","status":"phase-3","tldr":"A blood test screening for more than 50 cancers at once, before the FDA in September 2026."}],"trials":[],"papers":[]},{"era":"2021-2026","title":"Pivotal trials and first approvals","description":"NHS-Galleri randomises 140,000; PATHFINDER 2 enrols 35,000; Shield becomes the first FDA-approved blood test for CRC screening (2024) and Medicare covers it; Exact launches Cancerguard as an LDT (2025); GRAIL files PMA (Jan 2026), advisory committee 23 Sep 2026. AI mammography reading validated at scale (MASAI).","status":"current","refs":[{"id":"nhs-galleri","kind":"trial","name":"NHS-Galleri","route":"/trials/nhs-galleri/","status":"active","tldr":"The largest cancer screening trial ever run, testing whether a multi-cancer blood test reduces late-stage diagnoses; it reports that it did not, and its test-performance paper appeared in Nature Medicine on 22 September 2026."},{"id":"pathfinder-2","kind":"trial","name":"PATHFINDER 2","route":"/trials/pathfinder-2/","status":"active","tldr":"PATHFINDER 2 is the US real-world study of the Galleri test that forms the core of its FDA submission."},{"id":"shield","kind":"drug","name":"Shield","route":"/drugs/shield/","status":"approved","tldr":"The first FDA-approved blood test for colorectal cancer screening (2024), now optionally reporting other cancers too."},{"id":"galleri","kind":"drug","name":"Galleri","route":"/drugs/galleri/","status":"phase-3","tldr":"A blood test screening for more than 50 cancers at once, before the FDA in September 2026."},{"id":"radiology-ai-screening","kind":"technology","name":"AI in radiology","route":"/technologies/radiology-ai-screening/","status":"established","tldr":"Software that reads scans alongside radiologists, catching cancers earlier and predicting who is at risk."},{"id":"exact-sciences","kind":"company","name":"Exact Sciences (Abbott)","route":"/companies/exact-sciences/","tldr":"Exact Sciences makes Cologuard and Oncotype DX and is launching Cancerguard MCED and Oncodetect MRD; it is being acquired by Abbott for $21B."}],"trials":[{"id":"nhs-galleri","name":"NHS-Galleri","route":"/trials/nhs-galleri/","outcomes":[{"endpoint":"Stage III to IV incidence, 12 prespecified cancers (primary)","primary":true,"arms":[{"name":"Galleri + usual NHS care","note":"Not met, per the Nature Medicine test-performance paper (22 September 2026), which states the primary endpoint was not met and reported elsewhere; no peer-reviewed primary-endpoint paper was on Europe PMC by 23 September 2026, so no figures are recorded here."},{"name":"Usual NHS care"}],"source":"https://doi.org/10.1038/s41591-026-04652-8"},{"endpoint":"Positive test results by screening round","unit":"%","arms":[{"name":"Round 1","n":70325,"value":1.03,"note":"722, 518 and 561 positive results among evaluable intervention-arm participants"},{"name":"Round 2","n":64498,"value":0.8},{"name":"Round 3","n":62323,"value":0.9}],"source":"https://doi.org/10.1038/s41591-026-04652-8"},{"endpoint":"Cancer detection rate by screening round","unit":"%","arms":[{"name":"Round 1","n":70325,"value":0.6,"note":"937 participants had MCED-detected primary cancers across the three rounds"},{"name":"Round 2","n":64498,"value":0.4},{"name":"Round 3","n":62323,"value":0.41}],"source":"https://doi.org/10.1038/s41591-026-04652-8"},{"endpoint":"Positive predictive value by screening round","unit":"%","arms":[{"name":"Round 1","n":722,"value":58,"note":"419/722, 261/518 and 257/561"},{"name":"Round 2","n":518,"value":50.4},{"name":"Round 3","n":561,"value":45.8}],"source":"https://doi.org/10.1038/s41591-026-04652-8"},{"endpoint":"Negative predictive value by screening round","unit":"%","arms":[{"name":"Round 1","n":69603,"value":98.98,"note":"68,895/69,603, 63,278/63,980 and 61,058/61,762"},{"name":"Round 2","n":63980,"value":98.9},{"name":"Round 3","n":61762,"value":98.86}],"source":"https://doi.org/10.1038/s41591-026-04652-8"},{"endpoint":"Specificity, range across rounds","unit":"%","arms":[{"name":"Lowest round","value":99.5,"note":"The abstract gives the range across rounds 1 to 3, not per-round values"},{"name":"Highest round","value":99.6}],"source":"https://doi.org/10.1038/s41591-026-04652-8"},{"endpoint":"Episode sensitivity, all cancers, range across rounds","unit":"%","arms":[{"name":"Lowest round","value":26.7,"note":"Range across rounds 1 to 3 as given in the abstract"},{"name":"Highest round","value":37.2}],"source":"https://doi.org/10.1038/s41591-026-04652-8"},{"endpoint":"Episode sensitivity, 12 prespecified cancer types, range across rounds","unit":"%","arms":[{"name":"Lowest round","value":47.6,"note":"Range across rounds 1 to 3 as given in the abstract"},{"name":"Highest round","value":63.4}],"source":"https://doi.org/10.1038/s41591-026-04652-8"},{"endpoint":"Cancer signal origin accuracy, range across rounds","unit":"%","arms":[{"name":"Lowest round","value":91.1},{"name":"Highest round","value":93.6}],"source":"https://doi.org/10.1038/s41591-026-04652-8"},{"endpoint":"Relative reduction in stage IV diagnoses, rounds 2 and 3","unit":"%","arms":[{"name":"Round 2","value":22,"note":"Relative reduction versus control in the 12 prespecified cancers, from GRAIL's release of 30 May 2026; not in the Nature Medicine paper"},{"name":"Round 3","value":26}],"source":"https://grail.com/press-releases/grail-reports-full-results-from-nhs-galleri-trial-demonstrating-substantial-reduction-in-stage-iv-cancer-diagnoses-at-2026-asco-annual-meeting/"},{"endpoint":"Relative reduction in diagnosis through emergency presentation","unit":"%","arms":[{"name":"Galleri + standard screening","value":25,"note":"From GRAIL's release of 30 May 2026; not in the Nature Medicine paper"}],"source":"https://grail.com/press-releases/grail-reports-full-results-from-nhs-galleri-trial-demonstrating-substantial-reduction-in-stage-iv-cancer-diagnoses-at-2026-asco-annual-meeting/"}],"setting":"142,250 asymptomatic adults aged 50 to 77 in England, randomised 1:1 to three annual rounds of the Galleri multi-cancer early detection blood test added to usual NHS care, or to blood draws stored without results","enrolled":142250,"enrolledNote":"ClinicalTrials.gov NCT05611632 and ISRCTN91431511 list 142,318 participants (actual); the Nature Medicine test-performance paper reports 142,250 participants randomised 1:1.","enrolledBasis":"randomised"},{"id":"pathfinder-2","name":"PATHFINDER 2","route":"/trials/pathfinder-2/","outcomes":[{"endpoint":"Cancer signal detected","unit":"%","arms":[{"name":"Galleri, all participants","n":25578,"value":0.93}],"source":"https://clinicaltrials.gov/study/NCT05155605"},{"endpoint":"Positive predictive value","unit":"%","arms":[{"name":"Galleri","value":61.6}],"source":"https://clinicaltrials.gov/study/NCT05155605"},{"endpoint":"Specificity","unit":"%","arms":[{"name":"Galleri","value":99.6}],"source":"https://clinicaltrials.gov/study/NCT05155605"}],"setting":"~35,000 adults ≥50 receiving Galleri alongside standard screening, single-arm","enrolled":35883,"enrolledBasis":"registry"}],"papers":[]},{"era":"2026-2030","title":"Decision and integration","description":"FDA decision on Galleri; NHS decision on rollout; Medicare MCED coverage legislation; integration with risk-based screening (Mirai, polygenic scores); management pathways for positive signals with no imaging correlate; cost-effectiveness and overdiagnosis debates.","status":"emerging","refs":[{"id":"mced","kind":"technology","name":"Multi-cancer early detection (MCED)","route":"/technologies/mced/","status":"phase-3","tldr":"A single blood test intended to screen for dozens of cancers at once, including ones with no screening today."},{"id":"ppv","kind":"term","name":"Positive predictive value (PPV)","route":"/terms/ppv/","tldr":"Positive predictive value (PPV) is the chance that a positive test result is actually right: true positives divided by all positives. Because it falls as a disease becomes rarer, even a specific screening test gives mostly false alarms when prevalence is low, which is why PPV decides whether a multi-cancer blood test is useful."},{"id":"stage-shift","kind":"term","name":"Stage shift","route":"/terms/stage-shift/","tldr":"Stage shift means finding more cancers early and fewer late; it is the measurable goal of screening."}],"trials":[],"papers":[]},{"era":"2030+","title":"Speculative","description":"Annual multi-analyte blood screening for adults over 50 with tissue-of-origin-directed imaging; MCED-detected pancreatic and ovarian cancers at resectable stages; risk-adapted intervals from AI; proteomic and fragmentomic layers improving stage I sensitivity.","status":"speculative","refs":[{"id":"proteomics","kind":"technology","name":"Proteomics & phosphoproteomics","route":"/technologies/proteomics/","status":"emerging","tldr":"Measuring the proteins in a tumour, which is what drugs actually hit, rather than the genes that encode them."},{"id":"whole-body-mri","kind":"technology","name":"Whole-body MRI","route":"/technologies/whole-body-mri/","status":"established","tldr":"Whole-body MRI is an MRI of the entire body without radiation, used to find spread in myeloma and to screen people with high inherited cancer risk."}],"trials":[],"papers":[]}],"watch":[]}