{"entity":{"id":"b-early-detection","kind":"bottleneck","name":"The hardest cancers are found late","aka":[],"tldr":"Screening exists for only a few cancers. Pancreatic, ovarian, liver, oesophageal and most lung cancers are found when cure is unlikely.","summary":"Stage at diagnosis is the largest single determinant of survival: localised pancreatic cancer has a five-year relative survival around 44% in SEER data, distant disease about 3%. Organised population screening exists only for breast, cervical and colorectal cancer, low-dose CT for heavy smokers, and prostate in some systems, and uptake is incomplete even where it exists. The cancers that kill most people at a late stage (pancreas, ovary, liver, oesophagus, stomach, most lung cancers in never-smokers) have no screening test, and the largest randomised trial of ovarian screening (UKCTOCS) found no mortality benefit despite a stage shift. Multi-cancer early detection blood tests (Galleri, Shield, fragmentomics) can detect signals from dozens of cancers but have modest sensitivity for stage I disease and have not yet shown reduced mortality; the NHS-Galleri trial is the first randomised test of the concept. Risk-stratified surveillance (new-onset diabetes for pancreas, cirrhosis for liver, Barrett's for oesophagus) is the intermediate strategy.","asOf":"2026-09-08","links":[{"label":"Crosby et al., Early detection of cancer (Science 2022)","url":"https://doi.org/10.1126/science.aay9040"},{"label":"Menon et al., UKCTOCS ovarian screening mortality results (Lancet 2021)","url":"https://doi.org/10.1016/S0140-6736(21)00731-5"},{"label":"NLST, Reduced lung-cancer mortality with low-dose CT screening (NEJM 2011)","url":"https://doi.org/10.1056/NEJMoa1102873"},{"label":"NCI SEER Cancer Stat Facts","url":"https://seer.cancer.gov/statfacts/"}],"tags":[],"related":["early-detection-roadmap","idea-mced-new-onset-diabetes","idea-mced-plus-fapi","idea-hcc-blood-surveillance","idea-non-endoscopic-barretts-screening","seer","globocan","idea-prev-mced-change-control-plan","idea-prev-interval-cancer-audit-blood-tests","idea-prev-ldct-ai-negative-triage","idea-prev-opportunistic-ct-ai-registry","idea-prev-pancreas-ai-prediagnostic-ct","idea-prev-new-onset-diabetes-pancreas-pathway","idea-prev-breath-voc-symptomatic-ruleout","idea-prev-urine-dna-haematuria-triage","idea-prev-weight-loss-auto-alert","idea-prev-cgm-glycaemic-drift-pancreas","idea-prev-ehr-symptom-signature-prompts","idea-prev-mced-non-specific-symptom-triage","idea-prev-blood-count-trend-flags","idea-prev-blood-crc-test-for-non-responders","idea-prev-capsule-sponge-pharmacy","idea-prev-gastric-serology-migrant-screening","idea-prev-hcc-blood-surveillance-cirrhosis","idea-prev-mri-first-prostate-screening-prs","idea-prev-oral-cancer-community-smartphone-ai","idea-prev-lmic-five-cancer-methylation-test","idea-prev-fragmentomics-first-tier","idea-prev-live-stage-dashboard","idea-prev-open-stage-shift-microsimulation","idea-prev-emergency-department-cancer-test","idea-prev-ebv-dna-npc-screening-scaleup","idea-prev-dental-oral-exam-standard","idea-prev-bundled-cancer-check-at-60","idea-moon-population-interception"],"cancers":["pancreatic","ovarian","hcc","esophageal","gastric","nsclc","colorectal"],"sections":["early-detection"],"technologies":["mced","liquid-biopsy","fragmentomics","low-dose-ct-screening","colorectal-screening","hcc-surveillance","pancreatic-surveillance","methylation-profiling","radiology-ai-screening"],"targets":[],"drugs":["galleri","shield"],"companies":["grail","guardant-health","exact-sciences","freenome","delfi-diagnostics","harbinger-health"],"institutions":["nci","cruk","iarc"],"pathways":[],"terms":["stage-shift","ppv","ca19-9","afp","barretts-esophagus","fit-test"],"trials":["nhs-galleri","pathfinder-2","nlst-nelson","ukctocs"],"people":[],"bottlenecks":[],"keyPapers":["paper-crosby-science","paper-menon-lancet"],"journals":[],"dependsOn":[],"notes":[],"stage":"prevention-detection","severity":"critical","metrics":[{"label":"Five-year relative survival for pancreatic cancer diagnosed at localised vs distant stage (SEER, US)","value":"~44% vs ~3%","source":"NCI SEER Cancer Stat Facts: Pancreatic Cancer","url":"https://seer.cancer.gov/statfacts/html/pancreas.html"},{"label":"Reduction in lung cancer mortality with low-dose CT screening vs chest X-ray in heavy smokers (NLST)","value":"20%","source":"National Lung Screening Trial Research Team, NEJM 2011","url":"https://doi.org/10.1056/NEJMoa1102873"},{"label":"Ovarian cancer deaths prevented by annual multimodal screening over 16 years of follow-up (UKCTOCS)","value":"No significant reduction despite stage shift","source":"Menon et al., Lancet 2021","url":"https://doi.org/10.1016/S0140-6736(21)00731-5"},{"label":"New cancer cases and cancer deaths worldwide, 2022","value":"~20 million cases, 9.7 million deaths","source":"Bray et al., CA 2024 (GLOBOCAN 2022)","url":"https://doi.org/10.3322/caac.21834"}],"causes":["Most cancers that prove fatal arise in deep organs without symptoms until they are locally advanced or metastatic.","Screening tests for low-prevalence cancers need very high specificity to avoid harm, which few biomarkers achieve.","A stage shift does not guarantee a mortality reduction, so each test needs a long randomised trial that few sponsors fund.","Screening uptake is incomplete and unequal even for tests that work, because of access, cost and awareness.","Health systems lack the diagnostic capacity (imaging, endoscopy, pathology) to work up the positives a population test would generate."],"currentEfforts":["NHS-Galleri randomised about 140,000 people to GRAIL's multi-cancer blood test, the first trial of MCED on stage shift and mortality.","The NCI Cancer Screening Research Network's Vanguard study is piloting MCED evaluation in the US.","Guardant's Shield blood test was FDA-approved in 2024 for colorectal screening, and Exact Sciences' Cologuard has expanded stool DNA testing.","The USPSTF broadened lung screening eligibility in 2021 and the NHS is rolling out targeted lung health checks nationally.","Cirrhosis-based HCC surveillance and new-onset-diabetes pancreatic surveillance cohorts (NCI/NIDDK New-Onset Diabetes cohort) target high-risk groups.","Delfi, Freenome and Harbinger are developing fragmentomic and methylation-based tests aimed at earlier-stage sensitivity."],"successLooksLike":"A randomised trial shows that a multi-cancer or organ-specific test reduces late-stage incidence and cancer-specific mortality for at least one cancer without a current screening programme, and the share of pancreatic, ovarian, liver and oesophageal cancers diagnosed at stage I-II at least doubles."},"route":"/bottlenecks/b-early-detection/","neighbours":{"roadmap":[{"id":"colorectal-roadmap","kind":"roadmap","name":"Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation","route":"/roadmaps/colorectal-roadmap/"},{"id":"early-detection-roadmap","kind":"roadmap","name":"Early detection roadmap: organ screening → blood tests for many cancers","route":"/roadmaps/early-detection-roadmap/"},{"id":"gallbladder-cancer-roadmap","kind":"roadmap","name":"Gallbladder cancer roadmap: from a chance finding at gallstone surgery to a disease with its own trials","route":"/roadmaps/gallbladder-cancer-roadmap/"},{"id":"lung-cancer-evidence-roadmap","kind":"roadmap","name":"Lung cancer roadmap: from Doll and Hill and the naming of tobacco, through the cytotoxic plateau, computed tomography screening, EGFR and ALK, immunotherapy by PD-L1, the perioperative trials and PACIFIC, to DLL3 in small-cell disease and a 2032 registry watch","route":"/roadmaps/lung-cancer-evidence-roadmap/"},{"id":"pancreatic-roadmap","kind":"roadmap","name":"Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question","route":"/roadmaps/pancreatic-roadmap/"},{"id":"prostate-roadmap","kind":"roadmap","name":"Prostate cancer roadmap: from Huggins and the discovery that a cancer can depend on a hormone, through the PSA epidemic and what it cost, the androgen receptor drugs, the DNA repair subset and PSMA, to a 2032 registry watch","route":"/roadmaps/prostate-roadmap/"}],"idea":[{"id":"idea-prev-mced-positive-resolution-pathway","kind":"idea","name":"A 28-day national pathway for people with a positive multi-cancer blood test","route":"/ideas/idea-prev-mced-positive-resolution-pathway/"},{"id":"idea-prev-breath-voc-symptomatic-ruleout","kind":"idea","name":"A breath test to rule out cancer in people with vague symptoms","route":"/ideas/idea-prev-breath-voc-symptomatic-ruleout/"},{"id":"idea-prev-emergency-department-cancer-test","kind":"idea","name":"A cancer blood test for older people arriving at A&E with unexplained symptoms","route":"/ideas/idea-prev-emergency-department-cancer-test/"},{"id":"idea-pdac-uk-fast-track-diagnosis-to-treatment-pathway","kind":"idea","name":"A fast-track pathway from suspicion to treatment for pancreatic cancer in the NHS, measured from first scan to first treatment","route":"/ideas/idea-pdac-uk-fast-track-diagnosis-to-treatment-pathway/"},{"id":"idea-acc-28-day-diagnosis-standard","kind":"idea","name":"A legislated, publicly reported 28-day standard from urgent referral to diagnosis","route":"/ideas/idea-acc-28-day-diagnosis-standard/"},{"id":"idea-prev-live-stage-dashboard","kind":"idea","name":"A live national dashboard of stage at diagnosis as the scorecard for early detection","route":"/ideas/idea-prev-live-stage-dashboard/"},{"id":"idea-prev-bundled-cancer-check-at-60","kind":"idea","name":"A single 'cancer check at 60' appointment bundling all screening tests","route":"/ideas/idea-prev-bundled-cancer-check-at-60/"},{"id":"idea-prev-capsule-sponge-pharmacy","kind":"idea","name":"A swallowable sponge test for reflux patients, offered in pharmacies","route":"/ideas/idea-prev-capsule-sponge-pharmacy/"},{"id":"idea-prev-lmic-five-cancer-methylation-test","kind":"idea","name":"A ten-dollar blood test for the five cancers that kill most people in poorer countries","route":"/ideas/idea-prev-lmic-five-cancer-methylation-test/"},{"id":"idea-prev-urine-dna-haematuria-triage","kind":"idea","name":"A urine DNA test to decide who with blood in the urine needs a camera test","route":"/ideas/idea-prev-urine-dna-haematuria-triage/"},{"id":"idea-moon-population-interception","kind":"idea","name":"A whole-population cancer interception programme: risk-stratify every adult, detect and intercept early","route":"/ideas/idea-moon-population-interception/"},{"id":"idea-prev-ldct-ai-negative-triage","kind":"idea","name":"AI clears the normal lung screening scans so radiologists read only the suspicious ones","route":"/ideas/idea-prev-ldct-ai-negative-triage/"},{"id":"idea-prev-pancreas-ai-prediagnostic-ct","kind":"idea","name":"AI that spots pancreatic cancer on scans taken a year before diagnosis","route":"/ideas/idea-prev-pancreas-ai-prediagnostic-ct/"},{"id":"idea-rejuv-registry-randomised-screening-in-survivors","kind":"idea","name":"Ask whether survivorship screening saves lives, using registry-based randomisation","route":"/ideas/idea-rejuv-registry-randomised-screening-in-survivors/"},{"id":"idea-bio2-survivor-plasma-biobank","kind":"idea","name":"Bank yearly blood from cancer survivors so future tests can be validated","route":"/ideas/idea-bio2-survivor-plasma-biobank/"},{"id":"idea-prev-ebv-dna-npc-screening-scaleup","kind":"idea","name":"Blood EBV DNA screening for nasopharyngeal cancer across southern China and Southeast 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pack-years, including high-risk never-smokers","route":"/ideas/idea-prev-lung-screening-risk-model-eligibility/"},{"id":"idea-prev-dental-oral-exam-standard","kind":"idea","name":"Make a two-minute mouth cancer check part of every dental visit","route":"/ideas/idea-prev-dental-oral-exam-standard/"},{"id":"idea-prev-interval-cancer-audit-blood-tests","kind":"idea","name":"Mandatory interval-cancer audit for every blood-based screening test","route":"/ideas/idea-prev-interval-cancer-audit-blood-tests/"},{"id":"idea-acc-mobile-see-and-treat-units","kind":"idea","name":"Mobile diagnostic units that biopsy, scan and treat on the same visit","route":"/ideas/idea-acc-mobile-see-and-treat-units/"},{"id":"idea-moon-indolence-classifiers-with-screening","kind":"idea","name":"Molecular indolence classifiers bundled with every screening programme","route":"/ideas/idea-moon-indolence-classifiers-with-screening/"},{"id":"idea-prev-mri-first-prostate-screening-prs","kind":"idea","name":"MRI-first 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