{"entity":{"id":"diagnostics-roadmap","kind":"roadmap","name":"Diagnostics roadmap: stains → gene panels → blood tests that decide treatment","aka":[],"tldr":"Cancer diagnosis moved from what a tumour looks like under a microscope to what is driving it, and now to reading it from a blood sample. The next step is tests that tell the doctor what to do, not only what is there.","summary":"Histopathology and immunohistochemistry remain the foundation of every cancer diagnosis, and the first companion diagnostic (HER2 testing paired with trastuzumab in 1998) set the pattern that every targeted drug since has followed: no test, no drug. Single-gene tests gave way to comprehensive genomic profiling of hundreds of genes, tumour-agnostic biomarkers (mismatch repair deficiency, tumour mutational burden, NTRK fusions), and gene-expression signatures that let most women with early hormone-positive breast cancer skip chemotherapy.\n\nThe current shift is from tissue to blood and from description to decision. Circulating tumour DNA now genotypes lung cancer without a biopsy, detects molecular residual disease after surgery months before a scan would, and has changed treatment in randomised trials: DYNAMIC halved adjuvant chemotherapy in stage II colon cancer, SERENA-6 switched endocrine therapy on an ESR1 mutation found in blood, and IMvigor011 produced the first ctDNA-guided drug approval in 2026. Digital pathology is following the same path, with the first AI tests that predict treatment benefit from a routine slide cleared in 2025 and 2026.\n\nWhat decides the pace is validation rather than invention: prospective evidence that acting on a test improves outcomes, standardisation across laboratories, reimbursement for tests that avoid treatment rather than add it, and data that flows between the sequencer, the slide scanner, the record and the registry.","asOf":"2026-09-10","links":[{"label":"FDA: list of cleared or approved companion diagnostic devices","url":"https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools"},{"label":"DYNAMIC trial (NEJM 2022)","url":"https://www.nejm.org/doi/full/10.1056/NEJMoa2200075"}],"tags":[],"related":["signatera","foundationone-cdx","guardant360-cdx","oncotype-dx","her2-testing-assays","cobas-egfr-mutation-test","dako-pd-l1-22c3-pharmdx","guardant-reveal","radar-mrd","artera-ai-prostate","artera-ai-breast","fda-ldt-rule","idea-bio2-national-mrd-platform","idea-bio2-mrd-coverage-with-evidence","idea-ctdna-guided-adjuvant-crc","idea-tr2-ctdna-mrd-qualification","idea-tr2-biomarker-study-registry","idea-tr2-marker-stratified-default","idea-moon-universal-sequencing-learning-system","early-detection-roadmap","ai-oncology-clinic","trial-modernisation-roadmap"],"cancers":[],"sections":["diagnostics"],"technologies":["histopathology-ihc","companion-diagnostic","cgp","liquid-biopsy","mrd-testing","single-cell-spatial","methylation-profiling","digital-pathology-ai","pathology-foundation-model","msi-mmr-testing","tmb-testing","hrd-testing","rna-seq","wes-wgs","proteomics","long-read-sequencing","spatial-omics-guided-therapy","continuous-ctdna-monitoring","fragmentomics","variant-knowledgebases","reference-laboratories"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["tailorx","rxponder","dynamic","serena-6","imvigor011","circulate-japan","insight-gist","masai"],"people":[],"bottlenecks":["b-biomarker-validation","b-dormancy-mrd","b-data-silos","b-tumor-heterogeneity"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"steps":[{"era":"1940s-1990s","title":"Morphology, stains and the first companion test","description":"Haematoxylin and eosin, then immunohistochemistry and FISH, defined cancer by appearance and a handful of proteins. HER2 testing approved alongside trastuzumab in 1998 created the companion diagnostic: a test whose result is the gate to a drug. Every targeted therapy since has been launched with one.","refs":["histopathology-ihc","cytogenetics-fish","her2-testing-assays","companion-diagnostic","core-needle-biopsy"],"status":"historic"},{"era":"2000s-2010s","title":"Single-gene tests and gene-expression signatures","description":"PCR kits for EGFR, KRAS and BRAF matched the first kinase inhibitors to the right patients; the cobas EGFR test became the first blood-based companion diagnostic. Gene-expression signatures did the opposite job, identifying who could safely skip treatment: TAILORx (2018) and RxPONDER showed that most women with early hormone-positive breast cancer and a low Oncotype DX score gain nothing from chemotherapy.","refs":["cobas-egfr-mutation-test","therascreen-cdx","oncotype-dx","tailorx","rxponder","mammaprint","prosigna"],"status":"historic"},{"era":"2017-2022","title":"Comprehensive profiling and tumour-agnostic biomarkers","description":"Sequencing hundreds of genes at once (FoundationOne CDx, TruSight Oncology, Tempus xT) replaced serial single-gene tests, and the biomarker began to matter more than the organ: pembrolizumab for any mismatch-repair-deficient tumour and larotrectinib for any NTRK fusion made the test the indication. Guardant360 CDx did the same from blood. Variant knowledgebases and molecular tumour boards turned raw variants into decisions.","refs":["cgp","foundationone-cdx","trusight-oncology-comprehensive","tempus-xt-cdx","guardant360-cdx","msi-mmr-testing","tmb-testing","hrd-testing","variant-knowledgebases","multidisciplinary-tumour-board","tumour-agnostic"],"status":"current"},{"era":"2022-2026","title":"Blood tests that change treatment in randomised trials","description":"Molecular residual disease testing crossed from prognosis to action. DYNAMIC (2022) halved adjuvant chemotherapy in stage II colon cancer with no loss of recurrence-free survival; CIRCULATE-Japan runs the same question at national scale; SERENA-6 switched endocrine therapy when an ESR1 mutation appeared in blood before a scan showed progression; and IMvigor011 delivered the first ctDNA-guided approval, in bladder cancer, in 2026. Tumour-informed (Signatera, RaDaR) and tumour-naive (Guardant Reveal) assays now compete on sensitivity and turnaround.","refs":["mrd-testing","liquid-biopsy","dynamic","circulate-japan","serena-6","imvigor011","signatera","radar-mrd","guardant-reveal","insight-gist"],"status":"current"},{"era":"2024-2028","title":"Slides become data","description":"Whole-slide scanning made the microscope image computable, and foundation models trained on millions of slides now predict biomarkers, recurrence risk and treatment benefit from a routine stain. ArteraAI Prostate (2025) was the first AI test cleared to predict benefit from a therapy; ArteraAI Breast followed in 2026. MASAI showed in a randomised screening trial that AI reading finds more cancers with less radiologist workload. The open question is prospective proof that AI-derived biomarkers should change treatment, and a regulatory route for models that keep learning.","refs":["digital-pathology-ai","pathology-foundation-model","whole-slide-scanners","virchow","prov-gigapath","artera-ai-prostate","artera-ai-breast","masai","musk"],"status":"emerging"},{"era":"2027-2032","title":"Spatial, single-cell and protein layers guide the choice","description":"Genotype explains which drug could work; architecture and phenotype may explain which one will. Spatial and single-cell profiling map where immune cells sit relative to tumour cells, proteomics measures the drug's actual target, long-read sequencing resolves rearrangements and methylation together, and near-continuous ctDNA sampling turns monitoring into a running signal. Each is a research tool today; the work of this era is showing that any of them changes an outcome when used to choose treatment.","refs":["single-cell-spatial","spatial-omics-guided-therapy","spatial-biology-instruments","proteomics","long-read-sequencing","continuous-ctdna-monitoring","fragmentomics","methylation-profiling"],"status":"emerging"},{"era":"What sets the pace","title":"Validation, standardisation and payment","description":"Tests that decide who gets a drug are still often validated retrospectively, run differently in different laboratories, and paid for only when they add treatment rather than remove it. The fixes on the table: pre-registration of biomarker studies, a national platform every ctDNA-positive patient can join, coverage-with-evidence for residual disease tests, universal sequencing that feeds a shared learning system, and a clear regulatory status for laboratory-developed tests.","refs":["b-biomarker-validation","b-dormancy-mrd","b-data-silos","b-tumor-heterogeneity","idea-tr2-biomarker-study-registry","idea-bio2-national-mrd-platform","idea-bio2-mrd-coverage-with-evidence","idea-moon-universal-sequencing-learning-system","fda-ldt-rule","reference-laboratories"],"status":"current"}],"watch":[]},"route":"/roadmaps/diagnostics-roadmap/","neighbours":{"drug":[{"id":"artera-ai-breast","kind":"drug","name":"ArteraAI Breast","route":"/drugs/artera-ai-breast/"},{"id":"artera-ai-prostate","kind":"drug","name":"ArteraAI Prostate","route":"/drugs/artera-ai-prostate/"},{"id":"cobas-egfr-mutation-test","kind":"drug","name":"cobas EGFR Mutation Test v2","route":"/drugs/cobas-egfr-mutation-test/"},{"id":"foundationone-cdx","kind":"drug","name":"FoundationOne CDx / Liquid CDx","route":"/drugs/foundationone-cdx/"},{"id":"guardant-reveal","kind":"drug","name":"Guardant Reveal","route":"/drugs/guardant-reveal/"},{"id":"guardant360-cdx","kind":"drug","name":"Guardant360 CDx","route":"/drugs/guardant360-cdx/"},{"id":"her2-testing-assays","kind":"drug","name":"HER2 IHC and ISH companion assays (HercepTest, PATHWAY 4B5, HER2 Dual ISH)","route":"/drugs/her2-testing-assays/"},{"id":"mammaprint","kind":"drug","name":"MammaPrint (70-gene signature)","route":"/drugs/mammaprint/"},{"id":"oncotype-dx","kind":"drug","name":"Oncotype DX","route":"/drugs/oncotype-dx/"},{"id":"dako-pd-l1-22c3-pharmdx","kind":"drug","name":"PD-L1 IHC 22C3 pharmDx","route":"/drugs/dako-pd-l1-22c3-pharmdx/"},{"id":"prosigna","kind":"drug","name":"Prosigna (PAM50)","route":"/drugs/prosigna/"},{"id":"radar-mrd","kind":"drug","name":"RaDaR","route":"/drugs/radar-mrd/"},{"id":"signatera","kind":"drug","name":"Signatera","route":"/drugs/signatera/"},{"id":"tempus-xt-cdx","kind":"drug","name":"Tempus xT CDx","route":"/drugs/tempus-xt-cdx/"},{"id":"therascreen-cdx","kind":"drug","name":"therascreen companion diagnostic kits (KRAS, EGFR, PIK3CA, FGFR, BRAF)","route":"/drugs/therascreen-cdx/"},{"id":"trusight-oncology-comprehensive","kind":"drug","name":"TruSight Oncology Comprehensive","route":"/drugs/trusight-oncology-comprehensive/"}],"term":[{"id":"core-needle-biopsy","kind":"term","name":"Core needle biopsy and fine-needle aspiration (FNA)","route":"/terms/core-needle-biopsy/"},{"id":"fda-ldt-rule","kind":"term","name":"FDA laboratory-developed test (LDT) rule","route":"/terms/fda-ldt-rule/"},{"id":"tumour-agnostic","kind":"term","name":"Tumour-agnostic (tissue-agnostic) approval","route":"/terms/tumour-agnostic/"}],"idea":[{"id":"idea-bio2-national-mrd-platform","kind":"idea","name":"A national platform trial that every ctDNA-positive patient can join","route":"/ideas/idea-bio2-national-mrd-platform/"},{"id":"idea-ctdna-guided-adjuvant-crc","kind":"idea","name":"ctDNA-guided adjuvant therapy as the default in stage II-III colon cancer","route":"/ideas/idea-ctdna-guided-adjuvant-crc/"},{"id":"idea-tr2-ctdna-mrd-qualification","kind":"idea","name":"Formally qualify tumour-DNA blood tests as a surrogate endpoint for adjuvant trials","route":"/ideas/idea-tr2-ctdna-mrd-qualification/"},{"id":"idea-lung-resistance-directed-sequencing-at-every-progression","kind":"idea","name":"Make resistance a diagnosis: sequence at every progression and choose the next line from what the tumour became","route":"/ideas/idea-lung-resistance-directed-sequencing-at-every-progression/"},{"id":"idea-bio2-mrd-coverage-with-evidence","kind":"idea","name":"Pay for residual disease tests only inside a trial or registry","route":"/ideas/idea-bio2-mrd-coverage-with-evidence/"},{"id":"idea-tr2-biomarker-study-registry","kind":"idea","name":"Pre-register biomarker validation studies the way trials are registered","route":"/ideas/idea-tr2-biomarker-study-registry/"},{"id":"idea-lung-uk-screening-testing-and-access-gaps","kind":"idea","name":"Publish the four numbers the NHS lung cancer pathway does not currently measure: reflex testing rate, genomic turnaround, surgical access and a lung-specific waiting time in every nation","route":"/ideas/idea-lung-uk-screening-testing-and-access-gaps/"},{"id":"idea-tr2-marker-stratified-default","kind":"idea","name":"Test the drug in biomarker-negative patients too, so the biomarker can be validated","route":"/ideas/idea-tr2-marker-stratified-default/"},{"id":"idea-moon-universal-sequencing-learning-system","kind":"idea","name":"Universal tumour and germline sequencing at diagnosis feeding a shared learning system","route":"/ideas/idea-moon-universal-sequencing-learning-system/"}],"roadmap":[{"id":"ai-oncology-clinic","kind":"roadmap","name":"AI in the oncology clinic: from narrow cleared tools to multimodal decision support","route":"/roadmaps/ai-oncology-clinic/"},{"id":"ctdna-tests","kind":"roadmap","name":"ctDNA tests roadmap: from a curiosity in plasma to blood tests that decide treatment","route":"/roadmaps/ctdna-tests/"},{"id":"early-detection-roadmap","kind":"roadmap","name":"Early detection roadmap: organ screening → blood tests for many cancers","route":"/roadmaps/early-detection-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":"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/"},{"id":"trial-modernisation-roadmap","kind":"roadmap","name":"Trial modernisation roadmap: the randomised trial → platforms and adaptive designs → decentralised, pragmatic and always-on","route":"/roadmaps/trial-modernisation-roadmap/"}],"section":[{"id":"diagnostics","kind":"section","name":"Diagnostics & Biomarkers","route":"/fronts/diagnostics/"}],"technology":[{"id":"variant-knowledgebases","kind":"technology","name":"Cancer variant knowledgebases and molecular tumour boards","route":"/technologies/variant-knowledgebases/"},{"id":"fragmentomics","kind":"technology","name":"cfDNA fragmentomics","route":"/technologies/fragmentomics/"},{"id":"companion-diagnostic","kind":"technology","name":"Companion diagnostics","route":"/technologies/companion-diagnostic/"},{"id":"cgp","kind":"technology","name":"Comprehensive genomic profiling","route":"/technologies/cgp/"},{"id":"continuous-ctdna-monitoring","kind":"technology","name":"Continuous and near-continuous ctDNA monitoring","route":"/technologies/continuous-ctdna-monitoring/"},{"id":"cytogenetics-fish","kind":"technology","name":"Cytogenetics and FISH","route":"/technologies/cytogenetics-fish/"},{"id":"digital-pathology-ai","kind":"technology","name":"Digital pathology & AI","route":"/technologies/digital-pathology-ai/"},{"id":"methylation-profiling","kind":"technology","name":"DNA methylation profiling","route":"/technologies/methylation-profiling/"},{"id":"histopathology-ihc","kind":"technology","name":"Histopathology & immunohistochemistry","route":"/technologies/histopathology-ihc/"},{"id":"hrd-testing","kind":"technology","name":"HRD & BRCA testing","route":"/technologies/hrd-testing/"},{"id":"liquid-biopsy","kind":"technology","name":"Liquid biopsy (ctDNA)","route":"/technologies/liquid-biopsy/"},{"id":"long-read-sequencing","kind":"technology","name":"Long-read sequencing (PacBio, Oxford Nanopore)","route":"/technologies/long-read-sequencing/"},{"id":"mrd-testing","kind":"technology","name":"MRD / molecular residual disease testing","route":"/technologies/mrd-testing/"},{"id":"msi-mmr-testing","kind":"technology","name":"MSI and mismatch-repair testing","route":"/technologies/msi-mmr-testing/"},{"id":"multidisciplinary-tumour-board","kind":"technology","name":"Multidisciplinary tumour boards","route":"/technologies/multidisciplinary-tumour-board/"},{"id":"musk","kind":"technology","name":"MUSK (Stanford, vision-language pathology)","route":"/technologies/musk/"},{"id":"pathology-foundation-model","kind":"technology","name":"Pathology & radiology foundation models","route":"/technologies/pathology-foundation-model/"},{"id":"proteomics","kind":"technology","name":"Proteomics & phosphoproteomics","route":"/technologies/proteomics/"},{"id":"prov-gigapath","kind":"technology","name":"Prov-GigaPath (Microsoft, Providence)","route":"/technologies/prov-gigapath/"},{"id":"reference-laboratories","kind":"technology","name":"Reference laboratories and companion-diagnostic testing","route":"/technologies/reference-laboratories/"},{"id":"rna-seq","kind":"technology","name":"RNA sequencing & expression profiling","route":"/technologies/rna-seq/"},{"id":"single-cell-spatial","kind":"technology","name":"Single-cell & spatial profiling","route":"/technologies/single-cell-spatial/"},{"id":"spatial-biology-instruments","kind":"technology","name":"Spatial biology instruments","route":"/technologies/spatial-biology-instruments/"},{"id":"spatial-omics-guided-therapy","kind":"technology","name":"Spatial-omics-guided treatment selection","route":"/technologies/spatial-omics-guided-therapy/"},{"id":"tmb-testing","kind":"technology","name":"Tumour mutational burden testing","route":"/technologies/tmb-testing/"},{"id":"virchow","kind":"technology","name":"Virchow / Virchow2 (Paige, MSK)","route":"/technologies/virchow/"},{"id":"wes-wgs","kind":"technology","name":"Whole-exome & whole-genome sequencing","route":"/technologies/wes-wgs/"},{"id":"whole-slide-scanners","kind":"technology","name":"Whole-slide scanners and image management","route":"/technologies/whole-slide-scanners/"}],"trial":[{"id":"circulate-japan","kind":"trial","name":"CIRCULATE-Japan (GALAXY / VEGA / ALTAIR)","route":"/trials/circulate-japan/"},{"id":"dynamic","kind":"trial","name":"DYNAMIC","route":"/trials/dynamic/"},{"id":"imvigor011","kind":"trial","name":"IMvigor011","route":"/trials/imvigor011/"},{"id":"insight-gist","kind":"trial","name":"INSIGHT","route":"/trials/insight-gist/"},{"id":"masai","kind":"trial","name":"MASAI (Mammography Screening with Artificial Intelligence)","route":"/trials/masai/"},{"id":"rxponder","kind":"trial","name":"RxPONDER (SWOG S1007)","route":"/trials/rxponder/"},{"id":"serena-6","kind":"trial","name":"SERENA-6","route":"/trials/serena-6/"},{"id":"tailorx","kind":"trial","name":"TAILORx","route":"/trials/tailorx/"}],"bottleneck":[{"id":"b-biomarker-validation","kind":"bottleneck","name":"Biomarkers are not validated or standardised","route":"/bottlenecks/b-biomarker-validation/"},{"id":"b-data-silos","kind":"bottleneck","name":"Data silos","route":"/bottlenecks/b-data-silos/"},{"id":"b-dormancy-mrd","kind":"bottleneck","name":"Dormant cells and minimal residual disease","route":"/bottlenecks/b-dormancy-mrd/"},{"id":"b-tumor-heterogeneity","kind":"bottleneck","name":"Tumour heterogeneity and clonal evolution","route":"/bottlenecks/b-tumor-heterogeneity/"}]}}