Teaching pack: Diagnostics & Biomarkers

Pathology and immunohistochemistry remain the foundation. Layered on top: comprehensive genomic profiling (DNA and RNA), liquid biopsy for circulating tumour DNA, minimal residual disease monitoring, multi-cancer early detection, spatial and single-cell profiling, and AI read-outs of slides and scans.

• Active surveillance: For low-risk prostate cancer, monitoring with PSA, MRI, and repeat biopsy instead of treating, because most such cancers never cause harm.
• AFP, hCG and LDH in germ cell tumours (IGCCCG risk groups): In testicular and other germ cell cancers three blood tests, AFP, beta-hCG and LDH, are part of the staging itself: their levels after surgery sort patients into good, intermediate and poor risk groups that fix how many cycles of chemotherapy they get, and their return to normal defines cure.
• AI scoring of biomarkers and grade on pathology slides: Software that reads digitised biopsy slides to detect cancer, grade it, and score biomarkers such as HER2, PD-L1 and Ki-67 more consistently than the eye alone.
• Anxiety around scans, and what the evidence says about how often to scan: Anxiety around a scan has been measured in 57 studies using 81 different instruments, which is why reported rates run from 13 to 83 per cent; moderate to severe anxiety was reported by 4 to 28 per cent. Scanning more often does not lengthen life in breast cancer or in one common lymphoma, and in bowel cancer it found more curable recurrences but no fewer deaths.
• BH3 profiling (functional apoptosis testing): A lab test that measures how close a leukaemia cell is to self-destructing, and which survival protein is holding it back, to predict response to venetoclax-type drugs.
• Biobanking and tissue procurement: Freezers full of consented tumour samples with matched clinical data, which every biomarker and drug programme depends on.
• Bladder EpiCheck urine methylation test: A urine test from the Israeli company Nucleix that reads fifteen DNA methylation markers and gives a score for bladder cancer recurrence, aimed at sparing patients under surveillance some of their camera examinations.
• Breath and volatile-organic-compound detection: Smelling cancer: measuring the trace chemicals a tumour puts into exhaled breath.
• Cancer variant knowledgebases and molecular tumour boards: Curated databases that say what each mutation means for treatment, and the expert meetings that use them to decide on therapy.
• Capsule endoscopy (PillCam, EndoCapsule, CapsoCam): A camera the size of a large vitamin pill that the patient swallows; it photographs the whole small intestine, which ordinary endoscopes cannot reach, and newer versions look at the colon as an alternative to colonoscopy for people who cannot or will not have one.

• 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 · A cancer with a visible precursor, and the first proof that finding it early saves lives (historic)
• 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 · Total mesorectal excision, and radiotherapy before the operation (historic)
• 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 · Chemotherapy after the operation, and how small the benefit is when the nodes are clear (historic)
• 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 · The screening programmes, and the discovery that uptake is the whole game (current)
• 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 · Antibodies, and the two things that decide whether they work (current)
• 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 · The genome, the subtypes and the hypermutated sixth (historic)
• ctDNA tests roadmap: from a curiosity in plasma to blood tests that decide treatment · A curiosity in plasma (historic)
• ctDNA tests roadmap: from a curiosity in plasma to blood tests that decide treatment · Proof that blood tracks the tumour (historic)
• ctDNA tests roadmap: from a curiosity in plasma to blood tests that decide treatment · Regulators accept a blood genotype (historic)
• ctDNA tests roadmap: from a curiosity in plasma to blood tests that decide treatment · Tumour-informed residual disease tests reach the clinic and the payer (current)
• ctDNA tests roadmap: from a curiosity in plasma to blood tests that decide treatment · Randomised trials: sparing treatment works, adding it is harder (current)
• ctDNA tests roadmap: from a curiosity in plasma to blood tests that decide treatment · The first drug approval that depends on a ctDNA result (current)
• Diagnostics roadmap: stains → gene panels → blood tests that decide treatment · Morphology, stains and the first companion test (historic)
• Diagnostics roadmap: stains → gene panels → blood tests that decide treatment · Single-gene tests and gene-expression signatures (historic)
• Diagnostics roadmap: stains → gene panels → blood tests that decide treatment · Comprehensive profiling and tumour-agnostic biomarkers (current)
• Diagnostics roadmap: stains → gene panels → blood tests that decide treatment · Blood tests that change treatment in randomised trials (current)
• Diagnostics roadmap: stains → gene panels → blood tests that decide treatment · Slides become data (emerging)
• Diagnostics roadmap: stains → gene panels → blood tests that decide treatment · Spatial, single-cell and protein layers guide the choice (emerging)
• 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 · The cause is named, and cancer epidemiology is invented to name it (historic)
• 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 · Cytotoxic chemotherapy, and the ceiling it hit (historic)
• 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 · EGFR, ALK, and the invention of precision oncology in solid tumours (historic)
• 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 · Low-dose computed tomography earns its place, and chest radiography loses its (historic)
• 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 · Immunotherapy, and the trouble with PD-L1 as a gate (historic)
• 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 · Stage III, and treatment moving to either side of the operation (current)
• Lymphoma roadmap: from a jaw tumour in Uganda and the first human cancer virus to gene-expression subtypes, PET-adapted chemotherapy, CAR-T cells, bispecific antibodies and the genetics-directed trials now recruiting · Two viruses, found because lymphoma is the cancer you can get hold of (historic)
• Lymphoma roadmap: from a jaw tumour in Uganda and the first human cancer virus to gene-expression subtypes, PET-adapted chemotherapy, CAR-T cells, bispecific antibodies and the genetics-directed trials now recruiting · How little is enough: the Hodgkin de-escalation programme begins (historic)
• Lymphoma roadmap: from a jaw tumour in Uganda and the first human cancer virus to gene-expression subtypes, PET-adapted chemotherapy, CAR-T cells, bispecific antibodies and the genetics-directed trials now recruiting · Reading the genes, and the twenty years it took to make that useful (historic)
• Lymphoma roadmap: from a jaw tumour in Uganda and the first human cancer virus to gene-expression subtypes, PET-adapted chemotherapy, CAR-T cells, bispecific antibodies and the genetics-directed trials now recruiting · Everything that failed to beat R-CHOP, and the one thing that did (current)
• Lymphoma roadmap: from a jaw tumour in Uganda and the first human cancer virus to gene-expression subtypes, PET-adapted chemotherapy, CAR-T cells, bispecific antibodies and the genetics-directed trials now recruiting · The scan after two cycles, and what it is good for (current)
• Lymphoma roadmap: from a jaw tumour in Uganda and the first human cancer virus to gene-expression subtypes, PET-adapted chemotherapy, CAR-T cells, bispecific antibodies and the genetics-directed trials now recruiting · Indolent lymphoma: how long to treat, and the two-year mark that splits the disease (current)
• 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 · A cancer is shown to depend on a hormone, and systemic cancer therapy begins (historic)
• 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 · A blood test arrives, and an epidemic of diagnoses follows it (historic)
• 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 · Does treating localised disease help? Three trials, three answers, one rule (historic)
• 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 · The screening trials disagree, and the policy swings twice (historic)
• 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 · Chemotherapy works, a little, and then the receptor drugs arrive (historic)
• 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 · The genome: a quiet sequence, a rearranged structure, and one actionable fifth (historic)

• IMpower110 (phase 3, n=572): Overall survival (highest PD-L1 expression, EGFR and ALK wild-type): 20.2 months vs 13.1 months, HR 0.59
• TAILORx (phase 3, n=10,273): Invasive disease-free survival at 9 years (RS 11-25): 83.3% vs 84.3%, HR 1.08
• RxPONDER (SWOG S1007) (phase 3, n=5,018): 5-year iDFS, postmenopausal: 91.9% vs 91.3%, HR 1.02
• IMvigor011 (phase 3, n=761): Disease-free survival (ctDNA-positive, randomised): 9.9 months vs 4.8 months, HR 0.64
• MINDACT (phase 3, n=6,693): 5-year distant metastasis-free survival, clinical-high / genomic-low risk, no chemotherapy: 94.7%
• SANO (phase 3, n=309): Overall survival at 2 years (non-inferiority): pending

1. What questions should someone newly diagnosed with triple-negative breast cancer ask before surgery?
   Answer

   Whether chemo-immunotherapy before surgery (KEYNOTE-522) is planned and why; germline BRCA testing; PD-L1 and HER2-low status; TIL score; clinical trial options; fertility preservation; breast-conserving versus mastectomy and sentinel node approach; what response (pCR/RCB) will mean for treatment afterwards.
2. What is the first FDA-cleared AI pathology tool that predicts treatment benefit, and in which cancer?
   Answer

   ArteraAI Prostate (de novo authorisation, August 2025) predicts prognosis and benefit from short-term androgen deprivation with radiotherapy in localised prostate cancer.
3. What was the first cancer drug approved on the basis of a blood test for leftover disease?
   Answer

   Atezolizumab for ctDNA-positive muscle-invasive bladder cancer after cystectomy (IMvigor011, using Signatera), approved Q2 2026; DFS HR 0.64, OS HR 0.59.
4. Can a blood test decide who needs chemotherapy after colon cancer surgery?
   Answer

   Yes in stage II: the DYNAMIC trial used ctDNA to guide adjuvant chemotherapy, halving its use (15% vs 28%) with non-inferior recurrence-free survival (93.5% vs 92.4% at two years).
5. What is the Galleri test and where does it stand with the FDA?
   Answer

   GRAIL's methylation-based multi-cancer early detection blood test for more than 50 cancers; PMA submitted January 2026 on PATHFINDER 2 and NHS-Galleri data, FDA advisory committee 23 September 2026. NHS-Galleri missed its primary stage III-IV reduction endpoint (stage IV fell ~14%).
6. What is positive predictive value and why does it matter for a cancer screening blood test?
   Answer

   The chance that a positive result is truly cancer. With a low-prevalence disease even a highly specific test yields many false positives; Galleri's PPV in PATHFINDER 2 was around 40-60%, so roughly half of positives lead to a diagnostic workup that finds no cancer.

• NCI: Biomarker testing for cancer treatment: https://www.cancer.gov/about-cancer/treatment/types/biomarker-testing-cancer-treatment