The state of the war on cancer, 2026

Generated from the OnCo corpus: what was approved, what read out, where the roadmaps stand, and what is still unsolved. Every figure below is a count over the objects on this site, so it is auditable and it is incomplete in exactly the ways the corpus is.

Three things defined 2026 in oncology as recorded here. First, antibody-drug conjugates moved from rescue therapy to first choice: two TROP2 ADCs were approved for first-line triple-negative breast cancer, trastuzumab deruxtecan reached early-stage HER2-positive disease, and the first bispecific ADC succeeded in phase 3. Second, immunotherapy grew a new limb: a personalised mRNA vaccine met its phase 3 endpoints in melanoma, an oncolytic virus was approved after an earlier rejection, and a blood test for residual disease decided, for the first time, who receives adjuvant immunotherapy. Third, targeted protein degradation arrived, with the first PROTAC approved for ESR1-mutant breast cancer.

The failures matter as much. TIGIT blockade did not add to PD-1 inhibition; a CD47 antibody was abandoned; a second TOP1-payload ADC given straight after a first works poorly. Pancreatic cancer and glioblastoma remain the deadliest common cancers, though the first pan-RAS inhibitor is in a pivotal trial and tumour treating fields earned the first pancreatic approval in decades.

Corpus at a glance

Recruiting 2890Active 1204Positive 700Planned 590Approved 538Established 343Phase 3 277Phase 2 264Completed 239Standard of care 180Negative 171Emerging 132Mixed 98Withdrawn 30Phase 1 29Historic 17Preclinical 16Concept 6

Approvals recorded in 2026

57 label actions · 15 first-ever approvals

Product	Region	Indication
Acalabrutinib Calquence	US	Fixed-duration acalabrutinib + venetoclax, previously untreated CLL/SLL without del(17p)/TP53 (AMPLIFY)
Allogeneic regulatory T cell immunotherapy with HSPC and T cells-vldq Tregzi	US	Adults with haematological malignancies undergoing matched-donor haematopoietic stem cell transplantation with a myeloablative preparative regimen, for hematopoietic and immunologic reconstitution and to improve chronic graft-versus-host disease-free survival	first approval
Amivantamab Rybrevant	England (NICE)	Untreated advanced EGFR mutation-positive non-small-cell lung cancer (exon 19 deletion or L858R), with lazertinib
Amivantamab Rybrevant	England (NICE)	Untreated advanced non-small-cell lung cancer with an activating EGFR exon 20 insertion, with carboplatin and pemetrexed
ArteraAI Breast	US	Risk stratification in early-stage HR+/HER2- invasive breast cancer	first approval
Atezolizumab Tecentriq / Tecentriq Hybreza (SC)	US	Adjuvant muscle-invasive bladder cancer, ctDNA-positive after cystectomy
Aumolertinib Ameile	EU	Aumseqa: first-line advanced NSCLC with EGFR exon 19 deletion or L858R; advanced EGFR T790M-positive NSCLC
Belzutifan Welireg	US	Adjuvant clear-cell RCC with pembrolizumab
Bevacizumab Avastin (and biosimilars)	England (NICE)	First- and second-line metastatic colorectal cancer with fluoropyrimidine-based chemotherapy, only when targeted treatment or immunotherapy is unsuitable
Camizestrant Etcamah	US	HR+/HER2- advanced breast cancer with an emergent ESR1 mutation on AI + CDK4/6, with a CDK4/6 inhibitor (accelerated, 4 Sep 2026)	first approval
Camizestrant Etcamah	EU	ER+/HER2- advanced breast cancer with emergent ESR1 mutation, with a CDK4/6 inhibitor; 20 Jul 2026	first approval
Capivasertib Truqap	US	PTEN-deficient metastatic prostate cancer with abiraterone
Cemiplimab Libtayo	England (NICE)	Untreated locally advanced non-small-cell lung cancer unsuitable for definitive chemoradiation, or metastatic disease, with PD-L1 in 1 percent or more of tumour cells and no EGFR or ALK alteration, with platinum-based chemotherapy
Daratumumab Darzalex / Darzalex Faspro (SC)	US	With teclistamab after ≥1 line (MajesTEC-3); high-risk smouldering myeloma (AQUILA)
Daraxonrasib Rasonque	US	Metastatic pancreatic adenocarcinoma after at least one prior systemic therapy, or in adults who are not candidates for multiagent systemic therapy	first approval
Datopotamab deruxtecan Datroway	US	First-line unresectable/metastatic TNBC, PD-1/PD-L1 inhibitor ineligible
Decitabine + cedazuridine (oral) Inqovi	US	Newly diagnosed AML, unfit for intensive induction, with venetoclax (ASCERTAIN-V)
Durvalumab Imfinzi	US	High-risk NMIBC with BCG
Encorafenib Braftovi	US	First-line BRAF V600E mCRC with cetuximab and chemotherapy
Encorafenib Braftovi	US	Metastatic colorectal cancer with a BRAF V600E mutation
Gedatolisib Revtorpyk	US	HR+/HER2- advanced breast cancer after CDK4/6 inhibitor (July 2026)	first approval
Iberdomide Zenbexus	US	Multiple myeloma after at least one prior line including a proteasome inhibitor and an immunomodulatory agent, with subcutaneous daratumumab and dexamethasone (Zenbexus, label effective 13 August 2026)	first approval
Imlunestrant Inluriyo	EU	ESR1-mutant ER+/HER2- mBC; 9 Jan 2026
Isatuximab Sarclisa / Sarclisa Escena (SC)	US	Subcutaneous formulation (Sarclisa Escena)
Lazertinib Lazcluze	England (NICE)	Untreated advanced EGFR mutation-positive non-small-cell lung cancer (exon 19 deletion or L858R), with amivantamab
Lirafugratinib Lyrfigtu	US	Previously treated unresectable, locally advanced or metastatic cholangiocarcinoma with an FGFR2 fusion or other rearrangement	first approval
Lurbinectedin Zepzelca	EU	Maintenance with atezolizumab in ES-SCLC after first-line induction; 29 May 2026
Lutetium-177 vipivotide tetraxetan Pluvicto	US	Label expansion (July 2026)
Nadofaragene firadenovec Adstiladrin	EU	BCG-unresponsive NMIBC with CIS; 28 May 2026 (conditional)
Nivolumab Opdivo / Opdivo Qvantig (SC)	US	Untreated advanced classical Hodgkin lymphoma with AVD, age ≥12
Nivolumab Opdivo / Opdivo Qvantig (SC)	England (NICE)	Resectable non-small-cell lung cancer at high risk of recurrence without an EGFR mutation or ALK rearrangement: neoadjuvant with platinum chemotherapy then adjuvant alone
Nogapendekin alfa inbakicept Anktiva	EU	BCG-unresponsive NMIBC with CIS, with BCG; 16 Feb 2026 (conditional)
Optune / Optune Pax (TTFields) Optune	US	Locally advanced pancreatic cancer with chemotherapy
Osimertinib Tagrisso	England (NICE)	Unresectable stage III EGFR mutation-positive non-small-cell lung cancer that has not progressed after platinum-based chemoradiotherapy
Palbociclib Ibrance	US	HR+/HER2+ advanced breast cancer maintenance with anti-HER2 and endocrine therapy
Pembrolizumab Keytruda / Keytruda Qlex (SC)	US	Platinum-resistant PD-L1+ ovarian cancer; adjuvant RCC with belzutifan; with sacituzumab govitecan in 1L TNBC
Piflufolastat F-18 / Pylarify TruVu Pylarify	US	Pylarify TruVu formulation
Pivekimab sunirine Decnupaz	US	Blastic plasmacytoid dendritic cell neoplasm	first approval
Relacorilant Lifyorli	US	Platinum-resistant ovarian, fallopian tube, or primary peritoneal cancer with nab-paclitaxel	first approval
Rusfertide Mimrylo	US	Erythrocytosis in adults with polycythaemia vera	first approval
Sacituzumab govitecan Trodelvy	US	First-line metastatic TNBC: monotherapy (PD-1 ineligible) or with pembrolizumab (PD-L1 CPS ≥10)
Sacituzumab govitecan Trodelvy	EU	First-line unresectable locally advanced or metastatic TNBC in patients who are not candidates for PD-1 or PD-L1 inhibitor therapy (ASCENT-03); listed in the EMA therapeutic indications read on 24 September 2026
Selpercatinib Retevmo	US	Label update (July 2026)
Serplulimab Hansizhuang / Hetronifly	England (NICE)	Untreated extensive-stage small-cell lung cancer, with carboplatin and etoposide
Setmelanotide Imcivree	US	Acquired hypothalamic obesity in adults and children aged 4 years and older
SimpleScreen CRC SimpleScreen	US	Colorectal cancer screening in average-risk adults aged 45 and older	first approval
Sonrotoclax Beqalzi	US	Relapsed/refractory mantle cell lymphoma after ≥2 lines including a BTK inhibitor (accelerated)
Tarlatamab Imdelltra	EU	ES-SCLC after platinum-based chemotherapy; 29 May 2026
Teclistamab Tecvayli	US	Relapsed/refractory myeloma after ≥1 prior therapy
Tovorafenib Ojemda	EU	Relapsed/refractory paediatric low-grade glioma (conditional)
Trastuzumab deruxtecan Enhertu	US	Early-stage HER2+ breast cancer (neoadjuvant and post-neoadjuvant)
Vepdegestrant Veppanu	US	ESR1-mutated ER+/HER2- advanced or metastatic breast cancer after endocrine therapy	first approval
Vusolimogene oderparepvec Tudriqev	US	Unresectable/metastatic melanoma after anti-PD-1, with nivolumab (accelerated)	first approval
Zanidatamab Ziihera	UK	HER2-positive (IHC 3+) unresectable locally advanced or metastatic biliary tract cancer after at least one line of systemic treatment; MHRA 19 February 2026, NICE TA1153 published 7 May 2026 with a commercial arrangement
Zenocutuzumab Bizengri	US	NRG1-fusion cholangiocarcinoma
Zidesamtinib Jideytro	US	ROS1+ NSCLC (July 2026)	first approval
Zongertinib Hernexeos	US	First-line HER2-mutant non-squamous NSCLC

Trials reported in 2026

19 positive

ActiveA Study Investigating the Efficacy and Safety of Alcestobart (LBL-007) Plus Tislelizumab in Combination With Bevacizumab Plus Fluoropyrimidine Versus A Phase 1b/2, Randomized, Open-Label Study Investigating the Efficacy and Safety of LBL-007 Plus Tislelizumab in Combination With Bevacizumab Plus Fluoropyrimidine Versus Bevacizumab Plus Fluoropyrimidine as Maintenance Therapy in Patients With Unresectable or Metastatic Microsatellite Stable/Mismatch Repair Proficient Colorectal Cancer
ActiveA Study of Botensilimab and Balstilimab for the Treatment of Colorectal CancerA Randomized, Open-Label, Phase 2 Study of Botensilimab (AGEN1181) as Monotherapy and in Combination With Balstilimab (AGEN2034) or Investigator's Choice Standard of Care (Regorafenib or Trifluridine and Tipiracil) for the Treatment of Refractory Metastatic Colorectal Cancer
ActiveA Study of Brentuximab Vedotin in Combination With Cyclophosphamide, Doxorubicin (Hydroxydaunorubicin), Prednisone (CHP) in Chinese Participants With CD30-Positive (CD30+) Peripheral T-Cell Lymphomas (PTCL)A Phase 2, Single-Arm, Open-Label, Multicenter Study of Brentuximab Vedotin in Combination With Cyclophosphamide, Doxorubicin (Hydroxydaunorubicin), Prednisone (CHP) in the Frontline Treatment of Chinese Patients With CD30-Positive (CD30+) Peripheral T-Cell Lymphomas (PTCL)
ActiveA Study of Lazertinib With Subcutaneous Amivantamab Compared With Intravenous Amivantamab in Participants With Epidermal Growth Factor Receptor (EGFR)A Phase 3, Open-label, Randomized Study of Lazertinib With Subcutaneous Amivantamab Compared With Intravenous Amivantamab in Patients With EGFR-mutated Advanced or Metastatic Non-small Cell Lung Cancer After Progression on Osimertinib and Chemotherapy
ActiveA Study of Niraparib in Combination With Abiraterone Acetate and Prednisone Versus Abiraterone Acetate and Prednisone for the Treatment of Participants With Deleterious Germline or Somatic Homologous Recombination Repair (HRR) Gene-MutatedProstatic Neoplasms (mCSPC)A Phase 3 Randomized, Placebo-controlled, Double-blind Study of Niraparib in Combination With Abiraterone Acetate and Prednisone Versus Abiraterone Acetate and Prednisone for the Treatment of Participants With Deleterious Germline or Somatic Homologous Recombination Repair (HRR) Gene-Mutated Metastatic Castration-Sensitive Prostate Cancer (mCSPC)
ActiveA Study of Nofazinlimab (CS1003) in Subjects With Advanced Hepatocellular CarcinomaA Multi-Center, Double-Blind, Randomized, Phase III Study to Investigate the Efficacy and Safety of Nofazinlimab (CS1003) in Combination With Lenvatinib Compared to Placebo in Combination With Lenvatinib as First-Line Therapy in Subjects With Advanced Hepatocellular Carcinoma (HCC)
ActiveA Study of Novel Anti-cancer Agents in Patients With Metastatic Triple Negative Breast CancerA Phase IB/II, 2-stage, Open-label, Multicenter Study to Determine the Efficacy and Safety of Durvalumab (MEDI4736) + Paclitaxel and Durvalumab (MEDI4736) in Combination With Novel Oncology Therapies With or Without Paclitaxel for First-line Metastatic Triple Negative Breast Cancer
ActiveA Study of Oral LOXO-292 (Selpercatinib) in Pediatric Participants With Advanced Solid or Primary Central Nervous System (CNS) TumorsA Phase 1/2 Study of the Oral RET Inhibitor LOXO 292 in Pediatric Patients With Advanced RET-Altered Solid or Primary Central Nervous System Tumors
ActiveA Study of Osimertinib With or Without Chemotherapy Versus Chemotherapy Alone as Neoadjuvant Therapy for Patients With EGFRm Positive Resectable Non-SA Phase III, Randomised, Controlled, Multi-center, 3-Arm Study of Neoadjuvant Osimertinib as Monotherapy or in Combination With Chemotherapy Versus Standard of Care Chemotherapy Alone for the Treatment of Patients With Epidermal Growth Factor Receptor Mutation Positive, Resectable Non-small Cell Lung Cancer
ActiveA Study of Participant Reported Preference for Subcutaneous Pembrolizumab Coformulated With Berahyaluronidase Alfa (MK-3475A) Over Intravenous PembrolA Phase 2 Study to Evaluate Patient Reported Preference for Subcutaneous Pembrolizumab Coformulated With Hyaluronidase (MK-3475A) Over Intravenous Pembrolizumab Formulation in Participants With Multiple Tumor Types (MK-3475A-F11)
ActiveA Study of Selpercatinib (LOXO-292) in Participants With Advanced Solid Tumors, RET Fusion-Positive Solid Tumors, and Medullary Thyroid Cancer (LIBRETObjective response 64 percent after platinum chemotherapy and 85 percent in previously untreated RET fusion-positive non-small-cell lung cancer; intracranial response 91 percent.
ActiveA Study of Subcutaneous Nivolumab + Relatlimab Fixed-dose Combination (FDC) in Previously Untreated Metastatic or Unresectable MelanomaA Phase 3, Randomized, Open-label, Study of Subcutaneous Nivolumab + Relatlimab Fixed-dose Combination Versus Intravenous Nivolumab + Relatlimab Fixed-dose Combination in Participants With Previously Untreated Metastatic or Unresectable Melanoma
ActiveA Study of Subcutaneous Nivolumab Versus Intravenous Nivolumab in Participants With Previously Treated Clear Cell Renal Cell Carcinoma That is AdvanceA Phase 3, Open-label, Randomized, Noninferiority Trial of Subcutaneous Formulation of Nivolumab Versus Intravenous Nivolumab in Participants With Advanced or Metastatic Clear Cell Renal Cell Carcinoma Who Have Received Prior Systemic Therapy
ActiveA Study of TAK-853 in Adult Participants With Folate Receptor Alpha-Positive Advanced Ovarian Cancer And Other Solid TumorsA Phase 1/2 Open-label Study to Evaluate The Safety, Tolerability, Efficacy And Pharmacokinetics of Mirvetuximab Soravtansine (TAK-853) in Japanese Patients With Folate Receptor Alpha-Positive Advanced Ovarian Cancer And Other Solid Tumors
ActiveA Study of the Safety and Efficacy of Various Combinations of Avelumab as Therapy in Locally Advanced or Metastatic Urothelial Carcinoma (JAVELIN Bladder Medley)A Phase II, Multicenter, Randomized, Open Label, Parallel-Arm, Umbrella Study of Avelumab (MSB0010718C) in Combination With Other AntiTumor Agents as a Maintenance Treatment in Participants With Locally Advanced or Metastatic Urothelial Carcinoma Whose Disease Did Not Progress With First Line Platinum-Containing Chemotherapy (JAVELIN Bladder Medley)
A Study to Allow Continued Dosing and/or Follow-up of Patients Who Have Had Previous Exposure to PoziotinibAn Open-Label Extension Study to Allow Continued Dosing and/or Follow-up of Patients Who Have Had Previous Exposure to Poziotinib
ActiveA Study to Compare the Efficacy and Safety of Oral Azacitidine Plus Best Supportive Care Versus Best Supportive Care as Maintenance Therapy in Japanese Participants With Acute Myeloid Leukemia (AML) in Complete RemissionA Phase 2, Randomized, Double-Blind, Placebo-controlled Study to Compare Efficacy and Safety of Oral Azacitidine Plus Best Supportive Care Versus Best Supportive Care as Maintenance Therapy in Japanese Subjects With Acute Myeloid Leukemia in Complete Remission
ActiveA Study to Determine Dose, Safety, Tolerability and Efficacy of CC-220 Monotherapy, and in Combination With Other Treatments in Subjects With MultiplePhase 1b/2a Multicenter, Open-label, Dose-escalation Study to Determine the Maximum Tolerated Dose, Assess the Safety, Tolerability, Pharmacokinetics and Efficacy of CC-220 As Monotherapy and in Combination With Other Treatments in Subjects With Multiple Myeloma
ActiveA Study to Evaluate Chemotherapy Plus Osimertinib Against Chemotherapy Plus Placebo in Patients With Non-small Cell Lung Cancer (NSCLC)A Phase III, Randomized, Double-Blind, Placebo-Controlled Study of Platinum Plus Pemetrexed Chemotherapy Plus Osimertinib Versus Platinum Plus Pemetrexed Chemotherapy Plus Placebo in Patients With EGFRm, Locally Advanced or Metastatic NSCLC Who Have Progressed Extracranially Following First-Line Osimertinib Therapy (COMPEL)
ActiveA Study to Evaluate Enfortumab Vedotin in Subjects With Locally Advanced or Metastatic Malignant Solid Tumors (EV-202)An Open-label, Multicenter, Multicohort, Phase 2 Study to Evaluate Enfortumab Vedotin in Subjects With Locally Advanced or Metastatic Malignant Solid Tumors (EV-202)
ActiveA Study to Evaluate the Safety and Efficacy of Glofitamab in Combination With Rituximab (R) Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (CHOP) in Circulating Tumor (ct)DNA High-Risk Patients With Untreated Diffuse Large B-Cell LymphomaA Phase II Study Evaluating the Safety and Efficacy of Glofitamab in Combination With Rituximab (R) Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (CHOP) in Circulating Tumor (ct)DNA High-Risk Patients With Untreated Diffuse Large B-Cell Lymphoma
ActiveA Study to Evaluate Whether Participants With Melanoma Prefer Subcutaneous vs Intravenous Administration of Nivolumab and Nivolumab + Relatlimab FixedA Phase 2 Open-label, Two-cohort Study to Evaluate Patient Preference for Nivolumab + Relatlimab Fixed-dose Combination Subcutaneous Versus Nivolumab + Relatlimab Fixed-dose Combination Intravenous and Nivolumab Subcutaneous Versus Nivolumab Intravenous in Participants With Melanoma
ActiveA Study to Investigate Tolerability and Efficacy of Asciminib (Oral) Versus Nilotinib (Oral) in Adult Participants (≥18 Years of Age) With Newly Diagnosed Philadelphia Chromosome Positive Chronic Myelogenous Leukemia in Chronic Phase (Ph+ CML-CP)A Phase IIIb, Multi-center, Open-label, Randomized Study of Tolerability and Efficacy of Oral Asciminib Versus Nilotinib in Patients With Newly Diagnosed Philadelphia Chromosome Positive Chronic Myelogenous Leukemia in Chronic Phase.
NegativeALTAIRMedian disease-free survival 9.30 against 5.55 months (hazard ratio 0.79, p=0.107): primary endpoint not met.
NegativeAMPLIFY-7PPrimary DFS endpoint not met.
ActiveAn Efficacy and Safety Study of Luspatercept (ACE-536) Versus Placebo in Subjects With Myeloproliferative Neoplasm-Associated Myelofibrosis on ConcomiA Phase 3, Double-blind, Randomized Study to Compare the Efficacy and Safety of Luspatercept (ACE-536) Versus Placebo in Subjects With Myeloproliferative Neoplasm-Associated Myelofibrosis on Concomitant JAK Inhibitor Therapy and Who Require Red Blood Cell Transfusions
PositiveASCERTAIN-VCR 41.6%; median time to CR 2 months.
PositiveAZUR-1Primary endpoint (sustained cCR at 12 months) met; rates pending congress presentation.
PositiveBL-B01D1-307PFS and OS significantly improved at interim analysis (numbers presented ASCO 2026).
ActiveCAMPFIRE: A Study of Abemaciclib (LY2835219) in Participants With Ewing's SarcomaA Randomized, Open-Label, Phase 2 Study Evaluating Abemaciclib in Combination With Irinotecan and Temozolomide in Participants With Relapsed or Refractory Ewing's Sarcoma
ActiveCapivasertib+Paclitaxel as First Line Treatment for Patients With Locally Advanced or Metastatic TNBCOverall survival 17.7 vs 18.0 months (HR 0.92, p 0.32) overall and 20.4 vs 20.4 months (HR 1.05) in PIK3CA/AKT1/PTEN-altered tumours; PFS 5.6 vs 5.1 months (HR 0.72).
PositiveCLARITY-Gastric 01Co-primary endpoints including OS met (July 2026); numbers pending.
ActiveComparing the Efficacy and Safety of a New Additional Treatment With Tislelizumab in Non-Small Cell Lung Cancer (NSCLC)At the final analysis (median follow-up 38.5 months) overall survival favoured perioperative tislelizumab (hazard ratio 0.65, 95 percent confidence interval 0.45 to 0.93, p=0.009); 36-month overall survival 79.3 against 69.3 percent.
PositiveDeLLphi-305Met the primary overall survival endpoint at the pre-specified interim analysis (Amgen, 8 September 2026); progression-free survival and response rate also improved; figures not yet disclosed.
NegativeDREAM3RStopped early; primary endpoint not met.
ActiveEfficacy and Safety of Olaparib (MK-7339) in Participants With Previously Treated, Homologous Recombination Repair Mutation (HRRm) or Homologous Recombination Deficiency (HRD) Positive Advanced Cancer (MK-7339-002 / LYNK-002)A Phase 2 Study of Olaparib Monotherapy in Participants With Previously Treated, Homologous Recombination Repair Mutation (HRRm) or Homologous Recombination Deficiency (HRD) Positive Advanced Cancer
ActiveEfficacy Comparison of Cobolimab + Dostarlimab + Docetaxel to Dostarlimab + Docetaxel to Docetaxel Alone in Participants With Advanced Non-small Cell Lung Cancer Who Have Progressed on Prior Anti-PD-(L)1 Therapy and ChemotherapyA Randomized, Open Label Phase 2/3 Study Comparing Cobolimab + Dostarlimab + Docetaxel To Dostarlimab + Docetaxel To Docetaxel Alone In Participants With Advanced Non-small Cell Lung Cancer Who Have Progressed On Prior Anti-PD-(L)1 Therapy And Chemotherapy (COSTAR Lung)
PositiveEMERALD-3PFS HR ~0.70 (interim); OS immature.
MixedEPCORE DLBCL-1PFS HR 0.74; OS HR 0.96 (NS).
ActiveEvaluation of Co-formulated Pembrolizumab/Quavonlimab (MK-1308A) Versus Other Treatments in Participants With Microsatellite Instability-High (MSI-H) A Phase 2, Multicenter, Multi Arm, Study to Evaluate MK-1308A (Co-formulated Quavonlimab (MK-1308)/Pembrolizumab) Versus Other Treatments in Participants With Microsatellite Instability-High (MSI-H) or Mismatch Repair Deficient (dMMR) Stage IV Colorectal Cancer: (MK-1308A-008)
NegativeFianlimab + cemiplimab phase 3 (first-line melanoma)Primary PFS endpoint not met; numerical +5.1 months median PFS at the high dose.
WithdrawnFIGHT-302Untreated advanced cholangiocarcinoma with an FGFR2 rearrangement: pemigatinib against gemcitabine and cisplatin
PositiveFOURLIGHT-1PFS improved (HR not yet published in detail).
NegativeGeparDouze / NSABP B-59EFS HR 0.80 (0.62 to 1.03), p 0.083, not significant; OS HR 0.86 (0.62 to 1.19).
MixedHARMONi-3Interim PFS not statistically significant (May 2026); final readouts pending.
PositiveHERIZON-GEA-01PFS 12.4 vs 8.1 months (HR 0.63-0.65); OS significantly improved.
PositiveINTerpath-001 (V940-001)RFS and DMFS significantly improved (HRs pending presentation).
PositiveKrascendo 1Superior PFS and OS vs approved G12C inhibitors (topline, July 2026).
PositiveLITESPARK-011Final progression-free survival 14.8 vs 10.7 months (hazard ratio 0.70, 95% CI 0.59 to 0.84; one-sided p<0.0001). Interim overall survival 34.9 vs 27.6 months (hazard ratio 0.85, 0.68 to 1.05; one-sided p 0.061), not statistically significant. Data cutoff 9 April 2025.
NegativeLITESPARK-012Primary endpoint not met (ASCO GU 2026).
PositiveLITESPARK-022DFS significantly improved vs pembrolizumab (interim; HR presented ASCO GU 2026).
PositiveMATRix/IELSG43Three-year progression-free survival 78 percent after high-dose chemotherapy and autologous transplant against 51 percent after non-myeloablative R-DeVIC (hazard ratio 0.43, p 0.0003), with better overall survival and more toxicity.
PositiveMETRO PLUS (Tata Memorial Centre, Varanasi)Median OS 10 vs 5 months, HR 0.54.
ActiveNHS-Galleri142,250 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
ActiveOlaparib in Treating Patients With Metastatic Biliary Tract Cancer With Aberrant DNA Repair Gene MutationsA Phase II Study of Olaparib in Patients With Advanced Biliary Tract Cancer With Aberrant DNA Repair Gene Mutations
ActiveOsimertinib Plus Savolitinib in EGFRm+/MET+ NSCLC Following Prior OsimertinibA Phase II Study Assessing the Efficacy of Osimertinib in Combination With Savolitinib in Patients With EGFRm+ and MET+, Locally Advanced or Metastatic Non Small Cell Lung Cancer Who Have Progressed Following Treatment With Osimertinib.
PositivePANKU-Esophagus01 (BL-B01D1-305)OS and PFS significantly improved at interim analysis; numbers per ASCO 2026 presentation.
PositivePEACE-3 (EORTC 1333)Median overall survival 38.2 months with enzalutamide plus radium-223 against 32.6 months with enzalutamide alone (hazard ratio 0.76, 95 percent confidence interval 0.60 to 0.96, p=0.0096); radiological progression-free survival hazard ratio 0.71 (0.57 to 0.89). Bone-protecting agents mandatory.
NegativepersevERAPFS 33.1 vs 28.2 months, not significant.
ActivePhase 3 Study of MRTX849 With Cetuximab vs Chemotherapy in Patients With Advanced Colorectal Cancer With KRAS G12C Mutation (KRYSTAL-10)A Randomized Phase 3 Study of MRTX849 in Combination With Cetuximab Versus Chemotherapy in Patients With Advanced Colorectal Cancer With KRAS G12C Mutation With Disease Progression On or After Standard First-Line Therapy
PositivePOLARGOMedian overall survival 19.5 against 12.5 months (hazard ratio 0.6, p = 0.0017), with more peripheral neuropathy and more fatal infections.
PositiveRASolute 302OS 13.2 vs 6.7 months, HR 0.40.
ActiveSTAR-TRECOrgan preservation in early and intermediate rectal cancer: long-course chemoradiotherapy against short-course radiotherapy, both followed by response assessment and either watch and wait or local excision, against total mesorectal excision; 34 centres in England, Scotland, Wales, Denmark and the Netherlands; recruitment closed 31 December 2023, follow-up to 2027
ActiveStudy Evaluating Tarlatamab in Chinese Participants With Advanced Small Cell Lung Cancer After Two or More Prior Lines of TreatmentPhase 2a Study Evaluating the Efficacy, Safety, Tolerability and Pharmacokinetics of Tarlatamab in Chinese Subjects With Advanced Small Cell Lung Cancer After Two or More Prior Lines of Treatment (DeLLphi-307)
ActiveStudy of BGB-11417 Monotherapy in Participants With Relapsed or Refractory Mantle Cell LymphomaA Single-Arm, Open-Label, Multicenter Phase 1/2 Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of BCL2 Inhibitor BGB-11417 in Patients With Relapsed or Refractory Mantle Cell Lymphoma
ActiveStudy of Efficacy and Safety of Dabrafenib in Combination With Trametinib in Previously Treated Patients With Metastatic, Radio-active Iodine RefractoA Randomized, Double-blind, Placebo-controlled Phase III Study to Evaluate the Efficacy and Safety of Dabrafenib Plus Trametinib in Previously Treated Patients With Locally Advanced or Metastatic, Radio-active Iodine Refractory BRAFV600E Mutation-positive Differentiated Thyroid Cancer (DTC)
ActiveStudy of IMGN632 in Patients With Untreated BPDCN and Relapsed/Refractory BPDCNA Phase 1/2, Multi-center, Open-label Study of IMGN632 Monotherapy Administered Intravenously in Patients With CD123-positive Acute Myeloid Leukemia and Other CD123-positive Hematologic Malignancies
ActiveStudy of Pimicotinib (ABSK021) for Tenosynovial Giant Cell Tumor (MANEUVER)A Phase 3, Randomized, Double-blind, Placebo-Controlled, Multicenter Study of ABSK021 to Assess the Efficacy and Safety in Patients With Tenosynovial Giant Cell Tumor
ActiveStudy of Retinfanlimab in Combination With INCAGN02385 and INCAGN02390 as First-Line Treatment in Participants With PD-L1-Positive (CPS ≥ 1) Recurrent/Metastatic Squamous Cell Carcinoma of the Head and NeckA Randomized, Double-Blind, Multicenter, Phase 2 Study of Retifanlimab in Combination With INCAGN02385 (Anti-LAG-3) and INCAGN02390 (Anti-TIM-3) as First-Line Treatment in Participants With PD-L1-Positive (CPS ≥ 1) Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck
RecruitingStudy of RMC-6236 in Patients With Advanced Solid Tumors Harboring Specific Mutations in RASSecond-line daraxonrasib 300 mg in 26 patients with RAS G12-mutated pancreatic cancer: objective response 35 percent, median progression-free survival 8.5 months, median overall survival 13.1 months; grade 3 or higher treatment-related adverse events in 30 percent of 168 pancreatic patients.
ActiveStudy of Sacituzumab Govitecan in Participants With Metastatic Solid TumorsA Phase 2 Open-Label Study of Sacituzumab Govitecan (IMMU-132) in Subjects With Metastatic Solid Tumors
ActiveStudy to Evaluate Imetelstat in Patients With High-Risk MDS or AML Failing HMA-based TherapyA Phase II Study Evaluating the Efficacy and Safety of Imetelstat in Patients With HR Myelodysplastic Syndromes or AML Failing HMA-based Therapy
ActiveSub-study of Belantamab Mafodotin (GSK2857916) as Monotherapy and in Combination With Nirogacestat, Pomalidomide, and Dexamethasone in Participants WiA Phase I/II, Randomized, Open-label Platform Study Utilizing a Master Protocol to Study Belantamab Mafodotin (GSK2857916) as Monotherapy and in Combination With Anti-Cancer Treatments in Participants With Relapsed/Refractory Multiple Myeloma (RRMM)-DREAMM5 - Sub-study 7 - Belantamab Mafodotin, Nirogacestat, Pomalidomide, and Dexamethasone in Combination
ActiveSub-study of Belantamab Mafodotin (GSK2857916) in Combination With Feladilimab (GSK3359609) in Participants With RRMMA Phase I/II, Randomized, Open-label Platform Study Utilizing a Master Protocol to Study Belantamab Mafodotin (GSK2857916) as Monotherapy and in Combination With Anti-Cancer Treatments in Participants With Relapsed/Refractory Multiple Myeloma (RRMM)-DREAMM5 - Sub-study 2 - Belantamab Mafodotin and Feladilimab (GSK3359609) in Combination
ActiveSub-study of Belantamab Mafodotin (GSK2857916) in Combination With Isatuximab in Participants With RRMMA Phase I/II, Randomized, Open-label Platform Study Utilizing a Master Protocol to Study Belantamab Mafodotin (GSK2857916) as Monotherapy and in Combination With Anti-Cancer Treatments in Participants With Relapsed/Refractory Multiple Myeloma (RRMM)-DREAMM5- Sub-study 5 - Belantamab Mafodotin and Isatuximab in Combination
ActiveSub-study of Belantamab Mafodotin (GSK2857916) in Combination With Nirogacestat in Participants With RRMMA Phase I/II, Randomized, Open-label Platform Study Utilizing a Master Protocol to Study Belantamab Mafodotin (GSK2857916) as Monotherapy and in Combination With Anti-Cancer Treatments in Participants With Relapsed/Refractory Multiple Myeloma (RRMM)-DREAMM5 - Sub-study 3 - Belantamab Mafodotin and Nirogacestat in Combination
ActiveSub-study of Belantamab Mafodotin (GSK2857916) in Combination With Nirogacestat, Lenalidomide, and Dexamethasone in Participants With RRMMA Phase I/II, Randomized, Open-label Platform Study Utilizing a Master Protocol to Study Belantamab Mafodotin (GSK2857916) as Monotherapy and in Combination With Anti-Cancer Treatments in Participants With Relapsed/Refractory Multiple Myeloma (RRMM)-DREAMM5 - Sub-study 6 - Belantamab Mafodotin, Nirogacestat, Lenalidomide, and Dexamethasone in Combination
PositiveTRANSCENDLeast-squares mean change in body-mass index at 52 weeks minus 16.5% with setmelanotide vs plus 3.3% with placebo (P<0.001); hunger score change minus 2.73 vs minus 1.45 (P = 0.009).
ActiveVitamin D3 With Chemotherapy and Bevacizumab in Treating Patients With Advanced or Metastatic Colorectal CancerRandomized Double-Blind Phase III Trial of Vitamin D3 Supplementation in Patients With Previously Untreated Metastatic Colorectal Cancer (SOLARIS)
NegativeXPORT-EC-042 / ENGOT-EN20 / GOG-3083Primary PFS endpoint not met; mPFS 12.75 vs 7.43 months (mITT) not significant.

Negative, mixed, and withdrawn

failures are data

Trials

10TASQ10 A-BRAVE AALL1231 AALL1331 AAML1031 ACOSOG Z1071 (Alliance)ACT IV ADIUVO ADMEC-O (adjuvant nivolumab in completely resected Merkel cell carcinoma)AFFINITY AgeX Aldoxorubicin versus investigator's choice in relapsed or refractory soft tissue sarcoma ALEXANDRA / IMpassion030 Alliance A021501 Alliance N0147 Alliance/CALGB 50303 ALTAIR AMPLIFY-7P Anetumab ravtansine versus vinorelbine in relapsed mesothelin-positive pleural mesothelioma ANNOUNCE APACT ARMOR3-SV ARTISTIC meta-analysis ASCENDE-RT ASPEN (Waldenström macroglobulinaemia)ASPREE (ASPirin in Reducing Events in the Elderly)ASTRA ATEMPT ATLANTIS AVAglio AVENGER 500 BEAT-meso (ETOP 13-18)BELINDA Big Lung Trial BILCAP BRE12-158 (Hoosier Oncology Group)BROCADE3 BWEL (Breast Cancer Weight Loss, Alliance A011401)CA184-043 CAIRO5 CALGB 40603 (Alliance)CALGB 90401 CALGB/SWOG 80405 CALLA CanStem111P CAO/ARO/AIO-12 CheckMate 026 CheckMate 143 CheckMate 498 CheckMate 548 CheckMate 577 CheckMate 915 CLL12 COG ACNS0331 COG ACNS0332 COLOPEC COMET-1 CONKO-005 CONKO-007 CONTACT-03 CONVERT COSMIC-313 CREST: consolidation thoracic radiotherapy in extensive-stage small-cell lung cancer CROSSFIRE De-ESCALaTE HPV DREAM3R DUO-O / ENGOT-ov46 DYNAMIC-III ECLIPSE (GVAX pancreas and CRS-207)ECOG-ACRIN EA1131 ELM-PC 4 EMERALD-1 ENTHUSE M1 EORTC 10801 EORTC 22033-26033 EORTC 22911 EORTC 22961 EORTC 40983 EORTC/LYSA/FIL H10 EPCORE DLBCL-1 ERA 223 ERGO2: ketogenic diet and fasting during re-irradiation of recurrent glioma ESPAC-1 EURAMOS-1 Fianlimab + cemiplimab phase 3 (first-line melanoma)FIRSTANA FORTITUDE-101 GATSBY GEICAM/2003-11_CIBOMA/2004-01 GeparDouze / NSABP B-59 GETUG-AFU 15 GETUG-AFU 17 GHSG HD16 GOG-0218 & ICON7 (bevacizumab)GOYA HALO 109-301 HARMONi-3 HER2CLIMB-02 HERBY HERTHENA-Lung02 HORRAD IDEA collaboration IELSG-19 IMbassador250 IMblaze370 IMbrave050 IMpassion130 IMpassion131 IMPRESS (algenpantucel-L)INSITE INTELLANCE-1 Interfant-06 IPATunity130 Ivermectin plus losartan for COVID-19 in cancer patients (ICESP phase 2, terminated)JAVELIN Head and Neck 100 JCOG9801 JROSG 99-1 (Aoyama): stereotactic radiosurgery with or without whole-brain radiotherapy KEYNOTE-062 KEYNOTE-091 (PEARLS)KEYNOTE-119 KEYNOTE-412 KEYNOTE-641 KEYNOTE-921 KEYNOTE-991 KRISTINE LACC (Laparoscopic Approach to Cervical Cancer)LAP07 LAPIS LEAP-002 LEAP-012 LITESPARK-012 LUME-Lung 1 LUME-Meso Lung ART Lung-MAP S1400I: nivolumab with or without ipilimumab Lung-SEARCH MAGNITUDE MAJIC-ET MANIFEST-2 MARS 2 MoleMate UK Trial MORPHO MRC COIN NALIRICC (AIO)NCI9673 NEOLAP NEONAX NeoTRIP (NeoTRIPaPDL1)New EPOC NordICC (Nordic-European Initiative on Colorectal Cancer)NORPACT-1 NRG-HN002 & NRG-HN005 (HPV+ de-escalation)NSABP B-39/RTOG 0413 NSABP B-51 / RTOG 1304 ORATOR OUTBACK / ANZGOG 0902 / GOG-0274 PACIFIC-2 PALLAS & PENELOPE-B PALOMA-2 Patidegib gel in Gorlin syndrome (phase 2A)PENELOPE-B persevERA PETACC-3 PETACC-8 Photodynamic therapy against cryotherapy for superficial basal cell carcinoma Photodynamic therapy against surgery for nodular basal cell carcinoma PIVOT (Prostate Cancer Intervention Versus Observation Trial)PLCO, prostate component (Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial)POLO PREOPANC-1 PREOPANC-2 PRIMA PRIMA / ENGOT-OV26 PRODIGE 7 PROPHYLOCHIP-PRODIGE 15 PROSPECT QUARTZ RADICALS-RT RAPID (accelerated partial-breast irradiation)RAVES (TROG 08.03/ANZUP)READY RELATIVITY-098 RELEVANCE REMARC RESOLVE ROMAN ROMANA 1 and ROMANA 2 RTOG 0617 RTOG 1016 RTOG 92-02 SARAH and SIRveNIB SARC028 SCIN (curettage then imiquimod against excision for nodular basal cell carcinoma)SHINE Single-injection depot progesterone before breast surgery (Tata Memorial)SINS (surgical excision against imiquimod cream for basal cell carcinoma)SIOPEN HR-NBL1 SPINET SPLASH SQUIRE STARGLO STARS and ROSEL pooled analysis STELLAR (rectal cancer)STEVIE (vismodegib in ordinary practice)STOMP STRASS (EORTC 62092)SUPREMO (BIG 2-04)SWOG 9346 (intermittent androgen deprivation)SWOG S0421 SWOG S1815 SYNERGY Takahashi trial: prophylactic cranial irradiation with MRI surveillance in extensive-stage small-cell lung cancer TAPPAS TARGIT-A (targeted intraoperative radiotherapy)TIME2 TiNivo-2 TNT (Triple Negative Trial)TOSCA TPExtreme (GORTEC 2014-01)TreeTopp TrilynX TRITON3 TROG 05.01 (chemotherapy added to radiotherapy after surgery for high-risk skin squamous cell carcinoma)TROPION-Breast01 TROPION-Lung01 TRYbeCA-1 UKCTOCS VERITAC-2 VERONA VITAL (VITamin D and OmegA-3 TriaL)VOYAGER WHEL (Women's Healthy Eating and Living)WINTHER XPORT-EC-042 / ENGOT-EN20 / GOG-3083

Programmes and targets

ESSA PharmaMasofanitenRindopepimutFianlimabVeliparibPegvorhyaluronidase alfaPegilodecakinNapabucasinGaleteroneCustirsenOrteronelTasquinimodZibotentanAtrasentanPROSTVACTIGIT CD47 Gritstone bioTiragolumabMagrolimabRovalpituzumab tesirineIniparibBempegaldesleukinADU-S100 (MIW815)EprenetapoptTusamitamab ravtansineEpacadostatTrastuzumab duocarmazineMelphalan flufenamideTazemetostatMoxetumomab pasudotoxCopanlisibUmbralisibPanobinostatMobocertinibPixantroneAbarelixInfigratinibOlaratumabOlmutinibOprelvekinAnetumab ravtansineHomeopathy Alternative medicine used instead of standard treatment Laetrile (amygdalin, 'vitamin B17')Gerson therapy, coffee enemas and 'detox' regimens Shark cartilage (AE-941, Neovastat)Hydrazine sulfate Antineoplastons (Burzynski clinic)Black salve and other escharotic pastes Fenbendazole, ivermectin and other internet 'repurposed cures'Essiac, Hoxsey and other 'herbal cancer cures'Supplements sold for hair growth after cancer treatment Creams and lotions tried to prevent chemotherapy hair lossDevimistatPamrevlumabEryaspaseAlgenpantucel-LXevinapantDepatuxizumab mafodotinMifepristoneCarotuximabGI-6301PoziotinibPevonedistatEvofosfamide

Roadmap progress

Current (124 steps)

Third generation: TOP1 payloads and bystander killing
ADC roadmap · 2019-2022
Third generation matures: earlier lines, more targets, combinations
ADC roadmap · 2023-2026
Structure prediction and generative design
AI in oncology roadmap · 2020-2026
Foundation models and the first predictive tests
AI in oncology roadmap · 2023-2026
Validation, data and compute
AI in oncology roadmap · What sets the pace
Screening at scale and risk models
AI in the oncology clinic · 2022-2024
First predictive AI and foundation models in products
AI in the oncology clinic · 2025-2026
One dose, self-sampling and vaccines made where they are needed
Cancer prevention roadmap · 2021-2026
Aspirin and tamoxifen for the right people
Cancer prevention roadmap · 2022-2027
Deployment, funding and politics
Cancer prevention roadmap · What sets the pace
Solid tumours: TIL, TCR-T, CAR-T
Cell therapy roadmap · 2024-2026
The backbone that immunotherapy and ADCs are built on
Chemotherapy roadmap · 2010s-2026
Giving it to fewer people
Chemotherapy roadmap · 2018-2026
The warhead moves inside an antibody
Chemotherapy roadmap · 2019-2026
Generics, incentives and what trials measure
Chemotherapy roadmap · What sets the pace
The screening programmes, and the discovery that uptake is the whole game
Colorectal cancer roadmap · 1993-2022
Antibodies, and the two things that decide whether they work
Colorectal cancer roadmap · 2004-2017
Refractory lines measured in weeks, and de-escalation measured in months of chemotherapy avoided
Colorectal cancer roadmap · 2013-2023
Immunotherapy takes mismatch repair-deficient disease apart
Colorectal cancer roadmap · 2015-2025
BRAF, HER2 and the first KRAS allele
Colorectal cancer roadmap · 2016-2024
A blood test for the disease that is left behind
Colorectal cancer roadmap · 2016-2026
Keeping the rectum, and what surgery still has to carry
Colorectal cancer roadmap · 2004-2026
The disease is moving younger, and nobody can say why
Colorectal cancer roadmap · 2017-2026
Uptake, capacity, the microsatellite stable majority and who gets to the operating table
Colorectal cancer roadmap · What sets the pace
Tumour-informed residual disease tests reach the clinic and the payer
ctDNA tests roadmap · 2019-2021
Randomised trials: sparing treatment works, adding it is harder
ctDNA tests roadmap · 2022-2026
The first drug approval that depends on a ctDNA result
ctDNA tests roadmap · 2025-2026
Screening from blood: one cancer approved, many cancers under review
ctDNA tests roadmap · 2021-2026
Payment, standards and what to do with a positive
ctDNA tests roadmap · What sets the pace
Electric fields become a treatment
Devices and physical therapies roadmap · 2011-2026
Light-activated drugs and drug-releasing implants
Devices and physical therapies roadmap · 2020-2026
Devices that make treatment bearable and reachable
Devices and physical therapies roadmap · 2015-2028
Trials nobody owns, evidence nobody blinds
Devices and physical therapies roadmap · What sets the pace
Comprehensive profiling and tumour-agnostic biomarkers
Diagnostics roadmap · 2017-2022
Blood tests that change treatment in randomised trials
Diagnostics roadmap · 2022-2026
Validation, standardisation and payment
Diagnostics roadmap · What sets the pace
Exercise becomes a treatment
Diet, exercise and lifestyle roadmap · 2020-2026
Nutrition care as a standard of care
Diet, exercise and lifestyle roadmap · 2015-2026
No patent, no sponsor, plenty of noise
Diet, exercise and lifestyle roadmap · What sets the pace
Maps of dependency and models closer to the patient
Drug discovery roadmap · 2015-2024
Structure prediction and generative design
Drug discovery roadmap · 2020-2026
New modalities as platforms
Drug discovery roadmap · 2015-2026
Models, reproducibility and the valley of death
Drug discovery roadmap · What sets the pace
Pivotal trials and first approvals
Early detection roadmap · 2021-2026
Mutation-specific epigenetic drugs
Epigenetic therapy roadmap · 2017-2020
Hypomethylating agents as the backbone
Epigenetic therapy roadmap · 2020-2026
Menin inhibitors and the first brain tumour epigenetic drug
Epigenetic therapy roadmap · 2023-2026
Undruggable targets, plasticity and biomarkers
Epigenetic therapy roadmap · What sets the pace
The incidental cancer pathway: re-resect from T1b, but who, when and how much
Gallbladder cancer roadmap · 2007-2026
Adjuvant capecitabine and second-line FOLFOX, from UK trials
Gallbladder cancer roadmap · 2017-2021
Immunotherapy joins chemotherapy
Gallbladder cancer roadmap · 2022-2025
HER2: the first target where gallbladder cancer leads
Gallbladder cancer roadmap · 2017-2025
Prevention where the burden is: Chile, India and typhoid
Gallbladder cancer roadmap · 2006-2026
Under-studied relative to burden
Gallbladder cancer roadmap · What sets the pace
Frugal evidence: less drug, cheaper schedules, same result
Global access and affordability roadmap · 2015-2026
Homegrown innovation in India and China
Global access and affordability roadmap · 2018-2026
Screening and prevention that fit the budget
Global access and affordability roadmap · 2000s-2026
Pricing power, divergence and the absence of care
Global access and affordability roadmap · What sets the pace
Prostate cancer: earlier, deeper, combined
Hormonal therapy roadmap · 2011-2024
Breast cancer: CDK4/6 inhibitors and the pathway partners
Hormonal therapy roadmap · 2015-2026
Degrading the receptor, switching on a blood test
Hormonal therapy roadmap · 2023-2026
Resistance, price and tolerability
Hormonal therapy roadmap · What sets the pace
Earlier lines and combinations
Immunotherapy roadmap · 2018-2024
Beyond G12C
KRAS roadmap · 2023-2026
Stage III, and treatment moving to either side of the operation
Lung cancer roadmap · 2017 to 2024
The driver list grows, and first-line treatment starts to be intensified
Lung cancer roadmap · 2020 to 2026
Small-cell lung cancer, static for twenty-five years and then not
Lung cancer roadmap · 1999 to 2026
Everything that failed to beat R-CHOP, and the one thing that did
Lymphoma roadmap · 2005-2022
The scan after two cycles, and what it is good for
Lymphoma roadmap · 2006-2019
Indolent lymphoma: how long to treat, and the two-year mark that splits the disease
Lymphoma roadmap · 2011-2026
Cells and engagers: the immune treatments that work when chemotherapy does not
Lymphoma roadmap · 2015-2026
Mantle cell lymphoma: three ways to use a Bruton tyrosine kinase inhibitor, and none of them extends life
Lymphoma roadmap · 2017-2026
The T-cell lymphomas, where almost nothing has been randomised
Lymphoma roadmap · 2007-2026
Four things no trial on this page has fixed
Lymphoma roadmap · What sets the pace
Stromal PET and total-body scanners
Molecular imaging roadmap · 2018-2026
Engineered immunity, children first
Paediatric oncology roadmap · 2014-2026
Precision medicine and the regulatory lever
Paediatric oncology roadmap · 2017-2026
Protecting the child who is cured
Paediatric oncology roadmap · 2016-2026
Markets, regulators, late effects and geography
Paediatric oncology roadmap · What sets the pace
Adjuvant modified FOLFIRINOX, and the neoadjuvant question
Pancreatic cancer roadmap · 2017-2025
The first biomarker-directed drug, and the first stromal failure
Pancreatic cancer roadmap · 2019-2022
Surveillance for carriers and the new-onset diabetes signal
Pancreatic cancer roadmap · 2005-2022
KRAS becomes druggable
Pancreatic cancer roadmap · 2013-2026
Vaccines that last, a device that adds months, and a first-line chemotherapy answer
Pancreatic cancer roadmap · 2023-2026
Late presentation, fitness, wasting and who gets treated at all
Pancreatic cancer roadmap · What sets the pace
Removing every cell, and knowing that you did
Paths to cures · Eradication: established
Living with cancer as a chronic disease
Paths to cures · Control: established
Everything moves to the first day of metastatic diagnosis
Prostate cancer roadmap · 2013 to 2022
DNA repair: the first molecular subset of prostate cancer with a drug of its own
Prostate cancer roadmap · 2015 to 2026
PSMA: the same molecule used to see the cancer and then to irradiate it
Prostate cancer roadmap · 2017 to 2026
Ideas already being tested against a control arm
Radical oncology · Now (randomised data exists)
PSMA theranostics
Radiopharmaceutical roadmap · 2020-2022
Earlier lines, consolidation, and an M&A wave
Radiopharmaceutical roadmap · 2023-2026
Radiation plus drugs: what worked and what did not
Radiotherapy roadmap · 2017-2026
Particles, magnets and adaptation
Radiotherapy roadmap · 2010s-2026
Doing less: fewer visits and fewer treatments
Radiotherapy roadmap · 2016-2026
Machines, physicists and money
Radiotherapy roadmap · What sets the pace
Exercise becomes a treatment
Recovery and rejuvenation roadmap · 2017-2026
Biological ageing becomes measurable, and sellable
Recovery and rejuvenation roadmap · 2014-2026
No sponsor, no registry, no owner, no endpoint
Recovery and rejuvenation roadmap · What sets the pace
Supportive care that lengthens life
Supportive care and survivorship roadmap · 2010-2026
Cheap fixes with strong evidence
Supportive care and survivorship roadmap · 2015-2026
No sponsor, no registry, no organiser
Supportive care and survivorship roadmap · What sets the pace
The drug arrives before the surgeon
Surgery roadmap · 2018-2026
Organ preservation and no surgery at all
Surgery roadmap · 2022-2028
Treating through a needle or a catheter
Surgery roadmap · 2010s-2026
Funding, workforce and access
Surgery roadmap · What sets the pace
Designed for resistance, the brain and the adjuvant setting
Targeted therapy roadmap · 2014-2020
The undruggable drivers fall
Targeted therapy roadmap · 2021-2026
Resistance, combinations, biomarkers and price
Targeted therapy roadmap · What sets the pace
ADCs move to first line; bispecific ADC succeeds
TNBC roadmap · 2024-2026
Decentralised, pragmatic and more inclusive
Trial modernisation roadmap · 2016-2024
Better endpoints and evidence-based doses
Trial modernisation roadmap · 2022-2026
Enrolment, cost, exclusion and hidden failures
Trial modernisation roadmap · What sets the pace
Platinum
Triple-negative breast cancer roadmap · 2014-2022
Residual disease becomes treatable: capecitabine after neoadjuvant chemotherapy
Triple-negative breast cancer roadmap · 2017
PARP inhibition for germline BRCA carriers
Triple-negative breast cancer roadmap · 2017-2026
Immunotherapy: an assay dispute, then a new standard for early disease
Triple-negative breast cancer roadmap · 2018-2024
Antibody-drug conjugates move from third line to first
Triple-negative breast cancer roadmap · 2020-2026
Selection, sequence, sanctuary and who gets enrolled
Triple-negative breast cancer roadmap · What sets the pace
Second entrant: datopotamab deruxtecan
TROP2 ADC roadmap · 2023-2025
First line: three positive phase 3 trials
TROP2 ADC roadmap · 2025-2026
First single-cell foundation models
Virtual cell roadmap · 2023-2024
Data at scale and context-aware models
Virtual cell roadmap · 2025-2026

Emerging (60 steps)

Fourth generation, wave 1: bispecific ADCs
ADC roadmap · 2026-2028
Fourth generation, wave 2: new payload logic
ADC roadmap · 2026-2030
Language models enter the workflow
AI in oncology roadmap · 2025-2028
From prediction to prospective proof
AI in oncology roadmap · 2027-2032
Prospective evidence and regulatory frameworks
AI in the oncology clinic · 2026-2028
Weight, alcohol, tobacco and infection at population scale
Cancer prevention roadmap · 2025-2030
Inherited risk found before the cancer
Cancer prevention roadmap · 2026-2032
Manufacturing revolution: allogeneic and in vivo
Cell therapy roadmap · 2025-2028
The right dose, the right schedule, the right patient
Chemotherapy roadmap · 2024-2030
Fewer harms from the drugs we keep
Chemotherapy roadmap · 2024-2030
What the registry says is coming
Colorectal cancer roadmap · 2026-2032
The randomised answers arrive
ctDNA tests roadmap · 2026-2029
Deeper, cheaper and tumour-naive
ctDNA tests roadmap · 2026-2030
Focused sound: destroy, prime, open
Devices and physical therapies roadmap · 2024-2028
Slides become data
Diagnostics roadmap · 2024-2028
Spatial, single-cell and protein layers guide the choice
Diagnostics roadmap · 2027-2032
The microbiome and immunotherapy
Diet, exercise and lifestyle roadmap · 2024-2028
Metabolic interventions under randomised test
Diet, exercise and lifestyle roadmap · 2025-2030
Cachexia as a treatable disease
Diet, exercise and lifestyle roadmap · 2026-2030
Functional precision medicine
Drug discovery roadmap · 2026-2030
Perturbation data at the scale the problem needs
Drug discovery roadmap · 2026-2030
Decision and integration
Early detection roadmap · 2026-2030
Solid tumours and the transcriptional machinery
Epigenetic therapy roadmap · 2026-2030
What the registry says is coming
Gallbladder cancer roadmap · 2026-2030
Reliance, pooling and public manufacturing
Global access and affordability roadmap · 2026-2030
Paying for value in rich countries too
Global access and affordability roadmap · 2026-2030
Into the adjuvant setting and around the next resistance
Hormonal therapy roadmap · 2026-2030
Engineered immunity arrives
Immunotherapy roadmap · 2024-2027
Approval and combinations
KRAS roadmap · 2026-2029
Reading the tumour over time: heterogeneity, ctDNA and resistance-directed treatment
Lung cancer roadmap · 2017 to 2027
Never-smoker disease and the air people breathe
Lung cancer roadmap · 2021 to 2030
What the registry says is coming
Lymphoma roadmap · 2026-2032
Drug-target and immune PET
Molecular imaging roadmap · 2024-2028
Next trials, next targets, one global plan
Paediatric oncology roadmap · 2026-2030
What the registry says is coming
Pancreatic cancer roadmap · 2026-2031
Vaccinating and monitoring people who do not yet have cancer
Paths to cures · Interception: next
Killing the last cell, wherever it is hiding
Paths to cures · Eradication: next
Steering resistance instead of waiting for it
Paths to cures · Control: next
What the androgen receptor era created: splice variants, lineage switching and a cold tumour
Prostate cancer roadmap · 2014 to 2026
Reversing the adaptation instead of blocking it, and asking what order to give things in
Prostate cancer roadmap · 2018 to 2030
Living drugs, logic gates, and designed proteins reach decision points
Radical oncology · By 2027 (early clinical, readouts imminent)
Radiation and radiopharmaceuticals get a second act
Radical oncology · By 2030 (physics and chemistry maturing)
Monitoring becomes continuous and selection becomes spatial
Radical oncology · By 2030 (detection and decision-making)
Alpha emitters and new targets
Radiopharmaceutical roadmap · 2026-2029
FLASH, arcs, upright and new particles
Radiotherapy roadmap · 2026-2032
Services that exist, and follow-up somebody owns
Recovery and rejuvenation roadmap · 2026-2030
Endpoints the field does not yet have
Recovery and rejuvenation roadmap · 2027-2033
Cachexia gets a drug
Supportive care and survivorship roadmap · 2026-2029
Survivorship as a system, not a leaflet
Supportive care and survivorship roadmap · 2026-2030
Seeing the margin and preparing the patient
Surgery roadmap · 2026-2030
Fourth generations, degraders and switching on a blood test
Targeted therapy roadmap · 2026-2030
New modalities for the old targets
Targeted therapy roadmap · 2026-2032
Next: residual disease, de-escalation, selection
TNBC roadmap · 2026-2029
AI and data in trial operations
Trial modernisation roadmap · 2025-2029
Standing infrastructure: trials that never close
Trial modernisation roadmap · 2026-2032
Residual disease and the blood test that might guide it
Triple-negative breast cancer roadmap · 2020-2026
What the registry says is coming
Triple-negative breast cancer roadmap · 2026-2030
Third entrant: sacituzumab tirumotecan and the Merck programme
TROP2 ADC roadmap · 2024-2027
Unsolved: selection, sequencing, resistance
TROP2 ADC roadmap · 2026-2029
Patient-derived contexts and spatial niches
Virtual cell roadmap · 2027-2029

Late-stage pipeline

256 products in phase 3 · 4092 trials recruiting or active

177Lu-edotreotide177Lu-PSMA-I&TA166AAA817ABBV-706AbexinostatAcasunlimabActinium-225 DOTATATEActinium-225 PSMA agentsAdagloxad simoleninADI-PEG20Aglatimagene besadenovecAK117AL2846AL8326AldoxorubicinAnitocabtagene autoleucelArlocabtagene AutoleucelARX788ASC40ASP2138AtebimetinibAtigotatugAtirmociclibAvasopasem manganeseAZD0120AZD0486AZD5335AzenosertibBCD-100BCD-217BEBT-209BemarituzumabBexobrutidegBezuclastinibBGB-16673BGB-43395BleximenibBMS-986365BNT113BNT324BomedemstatBrenetafuspBrigimadlinBudigalimabCalderasibCAM2029 (octreotide subcutaneous depot)CeralasertibCetrelimabCevostamabChiauranibClifutinibCobolimabCretostimogene grenadenorepvecD-0502D07001DaromunDarovasertibDCVax-LDivarasibDomvanalimabDZD8586EIK1001ElenestinibElriterceptEmactuzumabESG401EvorpaceptF182112FavezelimabFDA018-ADCFianlimabFicerafusp alfaFiclatuzumabFlorastamin F-18GalleriGFH375GiredestrantGivinostatGLSI-100GolcadomideGotistobartGQ1005GR1803GRT-C901GRT-R902HB1801HLX11HLX22HLX43HMPL-306HMPL-453HMPL-760HR070803HRS-4357HRS-8080HS-20089HS-20093HS-20117IAH0968IBI310IBI343IBI354ICP-248IDRX-42Ifinatamab deruxtecanIfupinostatIMA203IN10018INBRX-106INCA33890INCB123667INCB161734INT230-6Intismeran autogeneIO102-IO103Iomab-BIpatasertibIvospeminIzalontamab brengitecanJDQ443JMT101JNJ-79635322JNJ-87189401JNJ-90301900JS105JSKN003JSKN016KC1036KL-A167KN026LAM561LerociclibLerotinibLivmoniplimabLM-108LM-302LNS8801Luveltamab tazevibulinM108M701MevrometostatMezigdomideMK-1045MonalizumabMRG002MRG003NaporafenibNavitoclaxNavlimetostatNB003NBTXR3 (hafnium oxide nanoparticles)NeladalkibNemtabrutinibObrixtamigOleclumabOlomorasibOlvimulogene nanivacirepvecOpevesostatOregovomabOSE2101PamiparibPasritamigPatidegibPatritumab deruxtecanPelabresibPetosemtamabPF-07248144PF-08046054PF-08634404PM8002PonsegromabPrecemtabart tocentecanPSMA-1007 F-18PurinostatQL1706QL2107QLC5508QLS31905QLS32015QuemliclustatRadotinibRaludotatug deruxtecanRC148Retlirafusp alfaRinatabart sesutecanRinzimetostatRO7771950RocbrutinibRondecabtagene autoleucelRPH-051SafusidenibSaruparibSasanlimabSCTB14SCTB35SCTB41SCTC21CSenaparib (IMP4297)SetidegrasibSG301SGM-101SHR-1501SHR-8068SHR-A1912SHR-A1921SHR-A2009SHR-A2102SI-B001SIM0270SitneprotafibSocazolimabSofetabart MipitecanSonesitatug vedotinSoquelitinibSPH4336Synthetic hypericinSYS6010TAK-928TAR-210TARA-002TBI-1301Telisotuzumab adizutecanTersolisibTGRX-326TinengotinibTovecimigTQ-B3234TQB2102TQB2450TQB3454TQB3616TrabedersenTrastuzumab brengitecanTrastuzumab pamirtecanTY-9591UGN-103UGN-104UliledlimabUtomilumabVaregacestatVC004VelzatinibVepugratinibVisugromabXaluritamigXZP-3287YL201YL202ZanzalintinibZG006Zilovertamab vedotinZipalertinibZirconium-89 girentuximabZL-1310Zovegalisib

Frontier technologies

ADC payload neutralisers AI-driven drug & target discovery Alpha-emitter nanogenerators and daughter trapping Antibody-oligonucleotide conjugates Armoured, logic-gated & next-gen CARs Auger-electron therapy Bacteriophage-based tumour delivery Bispecific ADC Breath and volatile-organic-compound detection Cachexia-directed therapy (GDF-15 blockade)Cancer interception vaccines Cancer neuroscience: cutting the nerve supply CAR-NK & CAR-macrophage CAR-T against stroma: fibroblasts and myeloid cells cfDNA fragmentomics Chronotherapy: timing treatment to the body clock Continuous and near-continuous ctDNA monitoring De novo designed protein binders Degrader-antibody conjugate (DAC)Digital twins and virtual control arms DNA origami nanorobots Dual-payload ADC Engineered bacteria as living cancer drugs Engineered exosomes as drug carriers Epigenetic editing (durable gene silencing)FLASH radiotherapy Histotripsy as an immune primer Hypoxia-activated prodrugs Immune-stimulating antibody conjugate (ISAC)In situ vaccination In vivo base and prime editing for cancer In vivo CAR-T Intratumoural gene electrotransfer (IL-12 plasmid)Lattice and GRID radiotherapy Logic-gated therapeutics (AND, NOT gates)Magnetic nanoparticle hyperthermia Masked / conditionally active ADC Metabolic therapy: starving the tumour of a nutrient Microbiome modulation to unlock immunotherapy Molecular glue discovery platforms N-of-1 and rapid platform trials Oligonucleotide therapeutics Organoid-guided therapy at scale Pathology & radiology foundation models Photothermal (plasmonic) nanoparticle ablation Programmable DNA-targeting therapeutics Proton arc therapy Quantum-dot and molecular ultrasound imaging agents Radio-antibody & radio-ADC Radiodynamic therapy and radiosensitising nanoparticles Radioligand plus DNA-repair inhibitor combinations Self-amplifying and circular RNA therapeutics Senolytics and senescence-directed therapy Sonodynamic therapy Spatial-omics-guided treatment selection STING & innate immune agonists Systematic drug repurposing Targeted alpha therapy Targeting the tumour's own microbes Targeting tumour mechanics and pressure Total-body PET for screening and ultra-low-dose imaging Trained innate immunity TROP2 PET Very-high-energy electron therapy

Open problems by cancer

Adolescent and young adult cancers: Trial enrolment in AYA remains far below that of children.
Adolescent and young adult cancers: Fertility preservation is offered unevenly and paid for inconsistently.
Breast cancer: The receptor result produces four boxes and the world is organised around three. One report gives a hormone receptor answer and a HER2 answer, and the four combinations are unequal: 70.1 percent hormone receptor-positive HER2-negative, 9.3 percent positive for both, 4.0 percent HER2-positive alone and 10.8 percent triple-negative (SEER 21, 2019 to 2023). Guidelines, trials and patient information are written for three subtypes, so the largest HER2-positive group, the people who are hormone receptor-positive as well, have to read two sets of advice and work out where they overlap.
Breast cancer: The classification a report is written against is two years behind the classification in print. The sixth edition of the WHO classification of breast tumours appeared in April 2026 and changed the vocabulary of subtype, pattern and variant, the HER2 reporting categories and the criteria for several types; the UK reporting dataset in force was written against the fifth edition and is due for review in November 2026. Every page in this family, and every report a patient is holding, is currently a fifth-edition document, and there is no mechanism that tells a patient which edition her report was written to.
Ductal carcinoma in situ: Distinguishing DCIS that would progress from DCIS that would not; molecular classifiers, mammographic AI and the monitoring trials are the route.
Ductal carcinoma in situ: Long-term safety of active monitoring beyond two years; LORIS and LORD follow-up and the COMET ten-year endpoint will tell.
Early HER2-positive breast cancer: Which women can skip chemotherapy entirely without losing cure.
Early HER2-positive breast cancer: Interstitial lung disease from trastuzumab deruxtecan in women who would otherwise have been cured.
Early triple-negative breast cancer: No trial has tested capecitabine or olaparib on top of adjuvant pembrolizumab for residual disease.
Early triple-negative breast cancer: About a third of patients do not reach a complete response and most relapses come from them.
HER2-low and HER2-ultralow metastatic breast cancer: Immunohistochemistry was never designed to score low expression and pathologists disagree at the 0 to 1+ boundary.
HER2-low and HER2-ultralow metastatic breast cancer: Whether a second topoisomerase I payload works after the first.
HER2-positive breast cancer: Sequencing after T-DXd: no randomised data on which HER2 ADC or TKI works after TOP1-payload failure.
HER2-positive breast cancer: Interstitial lung disease with T-DXd in curative settings, where patients would otherwise be cured.
HER2-positive breast cancer with brain metastases: No randomised trial has compared systemic therapy first with radiosurgery first for asymptomatic lesions.
HER2-positive breast cancer with brain metastases: Leptomeningeal disease still has no proven treatment.
High-risk early HR-positive breast cancer: No test yet identifies the women whose relapse will come after ten years, when endocrine therapy has stopped.
High-risk early HR-positive breast cancer: Two to three years of a CDK4/6 inhibitor is costly and its overall survival benefit is not yet proven.
HR-positive / HER2-negative breast cancer: Late recurrence: half of relapses occur after year 5 and no test reliably identifies who needs extended or intensified therapy.
HR-positive / HER2-negative breast cancer: Adherence: a third of women stop adjuvant endocrine therapy early because of arthralgia, hot flushes, and sexual side effects.
HR-positive metastatic breast cancer after CDK4/6 inhibitors: No trial has compared the sequence of oral SERD, pathway inhibitor and antibody-drug conjugate.
HR-positive metastatic breast cancer after CDK4/6 inhibitors: Whether to continue a CDK4/6 inhibitor after progression gives small gains and it is unclear for whom.
Inflammatory breast cancer: Diagnosis is delayed because the picture is mistaken for infection.
Inflammatory breast cancer: No molecular driver of the inflammatory phenotype has been found.
Male breast cancer: Men are still under-enrolled in breast cancer trials; regulatory guidance and label harmonisation are the response.
Male breast cancer: Aromatase inhibitor efficacy and the need for GnRH co-treatment rest on small studies; registries are collecting outcomes.
Metastatic triple-negative breast cancer: Cross-resistance between antibody-drug conjugates sharing a topoisomerase I payload.
Metastatic triple-negative breast cancer: No biomarker selects patients for TROP2 drugs.
Paget disease of the nipple: Months of delay while the nipple is treated as eczema.
Paget disease of the nipple: No randomised evidence exists for any treatment choice.
Phyllodes tumour of the breast: No randomised trial has tested margin width or radiotherapy.
Phyllodes tumour of the breast: Core biopsy cannot reliably distinguish phyllodes tumour from fibroadenoma.
Triple-negative breast cancer: Residual disease after KEYNOTE-522: no approved escalation beyond capecitabine/olaparib; ctDNA-guided trials needed.
Triple-negative breast cancer: ADC sequencing: does a second TOP1-payload ADC work after the first? SATEEN/BRE-354 suggest limited efficacy; chemotherapy interposition debated.
Astrocytoma, IDH-mutant: Whether vorasidenib should replace radiotherapy and chemotherapy or only defer them, and what to do at progression on it.
Astrocytoma, IDH-mutant: No IDH inhibitor has yet shown benefit in grade 3 or 4 IDH-mutant astrocytoma.
Brain and spinal cord tumours: Drugs rarely cross the blood-brain barrier at useful concentrations.
Brain and spinal cord tumours: Median survival in diffuse midline glioma is still about a year.
Brain metastases: Trials still often exclude patients with brain metastases, so drug activity in the brain is learned late.
Brain metastases: Leptomeningeal disease has no standard treatment and a survival of months.
Central nervous system germ cell tumours: Which non-germinomatous patients can safely avoid craniospinal irradiation.
Central nervous system germ cell tumours: Late endocrine, cognitive and vascular effects of radiotherapy in survivors treated as teenagers.
Glioma & glioblastoma: Blood-brain barrier.
Glioma & glioblastoma: Immunologically cold, heterogeneous, infiltrative.
Meningioma: No approved systemic therapy; grade 3 and recurrent unresectable tumours have few options.
Meningioma: Whether completely resected grade 2 meningiomas need radiotherapy (ROAM, NRG BN003).
Oligodendroglioma, IDH-mutant and 1p/19q-codeleted: Whether temozolomide can replace PCV without losing survival (CODEL).
Oligodendroglioma, IDH-mutant and 1p/19q-codeleted: How to sequence vorasidenib, chemotherapy and radiotherapy over a disease course of decades.
Primary CNS lymphoma: Most patients are over 65 and cannot tolerate curative-intent therapy.
Primary CNS lymphoma: Neurocognitive decline from disease and therapy.
Spinal cord tumours: Almost no trial evidence; treatment is extrapolated from brain tumours and case series.
Spinal cord tumours: Infiltrating cord astrocytomas cannot be removed and have no effective drug.
Vestibular schwannoma: No approved drug for NF2-related schwannomatosis; bevacizumab is off label and its effect wanes.
Vestibular schwannoma: Predicting which small tumours will grow, so that the rest can be left alone.
Adrenocortical carcinoma: No targeted therapy despite defined genomic subgroups.
Adrenocortical carcinoma: Mitotane toxicity and narrow therapeutic window.
Advanced and metastatic adrenocortical carcinoma: No second-line therapy has randomised evidence.
Advanced and metastatic adrenocortical carcinoma: Most tumours are immunologically cold and cortisol excess worsens that.
Anaplastic thyroid cancer: Most people diagnosed still die within a year, and the MD Anderson series that lifted one-year survival from about a fifth to over half came from one centre combining BRAF-targeted drugs, immunotherapy, surgery and radiotherapy; whether that holds outside specialist centres is what prospective work has to establish.
Anaplastic thyroid cancer: BRAF wild-type disease has no targeted option.
Extrapulmonary neuroendocrine carcinoma: No randomised trial has improved on platinum-etoposide in first line.
Extrapulmonary neuroendocrine carcinoma: Whether adding a PD-1 or PD-L1 antibody helps, as it does in small-cell lung cancer, is untested in a phase 3.
Follicular thyroid cancer: Telling adenoma from carcinoma without surgery.
Follicular thyroid cancer: Bone metastases respond poorly to iodine.
Grade 3 well-differentiated neuroendocrine tumour: The Ki-67 boundary between grade 3 tumour and carcinoma is not sharp, and some cases can only be settled by molecular testing.
Grade 3 well-differentiated neuroendocrine tumour: No trial has been run in grade 3 tumours alone; NETTER-2 and COMPOSE mix them with grade 2.
Hereditary pheochromocytoma and paraganglioma: Penetrance of SDHx mutations is incomplete and variable, so how intensively to screen carriers is debated.
Hereditary pheochromocytoma and paraganglioma: No treatment prevents new tumours in carriers.
Localised adrenocortical carcinoma: Whether adjuvant chemotherapy adds to mitotane in high-risk disease awaits ADIUVO-2.
Localised adrenocortical carcinoma: Mitotane is slow to reach therapeutic levels and causes neurological and gastrointestinal toxicity in many patients.
Medullary thyroid cancer: No cure once the disease has spread beyond the neck.
Medullary thyroid cancer: Resistance mutations to RET inhibitors (G810) are emerging.
Metastatic pheochromocytoma and paraganglioma: No randomised trial has compared radionuclide therapy with drugs or defined their order.
Metastatic pheochromocytoma and paraganglioma: Azedra's withdrawal leaves MIBG-avid, somatostatin-receptor-negative patients without a radionuclide option in many countries.
Multiple endocrine neoplasia syndromes: MEN1 has no menin-restoring or pathway-directed therapy; PanNET progression remains the main cause of death, addressed by earlier detection and NET therapies.
Multiple endocrine neoplasia syndromes: Timing and extent of pancreatic surgery in MEN1: prospective registries are comparing strategies.
Neuroendocrine tumours: Neuroendocrine carcinoma (high grade) behaves like SCLC.
Neuroendocrine tumours: Sequencing of PRRT vs targeted therapy.
Pancreatic neuroendocrine tumours: The best order of radioligand therapy, everolimus, sunitinib, cabozantinib and CAPTEM is unknown.
Pancreatic neuroendocrine tumours: Which small non-functioning tumours can safely be watched rather than resected.
Papillary thyroid cancer: Overdiagnosis and overtreatment of small tumours found by imaging.
Papillary thyroid cancer: Which intermediate-risk patients truly benefit from radioactive iodine.
Parathyroid carcinoma: Preoperative diagnosis: no reliable imaging or biochemical threshold, so many patients have inadequate first surgery.
Parathyroid carcinoma: No effective systemic anticancer therapy for metastatic disease; genomic profiling for actionable alterations and immunotherapy case series are the current approach.
Pheochromocytoma and paraganglioma: No reliable predictor of metastasis at diagnosis: molecular classifiers and SDHB status are being validated.
Pheochromocytoma and paraganglioma: Withdrawal of 131I-MIBG from the market left a gap that 177Lu-DOTATATE and alpha-emitters are filling.
Pituitary tumours (pituitary neuroendocrine tumours) and pituitary carcinoma: Predicting aggressive behaviour at diagnosis: lineage, Ki-67 and molecular markers are being combined into risk scores.
Pituitary tumours (pituitary neuroendocrine tumours) and pituitary carcinoma: Salvage after temozolomide: PRRT, immunotherapy and bevacizumab have only case-series evidence.
Small intestinal neuroendocrine tumours: No randomised trial orders radioligand therapy, everolimus and cabozantinib after somatostatin analogues.
Small intestinal neuroendocrine tumours: Whether removing the primary improves survival in patients with liver metastases has never been tested prospectively.
Thyroid cancer: Overdiagnosis of microcarcinoma.
Thyroid cancer: Anaplastic thyroid cancer: BRAF V600E cases now respond to dabrafenib-trametinib, often enough to allow surgery; the 60% without the mutation still have few options.
Adenosquamous carcinoma of the pancreas: No prospective trial; whether platinum or squamous-directed regimens help is unknown.
Adenosquamous carcinoma of the pancreas: The 30 percent threshold depends on sampling, so small biopsies under-diagnose it.
Advanced and metastatic small bowel adenocarcinoma: No randomised phase 3 trial has ever been completed in advanced small bowel adenocarcinoma.
Advanced and metastatic small bowel adenocarcinoma: Mismatch-repair-proficient tumours have no effective immunotherapy.
Advanced hepatocellular carcinoma: No trial has defined the best drug after progression on immunotherapy.
Advanced hepatocellular carcinoma: Patients with Child-Pugh B liver function are excluded from trials yet make up a large share of the clinic.
Ampullary cancer: No prospective randomised trial has compared subtype-directed adjuvant regimens; retrospective consortia and the NCCN guideline are the current basis.
Ampullary cancer: Which patients with node-positive disease benefit from neoadjuvant therapy; extrapolation from pancreatic trials is being tested.
Anal cancer: Screening programmes for high-risk groups exist almost nowhere despite ANCHOR.
Anal cancer: Late toxicity of pelvic chemoradiation (bowel, sexual, bone).
Anal high-grade squamous intraepithelial lesions: Most HSIL never progresses, and no marker yet says which lesions to treat and which to watch.
Anal high-grade squamous intraepithelial lesions: High-resolution anoscopy is scarce outside specialist centres.
Appendiceal adenocarcinoma: No adjuvant chemotherapy trial has ever been run in appendiceal adenocarcinoma.
Appendiceal adenocarcinoma: Which patients with peritoneal disease benefit from HIPEC is defined only by retrospective series.
Appendiceal cancer and pseudomyxoma peritonei: No effective systemic therapy for high-grade or signet-ring disease.
Appendiceal cancer and pseudomyxoma peritonei: Selection for CRS-HIPEC and management of recurrence after maximal surgery.
Biliary tract cancer: Most patients are diagnosed too late for surgery.
Biliary tract cancer: No screening even in high-incidence regions.
Biliary tract cancer: FGFR inhibitor resistance.
Biliary tract cancer: Late diagnosis.
Borderline resectable pancreatic ductal adenocarcinoma: Definitions of borderline disease differ between centres, so trial populations are not comparable.
Borderline resectable pancreatic ductal adenocarcinoma: CT underestimates response after chemotherapy, and there is no validated marker to tell fibrosis from viable tumour before surgery.
BRAF V600E-mutant colorectal cancer: No standard therapy after progression on encorafenib and cetuximab.
BRAF V600E-mutant colorectal cancer: Resistance through MAPK reactivation and MET amplification is common and untargeted.
BRCA or PALB2-mutant pancreatic ductal adenocarcinoma: Olaparib delays progression but has not lengthened overall survival, and the best duration of maintenance is unknown.
BRCA or PALB2-mutant pancreatic ductal adenocarcinoma: Somatic and non-BRCA repair gene alterations respond unpredictably, and there is no validated homologous recombination deficiency test for the pancreas.
Claudin 18.2-positive gastric cancer: Whether zolbetuximab or PD-1 blockade should come first when both PD-L1 and claudin 18.2 are positive.
Claudin 18.2-positive gastric cancer: Tumours below the 75 percent threshold have no approved claudin 18.2 therapy.
Colloid (mucinous non-cystic) carcinoma of the pancreas: Rarity: no trial, no registry code, so its share and outcomes come from single centres.
Colloid (mucinous non-cystic) carcinoma of the pancreas: Whether the favourable outlook justifies less adjuvant treatment is untested.
Colorectal cancer: Outcomes differ sharply by race, income and geography, and the gap survives adjustment for stage: five-year bowel cancer survival in England is 55 percent in the most deprived group against 62.9 percent in the least (Cancer Research UK), and emergency presentation, which carries the worst outlook, is concentrated in the same places.
Colorectal cancer: Microsatellite-stable disease, 95% of metastatic colorectal cancer, has no working immunotherapy: the phase 3 test of atezolizumab with or without a MEK inhibitor matched regorafenib, and the best signal so far, botensilimab plus balstilimab, comes from single-arm cohorts (17% of 101 response-evaluable patients in the phase 1, Bullock 2024; 21% of 123 patients selected for the absence of liver metastases in the 2026 report). No randomised trial has yet selected patients by immune biology rather than by line of therapy.
Early gastric cancer: Western countries have no screening and diagnose most gastric cancers late.
Early gastric cancer: Predicting nodal spread in submucosal tumours to spare more patients surgery.
Early hepatocellular carcinoma: Recurrence in the remaining cirrhotic liver after resection or ablation.
Early hepatocellular carcinoma: No adjuvant therapy has held up in a phase 3 trial.
Early-onset colorectal cancer: The cause of the rise is unknown; no exposure has been proven.
Early-onset colorectal cancer: Diagnostic delay in young adults with rectal bleeding remains long.
Extrahepatic cholangiocarcinoma: Most perihilar tumours are unresectable at presentation, and half of resections leave microscopic disease.
Extrahepatic cholangiocarcinoma: Biliary obstruction and cholangitis, not the cancer's growth, often end treatment.
Gallbladder cancer: No screening test and no surveillance programme even in the highest-incidence regions; ultrasound-based surveillance and cholecystectomy policies are unproven.
Gallbladder cancer: Whether T1b tumours need radical re-resection: no randomised trial exists, meta-analyses of retrospective cohorts disagree on disease-specific benefit, and the largest international series found five-year disease-specific survival of 93.7 versus 95.5 percent after simple versus extended cholecystectomy in 237 patients (Kim 2018); bile duct excision and port-site policy rest on the same kind of series.
Gastric & gastro-oesophageal junction cancer: Peritoneal metastasis.
Gastric & gastro-oesophageal junction cancer: Heterogeneous CLDN18.2/HER2 expression.
Gastrointestinal stromal tumour: Polyclonal resistance: different lesions carry different secondary KIT mutations.
Gastrointestinal stromal tumour: SDH-deficient and other wild-type GIST have no effective TKI.
Goblet cell adenocarcinoma of the appendix: No prospective trial has ever been conducted; all treatment is extrapolated.
Goblet cell adenocarcinoma of the appendix: The benefit of adjuvant chemotherapy in grade 1 node-negative disease is unknown.
Hepatocellular carcinoma: Liver function limits therapy.
Hepatocellular carcinoma: Surveillance uptake in cirrhosis is poor.
HER2-amplified colorectal cancer: No randomised evidence yet for HER2 blockade in first line.
HER2-amplified colorectal cancer: RAS co-mutation blunts dual HER2 blockade and the best option for those patients is unclear.
HER2-positive gastric cancer: HER2 heterogeneity and loss after treatment make a single biopsy unreliable.
HER2-positive gastric cancer: No HER2-directed therapy has yet improved cure rates in resectable disease.
Imatinib-resistant GIST: Polyclonal resistance means no single inhibitor covers every metastasis.
Imatinib-resistant GIST: Each later line adds months, not years, and toxicity accumulates.
Incidental gallbladder cancer: Whether T1b tumours need re-resection: two 2024 to 2026 analyses disagree on disease-specific benefit.
Incidental gallbladder cancer: How many UK patients with an incidental cancer reach a hepatobiliary centre is not published.
Intermediate hepatocellular carcinoma: No overall survival gain yet shown for TACE combinations.
Intermediate hepatocellular carcinoma: Which patients should skip embolisation and go straight to systemic therapy.
Intraductal papillary mucinous neoplasm and other pancreatic cystic precursors: Most cysts never progress, and no test yet identifies the minority that will.
Intraductal papillary mucinous neoplasm and other pancreatic cystic precursors: Surveillance of a common incidental finding is costly and causes anxiety, and when it can safely stop is unknown.
Intrahepatic cholangiocarcinoma: Most patients present unresectable, and recurrence after resection is common.
Intrahepatic cholangiocarcinoma: FGFR inhibitor resistance develops within a year through kinase domain mutations.
Invasive carcinoma arising in an intraductal papillary mucinous neoplasm: No trial has tested whether colloid-type cancers can be spared adjuvant chemotherapy.
Invasive carcinoma arising in an intraductal papillary mucinous neoplasm: Surveillance still misses cancers: the parent cyst page carries the unresolved questions of when to operate and when to stop watching.
KIT exon 11-mutant GIST: Whether adjuvant imatinib should continue for five years or longer.
KIT exon 11-mutant GIST: Resistance through secondary KIT mutations in nearly every metastatic patient.
KRAS G12C-mutant colorectal cancer: Responses last months, not years; acquired RAS and MAPK alterations drive resistance.
KRAS G12C-mutant colorectal cancer: G12D, the commonest colorectal KRAS allele, has no approved drug.
KRAS G12C-mutant pancreatic ductal adenocarcinoma: Responses to G12C-selective inhibitors are shallower and shorter in the pancreas than in the lung.
KRAS G12C-mutant pancreatic ductal adenocarcinoma: Neither sotorasib nor adagrasib has a pancreatic indication, so access depends on off-label use and trials.
KRAS wild-type pancreatic ductal adenocarcinoma: Fusion testing is still missed when DNA panels are used alone, so many actionable tumours go unrecognised.
KRAS wild-type pancreatic ductal adenocarcinoma: Each driver is too rare for pancreatic-specific randomised trials; evidence is extrapolated from lung cancer and basket studies.
Localised anal squamous cell carcinoma: Radiotherapy dose for early and for locally advanced tumours is still being settled in PLATO.
Localised anal squamous cell carcinoma: About a quarter of patients with locally advanced disease relapse and need major surgery.
Localised small bowel adenocarcinoma: Whether adjuvant chemotherapy improves survival awaits the full BALLAD results.
Localised small bowel adenocarcinoma: Diagnosis is often delayed by months because the small bowel is hard to image.
Locally advanced unresectable pancreatic ductal adenocarcinoma: No local therapy after chemotherapy has lengthened survival in a randomised trial apart from tumour treating fields.
Locally advanced unresectable pancreatic ductal adenocarcinoma: Conversion surgery is uncommon and its benefit over continued non-surgical treatment is unproven.
Low-grade appendiceal mucinous neoplasm and pseudomyxoma peritonei: Cytoreduction with HIPEC has never been compared with cytoreduction alone in this disease.
Low-grade appendiceal mucinous neoplasm and pseudomyxoma peritonei: Recurrence after complete cytoreduction is common and criteria for reoperation vary.
Metastatic and recurrent anal squamous cell carcinoma: Median survival remains under two years even with a PD-1 antibody added to chemotherapy.
Metastatic and recurrent anal squamous cell carcinoma: No second-line standard exists after chemo-immunotherapy.
Metastatic pancreatic ductal adenocarcinoma: Resistance to RAS inhibitors emerges within months and the best partner drugs are unknown.
Metastatic pancreatic ductal adenocarcinoma: Checkpoint inhibitors fail outside mismatch repair deficient disease because the tumour excludes T cells.
Microsatellite-unstable (MSI-high) gastric cancer: Whether surgery can be omitted after a complete response to neoadjuvant immunotherapy.
Microsatellite-unstable (MSI-high) gastric cancer: Whether chemotherapy should be dropped altogether in metastatic disease.
Mismatch repair deficient (MSI-high) pancreatic ductal adenocarcinoma: Response rates to PD-1 blockade are lower than in colorectal cancer and the reasons are not settled.
Mismatch repair deficient (MSI-high) pancreatic ductal adenocarcinoma: Whether checkpoint inhibitors should replace chemotherapy first line is untested in the pancreas.
Mismatch-repair deficient (MSI-high) colorectal cancer: A third of metastatic patients progress early on immunotherapy and the resistance mechanisms are only partly understood.
Mismatch-repair deficient (MSI-high) colorectal cancer: Whether surgery can be omitted after complete response in colon, as in rectal, cancer is untested.
Mucinous cystic neoplasm of the pancreas with associated invasive carcinoma: Whether small MCNs without nodules can be safely observed rather than resected divides the Japanese and European guidance.
Mucinous cystic neoplasm of the pancreas with associated invasive carcinoma: No trial addresses adjuvant treatment for MCN-associated carcinoma specifically.
Oesophageal and junctional adenocarcinoma: Barrett's surveillance finds few of the cancers that occur.
Oesophageal and junctional adenocarcinoma: Rising incidence with obesity.
Oesophageal cancer: Late presentation.
Oesophageal cancer: Squamous cell carcinoma lacks targets beyond EGFR/HER3.
Oesophageal squamous cell carcinoma: Whether surgery can be omitted after a complete response to chemoradiation.
Oesophageal squamous cell carcinoma: Most cases worldwide present late without access to endoscopy.
Pancreatic acinar cell carcinoma: No prospective trial has ever been completed in acinar cell carcinoma; all systemic therapy evidence is retrospective.
Pancreatic acinar cell carcinoma: BRAF fusions have no approved drug and MEK inhibitor evidence is case reports.
Pancreatic ductal adenocarcinoma: Resistance to RAS(ON) inhibitors: secondary RAS mutations, RTK bypass, and adaptive feedback are already described; combination strategies are unproven in phase 3.
Pancreatic ductal adenocarcinoma: Half of patients are too frail for FOLFIRINOX-class regimens; RAS inhibitors may change this but toxicity (rash, stomatitis) is not trivial.
Pancreatoblastoma: No prospective trial exists or is likely; treatment is extrapolated from hepatoblastoma and pooled registries.
Pancreatoblastoma: Relapsed and metastatic disease has no established second-line therapy.
PD-L1-high gastric cancer: Two assays with different thresholds leave patients near the cut-off in an uncertain position.
PD-L1-high gastric cancer: Most patients still progress within a year on chemo-immunotherapy.
PDGFRA D842V-mutant GIST: No proven therapy after progression on avapritinib.
PDGFRA D842V-mutant GIST: Cognitive side effects limit dose and quality of life for some patients.
Peritoneal mesothelioma: No randomised trial has compared surgery plus HIPEC with systemic therapy.
Peritoneal mesothelioma: Selection for surgery relies on centre experience rather than validated criteria.
Rectal cancer: No validated test predicts which clinical complete responders will regrow under watch and wait.
Rectal cancer: Long-term bowel, sexual and urinary function after total neoadjuvant therapy is poorly measured.
Resectable pancreatic ductal adenocarcinoma: Half of patients never complete adjuvant chemotherapy; whether giving it first helps clearly resectable tumours is unproven.
Resectable pancreatic ductal adenocarcinoma: Recurrence after a complete resection and full chemotherapy remains common, and no marker reliably identifies who is cured.
Small intestine cancer: Adjuvant chemotherapy benefit is unproven; BALLAD is the randomised answer.
Small intestine cancer: Second-line therapy for MSS disease is weak; HER2 antibody-drug conjugates and trials in rare GI tumours are the route.
Solid pseudopapillary neoplasm of the pancreas: No systemic therapy is established for the few patients with unresectable recurrence.
Solid pseudopapillary neoplasm of the pancreas: The optimal length of follow-up is unknown because recurrences are late and rare.
Undifferentiated carcinoma of the pancreas with osteoclast-like giant cells: No trial; adjuvant treatment is extrapolated.
Undifferentiated carcinoma of the pancreas with osteoclast-like giant cells: Whether the immune-rich microenvironment makes it a candidate for immunotherapy is unproven.
Biochemical recurrence of prostate cancer: Whether treating PSMA PET-detected metastases early lengthens life or only lowers PSA.
Biochemical recurrence of prostate cancer: How to spare men with slow doubling times from years of hormone therapy.
Bladder & urothelial cancer: BCG supply.
Bladder & urothelial cancer: Bladder preservation strategies.
Chromophobe renal cell carcinoma: No randomised trial has ever been run in chromophobe cancer.
Chromophobe renal cell carcinoma: Immunotherapy rarely works and the reason is not understood.
Clear cell renal cell carcinoma: No validated biomarker chooses between immunotherapy doublets.
Clear cell renal cell carcinoma: Most metastatic patients still progress within two to three years.
Extragonadal germ cell tumour: Cure rates for mediastinal non-seminoma remain well below those of testicular primaries.
Extragonadal germ cell tumour: The role of high-dose chemotherapy in first-line poor-risk disease is still being tested (TIGER trial).
Localised penile cancer: Local recurrence after organ-sparing surgery is common and needs long follow-up.
Localised penile cancer: Sentinel node biopsy misses some metastases, and the false-negative rate depends on centre experience.
Localised prostate cancer, high and very high risk: How long hormone therapy should last when abiraterone is added.
Localised prostate cancer, high and very high risk: Whether PSMA PET-detected nodes should change treatment when the trials were staged conventionally.
Localised prostate cancer, intermediate risk: Whether favourable intermediate risk can be safely watched in the long term.
Localised prostate cancer, intermediate risk: How to select men for hormone therapy without giving it to everyone in the unfavourable group.
Localised prostate cancer, very low and low risk: Which Grade Group 1 cancers will upgrade, and whether Grade Group 1 should be called cancer at all.
Localised prostate cancer, very low and low risk: How often to repeat biopsy on surveillance and whether MRI alone can replace it.
Metastatic castration-resistant prostate cancer: The best sequence of radioligand, PARP inhibitor and chemotherapy is untested.
Metastatic castration-resistant prostate cancer: Actinium-225 supply and the lack of alpha-emitter dosimetry.
Metastatic hormone-sensitive prostate cancer: Who needs triplet therapy and who is overtreated by it.
Metastatic hormone-sensitive prostate cancer: Whether intermittent or de-escalated therapy is safe after a deep PSA response.
Muscle-invasive and advanced bladder cancer: Cisplatin-ineligible patients still have fewer options.
Muscle-invasive and advanced bladder cancer: Choosing between cystectomy and bladder preservation lacks randomised evidence.
Neuroendocrine and small-cell prostate cancer: No approved therapy specific to the disease; every regimen is borrowed from lung cancer.
Neuroendocrine and small-cell prostate cancer: No blood test reliably detects the lineage switch before it shows on scans.
Node-positive and metastatic penile cancer: No randomised trial has ever shown that chemotherapy improves survival in penile cancer.
Node-positive and metastatic penile cancer: Lymphadenectomy causes lymphoedema and wound complications in a large share of patients.
Non-metastatic castration-resistant prostate cancer: Whether PSMA PET-detected metastases should be treated locally or the man treated as metastatic.
Non-metastatic castration-resistant prostate cancer: Cost and side effects of years of androgen receptor inhibition in men without symptoms.
Non-muscle-invasive bladder cancer: Recurrent BCG shortages.
Non-muscle-invasive bladder cancer: Predicting who will progress to muscle invasion.
Non-seminomatous germ cell tumour: Poor-risk disease still kills about half of those affected.
Non-seminomatous germ cell tumour: Whether high-dose chemotherapy is better than conventional salvage (TIGER).
Papillary renal cell carcinoma: Small trials; most evidence is extrapolated from clear cell disease.
Papillary renal cell carcinoma: No approved therapy specific to FH-deficient cancer.
Penile cancer: Node-positive disease: the best sequence of chemotherapy, radiotherapy and surgery is unknown; InPACT is designed to answer it.
Penile cancer: No approved systemic therapy beyond cisplatin combinations; checkpoint inhibitor trials (often HPV-stratified) are recruiting.
Prostate cancer: Screening trade-off: PSA reduces mortality by ~20% but overdiagnoses; MRI-first and risk-adapted intervals are only partly adopted.
Prostate cancer: Neuroendocrine / lineage-plastic transformation in 10.5 to 17% of late mCRPC (Kench 2022; 17% of metastatic biopsies in Aggarwal) has no targeted therapy; DLL3 and B7-H3 agents are being borrowed from SCLC.
Renal cell carcinoma: Non-clear-cell histologies understudied.
Renal cell carcinoma: No validated predictive biomarker for IO.
Seminoma: Predicting which stage I patients will relapse.
Seminoma: Late effects of platinum and radiotherapy decades on.
Testicular germ cell tumours: Platinum-refractory disease has no effective therapy; checkpoint inhibitors were inactive.
Testicular germ cell tumours: Late effects of cisplatin (cardiovascular disease, second cancers, hearing loss) in men cured in their 20s.
Urethral cancer: No prospective trials; international registries and inclusion in urothelial and HPV-squamous basket trials are the response.
Urethral cancer: Late diagnosis mimicking benign stricture; urethroscopy for unexplained stricture or bleeding is the practical fix.
Adult granulosa cell tumour of the ovary: No randomised trials guide adjuvant or relapse treatment.
Adult granulosa cell tumour of the ovary: Late relapse makes follow-up long and uncertain.
Advanced or recurrent endometrial cancer: What to give after progression on first-line immunotherapy.
Advanced or recurrent endometrial cancer: The small benefit and real toxicity of immunotherapy in proficient tumours.
Cervical cancer: Vaccine and screening access in LMICs.
Cervical cancer: Brachytherapy capacity.
Clear cell ovarian cancer: No effective treatment for platinum-resistant disease.
Clear cell ovarian cancer: Which early-stage patients can skip chemotherapy.
Early cervical cancer and fertility-sparing surgery: Whether sentinel node biopsy alone can replace lymphadenectomy (SENTICOL III).
Early cervical cancer and fertility-sparing surgery: Safe fertility-sparing options for tumours of two to four centimetres.
Endometrial cancer: p53-abnormal disease behaves like serous ovarian.
Endometrial cancer: Obesity-driven incidence rising.
Endometrial cancer with no specific molecular profile: Splitting the class into truly low-risk and higher-risk tumours with L1CAM, CTNNB1 and receptor status.
Endometrial cancer with no specific molecular profile: Whether progestins can replace chemotherapy after surgery.
Gestational trophoblastic neoplasia: Late diagnosis where hCG surveillance after molar pregnancy is absent (much of the world).
Gestational trophoblastic neoplasia: Fertility and psychological burden of a pregnancy-related cancer.
High-grade serous ovarian cancer: No screening test lowers mortality.
High-grade serous ovarian cancer: Homologous recombination proficient tumours gain little from PARP inhibitors.
High-risk gestational trophoblastic neoplasia: EMA-CO has never been tested against any other regimen in a randomised trial.
High-risk gestational trophoblastic neoplasia: Late diagnosis of choriocarcinoma after term pregnancy still costs lives.
HPV-associated vulvar squamous cell carcinoma: No treatment yet differs by HPV status despite the difference in behaviour.
HPV-associated vulvar squamous cell carcinoma: Recurrence of usual-type VIN after treatment is common.
HPV-independent vulvar squamous cell carcinoma: Differentiated VIN is hard to recognise and is often diagnosed only next to an invasive cancer.
HPV-independent vulvar squamous cell carcinoma: Whether wider margins or adjuvant radiotherapy prevent the frequent local recurrences has not been tested prospectively.
Locally advanced cervical cancer: Whether induction chemotherapy and pembrolizumab should be combined.
Locally advanced cervical cancer: Access to brachytherapy and PET-CT where most patients live.
Low-grade serous ovarian cancer: Whether first-line chemotherapy adds anything to surgery and hormone therapy.
Low-grade serous ovarian cancer: Options for MAPK wild-type tumours.
Low-risk gestational trophoblastic neoplasia: Methotrexate and actinomycin D have never been compared head to head with the regimens most centres use.
Low-risk gestational trophoblastic neoplasia: Which resistant patients should receive immunotherapy rather than EMA-CO is not settled.
Mismatch-repair-deficient endometrial cancer: Whether chemotherapy can be dropped in favour of immunotherapy alone.
Mismatch-repair-deficient endometrial cancer: Why a third of deficient tumours do not respond to checkpoint blockade.
Mucinous ovarian cancer: No proven chemotherapy for advanced disease.
Mucinous ovarian cancer: Trials cannot recruit enough patients.
Ovarian cancer: No effective screening.
Ovarian cancer: PARP resistance via BRCA reversion.
p53-abnormal endometrial cancer, including uterine serous carcinoma: Distant relapse after early-stage disease despite chemotherapy.
p53-abnormal endometrial cancer, including uterine serous carcinoma: Whether PARP inhibition helps p53-abnormal tumours as it does ovarian cancer.
Placental-site trophoblastic tumour and epithelioid trophoblastic tumour: Numbers are too small for any trial; all treatment rests on registry series.
Placental-site trophoblastic tumour and epithelioid trophoblastic tumour: hCG is an unreliable marker, so recurrence can be missed.
Platinum-resistant ovarian cancer: Sequencing antibody-drug conjugates that share topoisomerase or tubulin payloads.
Platinum-resistant ovarian cancer: Whether platinum resistance can be reversed rather than bypassed.
Platinum-sensitive ovarian cancer: Whether HRD-negative tumours gain enough from PARP inhibitors to justify two to three years of treatment.
Platinum-sensitive ovarian cancer: Resistance through BRCA reversion and restored homologous recombination.
POLE-ultramutated endometrial cancer: Deciding which non-hotspot POLE variants are pathogenic.
POLE-ultramutated endometrial cancer: Whether stage III and IV disease can also be de-escalated.
Recurrent or metastatic cervical cancer: Sequencing antibody-drug conjugates and immunotherapy after first-line chemo-immunotherapy.
Recurrent or metastatic cervical cancer: Fistula and bleeding risk with bevacizumab after pelvic radiotherapy.
Uterine carcinosarcoma: No dedicated randomised trials for a tumour that behaves worse than the serous cancers it is grouped with.
Uterine carcinosarcoma: Whether the sarcomatous component needs different drugs.
Uterine sarcoma: Preoperative distinction of leiomyosarcoma from fibroids: MRI and LDH criteria and imaging AI are under study.
Uterine sarcoma: Advanced LMS remains chemoresistant after two lines: PARP inhibitors for the HRD subset and antibody-drug conjugates are in trials.
Vaginal adenocarcinoma: No trial-based treatment exists; everything is extrapolated from cervical and ovarian cancer.
Vaginal adenocarcinoma: The natural history of late recurrence in clear cell tumours means decades of follow-up.
Vaginal cancer: No dedicated randomised trials; HPV-basket immunotherapy trials and international rare-tumour registries are filling the gap.
Vaginal cancer: Optimal brachytherapy technique and dose for vaginal primaries; MRI-guided adaptive brachytherapy series are maturing.
Vaginal squamous cell carcinoma: No randomised trial has ever been conducted in vaginal cancer.
Vaginal squamous cell carcinoma: Radiotherapy causes vaginal stenosis and sexual morbidity that are poorly addressed.
Vulvar cancer: HPV-independent p53-mutant disease recurs often and has no targeted therapy.
Vulvar cancer: Lichen sclerosus surveillance and prevention of malignant transformation.
Acute lymphoblastic leukaemia: Adult ALL outcomes.
Acute lymphoblastic leukaemia: CD19-negative relapse.
Acute myeloid leukaemia: TP53-mutant AML: no drug class has yet improved survival, so it is the priority for new mechanisms.
Acute myeloid leukaemia: Older patients.
Acute myeloid leukaemia in older or unfit patients: How long venetoclax needs to be given, and whether MRD-negative patients can stop.
Acute myeloid leukaemia in older or unfit patients: Whether fit older patients do better with venetoclax-azacitidine than with intensive chemotherapy.
Acute promyelocytic leukaemia: Early haemorrhagic death before treatment starts, especially where diagnosis is slow.
Acute promyelocytic leukaemia: Treatment of variant RARA fusions that do not respond to arsenic or retinoic acid.
Adult T-cell leukaemia/lymphoma: The treatment of this disease rests on consensus rather than on randomised evidence, and the authors of the consensus say so.
Adult T-cell leukaemia/lymphoma: The virus is preventable. Antenatal screening and avoidance of breastfeeding where it is safe to do so reduce transmission, and most of the world does not screen.
Advanced systemic mastocytosis: The associated myeloid neoplasm, not the mast cells, now causes most deaths in SM-AHN.
Advanced systemic mastocytosis: Whether KIT inhibitors improve survival has not been shown in a randomised trial.
Advanced-stage classical Hodgkin lymphoma: Long-term outcomes of nivolumab-AVD beyond a few years are not yet known.
Advanced-stage classical Hodgkin lymphoma: Nivolumab-AVD and BrECADD have never been compared.
ALK-negative anaplastic large cell lymphoma: The entity is defined by what it is not, and WHO-HAEM5 says so. Whether its genetic subgroups are real subtypes or prognostic markers is unresolved.
ALK-negative anaplastic large cell lymphoma: The prognostic meaning of DUSP22 rearrangement reversed between the first reports and the later ones, and treatment decisions have been made on the earlier version.
ALK-positive anaplastic large cell lymphoma: ECHELON-2 enrolled CD30-positive peripheral T-cell lymphoma and was weighted towards anaplastic large cell lymphoma, so the benefit in the other CD30-positive entities is extrapolated rather than demonstrated.
ALK-positive anaplastic large cell lymphoma: Whether an ALK inhibitor should be added to first-line treatment, or substituted for part of it, has not been tested in a randomised trial.
Blastic plasmacytoid dendritic cell neoplasm: No randomised trials; sequencing of CD123 agents unknown.
Blastic plasmacytoid dendritic cell neoplasm: Capillary leak syndrome with tagraxofusp.
Breast implant-associated anaplastic large cell lymphoma: The absolute risk is small and the exposure is very common, so the right advice to a woman who already has textured implants and no symptoms is a question about communication rather than about oncology; current guidance is not to remove them.
Breast implant-associated anaplastic large cell lymphoma: Why a textured surface and not a smooth one is not fully explained, and the proposed mechanisms, chronic inflammation and an allergic response to the surface, have not been shown to be the cause.
Burkitt lymphoma: Relapsed Burkitt lymphoma is rarely curable; CD19-directed CAR-T and bispecifics are being tested.
Burkitt lymphoma: Cure rates in sub-Saharan Africa remain far below high-income countries; adapted protocols, rituximab access and supportive-care investment are the response.
Chronic lymphocytic leukaemia: Double-refractory disease.
Chronic lymphocytic leukaemia: Richter transformation.
Chronic lymphocytic leukaemia, first treatment: Continuous BTK inhibitor or fixed-duration venetoclax first: no head-to-head survival data.
Chronic lymphocytic leukaemia, first treatment: Whether MRD should decide how long fixed-duration therapy lasts.
Chronic myeloid leukaemia: Blast-phase CML: median survival still under a year.
Chronic myeloid leukaemia: Predicting who can stop TKI safely; second TFR attempts.
Chronic myeloid leukaemia, accelerated and blast phase: Blast phase remains largely fatal without transplant, and few patients reach it in remission.
Chronic myeloid leukaemia, accelerated and blast phase: Trials are tiny because progression has become rare.
Chronic myeloid leukaemia, chronic phase: The leukaemic stem cells that survive kinase inhibition and cause relapse after stopping.
Chronic myeloid leukaemia, chronic phase: Cardiovascular toxicity over decades on second- and third-generation inhibitors.
Chronic myelomonocytic leukaemia and MDS/MPN overlap neoplasms: No drug alters the disease course; RAS-pathway inhibitors, GM-CSF antibodies and venetoclax combinations are in early trials.
Chronic myelomonocytic leukaemia and MDS/MPN overlap neoplasms: Transformation to AML in a substantial minority; sequential mutation tracking to intervene earlier is being studied.
Cutaneous T-cell lymphoma: Diagnosis takes years because early disease mimics eczema.
Cutaneous T-cell lymphoma: No cure without transplant.
Diffuse large B-cell lymphoma: Primary refractory disease.
Diffuse large B-cell lymphoma: CAR-T access and cost.
Early-stage classical Hodgkin lymphoma: Radiotherapy omission trades a few percent more relapses against late harms that take decades to appear.
Early-stage classical Hodgkin lymphoma: Bleomycin lung toxicity and doxorubicin cardiotoxicity persist even in short regimens.
EBV-positive diffuse large B-cell lymphoma: The classification itself says the boundary between this entity and a lymphoma arising from an ageing immune system is arbitrary, and nobody has defined immune senescence in a way that could settle it.
EBV-positive diffuse large B-cell lymphoma: The virus is present in the tumour and no treatment aims at it. Virus-specific T cells and other approaches used after transplant have not been tested here.
Enteropathy-associated T-cell lymphoma: No randomised trial has been run in this disease. The regimen with the best results was compared against a historical group from the same region.
Enteropathy-associated T-cell lymphoma: Many patients present as a surgical emergency in a malnourished state, so a substantial proportion are never well enough to receive the treatment that works best.
Erdheim-Chester disease: Kinase inhibitors are usually needed for life and relapse follows their withdrawal.
Erdheim-Chester disease: Long-term cardiac, skin and secondary-cancer effects of indefinite BRAF and MEK inhibition are unknown.
Erdheim-Chester disease, Rosai-Dorfman disease and other histiocytic neoplasms: Most patients relapse when BRAF or MEK inhibitors stop; intermittent dosing and ctDNA-guided discontinuation are being tested.
Erdheim-Chester disease, Rosai-Dorfman disease and other histiocytic neoplasms: Neurodegenerative ECD and LCH do not reverse with targeted therapy; earlier treatment and neuroprotective trials are the response.
Essential thrombocythaemia: No treatment has been shown to prevent progression to myelofibrosis or leukaemia.
Essential thrombocythaemia: Very low-risk patients receive nothing and low-risk patients aspirin, but the evidence for aspirin in CALR-mutated low-risk disease is thin and bleeding may outweigh benefit.
Extranodal NK/T-cell lymphoma: The disease is common in east Asia and Latin America and rare in the countries that run most randomised trials, so the regimens that work best were developed where most of the patients are and are least familiar where the rest of them are treated.
Extranodal NK/T-cell lymphoma: There is no randomised comparison between the asparaginase-containing regimens in use, and they differ substantially in toxicity.
FLT3-mutated acute myeloid leukaemia: Which FLT3 inhibitor to pair with intensive chemotherapy, and whether one inhibitor suits both ITD and TKD disease.
FLT3-mutated acute myeloid leukaemia: Whether post-transplant maintenance should be given to everyone or only to patients with detectable FLT3-ITD.
Follicular lymphoma: Transformation to DLBCL cannot be predicted or prevented.
Follicular lymphoma: Sequencing bispecifics vs CAR-T.
Gastric MALT lymphoma: Helicobacter pylori resistance to clarithromycin is rising in many countries, and the first treatment for this lymphoma is an antibiotic regimen that is becoming less reliable.
Gastric MALT lymphoma: There is no agreed definition of how long to watch residual lymphoma on biopsy before treating it, and the evidence that watching is safe comes from one prospective series.
Hairy cell leukaemia: Variant HCL and IGHV4-34 disease respond poorly to purine analogues.
Hairy cell leukaemia: Infection risk during induction neutropenia.
High-grade B-cell lymphoma with MYC and BCL2 rearrangements: No randomised trial has ever been run in this entity. The intensified regimens used for it were adopted from retrospective comparisons, and whether they are better than standard immunochemotherapy for an individual patient is not known.
High-grade B-cell lymphoma with MYC and BCL2 rearrangements: The test used to make the diagnosis identifies a narrower group than the biology does: the double-hit gene expression signature marks about twice as many patients as the rearrangements do, and those extra patients have the same outcome and are treated as ordinary diffuse large B-cell lymphoma.
Higher-risk myelodysplastic syndromes: Nothing has beaten azacitidine alone in a phase 3 trial.
Higher-risk myelodysplastic syndromes: TP53 multi-hit disease relapses after transplant and responds to no drug durably.
HIV-associated (AIDS-related) lymphomas: Primary effusion lymphoma and multicentric Castleman disease respond poorly to chemotherapy; pomalidomide, anti-IL-6 and HHV-8-directed approaches are in AMC trials.
HIV-associated (AIDS-related) lymphomas: Plasmablastic lymphoma lacks CD20 and relapses early; bortezomib and daratumumab combinations are being tested.
Hodgkin lymphoma: Late toxicity in survivors.
Hodgkin lymphoma: Older patients.
IDH1- and IDH2-mutated acute myeloid leukaemia: Ivosidenib-azacitidine or venetoclax-azacitidine first, or all three together.
IDH1- and IDH2-mutated acute myeloid leukaemia: Managing differentiation syndrome without stopping an effective drug.
Indolent and smouldering systemic mastocytosis: Whether avapritinib alters the long-term course or only symptoms is unknown.
Indolent and smouldering systemic mastocytosis: Anaphylaxis remains life-threatening and unpredictable.
Leukaemia: Adult ALL and TP53-mutated AML still have poor outcomes.
Leukaemia: Infant and relapsed childhood leukaemias.
Lower-risk myelodysplastic syndromes: No approved treatment for thrombocytopenia or neutropenia in lower-risk disease.
Lower-risk myelodysplastic syndromes: Whether early disease-modifying treatment changes the natural history rather than the transfusion count.
Lymphomatoid papulosis: No treatment has been shown to reduce the risk of a second lymphoma, so treatment is for symptoms only and over-treatment is a real harm in a condition that does not shorten life.
Lymphomatoid papulosis: There is no way to predict which patient will develop a second lymphoma, so everybody is followed up indefinitely.
Mantle cell lymphoma: TP53-mutant and blastoid MCL fail chemo-immunotherapy; need CAR-T or bispecific-based first-line trials.
Mantle cell lymphoma: MRD-guided treatment duration.
Marginal zone lymphoma: Transformation to diffuse large B-cell lymphoma in a minority.
Marginal zone lymphoma: No standard sequence of therapies is proven by randomised trials.
Mediastinal grey zone lymphoma: No randomised trial has been run in this entity and none is likely: it is about one lymphoma in 250, so the evidence will stay observational.
Mediastinal grey zone lymphoma: Pathologists disagree about the boundary with nodular sclerosis classic Hodgkin lymphoma more often than about almost any other lymphoma boundary, and the treatment that follows the two diagnoses is different.
Monomorphic epitheliotropic intestinal T-cell lymphoma: There is no randomised evidence of any kind in this disease, and the best comparison available is a retrospective cohort of 50 treated patients.
Monomorphic epitheliotropic intestinal T-cell lymphoma: Whether methotrexate should be included to prevent relapse in the central nervous system is unresolved: the regimen that performed better left it out, and the two-year risk of relapse in the brain or spinal cord was still 12.1 per cent.
Multiple myeloma: High-risk cytogenetics.
Multiple myeloma: Infections with T-cell redirecting therapy.
Mycosis fungoides: Nothing has been shown to change the natural history of early-stage mycosis fungoides, so every treatment given in early disease is for symptoms, and over-treatment is the commonest harm.
Mycosis fungoides: The time from first rash to diagnosis is measured in years, and no test identifies early mycosis fungoides reliably on a single biopsy.
Myelodysplastic syndromes / neoplasms: No drug has beaten azacitidine in higher-risk MDS.
Myelodysplastic syndromes / neoplasms: TP53-mutant and complex-karyotype disease: median survival about a year even after transplant.
Myeloproliferative neoplasms: No disease-modifying therapy in myelofibrosis short of transplant.
Myeloproliferative neoplasms: MPN in blast phase: outcomes as poor as secondary AML.
Newly diagnosed multiple myeloma, transplant-eligible: Whether high-dose melphalan is still necessary after a quadruplet that produces MRD negativity.
Newly diagnosed multiple myeloma, transplant-eligible: Whether MRD-negative patients can stop maintenance safely.
Newly diagnosed multiple myeloma, transplant-ineligible: Frail patients were excluded from the quadruplet trials and gain least from them.
Newly diagnosed multiple myeloma, transplant-ineligible: Whether treatment can be fixed in duration or MRD-guided rather than continued until progression.
Nodular lymphocyte-predominant Hodgkin lymphoma: No randomised trial has compared ABVD with rituximab-based chemotherapy.
Nodular lymphocyte-predominant Hodgkin lymphoma: Variant growth patterns are hard to reproduce between pathologists.
Non-Hodgkin lymphoma: Relapsed T-cell lymphomas still lack effective options.
Non-Hodgkin lymphoma: Access to CAR-T and bispecifics outside high-income countries.
NPM1-mutated and KMT2A-rearranged acute myeloid leukaemia: Whether a menin inhibitor added to first-line therapy raises cure rates in NPM1-mutated AML.
NPM1-mutated and KMT2A-rearranged acute myeloid leukaemia: MEN1 resistance mutations and how to sequence or combine inhibitors around them.
Ocular adnexal MALT lymphoma: Whether Chlamydia psittaci causes this lymphoma depends on where the series was collected, and the question has not been settled in twenty years. A patient in Britain cannot be told with confidence whether an antibiotic is worth trying.
Ocular adnexal MALT lymphoma: The right radiotherapy dose is unresolved: the conventional 24 to 36 Gy controls the lymphoma and causes cataract and dry eye, while very low doses of about 4 Gy spare both and have not been compared head to head here.
Peripheral T-cell lymphomas: Five-year survival under 40% for PTCL-NOS with no new first-line regimen for non-CD30 disease.
Peripheral T-cell lymphomas: Randomised evidence for transplant consolidation is lacking.
Plasma cell leukaemia: No randomised trials; treatment is extrapolated from high-risk myeloma.
Plasma cell leukaemia: Secondary plasma cell leukaemia has no effective standard.
Plasmablastic lymphoma: No randomised trial has been run in plasmablastic lymphoma, and the regimens in use are chosen by analogy with other aggressive lymphomas and with myeloma.
Plasmablastic lymphoma: There is no surface target. Every advance in B-cell lymphoma since 1997 has depended on CD20 or CD19, and this disease expresses neither reliably.
Polycythaemia vera: No treatment has yet been shown to prevent progression to myelofibrosis or leukaemia; interferon's molecular responses are the strongest hint.
Polycythaemia vera: Risk stratification still rests on age and clot history; leukocyte count, allele burden and additional mutations are not yet built into treatment decisions.
Post-transplant lymphoproliferative disorder: Rituximab-refractory and EBV-negative PTLD have poor outcomes; EBV-specific T cells, CAR-T and bispecific antibodies are the routes being tested.
Post-transplant lymphoproliferative disorder: US access to tabelecleucel awaits FDA resolution of manufacturing findings; academic virus-specific T-cell banks fill the gap.
Primary cutaneous anaplastic large cell lymphoma: The consensus recommendations that govern treatment state that most of the evidence behind them is small retrospective series and case reports, and that very few prospective or multicentre studies exist.
Primary cutaneous anaplastic large cell lymphoma: The line between this disease and lymphomatoid papulosis is drawn on the clinical course rather than on the biopsy, and in a person who has both there is no test that settles which lesion is which.
Primary effusion lymphoma: There has never been a randomised trial in primary effusion lymphoma, and median overall survival in the most recent population series was 12 months.
Primary effusion lymphoma: The boundaries between the conditions caused by Kaposi sarcoma herpesvirus are acknowledged by the classification itself to be unclear, and individual patients overlap between them.
Primary large B-cell lymphoma of the testis: Radiotherapy to the remaining testicle prevents relapse there and causes permanent infertility and low testosterone. Nobody has tested whether it can be omitted in men who receive modern systemic treatment.
Primary large B-cell lymphoma of the testis: The best way to protect the brain is not known. IELSG-10 used methotrexate into the spinal fluid; high-dose intravenous methotrexate reaches the brain tissue better and has not been compared against it in a randomised trial.
Primary mediastinal (thymic) large B-cell lymphoma: No validated way to identify the 10 to 15 percent who will fail first-line therapy before they do.
Primary mediastinal (thymic) large B-cell lymphoma: Checkpoint blockade in first line is untested in randomised trials.
Primary myelofibrosis: No drug has been shown to change the course of the disease rather than its symptoms.
Primary myelofibrosis: Transplant timing: too early risks a fatal procedure in someone with years to live, too late loses the window.
Relapsed and refractory classical Hodgkin lymphoma: Which patients in complete remission after immunotherapy salvage can safely skip transplantation is unproven.
Relapsed and refractory classical Hodgkin lymphoma: Salvage for patients already exposed to brentuximab and PD-1 antibodies in first line is undefined.
Relapsed or refractory chronic lymphocytic leukaemia: Double-refractory disease after BTK inhibitor and venetoclax has no durable option.
Relapsed or refractory chronic lymphocytic leukaemia: Whether venetoclax retreatment works as well the second time, and after how long an interval.
Relapsed or refractory multiple myeloma: Sequencing CAR-T and bispecifics, and whether a second T-cell therapy works after the first.
Relapsed or refractory multiple myeloma: Infections on continuous BCMA bispecifics, and whether fixed-duration dosing is safe.
Richter transformation of chronic lymphocytic leukaemia: No regimen reliably produces durable remission in clonally related disease.
Richter transformation of chronic lymphocytic leukaemia: Richter transformation is excluded from most trials, so evidence comes from small cohorts.
Rosai-Dorfman-Destombes disease: Which patients will regress spontaneously cannot be predicted.
Rosai-Dorfman-Destombes disease: Two thirds of cases have no identified driver mutation.
Secondary and therapy-related acute myeloid leukaemia: No regimen produces durable remissions in TP53-mutated AML.
Secondary and therapy-related acute myeloid leukaemia: Whether CPX-351 helps patients under 60 or those fit enough for transplant regardless of induction.
Smouldering multiple myeloma: No trial has shown that treating smouldering myeloma lengthens life rather than delaying the label of active disease.
Smouldering multiple myeloma: Risk models still misclassify many patients in both directions.
Systemic mastocytosis: Avapritinib carries intracranial bleeding risk at low platelet counts and cognitive effects; bezuclastinib and elenestinib are designed to avoid them.
Systemic mastocytosis: The associated neoplasm in SM-AHN, not the mast cells, usually determines survival; combination strategies with hypomethylating agents and transplant are being studied.
T-cell/histiocyte-rich large B-cell lymphoma: The line between this disease and the diffuse pattern of nodular lymphocyte predominant Hodgkin lymphoma cannot always be drawn, and the two are treated differently.
T-cell/histiocyte-rich large B-cell lymphoma: The cancer cells of the two conditions are not distinguishable by gene expression. What differs is the immune cells around them, and nobody knows why the same tumour cell produces an indolent disease in one person and an aggressive one in another.
Waldenström macroglobulinaemia: Indefinite BTKi therapy: cost, toxicity and resistance (BTK C481S).
Waldenström macroglobulinaemia: CXCR4-mutant disease responds slower and shallower.
Adenoid cystic carcinoma: No drug shrinks the disease reliably; kinase inhibitors only slow it.
Adenoid cystic carcinoma: When to start treatment for indolent lung metastases.
Buccal mucosa and gingivobuccal cancer: Late presentation and rising incidence as areca nut and gutka use spread.
Buccal mucosa and gingivobuccal cancer: Access to pembrolizumab, cetuximab and radiotherapy machines outside big cities.
Esthesioneuroblastoma: No prospective trial has ever been conducted; every recommendation rests on series.
Esthesioneuroblastoma: Late relapse after ten or more years makes cure hard to define.
Head and neck squamous cell carcinoma: Functional toxicity of chemoradiation.
Head and neck squamous cell carcinoma: Few targets beyond EGFR/PD-1.
HPV-negative head and neck squamous cell carcinoma: Cure rates for locally advanced HPV-negative disease have barely moved in twenty years.
HPV-negative head and neck squamous cell carcinoma: No predictive biomarker beyond PD-L1, which is imperfect.
HPV-positive oropharyngeal cancer: Which patients can safely have less treatment, and by what test.
HPV-positive oropharyngeal cancer: Long-term dry mouth, swallowing difficulty and fibrosis in people cured in their fifties.
Hypopharyngeal cancer: Survival has barely improved in thirty years.
Hypopharyngeal cancer: Choosing between preservation and laryngopharyngectomy in the most extensive tumours.
Laryngeal and hypopharyngeal cancer: Hypopharyngeal cancer survival has barely improved.
Laryngeal and hypopharyngeal cancer: Choosing between preservation and laryngectomy in T4 disease.
Lip cancer: Lip cancer in outdoor workers in sunny countries is under-recognised and under-protected.
Lip cancer: Function and appearance after resection of more than half the lip.
Locoregionally advanced nasopharyngeal carcinoma: Which patients can safely have less chemotherapy or radiotherapy is being defined trial by trial.
Locoregionally advanced nasopharyngeal carcinoma: Late toxicities of skull-base radiotherapy last for life.
Mucoepidermoid carcinoma: No targeted drug for the MAML2 fusion.
Mucoepidermoid carcinoma: Grading systems disagree, so treatment intensity varies between centres.
Nasal cavity and paranasal sinus cancers: Late presentation: most tumours are locally advanced at diagnosis; awareness in ENT clinics and imaging AI are the response.
Nasal cavity and paranasal sinus cancers: No randomised trials exist for any sinonasal histology; international consortia are pooling cases.
Nasopharyngeal carcinoma: Radiation late effects in a disease cured young.
Nasopharyngeal carcinoma: Western access to PD-1 inhibitors studied in Asia; regulatory lag.
NUT carcinoma: Misdiagnosis and delay: NUT immunohistochemistry should be routine in poorly differentiated midline tumours.
NUT carcinoma: BET inhibitor responses are short: degraders, CDK9 and HDAC combinations, and chemotherapy combinations are in trials.
Oral cavity cancer: Late presentation remains the norm in the highest-incidence countries.
Oral cavity cancer: Betel quid use is still rising in parts of Asia.
Oral tongue and floor of mouth cancer: Why tongue cancer is rising in young non-smokers.
Oral tongue and floor of mouth cancer: Whether sentinel node biopsy can replace elective neck dissection safely.
Oropharyngeal cancer: How far treatment can be reduced in HPV-positive disease without losing cures.
Oropharyngeal cancer: HPV-negative oropharyngeal cancer still has poor outcomes.
Recurrent and metastatic nasopharyngeal carcinoma: Median survival in metastatic disease is still a few years.
Recurrent and metastatic nasopharyngeal carcinoma: Which patients with local recurrence should have surgery rather than re-irradiation depends on surgical expertise concentrated in a few centres.
Recurrent or metastatic head and neck squamous cell carcinoma: Most patients still die within two years.
Recurrent or metastatic head and neck squamous cell carcinoma: No test yet identifies the minority who gain years from immunotherapy.
Salivary duct carcinoma: Almost all responses to targeted treatment are followed by relapse.
Salivary duct carcinoma: Whether to give anti-HER2 or anti-androgen treatment first when both targets are present.
Salivary gland cancers: Adenoid cystic carcinoma: no drug induces meaningful shrinkage; 20-year survival remains poor.
Salivary gland cancers: Trials are tiny; most evidence is phase 2 or retrospective.
Sinonasal undifferentiated carcinoma (SNUC) and SWI/SNF-deficient sinonasal carcinoma: No randomised trial exists and the induction-response strategy rests on one centre's series.
Sinonasal undifferentiated carcinoma (SNUC) and SWI/SNF-deficient sinonasal carcinoma: Enasidenib's activity in IDH2-mutant sinonasal carcinoma is unproven.
ALK-positive non-small-cell lung cancer: Whether any sequence of inhibitors cures metastatic ALK-positive disease or only holds it is unknown.
ALK-positive non-small-cell lung cancer: Lorlatinib's cognitive, mood and metabolic effects are managed by dose reduction without trials of the optimal dose.
BRAF V600E-mutant non-small-cell lung cancer: No randomised trial compares BRAF plus MEK inhibitors with chemoimmunotherapy first line or settles the sequence.
BRAF V600E-mutant non-small-cell lung cancer: Non-V600 BRAF mutations, half of cases, have no approved targeted therapy.
EGFR-mutated non-small-cell lung cancer: No head-to-head trial compares the three first-line strategies, and the added toxicity of the combinations falls on every patient for a benefit concentrated in some.
EGFR-mutated non-small-cell lung cancer: Most resistance to osimertinib has no identifiable mechanism and no targeted option.
Extensive-stage small-cell lung cancer: No biomarker identifies the minority who gain long-term benefit from immunotherapy; PD-L1 and mutational burden do not work in small-cell disease.
Extensive-stage small-cell lung cancer: Tarlatamab needs inpatient monitoring for cytokine release syndrome, which limits access outside specialist centres.
HER2-mutant non-small-cell lung cancer: No trial yet compares an oral HER2 inhibitor with an antibody-drug conjugate or settles the sequence.
HER2-mutant non-small-cell lung cancer: Interstitial lung disease from trastuzumab deruxtecan is unpredictable and occasionally fatal.
KRAS G12C-mutant non-small-cell lung cancer: Responses to G12C inhibitors are shallower and shorter in lung cancer than EGFR or ALK inhibitors achieve, and no overall survival benefit over docetaxel has been shown.
KRAS G12C-mutant non-small-cell lung cancer: Liver toxicity when a G12C inhibitor follows or accompanies a checkpoint inhibitor limits first-line combinations.
Limited-stage small-cell lung cancer: Whether prophylactic cranial irradiation still helps when MRI surveillance is available is being tested in randomised trials.
Limited-stage small-cell lung cancer: The best radiotherapy dose and schedule to combine with immunotherapy is unknown.
Lung cancer: Most of the world's lung cancer is in countries with no screening. Asia carries 65.6 percent of cases and 64.3 percent of deaths (GLOBOCAN 2024), and of the ten European countries surveyed in 2026 only three had a formal programme. A screening benefit demonstrated in the Netherlands and the United States has to be re-earned in each health system that tries to deliver it.
Lung cancer: The risk models that select people for screening cannot see never-smokers. Fifteen percent of UK lung cancers, and 15 to 25 percent worldwide, arise in people who have never smoked, and every eligibility rule in use starts from smoking history. Nothing currently offered would find those cancers early.
Lung neuroendocrine tumours: No randomised trial has tested somatostatin analogues or radioligand therapy specifically in lung neuroendocrine tumours.
Lung neuroendocrine tumours: Lung and gastroenteropancreatic grading systems disagree, so trial eligibility and guideline advice do not map cleanly.
MET exon 14 and MET-amplified non-small-cell lung cancer: MET amplification has no agreed threshold and results differ between assays.
MET exon 14 and MET-amplified non-small-cell lung cancer: Peripheral oedema limits the dose of every MET inhibitor and has no good treatment.
Non-small-cell lung cancer: Screening uptake is under 20% in the US and lower elsewhere; never-smoker adenocarcinoma has no screening pathway.
Non-small-cell lung cancer: Resistance to every TKI is near-universal in metastatic disease; C797S has no approved fourth-generation EGFR inhibitor and small-cell transformation is undetectable by ctDNA.
NTRK fusion-positive non-small-cell lung cancer: Fusions are missed when only DNA panels are run.
NTRK fusion-positive non-small-cell lung cancer: Neurological side effects from TRK inhibition are class-wide.
PD-L1-high non-small-cell lung cancer without a driver mutation: Half of PD-L1-high patients progress within a year and have no predictor to identify them in advance.
PD-L1-high non-small-cell lung cancer without a driver mutation: Whether adding chemotherapy to a checkpoint inhibitor prolongs survival in PD-L1-high disease has never been tested in a randomised trial.
Resectable stage I to III non-small-cell lung cancer: Whether adjuvant immunotherapy adds anything after neoadjuvant treatment and surgery, especially for complete pathological responders, has not been tested directly.
Resectable stage I to III non-small-cell lung cancer: Circulating tumour DNA after surgery identifies high-risk patients but no trial yet shows that acting on it improves survival.
RET fusion-positive non-small-cell lung cancer: Solvent-front resistance mutations have no approved inhibitor.
RET fusion-positive non-small-cell lung cancer: Whether adjuvant selpercatinib prevents recurrence is not yet known.
ROS1-positive non-small-cell lung cancer: No randomised trial compares the ROS1 inhibitors; choice rests on single-arm response rates and side-effect profiles.
ROS1-positive non-small-cell lung cancer: Dizziness, weight gain and paraesthesia from TRK inhibition limit the current brain-penetrant drugs.
Small-cell lung cancer: Extensive-stage disease almost always relapses after first-line therapy, so maintenance (lurbinectedin-atezolizumab, tarlatamab) is the current lever; median survival is still barely over a year.
Small-cell lung cancer: No validated predictive biomarker for immunotherapy benefit; PD-L1 and TMB do not work in SCLC.
Unresectable stage III non-small-cell lung cancer: Pneumonitis from radiotherapy followed by immunotherapy limits treatment in patients with poor lung function.
Unresectable stage III non-small-cell lung cancer: Whether ALK, RET, ROS1 or other driver subtypes should receive targeted rather than immune consolidation is untested.
Cancer of unknown primary: Whether finding the primary matters, or only finding the target.
Cancer of unknown primary: Median survival under a year for unfavourable CUP despite decades of trials.
Cancer of unknown primary, favourable subsets: Some favourable subsets rest on small series decades old.
Cancer of unknown primary, favourable subsets: Whether a tissue-of-origin classifier should ever override the clinical picture is unsettled.
Cancer of unknown primary, unfavourable: Median survival remains under a year for most patients.
Cancer of unknown primary, unfavourable: Only a third have an actionable alteration and the gain from targeting it is modest.
Metastatic cancer: Metastasis itself has no approved drug: treatments target the growing cells, not the spreading.
Metastatic cancer: Which patients with limited spread truly benefit from treating every site is still being tested in phase 3 trials.
Acute myeloid leukaemia in children: A third of children relapse and only half of those are cured.
Acute myeloid leukaemia in children: Infant AML with NUP98 or CBFA2T3::GLIS2 fusions has no effective therapy.
Atypical teratoid/rhabdoid tumour: Infants too young for radiotherapy and children with metastatic or ATRT-MYC disease still do poorly; SIOPE ATRT01 and COG successors are testing intensified and subgroup-directed therapy.
Atypical teratoid/rhabdoid tumour: Long-term neurocognitive and endocrine cost of intensive therapy in the first years of life; proton therapy and radiation-sparing arms aim to reduce it.
Childhood cancers: Most children with cancer live where cure rates are below 30%.
Childhood cancers: Late effects affect the majority of long-term survivors.
Childhood lung and airway tumours: Whether adjuvant chemotherapy helps type I PPB; the registry is comparing outcomes with and without it.
Childhood lung and airway tumours: Type III and recurrent PPB have poor outcomes and no targeted therapy; DICER1-dependent biology (miRNA processing) has not yet yielded a drug.
Craniopharyngioma: Hypothalamic obesity in survivors has no reliable treatment; GLP-1 agonists, setmelanotide and oxytocin are in trials.
Craniopharyngioma: No systemic therapy is established for adamantinomatous tumours; IL-6 blockade and MEK inhibition (downstream of the beta-catenin-driven inflammatory programme) are being tested.
Diffuse midline glioma, H3 K27-altered: Most tumours still progress; dordaviprone helps a minority and the phase 3 ACTION trial will show whether earlier use extends survival.
Diffuse midline glioma, H3 K27-altered: Drug delivery across the blood-brain barrier into infiltrating tumour: convection-enhanced delivery, focused ultrasound and intraventricular cell therapy are being tested.
Ependymoma: PF-A and ZFTA tumours relapse often and have no effective drug; EZHIP/PRC2 and NF-kB dependencies are being tested preclinically and in early trials.
Ependymoma: Whether radiotherapy can be omitted or reduced in PF-B, YAP1 and completely resected favourable tumours; SIOP Ependymoma II and COG successors are stratifying by group.
Ewing sarcoma: Metastatic-to-bone and relapsed disease: survival under 20-30%.
Ewing sarcoma: EWSR1-FLI1 remains undrugged after 30 years.
Germ cell tumours of childhood and adolescence: Whether carboplatin can fully replace cisplatin without losing cures in standard-risk disease; AGCT1531 is the answer trial.
Germ cell tumours of childhood and adolescence: Relapsed and platinum-refractory disease, especially mediastinal and CNS non-germinomatous tumours, where high-dose chemotherapy is the only option.
Group 3 and group 4 medulloblastoma: MYC and MYCN have no inhibitor, and relapse is almost always fatal.
Group 3 and group 4 medulloblastoma: Craniospinal radiotherapy dose cannot be reduced in young children without losing cures.
Hepatoblastoma: Metastatic and low-AFP disease.
Hepatoblastoma: Long-term effects of cisplatin (hearing, kidney) and doxorubicin (heart).
High-risk acute lymphoblastic leukaemia in children: No antibody or cell therapy target in routine use for T-ALL.
High-risk acute lymphoblastic leukaemia in children: Which high-risk children still need transplant once immunotherapy clears residual disease.
High-risk neuroblastoma: About half of children relapse and relapsed disease is rarely cured.
High-risk neuroblastoma: MYCN has no direct inhibitor; eflornithine and lorlatinib act around it.
Infant acute lymphoblastic leukaemia: Infants who relapse within the first year despite blinatumomab.
Infant acute lymphoblastic leukaemia: Lineage switch to myeloid leukaemia under CD19-directed therapy.
Intermediate-risk neuroblastoma: Children with 11q aberration or unfavourable histology still relapse and cannot have therapy shortened.
Intermediate-risk neuroblastoma: Whether telomere maintenance and ALK status should change risk assignment.
Langerhans cell histiocytosis: How long to give BRAF or MEK inhibitors and how to stop them without reactivation; combination with chemotherapy to allow cessation is being tested in the Histiocyte Society and NACHO networks.
Langerhans cell histiocytosis: Preventing and treating neurodegenerative LCH; MRI surveillance and early MAPK inhibition are the current approach.
Low-risk neuroblastoma: Distinguishing tumours that will regress from those that will grow without biopsy.
Low-risk neuroblastoma: When surgery to the kidney or spinal canal is riskier than watching.
Medulloblastoma: Group 3 MYC-amplified and SHH TP53-mutant tumours: survival under 50%.
Medulloblastoma: Relapse after craniospinal irradiation is rarely curable; it is where new approaches are most needed.
Multisystem Langerhans cell histiocytosis: Targeted therapy controls but does not cure; how to stop it safely is unknown.
Multisystem Langerhans cell histiocytosis: Neurodegenerative disease appears years later and has no proven treatment.
Neuroblastoma: Relapsed high-risk disease.
Neuroblastoma: Long-term toxicity of intensive therapy.
Osteosarcoma: No survival improvement since the 1980s; metastatic and relapsed disease ~20-30% survival.
Osteosarcoma: No recurrent druggable driver; genomic chaos.
Paediatric high-grade glioma: No systemic therapy has improved survival in H3 G34-mutant or H3- and IDH-wildtype tumours.
Paediatric high-grade glioma: How long to continue fusion or BRAF inhibitors in children who respond, and what happens on stopping.
Paediatric low-grade glioma: How long to continue MAPK inhibitors and whether tumours regrow on stopping; intermittent dosing and stop rules are being studied in FIREFLY-2 and the COG selumetinib trials.
Paediatric low-grade glioma: Long-term effects of RAF and MEK inhibition on growth plates, skin and heart in children who may take them for years; registries and trial follow-up are collecting these data.
Philadelphia chromosome-like acute lymphoblastic leukaemia: Whether kinase inhibitors improve cure rather than early response in Ph-like ALL.
Philadelphia chromosome-like acute lymphoblastic leukaemia: Screening is unavailable in most of the world, so most Ph-like patients are never identified.
Philadelphia chromosome-positive acute lymphoblastic leukaemia in children: Whether chemotherapy-free kinase inhibitor plus blinatumomab regimens can replace intensive chemotherapy in children.
Philadelphia chromosome-positive acute lymphoblastic leukaemia in children: Kinase domain resistance mutations and the lack of paediatric approval for ponatinib.
Rare cancers of childhood: Evidence remains observational for almost every entity; international registries and adult-paediatric joint protocols are the response.
Rare cancers of childhood: Adolescents with adult-type carcinomas fall between paediatric and adult services; AYA programmes and the RACE for Children Act (which requires paediatric evaluation of adult cancer drugs) aim to close the gap.
Relapsed and refractory acute lymphoblastic leukaemia in children: CD19-negative relapse and lineage switch after CD19-directed therapy.
Relapsed and refractory acute lymphoblastic leukaemia in children: Which children need transplant after a CAR T-cell remission.
Retinoblastoma: Late diagnosis in low-income countries; paediatric ophthalmology access is the lever.
Retinoblastoma: Second primary cancers in RB1 carriers across life.
Rhabdomyosarcoma: Metastatic alveolar RMS: survival <30% for 30 years.
Rhabdomyosarcoma: PAX3-FOXO1 is an undrugged fusion transcription factor.
SHH-activated medulloblastoma: No therapy improves TP53-mutant SHH medulloblastoma.
SHH-activated medulloblastoma: Smoothened inhibitors fuse growth plates and fail against downstream activation.
Single-system Langerhans cell histiocytosis: Which infants with skin-only disease will progress cannot be predicted.
Single-system Langerhans cell histiocytosis: Whether treating special-site lesions truly prevents neurodegeneration is inferred rather than proven.
Standard-risk B-cell acute lymphoblastic leukaemia in children: Whether blinatumomab allows chemotherapy to be shortened rather than only added to.
Standard-risk B-cell acute lymphoblastic leukaemia in children: Asparaginase hypersensitivity and silent inactivation, and osteonecrosis in older children.
Wilms tumour: Diffuse anaplastic and relapsed disease: survival ~50% or lower.
Wilms tumour: Global inequity: Wilms is curable, yet most children with it worldwide lack access to the treatment that cures it; adapted regimens (SIOP PODC) are the response.
WNT-activated medulloblastoma: How far craniospinal radiotherapy can be reduced without losing cures.
WNT-activated medulloblastoma: Whether adult and metastatic WNT tumours share the childhood prognosis.
Alveolar soft part sarcoma: Why a low-mutation fusion sarcoma responds to immunotherapy is not understood.
Alveolar soft part sarcoma: Brain metastases are common and hard to treat.
Angiosarcoma: Multifocal scalp disease escapes even wide surgery and radiotherapy.
Angiosarcoma: Median survival with metastases remains under a year.
Chondrosarcoma: No systemic therapy has ever been proven to help.
Chondrosarcoma: Dedifferentiated chondrosarcoma kills most patients within two years.
Chordoma: No approved systemic therapy: trials of brachyury-directed vaccines, degraders and EGFR inhibitors are the response.
Chordoma: Recurrent skull-base disease after full-dose radiotherapy: re-irradiation with particles and salvage surgery are being studied.
Desmoid tumour: Ovarian toxicity of gamma-secretase inhibitors in young women: dose interruption and intermittent schedules are being explored.
Desmoid tumour: Optimal treatment duration and whether responses persist after stopping nirogacestat.
Epithelioid haemangioendothelioma: No approved drug and no randomised trial.
Epithelioid haemangioendothelioma: Predicting which tumours will progress is unreliable.
Epithelioid sarcoma: No approved targeted therapy since the March 2026 withdrawal: next-generation PRC2 inhibitors such as rinzimetostat (EED) are being tested in other cancers, and whether one can be brought to epithelioid sarcoma is open.
Epithelioid sarcoma: The EZH-301 doxorubicin combination and immunotherapy combinations were still recruiting when tazemetostat was withdrawn; their read-outs would show whether the EZH2 axis is worth revisiting.
Inflammatory myofibroblastic tumour: How long to continue ALK inhibition in children with complete response, and whether surgery after response can allow stopping.
Inflammatory myofibroblastic tumour: The fusion-negative minority: RNA sequencing to find drivers.
Leiomyosarcoma: No targeted or immune therapy works in most patients.
Leiomyosarcoma: Uterine tumours are still discovered by accident after fibroid surgery.
Liposarcoma: Retroperitoneal dedifferentiated disease recurs in most patients despite complete surgery.
Liposarcoma: MDM2 inhibitors cause low platelets that limit dosing.
Malignant peripheral nerve sheath tumour: Metastasis is common even after complete local treatment.
Malignant peripheral nerve sheath tumour: Chemotherapy works less well in the NF1-associated tumours that make up half of cases.
Myxofibrosarcoma: Local recurrence remains the highest of any sarcoma.
Myxofibrosarcoma: No targetable driver has been found.
Perivascular epithelioid cell tumour: Malignancy cannot always be predicted from histology.
Perivascular epithelioid cell tumour: Resistance to mTOR inhibition eventually develops.
Retroperitoneal sarcoma: Liposarcoma recurs in the abdomen in most patients even after complete surgery.
Retroperitoneal sarcoma: Neither radiotherapy nor chemotherapy has a proven adjuvant benefit.
Sarcomas: Rarity limits trials.
Sarcomas: Chemoresistance of most subtypes.
Soft tissue sarcoma of the extremity: A third to a half of high-risk limb sarcomas still metastasise to the lungs.
Soft tissue sarcoma of the extremity: Chemotherapy prolongs control but rarely survival in advanced disease.
Synovial sarcoma: TCR therapy needs a matching HLA type and antigen, excluding most patients.
Synovial sarcoma: Late lung metastases years after treatment.
Tenosynovial giant cell tumour: Duration of CSF1R therapy and rebound after stopping: extension cohorts and intermittent schedules are being studied.
Tenosynovial giant cell tumour: Hepatotoxicity of pexidartinib: newer agents (vimseltinib, emactuzumab) are designed to avoid it.
Undifferentiated pleomorphic sarcoma: No molecular driver to target; the diagnosis is defined by what the tumour is not.
Undifferentiated pleomorphic sarcoma: A third of high-grade limb tumours still metastasise to the lungs.
Vascular tumours: Angiosarcoma outside the UV-exposed skin remains chemoresistant: immunotherapy combinations and antiangiogenic agents are being tested.
Vascular tumours: EHE: which patients will progress, and TEAD inhibitors as the first fusion-directed therapy.
Acral melanoma: Late diagnosis remains the main cause of poor outcomes and awareness in people with darker skin is low.
Acral melanoma: No trial has been designed for acral melanoma alone outside East Asia.
Advanced cutaneous squamous cell carcinoma: Transplant recipients, who have the highest incidence, cannot safely receive the most effective drugs.
Advanced cutaneous squamous cell carcinoma: About half of patients do not respond to PD-1 blockade and there is no approved second-line therapy.
Advanced melanoma: About four in ten patients never respond to PD-1 blockade and no biomarker reliably identifies them.
Advanced melanoma: Who needs the ipilimumab component and its toxicity, and whether relatlimab can replace it, has not been settled.
Basal cell carcinoma: Hedgehog-inhibitor tolerability leads most patients to stop within a year.
Basal cell carcinoma: Resistance via SMO mutations has no approved next-in-class agent.
Bowen's disease: Nobody knows how common it is. Carcinoma in situ of the skin sits outside the non-melanoma skin cancer totals, and those totals are themselves counted on a rule that misses repeat tumours, so there is no dependable national figure for a diagnosis many thousands of people are given every year.
Bowen's disease: The 3 to 5 percent who progress cannot be identified in advance. There is no marker that separates the lesion that will become invasive from the one that will not, so everybody is treated, and most of that treatment is for lesions that would never have caused harm.
BRAF V600-mutant melanoma: Responses to targeted therapy are almost universal but most are not durable, and resistance through MAPK reactivation has no approved answer.
BRAF V600-mutant melanoma: Whether a short targeted-therapy induction before immunotherapy helps has not been settled in a phase 3 trial.
Cutaneous squamous cell carcinoma: Organ-transplant recipients: high incidence, no safe immunotherapy.
Cutaneous squamous cell carcinoma: Who needs adjuvant therapy: gene-expression tests vs clinicopathologic staging.
Dermatofibrosarcoma protuberans: Diagnosis is delayed for years because the tumour looks like a scar, keloid or cyst.
Dermatofibrosarcoma protuberans: Responses to imatinib are not permanent and the drugs after it have only small series behind them.
Kaposi sarcoma: Access to effective chemotherapy and ART-linked cancer care in sub-Saharan Africa.
Kaposi sarcoma: KS in people with suppressed HIV and normal CD4 counts (unexplained).
Locally advanced and metastatic basal cell carcinoma: Hedgehog inhibitor side effects lead many patients to stop before the tumour is controlled.
Locally advanced and metastatic basal cell carcinoma: Only about a third of patients respond to cemiplimab after hedgehog inhibitor failure and there is no third line.
Melanoma: Primary IO resistance in ~40%.
Melanoma: Uveal and mucosal subtypes.
Merkel cell carcinoma: Half of patients do not respond to PD-1 blockade and have no effective second line.
Merkel cell carcinoma: Immunosuppressed patients: high incidence, poor outcomes, contraindications to immunotherapy.
Mucosal melanoma: No phase 3 trial has been run specifically in mucosal melanoma outside China.
Mucosal melanoma: Local control at head and neck and anorectal sites is poor without mutilating surgery.
Skin cancer: Melanoma incidence continues to rise in fair-skinned populations.
Skin cancer: The commonest cancer in the world is the one nobody can count. UK registries long recorded only the first basal cell carcinoma and the first squamous cell carcinoma in a person's lifetime; counting one of each per person per year instead finds 67 percent more basal cell carcinomas and 42 percent more squamous cell carcinomas, and still misses about 14 basal cell carcinomas per 100 patients. The Office for National Statistics leaves the whole group out of the national cancer total on the stated ground that it is greatly under-registered. Services are planned on the number that is published.
Stage IIB and IIC melanoma: Roughly four in five patients would have been cured by surgery alone and cannot yet be told apart from the fifth.
Stage IIB and IIC melanoma: No overall survival benefit has yet been shown for adjuvant therapy in stage II.
Stage III melanoma: Most stage IIIA patients would never have relapsed, so a year of immunotherapy with lifelong endocrine side effects in some is given to many who do not need it.
Stage III melanoma: No biomarker yet tells who can safely skip adjuvant therapy; circulating tumour DNA trials are testing this.
Uveal melanoma: Half of patients metastasise with no adjuvant therapy despite accurate prediction.
Uveal melanoma: Tebentafusp only for HLA-A*02:01 (about 45% of white patients, fewer elsewhere) and gives few objective responses despite OS benefit.
Mesothelioma: Sarcomatoid subtype.
Mesothelioma: No early detection despite known exposure.
Pleural mesothelioma: No curative treatment for the majority; median survival with the best regimens is about 18 months.
Pleural mesothelioma: Sarcomatoid disease responds poorly to everything except immunotherapy.
Thymic carcinoma: No randomised trial has compared any two regimens in thymic carcinoma.
Thymic carcinoma: The sequence of kinase inhibitors and immunotherapy is unstudied.
Thymoma: Randomised trials are almost absent; postoperative radiotherapy for stage II disease rests on registry data.
Thymoma: No systemic therapy is approved specifically for thymoma.
Thymoma and thymic carcinoma: No randomised trials have ever been completed in thymic epithelial tumours.
Thymoma and thymic carcinoma: Immunotherapy safety in a tumour that disturbs central tolerance.

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