OnCo
cancersCancer

Renal cell carcinoma

Kidney cancer is where anti-angiogenic drugs and immunotherapy came together, and where a Nobel-winning oxygen-sensing pathway yielded a drug, belzutifan.

Renal cell carcinoma is a cancer of the kidney's tubules, increasingly found by chance on scans done for other reasons. Three quarters are clear-cell tumours defined by loss of the VHL gene, which leaves the oxygen-sensing HIF-2α switch permanently on and makes the tumour intensely vascular and immune-infiltrated. That biology explains the whole modern treatment story: anti-VEGF pills (2005-2012), immunotherapy (2015 onward), their combination (2018 onward), and the first HIF-2α inhibitor, belzutifan (2021).

For metastatic disease, four immunotherapy-based first-line regimens have survival benefit: nivolumab-ipilimumab (CheckMate 214, durable remissions in a fifth of intermediate/poor-risk patients, still visible at eight years) and three IO-TKI doublets (pembrolizumab-axitinib, nivolumab-cabozantinib, lenvatinib-pembrolizumab). Attempts to do better in first line with triplets failed on survival (COSMIC-313) or fell short (LITESPARK-012), and two trials (CONTACT-03, TiNivo-2) showed that restarting immunotherapy after it fails does not help. After surgery, adjuvant pembrolizumab (KEYNOTE-564) was the first adjuvant immunotherapy in any solid tumour to improve overall survival, and in 2026 belzutifan plus pembrolizumab (LITESPARK-022) became the first adjuvant combination, though three other adjuvant immunotherapy trials were negative.

What comes next: selecting who needs adjuvant therapy (ctDNA is weak in RCC; CAIX PET and gene signatures are candidates); CAIX theranostics with radiolabelled girentuximab; zanzalintinib and next-generation TKIs; HIF-2α combinations in the right setting; CD70 and CAIX cell therapies; treatment-free survival as an endpoint; and better management of the small renal masses that make up an increasing share of diagnoses, many of which need no treatment at all. Non-clear-cell histologies (papillary, chromophobe, translocation) remain under-served.

State of the art today

  • Adjuvant immunotherapy with OS benefit.
  • HIF-2α inhibition.
  • Belzutifan validates HIF-2α as a target in VHL disease and pretreated RCC.
  • Two negative rechallenge trials (CONTACT-03, TiNivo-2) and two failed first-line intensification trials (COSMIC-313, LITESPARK-012) have sharpened the algorithm rather than widened it.
  • Active surveillance and nephron-sparing approaches are standard for small renal masses.
  • CAIX PET (ZIRCON) offers non-invasive diagnosis of clear-cell RCC; approval delayed by a 2025 CRL.
Show survival figures (2)

Averages across everyone diagnosed, often years ago. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.

  • Four immunotherapy-based first-line regimens with survival benefit; durable remissions off treatment in ~20% with nivolumab-ipilimumab at 8 years.
  • Adjuvant pembrolizumab improves overall survival (KEYNOTE-564); pembrolizumab + belzutifan approved as adjuvant combination (2026).
Who it affects
Show survival figures (2)

Averages across everyone diagnosed, often years ago. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.

  • Renal cell carcinoma causes about 430,000 cases and 180,000 deaths a year worldwide, with incidence rising as imaging finds more tumours; ~20-30% are metastatic at diagnosis.
  • Five-year survival is ~15% for metastatic disease overall, higher with modern IO regimens.

Where the cases are

Cases by country · GLOBOCAN 2022
All countries →

Site: Kidney. World: 434,840 new cases, 155,953 deaths.

#CountryNew casesDeaths
1China73,65623,991
2United States of America71,75914,295
3Russian Federation29,1099,148
4Japan21,2076,926
5Germany20,5147,856
6India17,48010,464
7France (metropolitan)14,5415,058
8United Kingdom13,7144,736
9Italy13,6664,592
10Brazil11,0904,460

The kidney site (C64) includes all renal parenchymal cancers; RCC is over 90%.

Standard of care

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Localised

Partial/radical nephrectomy or ablation; adjuvant pembrolizumab ± belzutifan for high risk.

NCCN Guidelines: Kidney Cancer
Robotic & minimally invasive surgeryThermal ablation (RFA, microwave, cryo)PembrolizumabBelzutifan
Metastatic

IO-TKI or IO-IO doublet; belzutifan, cabozantinib, lenvatinib-everolimus later.

NCCN Guidelines: Kidney Cancer
NivolumabIpilimumabPembrolizumabBelzutifan
Small renal mass (<4 cm)

Active surveillance, partial nephrectomy (usually robotic), or thermal ablation depending on growth, comorbidity, and biopsy; renal mass biopsy increasingly used.

NCCN · 2A
Partial nephrectomy, ablation & active surveillance of small renal massesRobotic & minimally invasive surgeryThermal ablation (RFA, microwave, cryo)
Localised T1b-T3

Partial or radical nephrectomy; no adjuvant therapy for low/intermediate risk.

NCCN · 1 (surgery)
Robotic & minimally invasive surgery
High-risk after nephrectomy (clear-cell)

Adjuvant pembrolizumab for 1 year (KEYNOTE-564, OS benefit); pembrolizumab + belzutifan approved 2026 (LITESPARK-022); sunitinib adjuvant rarely used.

NCCN · 1 (pembrolizumab)ESMO-MCBS · A
PembrolizumabKEYNOTE-564BelzutifanLITESPARK-022
Metastatic, intermediate/poor risk, first line

Nivolumab + ipilimumab, or an IO-TKI doublet (pembrolizumab + axitinib, nivolumab + cabozantinib, lenvatinib + pembrolizumab); cytoreductive nephrectomy deferred or omitted (CARMENA) except in selected cases.

NCCN · 1 (preferred: all four regimens)ESMO-MCBS · 4
NivolumabIpilimumabCheckMate 214PembrolizumabAxitinibKEYNOTE-426CabozantinibCheckMate 9ERLenvatinibCLEAR (KEYNOTE-581)IMDC risk → first-line regimen choice (RCC)
Metastatic, favourable risk, first line

IO-TKI doublet (PFS benefit; OS benefit unproven in this group) or single-agent TKI (sunitinib, pazopanib) with deferred IO; active surveillance for indolent low-volume disease.

NCCN · 1 (IO-TKI); 2A (TKI alone)
PembrolizumabAxitinibLenvatinibCabozantinibSunitinibIMDC risk groups (favourable / intermediate / poor)
Second line after IO-based therapy

Single-agent TKI (cabozantinib, axitinib, lenvatinib + everolimus, tivozanib); belzutifan after both IO and VEGF-TKI (LITESPARK-005). Do not rechallenge PD-1 (CONTACT-03, TiNivo-2).

NCCN · 1 (cabozantinib, belzutifan)
CabozantinibBelzutifanLITESPARK-005TivozanibEverolimusCaution: PD-1 rechallenge after progression on immunotherapy (RCC)CONTACT-03TiNivo-2
Oligometastatic / oligoprogressive disease

Metastasectomy or SBRT to limited sites with continuation of systemic therapy or observation.

NCCN · 2A
SBRT / SABR (stereotactic radiotherapy)
Non-clear-cell RCC

Cabozantinib (PAPMET), lenvatinib + pembrolizumab (KEYNOTE-B61), or nivolumab + cabozantinib; MET inhibitors for MET-driven papillary; trials preferred.

NCCN · 2A
CabozantinibLenvatinibPembrolizumabNivolumab
VHL disease

Belzutifan for VHL-associated RCC, CNS haemangioblastoma, and pNET not requiring immediate surgery (LITESPARK-004).

NCCN · 1
Belzutifan

Subtypes & biomarkers

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Subtypes
  • Clear-cell (~75%; VHL loss, HIF-2α driven)
  • Papillary type 1 (MET) and type 2 (FH, others)
  • Chromophobe
  • Translocation (TFE3/TFEB)
  • Collecting duct and medullary (SMARCB1)
  • Sarcomatoid differentiation (any histology, ~10%)
  • Hereditary syndromes : VHL, HLRCC (FH), BHD (FLCN), HPRC (MET)
Biomarkers clinicians test

Target prevalence in this cancer

Target / alterationPrevalenceSource
VEGF / VEGFR
>90%
cBioPortal (TCGA)
HIF-2α
85-90%
cBioPortal (TCGA)
CD70
80-90%
Wikipedia
CDH6
60-80%
Wikipedia
PSMA
Clear-cell; imaging studies
60-80%
PMC
MET
10-15%
cBioPortal (TCGA)

How common each drug target or alteration is in this cancer. Population-level and approximate; see the target page for detail. Full matrix.

History

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  1. 1992High-dose IL-2 approved
  2. 1992High-dose IL-2 approved: first immunotherapy for RCC, with rare cures
    Cytokines & engineered cytokines
  3. 1993VHL gene identified; the molecular basis of clear-cell RCC
    HIF-2α
  4. 2001Cytoreductive nephrectomy improves survival with interferon (SWOG 8949)
  5. 2005Sorafenib/sunitinib: VEGF era
  6. 2005Sorafenib approved: first VEGF-pathway TKI in RCC
    Anti-angiogenic therapy
  7. 2006Sunitinib approved; replaces interferon
    Sunitinib
  8. 2009Everolimus approved second line (RECORD-1)
    Everolimus
  9. 2012Axitinib approved (AXIS)
    Axitinib
  10. 2015Nivolumab beats everolimus (CheckMate 025): immunotherapy returns to RCC
    Nivolumab
  11. 2016Cabozantinib approved (METEOR)
    Cabozantinib
  12. 2018Nivolumab-ipilimumab first line
  13. 2018Nivolumab-ipilimumab first line (CheckMate 214); CARMENA questions cytoreductive nephrectomy
    CheckMate 214
  14. 2019Pembrolizumab-axitinib and avelumab-axitinib: IO-TKI era begins
    KEYNOTE-426AxitinibAvelumab
  15. 2021Belzutifan approved
    Belzutifan
  16. 2021Nivolumab-cabozantinib, lenvatinib-pembrolizumab, adjuvant pembrolizumab, belzutifan (VHL), tivozanib approved
    CheckMate 9ERCLEAR (KEYNOTE-581)KEYNOTE-564BelzutifanTivozanib
  17. 2023COSMIC-313 triplet fails on OS; CONTACT-03 closes IO rechallenge; belzutifan approved after IO/TKI (LITESPARK-005); ZIRCON validates CAIX PET
    COSMIC-313CONTACT-03LITESPARK-005CAIX PET (89Zr-girentuximab)
  18. 2024KEYNOTE-564 shows OS benefit; CheckMate 214 8-year data; TiNivo-2 negative
    KEYNOTE-564CheckMate 214TiNivo-2
  19. 2026LITESPARK-022 positive and approved (adjuvant belzutifan + pembrolizumab); LITESPARK-012 first-line triplet falls short
    LITESPARK-022LITESPARK-012

Pipeline

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Phase 3ADC
Raludotatug deruxtecan
Phase 3Personalised mRNA neoantigen vaccine
Intismeran autogene
ApprovedSmall-molecule HIF-2α inhibitor
Belzutifan · Welireg
LITESPARK-022CAIX PET (89Zr-girentuximab)CAIX theranostics: 89Zr-girentuximab PET and 177Lu/225Ac-girentuximab therapyBiomarker-selected adjuvant therapy in RCC (ctDNA, CAIX PET, gene signatures)IMDC risk → first-line regimen choice (RCC)Caution: PD-1 rechallenge after progression on immunotherapy (RCC)Allogeneic (off-the-shelf) cell therapyPartial nephrectomy, ablation & active surveillance of small renal massesRadio-antibody & radio-ADC

Open problems

  • Non-clear-cell histologies understudied.
  • No validated predictive biomarker for IO.
  • No predictive biomarker to choose between IO-IO and IO-TKI, or to identify the 20% who achieve durable remission.
  • Adjuvant therapy treats many who would never relapse; ctDNA shedding is too low for standard MRD approaches.
  • Favourable-risk disease has no proven OS benefit from any first-line combination.
  • Non-clear-cell histologies lack dedicated phase 3 evidence.
  • First-line intensification (triplets) has failed twice; the next step in first line is unclear.
  • Treatment-free survival and de-escalation after deep response are unstudied prospectively.
  • Toxicity and dose reductions with lenvatinib-pembrolizumab limit real-world durability.
  • Small renal mass overtreatment and the absence of a reliable non-invasive diagnostic (CAIX PET awaits approval).

Trials

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Recruiting now (live from ClinicalTrials.gov)

Recruiting trials near you · live from ClinicalTrials.gov
Renal cell carcinoma
condition: renal cell carcinoma
Open on ClinicalTrials.gov →

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Landmark trials in OnCo

CheckMate 214CheckMate 9ERCLEAR (KEYNOTE-581)CONTACT-03COSMIC-313KEYNOTE-426KEYNOTE-564LITESPARK-005LITESPARK-012LITESPARK-022TiNivo-2

Expert centres

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Where the expertise is

Centres linked to this cancer in OnCo

Seeking a second opinion: ask your oncologist for a referral to a high-volume centre; most accept records and pathology by mail or telehealth. In the US, use the NCI's Find a Cancer Center tool or the nonprofit Cancer Commons, which navigates options for advanced cancers at no cost.

Questions to ask

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Bring to your appointment

Questions to ask your oncologist about Renal cell carcinoma

Generated from this cancer's standard of care, biomarkers, and pipeline · 31 questions

Newly diagnosed

  1. What is my exact diagnosis, stage, and grade, and which tests established them?
    Why: Everything else follows from an accurate stage and subtype.
  2. Which biomarkers have been tested on my tumour (for example Clear-cell vs non-clear-cell histology, VHL, IMDC risk, CAIX, IMDC risk group), and what were the results?
    Why: These results decide eligibility for targeted therapy, immunotherapy, and trials.
  3. Which subtype is my cancer, and does that change the recommended treatment?
    Why: Recognised subtypes for this cancer include Clear-cell, Papillary type 1and type 2, Chromophobe.
  4. Is germline (inherited) genetic testing recommended for me or my family?
    Why: Inherited variants can change treatment and matter for relatives.

Localised

  1. For my situation (localised), which of the standard options do you recommend and why?
    Why: Guideline options include: Partial/radical nephrectomy or ablation; adjuvant pembrolizumab ± belzutifan for high risk.
  2. Am I a candidate for Pembrolizumab, Belzutifan, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Metastatic

  1. For my situation (metastatic), which of the standard options do you recommend and why?
    Why: Guideline options include: IO-TKI or IO-IO doublet; belzutifan, cabozantinib, lenvatinib-everolimus later.
  2. Am I a candidate for Nivolumab, Ipilimumab, Pembrolizumab or related drugs, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Small renal mass (<4 cm)

  1. For my situation (small renal mass (<4 cm)), which of the standard options do you recommend and why?
    Why: Guideline options include: Active surveillance, partial nephrectomy (usually robotic), or thermal ablation depending on growth, comorbidity, and biopsy; renal mass biopsy increasingly used.

Localised T1b-T3

  1. For my situation (localised t1b-t3), which of the standard options do you recommend and why?
    Why: Guideline options include: Partial or radical nephrectomy; no adjuvant therapy for low/intermediate risk.

High-risk after nephrectomy (clear-cell)

  1. For my situation (high-risk after nephrectomy (clear-cell)), which of the standard options do you recommend and why?
    Why: Guideline options include: Adjuvant pembrolizumab for 1 year (KEYNOTE-564, OS benefit); pembrolizumab + belzutifan approved 2026 (LITESPARK-022); sunitinib adjuvant rarely used.
  2. Am I a candidate for Pembrolizumab, Belzutifan, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
  3. How do the results of KEYNOTE-564 and LITESPARK-022 apply to someone like me?
    Why: Trial populations differ from individual patients; ask how closely you match.

Metastatic, intermediate/poor risk, first line

  1. For my situation (metastatic, intermediate/poor risk, first line), which of the standard options do you recommend and why?
    Why: Guideline options include: Nivolumab + ipilimumab, or an IO-TKI doublet (pembrolizumab + axitinib, nivolumab + cabozantinib, lenvatinib + pembrolizumab); cytoreductive nephrectomy deferred or omitted (CARMENA) except in selected cases.
  2. Am I a candidate for Nivolumab, Ipilimumab, Pembrolizumab or related drugs, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
  3. How do the results of CheckMate 214 and KEYNOTE-426 apply to someone like me?
    Why: Trial populations differ from individual patients; ask how closely you match.

Metastatic, favourable risk, first line

  1. For my situation (metastatic, favourable risk, first line), which of the standard options do you recommend and why?
    Why: Guideline options include: IO-TKI doublet (PFS benefit; OS benefit unproven in this group) or single-agent TKI (sunitinib, pazopanib) with deferred IO; active surveillance for indolent low-volume disease.
  2. Am I a candidate for Pembrolizumab, Axitinib, Lenvatinib or related drugs, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Second line after IO-based therapy

  1. For my situation (second line after io-based therapy), which of the standard options do you recommend and why?
    Why: Guideline options include: Single-agent TKI (cabozantinib, axitinib, lenvatinib + everolimus, tivozanib); belzutifan after both IO and VEGF-TKI (LITESPARK-005). Do not rechallenge PD-1 (CONTACT-03, TiNivo-2).
  2. Am I a candidate for Cabozantinib, Belzutifan, Tivozanib or related drugs, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
  3. How do the results of LITESPARK-005 and CONTACT-03 apply to someone like me?
    Why: Trial populations differ from individual patients; ask how closely you match.

Oligometastatic / oligoprogressive disease

  1. For my situation (oligometastatic / oligoprogressive disease), which of the standard options do you recommend and why?
    Why: Guideline options include: Metastasectomy or SBRT to limited sites with continuation of systemic therapy or observation.

Non-clear-cell RCC

  1. For my situation (non-clear-cell rcc), which of the standard options do you recommend and why?
    Why: Guideline options include: Cabozantinib (PAPMET), lenvatinib + pembrolizumab (KEYNOTE-B61), or nivolumab + cabozantinib; MET inhibitors for MET-driven papillary; trials preferred.
  2. Am I a candidate for Cabozantinib, Lenvatinib, Pembrolizumab or related drugs, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

VHL disease

  1. For my situation (vhl disease), which of the standard options do you recommend and why?
    Why: Guideline options include: Belzutifan for VHL-associated RCC, CNS haemangioblastoma, and pNET not requiring immediate surgery (LITESPARK-004).
  2. Am I a candidate for Belzutifan, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Any stage

  1. Are there clinical trials I could join, for example of Raludotatug deruxtecan, Intismeran autogene, LITESPARK-022, CAIX PET (89Zr-girentuximab)?
    Why: Trials are how the next standard of care is set; asking early keeps options open.
  2. Would a second opinion at a high-volume centre change anything, and can you help arrange it?
    Why: Rare or high-stakes decisions benefit from a centre that treats many similar patients.
  3. What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?
    Why: Supportive care improves quality of life and helps patients complete treatment.
  4. I read that “Non-clear-cell histologies understudied”. How does that affect my plan?
    Why: Open problems are where trials and second opinions matter most.
  5. I read that “No validated predictive biomarker for IO”. How does that affect my plan?
    Why: Open problems are where trials and second opinions matter most.

Print this page for your appointment (your browser's print command). These prompts are for discussion; your clinical team knows your case.

Everything relevant

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Direct links plus the targets, companies, and technologies of this cancer's products.

technologies

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Allogeneic (off-the-shelf) cell therapyAnti-angiogenic therapyAntibody-drug conjugate (ADC)Bariatric surgery and cancer incidenceBone-modifying agents (bisphosphonates, denosumab)CAIX PET (89Zr-girentuximab)Cytokines & engineered cytokinesDietary fibre and the gut microbiome for immunotherapy responseFaecal microbiota transplantation for PD-1 non-respondersGLP-1 receptor agonists and obesity-related cancer riskImmune checkpoint inhibitorsMicrobiome modulation to unlock immunotherapyMonoclonal antibodiesPartial nephrectomy, ablation & active surveillance of small renal massesPersonalised neoantigen (mRNA) vaccinesProbiotics, antibiotics and stewardship around immunotherapyRadio-antibody & radio-ADCRobotic & minimally invasive surgerySBRT / SABR (stereotactic radiotherapy)Small-molecule kinase inhibitorsThermal ablation (RFA, microwave, cryo)TIL therapy

targets

15
AKTBRAFCD70CD73 / adenosine axisCDH6CTLA-4FGFR2HIF-2αKITMETPD-1PD-L1PIK3CA / PI3K-alphaRETVEGF / VEGFR

drugs

20
Not mapped hereRecombinant interleukin-2 (cytokine)
Aldesleukin (high-dose IL-2) · Proleukin
ApprovedMonoclonal antibody (anti-PD-L1)
Avelumab · Bavencio
ApprovedSmall-molecule kinase inhibitor (VEGFR)
Axitinib · Inlyta
ApprovedSmall-molecule HIF-2α inhibitor
Belzutifan · Welireg
NegativeEngineered cytokine (PEGylated IL-2)
Bempegaldesleukin
ApprovedMonoclonal antibody (anti-VEGF)
Bevacizumab · Avastin (and biosimilars)
ApprovedSmall-molecule multi-kinase inhibitor (MET, VEGFR2, AXL, RET)
Cabozantinib · Cabometyx
ApprovedSmall-molecule mTOR inhibitor
Everolimus · Afinitor
HistoricRecombinant type I interferon (cytokine)
Interferon alfa-2a/2b · Roferon-A / Intron A / Sylatron
Phase 3Personalised mRNA neoantigen vaccine
Intismeran autogene
ApprovedMonoclonal antibody (anti-CTLA-4)
Ipilimumab · Yervoy
ApprovedSmall-molecule multi-kinase inhibitor (VEGFR, FGFR, PDGFR, RET, KIT)
Lenvatinib · Lenvima
ApprovedMonoclonal antibody (anti-PD-1)
Nivolumab · Opdivo / Opdivo Qvantig (SC)
ApprovedSmall-molecule kinase inhibitor (VEGFR/PDGFR/KIT)
Pazopanib · Votrient
ApprovedMonoclonal antibody (anti-PD-1)
Pembrolizumab · Keytruda / Keytruda Qlex (SC)
Phase 3ADC
Raludotatug deruxtecan
ApprovedSmall-molecule multi-kinase inhibitor (VEGFR, PDGFR, RAF)
Sorafenib · Nexavar
ApprovedSmall-molecule multi-kinase inhibitor (VEGFR, PDGFR, KIT)
Sunitinib · Sutent
Not mapped hereIntravenous mTOR inhibitor (rapamycin analogue)
Temsirolimus · Torisel
ApprovedSmall-molecule kinase inhibitor (VEGFR)
Tivozanib · Fotivda

companies

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Allogene TherapeuticsArsenal BiosciencesAVEO Oncology (LG Chem)BayerBristol Myers SquibbDaiichi SankyoEisaiExelixisIpsenMerck & Co. (MSD)ModernaNovartisPfizer (incl. Seagen)Roche / GenentechTelix PharmaceuticalsXencor

institutions

9
ANZUP Cancer Trials GroupCedars-Sinai CancerCleveland Clinic Taussig Cancer InstituteDana-Farber Brigham Cancer CenterFox Chase Cancer CenterGustave RoussyHarold C. Simmons Comprehensive Cancer Center, UT SouthwesternMD Anderson Cancer CenterMemorial Sloan Kettering Cancer Center

pathways

7
Glutamine addictionPD-1 / PD-L1 immune checkpoint & T-cell activationPI3K / AKT / mTORSWI/SNF chromatin remodellingThe angiogenic switch & tumour vesselsVEGF angiogenesisVHL / HIF oxygen sensing

terms

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Active surveillance and observationBone metastases and skeletal-related eventsCryoablationDebulking (cytoreductive surgery)IMDC risk groups (favourable / intermediate / poor)Neoadjuvant / adjuvant / perioperativeNephrectomyObesity-related cancers (IARC list of 13)Oligometastatic diseasePortal vein tumour thrombus (macrovascular invasion)Radiofrequency ablation (RFA)RetroperitoneumSarcomatoid differentiation (RCC)Von Hippel-Lindau disease

trials

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CheckMate 214CheckMate 9ERCLEAR (KEYNOTE-581)CONTACT-03COSMIC-313KEYNOTE-426KEYNOTE-564LITESPARK-005LITESPARK-012LITESPARK-022TiNivo-2

pairings

3
Caution: PD-1 rechallenge after progression on immunotherapy (RCC)IMDC risk → first-line regimen choice (RCC)PD-1 blockade + VEGF inhibition

ideas

19
Bank three spatially separate tumour blocks from every resectionBiomarker-selected adjuvant therapy in RCC (ctDNA, CAIX PET, gene signatures)CAIX theranostics: 89Zr-girentuximab PET and 177Lu/225Ac-girentuximab therapyCapture diet, fibre and antibiotic exposure in every immunotherapy pivotal trialDevice-agnostic public trials of ablation technologies against surgeryEvery routine CT scan checked by AI for early cancer signs, with a tracked follow-up pathwayGrow immune command posts inside tumoursInhaled immune therapy to make the lung hostile to arriving tumour cellsKidney and liver impairment dosing studies completed before approval, not years afterLink bariatric and GLP-1 registries to cancer registries in every country that has bothMap metabolic dependencies in the patient, not the dishMulti-arm, multi-stage trials to answer which order to give approved drugsProtect the gut flora of patients about to start immunotherapyReplace fixed kidney and liver cut-offs with drug-specific, pharmacology-based thresholdsTake faecal transplant plus immunotherapy to a definitive trialTest protein and resistance training during immunotherapyTreat immunotherapy side-effects without wiping out the responseUse a hypoxia scan to pick patients for adenosine-pathway drugsWatch small kidney tumours rather than remove them, with a national registry

people

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Dingwei YeJae Lyun LeeJames LarkinNeeraj AgarwalPadmanee SharmaPrimo N. Lara Jr.Shilpa GuptaSuzanne L. TopalianToni K. ChoueiriWilliam G. Kaelin Jr.

bottlenecks

3
Overdiagnosis and false alarmsSurgery and radiotherapy cure most, get leastTumour heterogeneity and clonal evolution

key papers

4
CLEAR: lenvatinib plus pembrolizumab versus sunitinib as first treatment for advanced kidney cancerGerlinger: a single biopsy misses most of the mutations in a kidney tumourIARC verdict: excess body fat causes 13 cancersKEYNOTE-564: a year of pembrolizumab after kidney cancer surgery

Key papers

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rctNew England Journal of Medicine 2021changed practice
CLEAR: lenvatinib plus pembrolizumab versus sunitinib as first treatment for advanced kidney cancer

Patients with newly diagnosed advanced clear-cell kidney cancer should receive an immunotherapy-based combination; lenvatinib plus pembrolizumab gives the highest response rate and longest PFS of the available options, at the cost of more side effects requiring dose adjustment. Sunitinib alone is no longer an appropriate standard. Choosing among the combinations depends on risk group, symptoms, comorbidity and the value placed on treatment-free survival, which favours nivolumab plus ipilimumab in intermediate and poor risk.

rctNew England Journal of Medicine 2021changed practice
KEYNOTE-564: a year of pembrolizumab after kidney cancer surgery

Patients whose kidney cancer has been removed but who are at high risk of recurrence (large or high-grade tumours, node involvement, or resected metastases) can now be offered a year of pembrolizumab, which increases the chance of being alive and cancer-free several years later. Roughly nine patients need treatment to prevent one recurrence at two years, and some will have permanent side effects, so shared decision-making matters. Why pembrolizumab succeeded where similar drugs failed is not fully understood.

reviewNew England Journal of Medicine 2016changed practice
IARC verdict: excess body fat causes 13 cancers

Maintaining a healthy weight is now established cancer prevention for over a dozen cancer types. For clinicians and policymakers, obesity belongs alongside tobacco and alcohol in prevention strategy. Whether intentional weight loss in adulthood reverses risk is still being studied, including in trials of GLP-1 drugs.

translationalNew England Journal of Medicine 2012
Gerlinger: a single biopsy misses most of the mutations in a kidney tumour

A single biopsy is an incomplete picture of a patient's cancer. Truncal mutations shared by all cells (in kidney cancer, VHL) are the most reliable drug targets, whereas mutations in only some branches predict resistance. This is why liquid biopsy and multi-region sampling matter.

Latest papers

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Literature trend2,956 papers in the last 12 months+11% vs prior 12How this is computed
Latest papers · live from Europe PMC
Open in Europe PMC

Query for this cancer: (TITLE:"Renal cell carcinoma" OR ABSTRACT:"Renal cell carcinoma") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Renal cell carcinoma, not a curated reading list.

Connected

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Pages like this

not linked directly; found by shared links

technologies

19
Allogeneic (off-the-shelf) cell therapyAnti-angiogenic therapyBariatric surgery and cancer incidenceBone-modifying agents (bisphosphonates, denosumab)CAIX PET (89Zr-girentuximab)Cytokines & engineered cytokinesDietary fibre and the gut microbiome for immunotherapy responseFaecal microbiota transplantation for PD-1 non-respondersGLP-1 receptor agonists and obesity-related cancer riskImmune checkpoint inhibitorsMicrobiome modulation to unlock immunotherapyPartial nephrectomy, ablation & active surveillance of small renal massesPersonalised neoantigen (mRNA) vaccinesProbiotics, antibiotics and stewardship around immunotherapyRadio-antibody & radio-ADCRobotic & minimally invasive surgerySBRT / SABR (stereotactic radiotherapy)Small-molecule kinase inhibitorsThermal ablation (RFA, microwave, cryo)

targets

9
AKTCD70CD73 / adenosine axisCDH6CTLA-4HIF-2αMETPD-1VEGF / VEGFR

drugs

20
Not mapped hereRecombinant interleukin-2 (cytokine)
Aldesleukin (high-dose IL-2) · Proleukin
ApprovedMonoclonal antibody (anti-PD-L1)
Avelumab · Bavencio
ApprovedSmall-molecule kinase inhibitor (VEGFR)
Axitinib · Inlyta
ApprovedSmall-molecule HIF-2α inhibitor
Belzutifan · Welireg
NegativeEngineered cytokine (PEGylated IL-2)
Bempegaldesleukin
ApprovedMonoclonal antibody (anti-VEGF)
Bevacizumab · Avastin (and biosimilars)
ApprovedSmall-molecule multi-kinase inhibitor (MET, VEGFR2, AXL, RET)
Cabozantinib · Cabometyx
ApprovedSmall-molecule mTOR inhibitor
Everolimus · Afinitor
HistoricRecombinant type I interferon (cytokine)
Interferon alfa-2a/2b · Roferon-A / Intron A / Sylatron
Phase 3Personalised mRNA neoantigen vaccine
Intismeran autogene
ApprovedMonoclonal antibody (anti-CTLA-4)
Ipilimumab · Yervoy
ApprovedSmall-molecule multi-kinase inhibitor (VEGFR, FGFR, PDGFR, RET, KIT)
Lenvatinib · Lenvima
ApprovedMonoclonal antibody (anti-PD-1)
Nivolumab · Opdivo / Opdivo Qvantig (SC)
ApprovedSmall-molecule kinase inhibitor (VEGFR/PDGFR/KIT)
Pazopanib · Votrient
ApprovedMonoclonal antibody (anti-PD-1)
Pembrolizumab · Keytruda / Keytruda Qlex (SC)
Phase 3ADC
Raludotatug deruxtecan
ApprovedSmall-molecule multi-kinase inhibitor (VEGFR, PDGFR, RAF)
Sorafenib · Nexavar
ApprovedSmall-molecule multi-kinase inhibitor (VEGFR, PDGFR, KIT)
Sunitinib · Sutent
Not mapped hereIntravenous mTOR inhibitor (rapamycin analogue)
Temsirolimus · Torisel
ApprovedSmall-molecule kinase inhibitor (VEGFR)
Tivozanib · Fotivda

companies

12
Allogene TherapeuticsArsenal BiosciencesAVEO Oncology (LG Chem)Bristol Myers SquibbEisaiExelixisMerck & Co. (MSD)NovartisPfizer (incl. Seagen)Roche / GenentechTelix PharmaceuticalsXencor

institutions

9
ANZUP Cancer Trials GroupCedars-Sinai CancerCleveland Clinic Taussig Cancer InstituteDana-Farber Brigham Cancer CenterFox Chase Cancer CenterGustave RoussyHarold C. Simmons Comprehensive Cancer Center, UT SouthwesternMD Anderson Cancer CenterMemorial Sloan Kettering Cancer Center

pathways

7
Glutamine addictionPD-1 / PD-L1 immune checkpoint & T-cell activationPI3K / AKT / mTORSWI/SNF chromatin remodellingThe angiogenic switch & tumour vesselsVEGF angiogenesisVHL / HIF oxygen sensing

terms

14
Active surveillance and observationBone metastases and skeletal-related eventsCryoablationDebulking (cytoreductive surgery)IMDC risk groups (favourable / intermediate / poor)Neoadjuvant / adjuvant / perioperativeNephrectomyObesity-related cancers (IARC list of 13)Oligometastatic diseasePortal vein tumour thrombus (macrovascular invasion)Radiofrequency ablation (RFA)RetroperitoneumSarcomatoid differentiation (RCC)Von Hippel-Lindau disease

trials

11
CheckMate 214CheckMate 9ERCLEAR (KEYNOTE-581)CONTACT-03COSMIC-313KEYNOTE-426KEYNOTE-564LITESPARK-005LITESPARK-012LITESPARK-022TiNivo-2

pairings

3
Caution: PD-1 rechallenge after progression on immunotherapy (RCC)IMDC risk → first-line regimen choice (RCC)PD-1 blockade + VEGF inhibition

ideas

19
Bank three spatially separate tumour blocks from every resectionBiomarker-selected adjuvant therapy in RCC (ctDNA, CAIX PET, gene signatures)CAIX theranostics: 89Zr-girentuximab PET and 177Lu/225Ac-girentuximab therapyCapture diet, fibre and antibiotic exposure in every immunotherapy pivotal trialDevice-agnostic public trials of ablation technologies against surgeryEvery routine CT scan checked by AI for early cancer signs, with a tracked follow-up pathwayGrow immune command posts inside tumoursInhaled immune therapy to make the lung hostile to arriving tumour cellsKidney and liver impairment dosing studies completed before approval, not years afterLink bariatric and GLP-1 registries to cancer registries in every country that has bothMap metabolic dependencies in the patient, not the dishMulti-arm, multi-stage trials to answer which order to give approved drugsProtect the gut flora of patients about to start immunotherapyReplace fixed kidney and liver cut-offs with drug-specific, pharmacology-based thresholdsTake faecal transplant plus immunotherapy to a definitive trialTest protein and resistance training during immunotherapyTreat immunotherapy side-effects without wiping out the responseUse a hypoxia scan to pick patients for adenosine-pathway drugsWatch small kidney tumours rather than remove them, with a national registry

people

10
Dingwei YeJae Lyun LeeJames LarkinNeeraj AgarwalPadmanee SharmaPrimo N. Lara Jr.Shilpa GuptaSuzanne L. TopalianToni K. ChoueiriWilliam G. Kaelin Jr.

bottlenecks

3
Overdiagnosis and false alarmsSurgery and radiotherapy cure most, get leastTumour heterogeneity and clonal evolution

key papers

4
CLEAR: lenvatinib plus pembrolizumab versus sunitinib as first treatment for advanced kidney cancerGerlinger: a single biopsy misses most of the mutations in a kidney tumourIARC verdict: excess body fat causes 13 cancersKEYNOTE-564: a year of pembrolizumab after kidney cancer surgery