# Renal cell carcinoma

Source: https://onco.cc/cancers/rcc/  
OnCo record `rcc` (Cancer). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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

## Summary

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.

## Fields

- Kind: Cancer
- Last checked: 2026-09-07
- Also known as: RCC
- Tags: gu
- Group: genitourinary
- Burden: Renal cell carcinoma causes about 430,000 cases a year worldwide, with incidence rising as imaging finds more small tumours, many of which need no treatment; ~20-30% are metastatic at diagnosis, and immunotherapy doublets now give durable remissions in about a fifth of those patients. ~180,000 deaths a year; registry five-year survival for metastatic disease is ~15% overall, higher with modern IO regimens.
- 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: Clear-cell vs non-clear-cell histology; VHL; IMDC risk; CAIX (imaging, 89Zr-girentuximab); IMDC risk group (six clinical factors); Histology and sarcomatoid features; VHL / HIF-2α axis (belzutifan); PD-L1 (not used for selection); CAIX (imaging; theranostic target); CD70 (CAR-T target); MET (papillary type 1); Gene-expression signatures (angiogenesis vs T-effector; research); ctDNA (low shedding; research)

## Sections of this record

The page is a hub with ten sections in reading order; large sections have their own page. The same plan as JSON: https://onco.cc/api/v1/cancers/rcc/sections.json

- Overview (on the hub): The TL;DR, the family this cancer belongs to, the organ, who gets it and what the state of the art is. https://onco.cc/cancers/rcc/#overview [11 subtypes, 8 state-of-the-art points]
- What it is (on the hub): Anatomy, the subtypes and how they differ, how it is staged, and where advanced disease spreads. https://onco.cc/cancers/rcc/#what-it-is [18 subtypes, 7 sites of spread]
- Finding it (on the hub): How it shows itself, how it is confirmed, what screening exists, and the biomarkers clinicians test for. https://onco.cc/cancers/rcc/#finding-it [13 biomarkers, 7 prevalence rows]
- Treating it (on the hub): The standard of care by setting, the medicines, surgery and radiotherapy named in it, and the regimens behind them. https://onco.cc/cancers/rcc/#treating-it [11 settings, 4 regimens, 8 decisions with options]
- Evidence (own page): Trials recruiting now, the landmark trials, the key papers and what they mean, the latest literature, and the milestones year by year. https://onco.cc/cancers/rcc/evidence/ [72 trials, 6 key papers, 19 milestones]
- The science (own page): The molecular landscape: the targets and how often each appears, the pathways, the mechanics stages and the preclinical models. https://onco.cc/cancers/rcc/science/ [91 targets, 8 pathways, 5 preclinical models]
- Where you are (own page): Cases by country, the UK and NHS pathway and other country lenses, and the expert centres with trials on record. https://onco.cc/cancers/rcc/where-you-are/ [8 centres]
- Living with it (on the hub): The decisions you may face, the aids that walk through them, the warnings on record, the first sixty days and the questions to ask. https://onco.cc/cancers/rcc/#living-with-it [31 questions, 6 red cards]
- What is coming (own page): Everything in development, the open problems and what is being done about them, the roadmaps, and what changed on this record. https://onco.cc/cancers/rcc/coming/ [33 medicines, 72 trials, 19 ideas, 10 open problems]
- Data (own page): Every connected record, the notes, the JSON, Markdown and RDF twins, and where the record came from and when it was checked. https://onco.cc/cancers/rcc/data/ [362 connected records]

## Standard of care

- Localised: Partial/radical nephrectomy or ablation; adjuvant pembrolizumab ± belzutifan for high risk. ([Robotic & minimally invasive surgery](https://onco.cc/technologies/robotic-surgery/), [Thermal ablation (RFA, microwave, cryo)](https://onco.cc/technologies/thermal-ablation/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/), [Belzutifan](https://onco.cc/drugs/belzutifan/))
- Metastatic: IO-TKI or IO-IO doublet; belzutifan, cabozantinib, lenvatinib-everolimus later. ([Nivolumab](https://onco.cc/drugs/nivolumab/), [Ipilimumab](https://onco.cc/drugs/ipilimumab/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/), [Belzutifan](https://onco.cc/drugs/belzutifan/))
- 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. ([Partial nephrectomy, ablation & active surveillance of small renal masses](https://onco.cc/technologies/partial-nephrectomy-active-surveillance/), [Robotic & minimally invasive surgery](https://onco.cc/technologies/robotic-surgery/), [Thermal ablation (RFA, microwave, cryo)](https://onco.cc/technologies/thermal-ablation/))
- Localised T1b-T3: Partial or radical nephrectomy; no adjuvant therapy for low/intermediate risk. ([Robotic & minimally invasive surgery](https://onco.cc/technologies/robotic-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. ([Pembrolizumab](https://onco.cc/drugs/pembrolizumab/), [KEYNOTE-564](https://onco.cc/trials/keynote-564/), [Belzutifan](https://onco.cc/drugs/belzutifan/), [LITESPARK-022](https://onco.cc/trials/litespark-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. ([Nivolumab](https://onco.cc/drugs/nivolumab/), [Ipilimumab](https://onco.cc/drugs/ipilimumab/), [CheckMate 214](https://onco.cc/trials/checkmate-214/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/), [Axitinib](https://onco.cc/drugs/axitinib/), [KEYNOTE-426](https://onco.cc/trials/keynote-426/), [Cabozantinib](https://onco.cc/drugs/cabozantinib/), [CheckMate 9ER](https://onco.cc/trials/checkmate-9er/), [Lenvatinib](https://onco.cc/drugs/lenvatinib/), [CLEAR (KEYNOTE-581)](https://onco.cc/trials/clear/), [IMDC risk → first-line regimen choice (RCC)](https://onco.cc/pairings/risk-directed-first-line-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. ([Pembrolizumab](https://onco.cc/drugs/pembrolizumab/), [Axitinib](https://onco.cc/drugs/axitinib/), [Lenvatinib](https://onco.cc/drugs/lenvatinib/), [Cabozantinib](https://onco.cc/drugs/cabozantinib/), [Sunitinib](https://onco.cc/drugs/sunitinib/), [IMDC risk groups (favourable / intermediate / poor)](https://onco.cc/terms/imdc-risk/))
- 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). ([Cabozantinib](https://onco.cc/drugs/cabozantinib/), [Belzutifan](https://onco.cc/drugs/belzutifan/), [LITESPARK-005](https://onco.cc/trials/litespark-005/), [Tivozanib](https://onco.cc/drugs/tivozanib/), [Everolimus](https://onco.cc/drugs/everolimus/), [Caution: PD-1 rechallenge after progression on immunotherapy (RCC)](https://onco.cc/pairings/io-rechallenge-caution-rcc/), [CONTACT-03](https://onco.cc/trials/contact-03/), [TiNivo-2](https://onco.cc/trials/tinivo-2/))
- Oligometastatic / oligoprogressive disease: Metastasectomy or SBRT to limited sites with continuation of systemic therapy or observation. ([SBRT / SABR (stereotactic radiotherapy)](https://onco.cc/technologies/sbrt/))
- Non-clear-cell RCC: Cabozantinib (PAPMET), lenvatinib + pembrolizumab (KEYNOTE-B61), or nivolumab + cabozantinib; MET inhibitors for MET-driven papillary; trials preferred. ([Cabozantinib](https://onco.cc/drugs/cabozantinib/), [Lenvatinib](https://onco.cc/drugs/lenvatinib/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/), [Nivolumab](https://onco.cc/drugs/nivolumab/))
- VHL disease: Belzutifan for VHL-associated RCC, CNS haemangioblastoma, and pNET not requiring immediate surgery (LITESPARK-004). ([Belzutifan](https://onco.cc/drugs/belzutifan/))

## State of the art

- Adjuvant immunotherapy with OS benefit.
- HIF-2α inhibition.
- 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).
- 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.

## 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).

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Renal_cell_carcinoma
- NCI PDQ: renal cell cancer treatment: https://www.cancer.gov/types/kidney/hp/kidney-treatment-pdq
- CheckMate 214 8-year follow-up: https://www.annalsofoncology.org/article/S0923-7534(24)01516-3/fulltext

## Connected records

- collections: [UroToday](https://onco.cc/collections/src-urotoday/)
- technologies: [Allogeneic (off-the-shelf) cell therapy](https://onco.cc/technologies/allogeneic-cell-therapy/), [Anti-angiogenic therapy](https://onco.cc/technologies/antiangiogenic/), [Bariatric surgery and cancer incidence](https://onco.cc/technologies/bariatric-surgery-cancer-incidence/), [Bone-modifying agents (bisphosphonates, denosumab)](https://onco.cc/technologies/bone-modifying-agents/), [CAIX PET (89Zr-girentuximab)](https://onco.cc/technologies/caix-pet/), [Clonal evolution and branching models](https://onco.cc/technologies/clonal-evolution-models/), [Cryoablation systems](https://onco.cc/technologies/cryoablation-systems/), [Cytokines & engineered cytokines](https://onco.cc/technologies/cytokine-therapy/), [Dietary fibre and the gut microbiome for immunotherapy response](https://onco.cc/technologies/dietary-fibre-microbiome-io/), [Dual-energy and spectral CT](https://onco.cc/technologies/dual-energy-spectral-ct/), [Elastography and contrast-enhanced ultrasound](https://onco.cc/technologies/ultrasound-elastography-ceus/), [Faecal microbiota transplantation for PD-1 non-responders](https://onco.cc/technologies/fmt-checkpoint-nonresponders/), [GLP-1 receptor agonists and obesity-related cancer risk](https://onco.cc/technologies/glp1-agonists-cancer-risk/), [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/), [Microbiome modulation to unlock immunotherapy](https://onco.cc/technologies/microbiome-modulation-io/), [Microwave and radiofrequency ablation systems](https://onco.cc/technologies/microwave-rf-ablation/), [Partial nephrectomy, ablation & active surveillance of small renal masses](https://onco.cc/technologies/partial-nephrectomy-active-surveillance/), [Personalised neoantigen (mRNA) vaccines](https://onco.cc/technologies/neoantigen-mrna-vaccine/), [PI3K, AKT and mTOR inhibitors](https://onco.cc/technologies/pi3k-akt-mtor-inhibitors/), [Probiotics, antibiotics and stewardship around immunotherapy](https://onco.cc/technologies/probiotics-antibiotic-stewardship-io/), [Radio-antibody & radio-ADC](https://onco.cc/technologies/radioimmunotherapy/), [Robotic & minimally invasive surgery](https://onco.cc/technologies/robotic-surgery/), [SBRT / SABR (stereotactic radiotherapy)](https://onco.cc/technologies/sbrt/), [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/), [Stereotactic ablative radiotherapy for oligometastatic disease](https://onco.cc/technologies/sabr-oligometastases/), [Surgical robots: da Vinci, Hugo, Versius and single-port systems](https://onco.cc/technologies/surgical-robot-platforms/), [Thermal ablation (RFA, microwave, cryo)](https://onco.cc/technologies/thermal-ablation/), [Tumour volume doubling time](https://onco.cc/technologies/tumour-doubling-time/)
- targets: [AKAP9](https://onco.cc/targets/akap9/), [AKT](https://onco.cc/targets/akt/), [ARHGAP35](https://onco.cc/targets/arhgap35/), [ARHGEF10L](https://onco.cc/targets/arhgef10l/), [ARHGEF12](https://onco.cc/targets/arhgef12/), [ARID1B](https://onco.cc/targets/arid1b/), [ASXL1](https://onco.cc/targets/asxl1/), [ATG7](https://onco.cc/targets/atg7/), [ATRX](https://onco.cc/targets/atrx/), [AXL](https://onco.cc/targets/axl/), [B4GALT1](https://onco.cc/targets/b4galt1/), [BAP1](https://onco.cc/targets/bap1/), [BIRC6](https://onco.cc/targets/birc6/), [CACNA1D](https://onco.cc/targets/cacna1d/), [CCND1](https://onco.cc/targets/ccnd1/), [CD70](https://onco.cc/targets/cd70/), [CD73 / adenosine axis](https://onco.cc/targets/cd73-adenosine/), [CDH6](https://onco.cc/targets/cdh6/), [CDK12](https://onco.cc/targets/cdk12/), [CDKN1A](https://onco.cc/targets/cdkn1a/), [CDKN2B](https://onco.cc/targets/cdkn2b/), [CHD2](https://onco.cc/targets/chd2/), [CHD4](https://onco.cc/targets/chd4/), [CLTC](https://onco.cc/targets/cltc/), [CRAF (RAF1)](https://onco.cc/targets/raf1/), [CTLA-4](https://onco.cc/targets/ctla4/), [CTNNB1](https://onco.cc/targets/ctnnb1/), [CUL3](https://onco.cc/targets/cul3/), [CYLD](https://onco.cc/targets/cyld/), [CYP11B1](https://onco.cc/targets/cyp11b1/), [ELP4](https://onco.cc/targets/elp4/), [FAT3](https://onco.cc/targets/fat3/), [FKBP12 (FKBP1A)](https://onco.cc/targets/fkbp12/), [FLCN](https://onco.cc/targets/flcn/), [GRM3](https://onco.cc/targets/grm3/), [HIF-1α (HIF1A)](https://onco.cc/targets/hif1a/), [HIF-2α](https://onco.cc/targets/hif2a/), [HMOX1](https://onco.cc/targets/hmox1/), [HNF1A](https://onco.cc/targets/hnf1a/), [HNF1B](https://onco.cc/targets/hnf1b/), [IL2RB](https://onco.cc/targets/il2rb/), [IL2RG](https://onco.cc/targets/il2rg/), [ITK](https://onco.cc/targets/itk/), [KDM5C](https://onco.cc/targets/kdm5c/), [KLLN](https://onco.cc/targets/klln/), [KMT2C](https://onco.cc/targets/kmt2c/), [LCK](https://onco.cc/targets/lck/), [MAP3K1](https://onco.cc/targets/map3k1/), [MET](https://onco.cc/targets/met/), [MPRIP](https://onco.cc/targets/mprip/), [MSN](https://onco.cc/targets/msn/), [mTOR](https://onco.cc/targets/mtor/), [NF2](https://onco.cc/targets/nf2/), [NFE2L2](https://onco.cc/targets/nfe2l2/), [NUP214](https://onco.cc/targets/nup214/), [PAX6](https://onco.cc/targets/pax6/), [PBRM1](https://onco.cc/targets/pbrm1/), [PCBP1](https://onco.cc/targets/pcbp1/), [PD-1](https://onco.cc/targets/pd1/), [PLCG1](https://onco.cc/targets/plcg1/), [PRDM2](https://onco.cc/targets/prdm2/), [PRKAR1A](https://onco.cc/targets/prkar1a/), [PTPRK](https://onco.cc/targets/ptprk/), [RANBP2](https://onco.cc/targets/ranbp2/), [RAP1GDS1](https://onco.cc/targets/rap1gds1/), [RHEB](https://onco.cc/targets/rheb/), [RNF213](https://onco.cc/targets/rnf213/), [ROBO2](https://onco.cc/targets/robo2/), [SDHA](https://onco.cc/targets/sdha/), [SETD2](https://onco.cc/targets/setd2/), [SGK1](https://onco.cc/targets/sgk1/), [SMARCB1](https://onco.cc/targets/smarcb1/), [SPEN](https://onco.cc/targets/spen/), [STAG2](https://onco.cc/targets/stag2/), [TET1](https://onco.cc/targets/tet1/), [TFE3](https://onco.cc/targets/tfe3/), [TGFBR2](https://onco.cc/targets/tgfbr2/), [TIE2 receptor (TEK)](https://onco.cc/targets/tie2/), [TRRAP](https://onco.cc/targets/trrap/), [TSC1](https://onco.cc/targets/tsc1/), [TSC2](https://onco.cc/targets/tsc2/), [UBR5](https://onco.cc/targets/ubr5/), [VEGF / VEGFR](https://onco.cc/targets/vegf/), [VHL](https://onco.cc/targets/vhl/)
- companies: [A2 Biotherapeutics](https://onco.cc/companies/a2-biotherapeutics/), [Allogene Therapeutics](https://onco.cc/companies/allogene/), [ANZUP Cancer Trials Group](https://onco.cc/companies/anzup/), [Arcus Biosciences](https://onco.cc/companies/arcus-biosciences/), [Argos Therapeutics](https://onco.cc/companies/argos-therapeutics/), [Arsenal Biosciences](https://onco.cc/companies/arsenal-bio/), [Asher Biotherapeutics](https://onco.cc/companies/asher-bio/), [AVEO Oncology (LG Chem)](https://onco.cc/companies/aveo/), [Bristol Myers Squibb](https://onco.cc/companies/bms/), [Eisai](https://onco.cc/companies/eisai/), [Elypta](https://onco.cc/companies/elypta/), [Exelixis](https://onco.cc/companies/exelixis/), [GI Innovation](https://onco.cc/companies/gi-innovation/), [IceCure Medical](https://onco.cc/companies/icecure-medical/), [Merck & Co. (MSD)](https://onco.cc/companies/merck/), [Nektar Therapeutics](https://onco.cc/companies/nektar-therapeutics/), [Neomorph](https://onco.cc/companies/neomorph/), [Novartis](https://onco.cc/companies/novartis/), [OncoC4](https://onco.cc/companies/oncoc4/), [Outcomes4Me](https://onco.cc/companies/outcomes4me/), [Pfizer (incl. Seagen)](https://onco.cc/companies/pfizer/), [Quantum Surgical](https://onco.cc/companies/quantum-surgical/), [Roche / Genentech](https://onco.cc/companies/roche-genentech/), [Scancell](https://onco.cc/companies/scancell/), [Telix Pharmaceuticals](https://onco.cc/companies/telix/), [Vyriad](https://onco.cc/companies/vyriad/), [XACT Robotics](https://onco.cc/companies/xact-robotics/), [Xencor](https://onco.cc/companies/xencor/)
- institutions: [Cedars-Sinai Cancer](https://onco.cc/institutions/cedars-sinai-cancer/), [Cleveland Clinic Taussig Cancer Institute](https://onco.cc/institutions/cleveland-clinic/), [Dana-Farber Brigham Cancer Center](https://onco.cc/institutions/dana-farber/), [Fox Chase Cancer Center](https://onco.cc/institutions/fox-chase/), [Gustave Roussy](https://onco.cc/institutions/gustave-roussy/), [Harold C. Simmons Comprehensive Cancer Center, UT Southwestern](https://onco.cc/institutions/utsw-simmons/), [MD Anderson Cancer Center](https://onco.cc/institutions/md-anderson/), [Memorial Sloan Kettering Cancer Center](https://onco.cc/institutions/mskcc/)
- pathways: [Glutamine addiction](https://onco.cc/pathways/glutamine-metabolism/), [PD-1 / PD-L1 immune checkpoint & T-cell activation](https://onco.cc/pathways/pd1-checkpoint/), [PI3K / AKT / mTOR](https://onco.cc/pathways/pi3k-akt-mtor/), [Renal cell carcinoma (KEGG map)](https://onco.cc/pathways/renal-cell-carcinoma-signalling/), [SWI/SNF chromatin remodelling](https://onco.cc/pathways/swi-snf-chromatin/), [The angiogenic switch & tumour vessels](https://onco.cc/pathways/angiogenic-switch/), [VEGF angiogenesis](https://onco.cc/pathways/vegf-angiogenesis/), [VHL / HIF oxygen sensing](https://onco.cc/pathways/hif-vhl/)
- terms: [Active surveillance and observation](https://onco.cc/terms/active-surveillance-term/), [Bone metastases and skeletal-related events](https://onco.cc/terms/bone-metastases/), [Cryoablation](https://onco.cc/terms/cryoablation/), [Debulking (cytoreductive surgery)](https://onco.cc/terms/debulking/), [IMDC risk groups (favourable / intermediate / poor)](https://onco.cc/terms/imdc-risk/), [Neoadjuvant / adjuvant / perioperative](https://onco.cc/terms/neoadjuvant-adjuvant/), [Nephrectomy](https://onco.cc/terms/nephrectomy/), [Obesity-related cancers (IARC list of 13)](https://onco.cc/terms/obesity-related-cancers/), [Oligometastatic disease](https://onco.cc/terms/oligometastatic/), [Portal vein tumour thrombus (macrovascular invasion)](https://onco.cc/terms/portal-vein-tumour-thrombus/), [Radiofrequency ablation (RFA)](https://onco.cc/terms/radiofrequency-ablation/), [Retroperitoneum](https://onco.cc/terms/retroperitoneum/), [Sarcomatoid differentiation (RCC)](https://onco.cc/terms/sarcomatoid-rcc/), [Von Hippel-Lindau disease](https://onco.cc/terms/vhl-disease/)
- trials: [89Zr-TLX250 for PET/CT Imaging of ccRCC - ZIRCON-CP Study](https://onco.cc/trials/nct06750419/), [A Beta-only IL-2 ImmunoTherapY Study](https://onco.cc/trials/nct05086692/), [A Clinical Study of Belzutifan (MK-6482) and Zanzalintinib in People With Renal Cell Carcinoma (RCC) (LITESPARK-034/LS-034/MK-6482-034)](https://onco.cc/trials/nct07489495/), [A Clinical Study of Belzutifan and Zanzalintinib in People With Recurrent Kidney Cancer Following Adjuvant Therapy (MK-6482-033)](https://onco.cc/trials/nct07227402/), [A First-In Human (FIH) Study to Find Out How Well REGN10597 Medicine Given Alone or in Combination With Cemiplimab Works in Adult Participants Who Hav](https://onco.cc/trials/nct06413680/), [A Phase 1 and 2 Study of VMD-102 in Hepatocellular Carcinoma and Other Solid Tumors](https://onco.cc/trials/nct07636785/), [A Phase 1/2 Trial of ADI-270 in ccRCC](https://onco.cc/trials/nct06480565/), [A Phase 1/2a Study of 23ME-00610 in Patients With Advanced Solid Malignancies](https://onco.cc/trials/nct05199272/), [A Study of Adjuvant Intismeran Autogene (V940) and Pembrolizumab in Renal Cell Carcinoma (V940-004).](https://onco.cc/trials/nct06307431/), [A Study of Belzutifan (MK-6482) in Combination With Palbociclib Versus Belzutifan Monotherapy in Participants With Advanced Renal Cell Carcinoma (MK-6](https://onco.cc/trials/nct05468697/), [A Study of Belzutifan (MK-6482) in Participants With Advanced Renal Cell Carcinoma (MK-6482-013)](https://onco.cc/trials/nct04489771/), [A Study of Bempegaldesleukin (NKTR-214: BEMPEG) in Combination With Nivolumab Compared With the Investigator's Choice of a Tyrosine Kinase Inhibitor (TKI) Therapy (Either Sunitinib or Cabozantinib Monotherapy) for Advanced Metastatic Renal Cell Carcinoma (RCC)](https://onco.cc/trials/nct03729245/), [A Study of GI-108, an Anti-CD73-IgG4 Fc-IL-2v Bispecific Fusion Protein, as Monotherapy in Patients With Advanced or Metastatic Solid Tumors](https://onco.cc/trials/nct07172802/), [A Study of IBR854 Combined With Pazopanib Versus Pazopanib in Advanced Renal Cell Carcinoma](https://onco.cc/trials/nct07087158/), [A Study of Immune Checkpoint Inhibitor Combinations With Axitinib in Participants With Untreated Locally Advanced Unresectable or Metastatic Renal Cel](https://onco.cc/trials/nct05805501/), [A Study of NDI 1150-101 in Patients With Solid Tumors](https://onco.cc/trials/nct05128487/), [A Study of Nivolumab Combined With Ipilimumab Versus Nivolumab Alone in Participants With Advanced Kidney Cancer](https://onco.cc/trials/nct03873402/), [A Study of Oral 7HP349 (Alintegimod) in Combination With Ipilimumab Followed by Nivolumab Monotherapy](https://onco.cc/trials/nct06362369/), [A Study of Participant Reported Preference for Subcutaneous Pembrolizumab Coformulated With Berahyaluronidase Alfa (MK-3475A) Over Intravenous Pembrol](https://onco.cc/trials/nct06099782/), [A Study of Pazopanib With or Without Abexinostat in Patients With Locally Advanced or Metastatic Renal Cell Carcinoma (RENAVIV)](https://onco.cc/trials/renaviv/), [A Study of Pembrolizumab (MK-3475) in Combination With Belzutifan (MK-6482) and Lenvatinib (MK-7902), or Pembrolizumab/Quavonlimab (MK-1308A) in Combination With Lenvatinib, vs Pembrolizumab and Lenvatinib, for Treatment of Advanced Clear Cell Renal Cell Carcinoma (MK-6482-012)-China Extension Study](https://onco.cc/trials/nct05899049/), [A Study of Subcutaneous Nivolumab Versus Intravenous Nivolumab in Participants With Previously Treated Clear Cell Renal Cell Carcinoma That is Advance](https://onco.cc/trials/nct04810078/), [A Study of TQB2450 Injection Combined With Anlotinib Hydrochloride Capsule Versus Sunitinib in Subjects With Advanced Renal Cancer](https://onco.cc/trials/nct04523272/), [A Study to Assess Safety, Tolerability and Imaging Characteristics of [68Ga]Ga-DPI-4452 and to Assess Safety, Tolerability, and Efficacy of [177Lu]Lu-DPI-4452 in Participants With Unresectable Locally Advanced or Metastatic Solid Tumors](https://onco.cc/trials/nct05706129/), [A Study to Evaluate the Safety and Efficacy of A2B395, an Allogeneic Logic-gated CAR T, in Participants With Solid Tumors That Express EGFR and Have Lost HLA-A*02 Expression](https://onco.cc/trials/nct06682793/), [A Study to Evaluate the Safety, Tolerability, and Efficacy of Pumitamig Alone or in Combination With Other Agents in Participants With Advanced Renal ](https://onco.cc/trials/nct07293351/), [A Study to Investigate Safety of AZD6750 in Adult Participants With Select Advanced or Metastatic Solid Tumors](https://onco.cc/trials/nct07115043/), [A Study to Investigate the Antitumor Activity, Safety, Tolerability, and Pharmacokinetics of BGB-A445 in Combination With Tislelizumab in Participants](https://onco.cc/trials/nct05661955/), [A Trial of Belzutifan (PT2977, MK-6482) in Combination With Cabozantinib in Patients With Clear Cell Renal Cell Carcinoma (ccRCC) (MK-6482-003)](https://onco.cc/trials/nct03634540/), [A Trial to Find Out if REGN5678 (Nezastomig) is Safe and How Well it Works Alone or in Combination With Cemiplimab for Adult Participants With Metasta](https://onco.cc/trials/nct03972657/), [AB-2100, an Integrated Circuit T Cell Therapy in Patients With Recurrent Clear-cell Renal Cell Carcinoma (ccRCC)](https://onco.cc/trials/nct06245915/), [An Investigational Scan (89Zr-DFO-GmAb PET/CT) Compared to Contrast-Enhanced CT for the Detection of Recurrent Clear Cell Renal Cell Cancer After Surgery Comparing Carbonic Anhydrase IX (CAIX) PET CT to Conventional PET CT for Post-Op Staging in Kidney Cancer](https://onco.cc/trials/nct06447103/), [CARMENA](https://onco.cc/trials/carmena/), [CheckMate 025](https://onco.cc/trials/checkmate-025/), [CheckMate 214](https://onco.cc/trials/checkmate-214/), [CheckMate 9ER](https://onco.cc/trials/checkmate-9er/), [CLEAR (KEYNOTE-581)](https://onco.cc/trials/clear/), [CONTACT-03](https://onco.cc/trials/contact-03/), [COSMIC-313](https://onco.cc/trials/cosmic-313/), [Dual-target CD70/CAIX CAR-NK Cells for Advanced Clear Cell Renal Cell Carcinoma](https://onco.cc/trials/nct07551349/), [GM103 Intratumoral Injection in Patients With Locally Advanced, Unresectable, Refractory and/or Metastatic Solid Tumors](https://onco.cc/trials/nct06265025/), [KEYNOTE-426](https://onco.cc/trials/keynote-426/), [KEYNOTE-564](https://onco.cc/trials/keynote-564/), [LITESPARK-005](https://onco.cc/trials/litespark-005/), [LITESPARK-011](https://onco.cc/trials/nct04586231/), [LITESPARK-012](https://onco.cc/trials/litespark-012/), [LITESPARK-022](https://onco.cc/trials/litespark-022/), [Modi-1 Moditope in Breast, Head and Neck, Ovarian, or Renal Cancer](https://onco.cc/trials/nct05329532/), [PAPMET (SWOG S1500)](https://onco.cc/trials/papmet/), [Pembrolizumab (MK-3475) Plus Epacadostat vs Standard of Care in mRCC (KEYNOTE-679/ECHO-302)](https://onco.cc/trials/nct03260894/), [Ph I/II Trial of Systemic VSV-IFNβ-NIS in Combination With Checkpoint Inhibitor Therapy in Patients With Select Solid Tumors](https://onco.cc/trials/nct03647163/), [Phase 1a and Phase 2 Study for Safety, Preliminary Efficacy, PK and PD of ST-067](https://onco.cc/trials/nct04787042/), [Phase 2 Study for the Patient, Who Has Diagnosed With Small Cell Lung Cancer (SCLC) or Non Small Cell Lung Cancer (NSCLC) or Renal Cell Carcinoma (RCC) and Finished the First Line Stand Treatment , Need More Treatment](https://onco.cc/trials/nct05363280/), [Phase 3 Study to Assess Safety and Efficacy of 177Lu-TLX250 in Advanced Relapsed or Recurrent ccRCC](https://onco.cc/trials/nct07197580/), [Phase Ib/II Clinical Study of SHR-8068 Combined Anti-tumor Drugs in the Treatment of Advanced Renal Cell Carcinom](https://onco.cc/trials/nct07239596/), [Phase Ib/II Trial of Envafolimab Plus Lenvatinib for Subjects With Solid Tumors](https://onco.cc/trials/nct05024214/), [REGN15505 (PSMAx4-1BB) Alone or in Combination With Cemiplimab or REGN4336 (PSMAxCD3) in Adult Patients With Metastatic Castration-Resistant Prostate ](https://onco.cc/trials/nct07594106/), [Safety, PK and Efficacy of ONC-392 in Monotherapy and in Combination of Anti-PD-1 in Advanced Solid Tumors and NSCLC](https://onco.cc/trials/nct04140526/), [Savolitinib Plus Durvalumab Versus Sunitinib and Durvalumab Monotherapy in MET-Driven, Unresectable and Locally Advanced or Metastatic PRCC](https://onco.cc/trials/nct05043090/), [Savolitinib vs. Sunitinib in MET-driven PRCC.](https://onco.cc/trials/nct03091192/), [Study of Casdatifan and Cabozantinib Versus Placebo and Cabozantinib in Patients With Advanced Clear Cell Renal Cell Carcinoma](https://onco.cc/trials/nct07011719/), [Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalen](https://onco.cc/trials/nct04198766/), [Study of Orellanine in Metastatic Clear-Cell or Papillary Renal Cell Carcinoma](https://onco.cc/trials/nct05287945/), [Study of ST-1898 in Advanced Renal Cell Carcinoma](https://onco.cc/trials/nct06127238/), [Substudy 03A: A Study of Immune and Targeted Combination Therapies in Participants With First Line (1L) Renal Cell Carcinoma (MK-3475-03A)](https://onco.cc/trials/nct04626479/), [Substudy 03B: A Study of Immune and Targeted Combination Therapies in Participants With Second Line Plus (2L+) Renal Cell Carcinoma (MK-3475-03B/KEYMAKER-U03)](https://onco.cc/trials/nct04626518/), [Substudy 03C: A Study of Combination Therapies in Participants With Renal Cell Carcinoma With Recurrent Disease During or After Anti-PD-(L)1 Therapy (](https://onco.cc/trials/nct07049926/), [Symbiotic-GU-08: A Study to Learn About the Medicine Called PF-08634404 Dosed Alone and in Combination With Other Anticancer Therapies in Adults With ](https://onco.cc/trials/nct07227415/), [TiNivo-2](https://onco.cc/trials/tinivo-2/), [TT-4 and TT-10 as Single Agents and in Combination in Subjects With Advanced Selected Solid Tumors and Pleural Mesothelioma](https://onco.cc/trials/nct04969315/), [Vorolanib Monotherapy or in Combination With Toripalimab as Adjuvant Therapy for Patients With Intermediate-high Risk of Recurrence in Renal Cell Carcinoma](https://onco.cc/trials/nct07047001/), [Vorolanib Plus Sintilimab for Advanced Renal Cell Carcinoma After Failure of Prior Immune Checkpoint Inhibitors Based Combination Therapy](https://onco.cc/trials/nct06523049/)
- people: [Arnaud Méjean](https://onco.cc/people/arnaud-mejean/), [Brian I. Rini](https://onco.cc/people/brian-rini/), [Dingwei Ye](https://onco.cc/people/ye-dingwei/), [Eric Jonasch](https://onco.cc/people/eric-jonasch/), [Georges-Pascal Haber](https://onco.cc/people/georges-pascal-haber/), [Ian Davis](https://onco.cc/people/ian-davis/), [Jae Lyun Lee](https://onco.cc/people/lee-jae-lyun/), [James Larkin](https://onco.cc/people/james-larkin/), [Jun Guo](https://onco.cc/people/guo-jun/), [Laurence Albiges](https://onco.cc/people/laurence-albiges/), [Michael B. Atkins](https://onco.cc/people/michael-atkins/), [Neeraj Agarwal](https://onco.cc/people/neeraj-agarwal/), [Padmanee Sharma](https://onco.cc/people/padmanee-sharma/), [Primo N. Lara Jr.](https://onco.cc/people/primo-lara/), [Rana McKay](https://onco.cc/people/rana-mckay/), [Robert J. Motzer](https://onco.cc/people/robert-motzer/), [Samra Turajlić](https://onco.cc/people/samra-turajlic/), [Shankar Siva](https://onco.cc/people/shankar-siva/), [Shilpa Gupta](https://onco.cc/people/shilpa-gupta/), [Sumanta K. Pal](https://onco.cc/people/sumanta-pal/), [Suzanne L. Topalian](https://onco.cc/people/suzanne-topalian/), [Thomas Powles](https://onco.cc/people/thomas-powles/), [Toni K. Choueiri](https://onco.cc/people/toni-choueiri/), [William G. Kaelin Jr.](https://onco.cc/people/william-kaelin/)
- journals: [Clinical genitourinary cancer](https://onco.cc/journals/clinical-genitourinary-cancer/), [European Urology Oncology](https://onco.cc/journals/european-urology-oncology/), [Urologic oncology](https://onco.cc/journals/urologic-oncology/)
- drugs: [Abexinostat](https://onco.cc/drugs/abexinostat/), [ADI-270](https://onco.cc/drugs/adi-270/), [AL8326](https://onco.cc/drugs/al8326/), [Aldesleukin (high-dose IL-2)](https://onco.cc/drugs/aldesleukin/), [Avelumab](https://onco.cc/drugs/avelumab/), [Axitinib](https://onco.cc/drugs/axitinib/), [Belzutifan](https://onco.cc/drugs/belzutifan/), [Bempegaldesleukin](https://onco.cc/drugs/bempegaldesleukin/), [Bevacizumab](https://onco.cc/drugs/bevacizumab/), [Cabozantinib](https://onco.cc/drugs/cabozantinib/), [Everolimus](https://onco.cc/drugs/everolimus/), [Gotistobart](https://onco.cc/drugs/gotistobart/), [IBI363](https://onco.cc/drugs/ibi363/), [Interferon alfa-2a/2b](https://onco.cc/drugs/interferon-alfa/), [Intismeran autogene](https://onco.cc/drugs/intismeran-autogene/), [Ipilimumab](https://onco.cc/drugs/ipilimumab/), [JK08](https://onco.cc/drugs/jk08/), [Lenvatinib](https://onco.cc/drugs/lenvatinib/), [Nivolumab](https://onco.cc/drugs/nivolumab/), [Pazopanib](https://onco.cc/drugs/pazopanib/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/), [PF-08634404](https://onco.cc/drugs/pf-08634404/), [Raludotatug deruxtecan](https://onco.cc/drugs/raludotatug-deruxtecan/), [Savolitinib](https://onco.cc/drugs/savolitinib/), [Sorafenib](https://onco.cc/drugs/sorafenib/), [Sunitinib](https://onco.cc/drugs/sunitinib/), [Temsirolimus](https://onco.cc/drugs/temsirolimus/), [Tivozanib](https://onco.cc/drugs/tivozanib/), [TQB2450](https://onco.cc/drugs/tqb2450/), [Vorolanib](https://onco.cc/drugs/vorolanib/), [Zanzalintinib](https://onco.cc/drugs/zanzalintinib/), [Zirconium-89 girentuximab](https://onco.cc/drugs/girentuximab-zr89/), [Zoledronic acid](https://onco.cc/drugs/zoledronic-acid/)
- ideas: [Bank three spatially separate tumour blocks from every resection](https://onco.cc/ideas/idea-bio1-multiregion-blocks-default/), [Biomarker-selected adjuvant therapy in RCC (ctDNA, CAIX PET, gene signatures)](https://onco.cc/ideas/idea-adjuvant-selection-rcc/), [CAIX theranostics: 89Zr-girentuximab PET and 177Lu/225Ac-girentuximab therapy](https://onco.cc/ideas/idea-caix-theranostics/), [Capture diet, fibre and antibiotic exposure in every immunotherapy pivotal trial](https://onco.cc/ideas/idea-nl-diet-covariates-io-trials/), [Device-agnostic public trials of ablation technologies against surgery](https://onco.cc/ideas/idea-fund-ablation-versus-surgery-trials/), [Every routine CT scan checked by AI for early cancer signs, with a tracked follow-up pathway](https://onco.cc/ideas/idea-prev-opportunistic-ct-ai-registry/), [Grow immune command posts inside tumours](https://onco.cc/ideas/idea-bio2-tertiary-lymphoid-induction/), [Inhaled immune therapy to make the lung hostile to arriving tumour cells](https://onco.cc/ideas/idea-bio2-inhaled-lung-niche-immunotherapy/), [Kidney and liver impairment dosing studies completed before approval, not years after](https://onco.cc/ideas/idea-tr1-organ-impairment-pk-before-approval/), [Link bariatric and GLP-1 registries to cancer registries in every country that has both](https://onco.cc/ideas/idea-nl-bariatric-cancer-registry-linkage/), [Map metabolic dependencies in the patient, not the dish](https://onco.cc/ideas/idea-metabolic-vulnerability-mapping/), [Multi-arm, multi-stage trials to answer which order to give approved drugs](https://onco.cc/ideas/idea-tr1-mams-for-sequencing-questions/), [Protect the gut flora of patients about to start immunotherapy](https://onco.cc/ideas/idea-bio2-antibiotic-stewardship-io/), [Replace fixed kidney and liver cut-offs with drug-specific, pharmacology-based thresholds](https://onco.cc/ideas/idea-tr1-pk-informed-organ-thresholds/), [Take faecal transplant plus immunotherapy to a definitive trial](https://onco.cc/ideas/idea-bio2-fmt-plus-checkpoint-phase3/), [Test protein and resistance training during immunotherapy](https://onco.cc/ideas/idea-bio2-protein-plus-training-during-io/), [Treat immunotherapy side-effects without wiping out the response](https://onco.cc/ideas/idea-bio2-steroid-sparing-irae/), [Use a hypoxia scan to pick patients for adenosine-pathway drugs](https://onco.cc/ideas/idea-bio2-hypoxia-guided-adenosine/), [Watch small kidney tumours rather than remove them, with a national registry](https://onco.cc/ideas/idea-prev-small-renal-mass-surveillance/)
- pairings: [Caution: PD-1 rechallenge after progression on immunotherapy (RCC)](https://onco.cc/pairings/io-rechallenge-caution-rcc/), [IMDC risk → first-line regimen choice (RCC)](https://onco.cc/pairings/risk-directed-first-line-rcc/), [PD-1 blockade + VEGF inhibition](https://onco.cc/pairings/io-plus-vegf/)
- bottlenecks: [Overdiagnosis and false alarms](https://onco.cc/bottlenecks/b-overdiagnosis/), [Surgery and radiotherapy cure most, get least](https://onco.cc/bottlenecks/b-surgery-radiation-innovation/), [Tumour heterogeneity and clonal evolution](https://onco.cc/bottlenecks/b-tumor-heterogeneity/)
- key papers: [Belzutifan plus lenvatinib versus cabozantinib in patients with previously treated advanced renal cell carcinoma (LITESPARK-011): an open-label, randomised, controlled, phase 3 trial](https://onco.cc/key-papers/paper-litespark-011-motzer-lancet-2026/), [Calle 2003: overweight, obesity and death from cancer in 900,000 US adults](https://onco.cc/key-papers/paper-calle-obesity-cancer-mortality-nejm-2003/), [CLEAR: lenvatinib plus pembrolizumab versus sunitinib as first treatment for advanced kidney cancer](https://onco.cc/key-papers/paper-clear-nejm-2021/), [Gerlinger: a single biopsy misses most of the mutations in a kidney tumour](https://onco.cc/key-papers/paper-gerlinger-intratumour-heterogeneity-nejm-2012/), [IARC verdict: excess body fat causes 13 cancers](https://onco.cc/key-papers/paper-body-fatness-iarc-nejm-2016/), [KEYNOTE-564: a year of pembrolizumab after kidney cancer surgery](https://onco.cc/key-papers/paper-keynote-564-nejm-2021/)
- cancers: [Chromophobe renal cell carcinoma](https://onco.cc/cancers/chromophobe-rcc/), [Clear cell papillary renal cell tumour](https://onco.cc/cancers/clear-cell-papillary-renal-cell-tumour/), [Clear cell renal cell carcinoma](https://onco.cc/cancers/clear-cell-rcc/), [Collecting duct carcinoma of the kidney](https://onco.cc/cancers/collecting-duct-carcinoma/), [Eosinophilic solid and cystic renal cell carcinoma](https://onco.cc/cancers/eosinophilic-solid-cystic-renal-cell-carcinoma/), [Fumarate hydratase-deficient renal cell carcinoma (HLRCC-associated)](https://onco.cc/cancers/fh-deficient-renal-cell-carcinoma/), [Mucinous tubular and spindle cell carcinoma of the kidney](https://onco.cc/cancers/mucinous-tubular-spindle-cell-carcinoma/), [Papillary renal cell carcinoma](https://onco.cc/cancers/papillary-rcc/), [Renal medullary carcinoma (SMARCB1-deficient)](https://onco.cc/cancers/renal-medullary-carcinoma/), [Succinate dehydrogenase-deficient renal cell carcinoma](https://onco.cc/cancers/sdh-deficient-renal-cell-carcinoma/), [TFE3-rearranged (translocation) renal cell carcinoma](https://onco.cc/cancers/tfe3-rearranged-renal-cell-carcinoma/)

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JSON: https://onco.cc/api/v1/entities/rcc.json