The first 60 days: 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. Below, week by week, is what OnCo's record of Renal cell carcinoma says about the first two months: the order is typical, the timing is yours to ask about. Sections appear only where the record has something to say. Orientation, not medical advice.
What happens now
Staging tests establish exactly what and where the cancer is. Everything else follows from the answers.
Ask which of these were tested and what the results were; see the report reader for what each value means.
These specialties appear in the standard of care for this cancer. In most centres they meet weekly as a tumour board to agree each plan; you can ask when yours was discussed and what was decided.
- PathologistNamed in the standard of care for: Small renal mass (<4 cm).
- SurgeonNamed in the standard of care for: Localised, Small renal mass (<4 cm), Localised T1b-T3, Metastatic, intermediate/poor risk, first line and 2 more.
- Medical oncologistNamed in the standard of care for: Localised, Metastatic, Localised T1b-T3, High-risk after nephrectomy (clear-cell) and 6 more.
- Clinical oncologist (radiotherapy)Named in the standard of care for: Oligometastatic / oligoprogressive disease.
A second opinion from a centre that treats many similar cases is normal, not rude; the standard of care tells you what to compare it against.
Each row is a setting from the standard of care, in the order it usually arises. Not all will apply to you; your stage and biomarkers decide which do. The guideline grade, where recorded, says how strong the evidence is.
Partial/radical nephrectomy or ablation; adjuvant pembrolizumab ± belzutifan for high risk.
Partial or radical nephrectomy; no adjuvant therapy for low/intermediate risk.
Adjuvant pembrolizumab for 1 year (KEYNOTE-564, OS benefit); pembrolizumab + belzutifan approved 2026 (LITESPARK-022); sunitinib adjuvant rarely used.
IO-TKI or IO-IO doublet; belzutifan, cabozantinib, lenvatinib-everolimus later.
Active surveillance, partial nephrectomy (usually robotic), or thermal ablation depending on growth, comorbidity, and biopsy; renal mass biopsy increasingly used.
- 6.Metastatic, intermediate/poor risk, first lineNCCN category 1 (preferred: all four regimens), ESMO-MCBS 4
Nivolumab + ipilimumab, or an IO-TKI doublet (pembrolizumab + axitinib, nivolumab + cabozantinib, lenvatinib + pembrolizumab); cytoreductive nephrectomy deferred or omitted (CARMENA) except in selected cases.
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.
Metastasectomy or SBRT to limited sites with continuation of systemic therapy or observation.
Cabozantinib (PAPMET), lenvatinib + pembrolizumab (KEYNOTE-B61), or nivolumab + cabozantinib; MET inhibitors for MET-driven papillary; trials preferred.
Belzutifan for VHL-associated RCC, CNS haemangioblastoma, and pNET not requiring immediate surgery (LITESPARK-004).
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).
Generated from this cancer's standard of care, biomarkers and open problems. Take the group that matches where you are. To tick, add your own and print, open the one-page appointment sheet.
Newly diagnosed
- What is my exact diagnosis, stage, and grade, and which tests established them?Everything else follows from an accurate stage and subtype.
- 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?These results decide eligibility for targeted therapy, immunotherapy, and trials.
- Which subtype is my cancer, and does that change the recommended treatment?Recognised subtypes for this cancer include Clear-cell, Papillary type 1and type 2, Chromophobe.
- Is germline (inherited) genetic testing recommended for me or my family?Inherited variants can change treatment and matter for relatives.
Localised
- For my situation (localised), which of the standard options do you recommend and why?Guideline options include: Partial/radical nephrectomy or ablation; adjuvant pembrolizumab ± belzutifan for high risk.
- Am I a candidate for Pembrolizumab, Belzutifan, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
Metastatic
- For my situation (metastatic), which of the standard options do you recommend and why?Guideline options include: IO-TKI or IO-IO doublet; belzutifan, cabozantinib, lenvatinib-everolimus later.
- Am I a candidate for Nivolumab, Ipilimumab, Pembrolizumab or related drugs, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
Small renal mass (<4 cm)
- For my situation (small renal mass (<4 cm)), which of the standard options do you recommend and 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
- For my situation (localised t1b-t3), which of the standard options do you recommend and why?Guideline options include: Partial or radical nephrectomy; no adjuvant therapy for low/intermediate risk.
High-risk after nephrectomy (clear-cell)
- For my situation (high-risk after nephrectomy (clear-cell)), which of the standard options do you recommend and why?Guideline options include: Adjuvant pembrolizumab for 1 year (KEYNOTE-564, OS benefit); pembrolizumab + belzutifan approved 2026 (LITESPARK-022); sunitinib adjuvant rarely used.
- Am I a candidate for Pembrolizumab, Belzutifan, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of KEYNOTE-564 and LITESPARK-022 apply to someone like me?Trial populations differ from individual patients; ask how closely you match.
Metastatic, intermediate/poor risk, first line
- For my situation (metastatic, intermediate/poor risk, first line), which of the standard options do you recommend and 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.
- Am I a candidate for Nivolumab, Ipilimumab, Pembrolizumab or related drugs, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of CheckMate 214 and KEYNOTE-426 apply to someone like me?Trial populations differ from individual patients; ask how closely you match.
Metastatic, favourable risk, first line
- For my situation (metastatic, favourable risk, first line), which of the standard options do you recommend and 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.
- Am I a candidate for Pembrolizumab, Axitinib, Lenvatinib or related drugs, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
Second line after IO-based therapy
- For my situation (second line after io-based therapy), which of the standard options do you recommend and 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).
- Am I a candidate for Cabozantinib, Belzutifan, Tivozanib or related drugs, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of LITESPARK-005 and CONTACT-03 apply to someone like me?Trial populations differ from individual patients; ask how closely you match.
Oligometastatic / oligoprogressive disease
- For my situation (oligometastatic / oligoprogressive disease), which of the standard options do you recommend and why?Guideline options include: Metastasectomy or SBRT to limited sites with continuation of systemic therapy or observation.
Non-clear-cell RCC
- For my situation (non-clear-cell rcc), which of the standard options do you recommend and why?Guideline options include: Cabozantinib (PAPMET), lenvatinib + pembrolizumab (KEYNOTE-B61), or nivolumab + cabozantinib; MET inhibitors for MET-driven papillary; trials preferred.
- Am I a candidate for Cabozantinib, Lenvatinib, Pembrolizumab or related drugs, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
VHL disease
- For my situation (vhl disease), which of the standard options do you recommend and why?Guideline options include: Belzutifan for VHL-associated RCC, CNS haemangioblastoma, and pNET not requiring immediate surgery (LITESPARK-004).
- Am I a candidate for Belzutifan, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
Any stage
- Are there clinical trials I could join, for example of Raludotatug deruxtecan, Intismeran autogene, PF-08634404, Zanzalintinib?Trials are how the next standard of care is set; asking early keeps options open.
- Would a second opinion at a high-volume centre change anything, and can you help arrange it?Rare or high-stakes decisions benefit from a centre that treats many similar patients.
- What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?Supportive care improves quality of life and helps patients complete treatment.
- I read that “Non-clear-cell histologies understudied”. How does that affect my plan?Open problems are where trials and second opinions matter most.
- I read that “No validated predictive biomarker for IO”. How does that affect my plan?Open problems are where trials and second opinions matter most.
Trials open now for this cancer in OnCo, largest phase first. Joining a trial is a decision like any other: ask what the comparison arm is, whether a placebo is used, and what happens if you leave. The cancer page searches ClinicalTrials.gov live for more.
- 89Zr-TLX250 for PET/CT Imaging of ccRCC - ZIRCON-CP StudyPhase 3 · recruiting · NCT06750419A Confirmatory, Open-label, Single-arm, Multi-centre Study to Evaluate Safety, Tolerability and Diagnostic Performance of 89Zirconium-labelled Girentuximab (89Zr-TLX250) to Non-invasively Detect Clear Cell Renal Cell Carcinoma (ccRCC) by Positron Emission Tomography/Computed Tomography (PET/CT) Imaging in Chinese Patients With Indeterminate Renal Masses (ZIRCON-CP Study)
- A Clinical Study of Belzutifan (MK-6482) and Zanzalintinib in People With Renal Cell Carcinoma (RCC) (LITESPARK-034/LS-034/MK-6482-034)Phase 3 · recruiting · NCT07489495A Phase 3, Randomized, Double-blind, Study of Belzutifan + Zanzalintinib Versus Belzutifan + Placebo in Participants With Advanced RCC Who Have Progressed on or After Both PD-1/L1 and VEGF-TKI Therapies in Sequence or in Combination (LITESPARK-034)
- A Clinical Study of Belzutifan and Zanzalintinib in People With Recurrent Kidney Cancer Following Adjuvant Therapy (MK-6482-033)Phase 3 · recruiting · NCT07227402A Phase 3, Randomized, Open-label Study of Belzutifan + Zanzalintinib Versus Cabozantinib in Participants With Advanced RCC Who Experienced Disease Recurrence During or After Prior Adjuvant Anti-PD-1/L1 Therapy (LITESPARK-033)
- A Study of Belzutifan (MK-6482) in Combination With Lenvatinib Versus Cabozantinib for Treatment of Renal Cell Carcinoma (MK-6482-011)Phase 3 · active · NCT04586231An Open-label, Randomized, Phase 3 Study of MK-6482 in Combination With Lenvatinib (MK-7902) vs Cabozantinib in Participants With Advanced Renal Cell Carcinoma Who Have Progressed After Prior Anti-PD-1/L1 Therapy
- A Study of Nivolumab Combined With Ipilimumab Versus Nivolumab Alone in Participants With Advanced Kidney CancerPhase 3 · active · NCT03873402A Phase 3b, Randomized, Double-blind Study of Nivolumab Combined With Ipilimumab Versus Nivolumab Monotherapy for Patients With Previously Untreated Advanced Renal Cell Carcinoma and Intermediate- or Poor-Risk Factors
Much of what helps in the first weeks is free if you know to ask: testing, helplines, rides and lodging, second opinions, trial travel.
- Renal cell carcinoma: the full pageKidney cancer is where anti-angiogenic drugs and immunotherapy came together, and where a Nobel-winning oxygen-sensing pathway yielded a drug, belzutifan.
- One-page appointment sheetYour questions, the words you may hear, what to bring, and space for the answers. Print it.
- Guidelines comparedNCCN, ESMO and NICE side by side for this cancer.
- Treatment sequencingWhich treatment tends to follow which, line by line.
- NavigatorStandard of care for your stage, what you have tried, and trials near you.
- IMDC risk groups (favourable / intermediate / poor): The IMDC score uses six factors to sort metastatic kidney cancer into three risk groups.
- Sarcomatoid differentiation (RCC): A spindle-cell change found in about 10% of kidney cancers that makes them aggressive and, unexpectedly, unusually responsive to immunotherapy.
- Debulking (cytoreductive surgery): Surgery that removes as much tumour as possible when it cannot all be removed cleanly; leaving nothing visible behind is what matters.
- Nephrectomy: Removing a kidney (radical) or just the tumour-bearing part of it (partial).
- Portal vein tumour thrombus (macrovascular invasion): Liver cancer growing into the main vein that brings blood from the gut to the liver.
- Von Hippel-Lindau disease: Von Hippel-Lindau disease is an inherited condition causing kidney cancers, adrenal tumours, and blood-vessel tumours of the brain, spine, eye and pancreas from early adulthood.
- Radiofrequency ablation (RFA): Killing a tumour by heating it with an electrical current through a needle placed under image guidance, without removing it.
- Cryoablation: Destroying a tumour by freezing it with a needle that reaches minus 40°C or below; the ice ball is visible on CT, so the treated zone can be watched forming.
- Active surveillance and observation: Deliberately not treating a cancer yet, but checking it regularly with blood tests, scans or biopsies and treating only if it shows signs of progressing.
- Oligometastatic disease: Cancer that has spread to only a few places, which may still be curable by treating each spot.
Every term links to the glossary.