Key points
- Standard chemotherapy has no role in kidney cancer; advanced disease is treated with immunotherapy and targeted tablets [1].
- Today the first treatment for most patients is a combination: an immunotherapy drug with a targeted tablet, or two immunotherapy drugs together; these combinations lengthened patients' lives more than older tablets [1, 2].
- Your risk group (good, intermediate, poor) is set with a few simple tests and helps in choosing treatment [5, 1].
- After surgery for a high-risk tumour, a year of immunotherapy with pembrolizumab lowered the risk of the cancer coming back and of death [11].
- Not every small kidney mass needs treatment straight away; in some patients, regular monitoring with scans is enough [1, 6].
The story of treating advanced kidney cancer
Kidney cancer is one of the cancers that do not respond to standard chemotherapy [1]. So for years, the only treatments for disease that had spread were drugs that stimulated the immune system in a general way: interferon and interleukin-2 [3, 4]. High-dose interleukin-2 shrank the tumour in about 1 in every 7 patients and cleared the disease completely and for a long time in a few of them, but it had very severe side effects and was given only to selected patients [3]. With interferon, the tumour shrank in fewer than 1 in every 10 patients [4].
The first big change was tablets that target the way tumours grow their blood vessels (the VEGF pathway) [5]. In 2007, in a large study, the tablet sunitinib controlled the disease more than twice as long as interferon, with better quality of life [4].
The second big change was modern immunotherapy: drugs such as pembrolizumab and nivolumab that take the brakes off the immune system [19]. From 2018 onwards, four combinations lengthened patients' lives more than sunitinib in large studies [7, 8, 9, 10]. In one of them, about 3 in every 10 patients at intermediate or poor risk were still alive 9 years later [10]. Then immunotherapy also moved to after surgery: a year of pembrolizumab after removal of a high-risk tumour both lowered the chance of the cancer coming back and lengthened patients' lives [12, 11].
Risk group: good, intermediate or poor
When kidney cancer has spread, your doctor sets your risk group using six simple signs [5]:
- anaemia (haemoglobin below normal)
- blood calcium above normal
- low physical ability for daily activities
- less than a year between diagnosis and starting drug treatment
- neutrophils (a type of white blood cell) above normal
- platelets above normal
If none is present, the risk group is good; with 1 or 2 signs it is intermediate, and with 3 or more it is poor [5]. This grouping estimates how the disease is likely to behave and helps in choosing the first treatment and in deciding about kidney surgery [1]. See the details in Diagnosis, staging and risk groups.
Treatment today, step by step
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Will the kidney be removed?
If the disease has spread from the start, not always. In a large study, drug treatment alone was not worse for length of life than surgery plus drug treatment [13]. The European guideline does not recommend immediate surgery in the poor-risk group, and in the intermediate-risk group, when drug treatment is needed, it suggests starting drugs without immediate surgery; in some selected patients surgery still has a place [1].
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First treatment: an immunotherapy combination
One of four combinations: lenvatinib with pembrolizumab, nivolumab with cabozantinib, pembrolizumab with axitinib, or nivolumab with ipilimumab. All four lengthened patients' lives more than sunitinib in large studies [7, 8, 9, 10], and guidelines consider any of them acceptable [1, 2]. The combinations that include a targeted tablet shrank the tumour in more patients [7, 8, 9]; two immunotherapy drugs gave a very long-lasting response in some patients [10].
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If the disease progresses
Repeating immunotherapy usually brings no benefit [2]. Your doctor chooses a targeted tablet you have not taken before: cabozantinib, which lengthened patients' lives in a large study [14, 1], or lenvatinib with everolimus [15, 1]. The newer tablet belzutifan blocks tumour growth in a different way; it shrank tumours more often than everolimus, but did not clearly lengthen patients' lives [16].
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After surgery for a high-risk tumour
If the tumour was of the clear cell type and its risk of coming back is high, a year of pembrolizumab (every 3 weeks, 17 doses) lowered the risk of the cancer coming back and of death [11]. Serious side effects were also more common [12], so make the decision with your oncologist. The European guideline makes a strong recommendation for this treatment [1].
A small kidney mass: immediate treatment is not always needed
Today most kidney masses are found by chance, on an ultrasound or CT scan done for another problem [1]. Many small masses (usually up to 4 cm) grow slowly, and some are not cancer at all [1]. For a small mass that does not need immediate treatment, especially in older people or those with other illnesses, regular monitoring is suggested: the size of the mass is measured with regular scans, and treatment starts only if it grows [1].
If treatment is needed, usually only the mass is removed and the rest of the kidney is kept [1, 6]. For people for whom surgery is not suitable, destroying the tumour with heat (ablation, which works well for masses up to 3 cm) or precise radiotherapy is an option [6, 1]. See: What are the symptoms of kidney cancer?
When should I call my doctor?
With immunotherapy (pembrolizumab, nivolumab, ipilimumab): report a new cough, chest pain or breathlessness, diarrhoea or severe stomach pain, yellowing of the skin or eyes, severe nausea or vomiting, easy bruising or bleeding, signs of kidney problems, a severe skin rash, and signs of thyroid or blood sugar problems straight away; these side effects can appear even after treatment has ended [19]. With targeted tablets (such as lenvatinib): check your blood pressure regularly and tell your doctor if it is high; call if diarrhoea stops you drinking enough fluids or if you have severe stomach pain [20]. If you have new chest pain, sudden weakness on one side of the body or sudden difficulty speaking, call your local emergency number straight away [20]. See: Side effects of immunotherapy
Frequently asked questions
Can advanced kidney cancer be cured?
Usually the aim is long-term control of the disease. But in some patients the response to treatment lasts a very long time: in one study, in almost half of the patients who responded to two immunotherapy drugs, the response was still holding 8 years later [10].
Is chemotherapy given for kidney cancer?
Usually not. Kidney cancer does not respond to standard chemotherapy, and the main treatments for advanced disease are immunotherapy and targeted tablets [1]. See: What is cancer immunotherapy?
Which combination is best?
These four combinations have never been compared directly with each other, and guidelines consider any of them acceptable [2, 1]. Your doctor chooses according to your risk group, the features of the tumour, your other illnesses and the side effects of each drug [1]. In tumours with a particular feature called "sarcomatoid", two immunotherapy drugs are preferred [2].
What side effects do the targeted tablets have?
High blood pressure, diarrhoea, tiredness and sometimes liver or kidney problems are common side effects of this group; this is why blood pressure and blood and urine tests are checked regularly [20]. See: Lenvatinib
Do I need immunotherapy after surgery?
Only if the tumour is of the clear cell type and its risk of coming back is high. In these patients, a year of pembrolizumab lowered the chance of the cancer coming back and of death [11], but serious side effects were also more common [12]; make the decision with your oncologist.
For physicians
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Background: High-dose IL-2 (255 patients in 7 phase 2 trials): objective response 14% (complete 5%), deaths possibly related to treatment 4% [3]. Sunitinib versus interferon alfa (750 patients): median PFS 11 versus 5 months (HR 0.42) and objective response 31% versus 6% [4]. IMDC model (645 patients treated with anti-VEGF agents): six factors; median OS not reached in the favourable-risk group (2-year survival 75%), 27 months in the intermediate-risk group (53%) and 8.8 months in the poor-risk group (7%) [5].
First line (versus sunitinib, latest report): CLEAR (712 patients in this comparison): median PFS 23.9 versus 9.2 months (HR 0.47), HR for overall survival 0.79 and 36-month OS 66.4% versus 60.2%, objective response 71.3% versus 36.7% [7]. CheckMate 9ER (651 patients; follow-up 5.6 years): median OS 46.5 versus 35.5 months (HR 0.79), PFS 16.4 versus 8.3 months (HR 0.58), objective response 55.7% versus 27.4% [8]. KEYNOTE-426 (861 patients; 5-year follow-up): HR for overall survival 0.84 and for PFS 0.69, objective response 60.6% versus 39.6% [9]. CheckMate 214 (1,096 patients, 847 at intermediate/poor risk; follow-up 9.3 years): in intermediate/poor risk, HR for overall survival 0.69 and 108-month survival 30.2% versus 18.7%; in favourable risk HR 0.80 (95% CI 0.59 to 1.09); durable response to 96 months 48.0% versus 19.0%; grade 3–4 treatment-related adverse events 48.6% versus 64.1% [10]. EAU 2025: in IMDC intermediate and poor risk, one of the four combinations (strong); sunitinib or pazopanib for patients who cannot receive or tolerate ICI (strong) [1]. SITC 2026: all four regimens (LE:1) and nivolumab + ipilimumab preferred with sarcomatoid features (LE:1) [2]. CARMENA (450 patients): sunitinib alone versus nephrectomy and sunitinib, median OS 19.8 versus 15.6 months (HR 0.97) [13]. Doses: Lenvatinib + pembrolizumab · Nivolumab + cabozantinib · Pembrolizumab + axitinib and nivolumab + ipilimumab · Sunitinib · Pazopanib.
Adjuvant treatment: KEYNOTE-564 (994 patients with ccRCC at intermediate-high or high risk or M1 NED; pembrolizumab for 17 cycles): 48-month OS 91.2% versus 86.0% (HR 0.62; P=0.005) [12]; in the 5-year report, 5-year DFS 60.9% versus 52.2% (HR 0.71) and 5-year OS 87.7% versus 82.3% (HR 0.66) [11]; grade 3–4 treatment-related adverse events 18.6% versus 1.2% and serious adverse events of any cause 20.7% versus 11.5% [12]. LITESPARK-022 (1,841 patients): pembrolizumab + belzutifan versus pembrolizumab, 24-month DFS 80.7% versus 73.7% (HR 0.72), OS not significant at the interim analysis (HR 0.78) and grade ≥3 adverse events 52.1% versus 30.2% [18]. Dose: Adjuvant pembrolizumab.
Later lines: METEOR (658 patients after a VEGF-TKI): cabozantinib versus everolimus, median OS 21.4 versus 16.5 months (HR 0.66) [14]. Lenvatinib + everolimus (randomised phase 2, 153 patients after anti-VEGF therapy) versus everolimus: median PFS 14.6 versus 5.5 months (HR 0.40) [15]. LITESPARK-005 (746 patients after ICI and VEGF-TKI): belzutifan versus everolimus, 18-month PFS 24.0% versus 8.3%, objective response 21.9% versus 3.5% and OS not significant (HR 0.88) [16]. LITESPARK-011 (747 patients after ICI): belzutifan + lenvatinib versus cabozantinib, median PFS 14.8 versus 10.7 months (HR 0.70) and OS not significant (HR 0.85) [17]. EAU: after ICI combinations, cabozantinib or another VEGF-TKI (strong); belzutifan as an alternative to everolimus (weak) [1]. SITC: after ICI, a TKI-based regimen or belzutifan; continuing or repeating anti-PD-(L)1 has no proven role [2]. Doses: Cabozantinib · Lenvatinib + everolimus · Belzutifan.
Small masses: EAU: active surveillance in cT1a not needing immediate treatment; ablation or stereotactic radiotherapy in cT1 unsuitable for surgery (weak); partial nephrectomy in T1 (strong) [1]. AUA 2021: partial nephrectomy prioritised in T1a and selective thermal ablation, with good efficacy in tumours of 3 cm or smaller [6].
Scientific evidence
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Scientific evidence
13 itemsAdjuvant pembrolizumab for the treatment of clear cell renal cell carcinoma: five-year results from the phase III KEYNOTE-564 study
Lenvatinib Plus Pembrolizumab Versus Sunitinib in First-Line Treatment of Advanced Renal Cell Carcinoma: Final Prespecified Overall Survival Analysis of CLEAR, a Phase III Study
Final analysis of nivolumab plus cabozantinib for advanced renal cell carcinoma from the randomized phase III CheckMate 9ER trial
Pembrolizumab plus axitinib versus sunitinib for advanced clear cell renal cell carcinoma: 5-year survival and biomarker analyses of the phase 3 KEYNOTE-426 trial
Prognostic Factors for Overall Survival in Patients With Metastatic Renal Cell Carcinoma Treated With Vascular Endothelial Growth Factor–Targeted Agents: Results From a Large, Multicenter Study
Sunitinib Alone or After Nephrectomy for Patients with Metastatic Renal Cell Carcinoma: Is There Still a Role for Cytoreductive Nephrectomy?
European Association of Urology Guidelines on Renal Cell Carcinoma: The 2025 Update
Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of renal cell carcinoma, version 3.0
Renal Mass and Localized Renal Cancer: Evaluation, Management, and Follow-Up: AUA Guideline: Part I
Belzutifan plus lenvatinib versus cabozantinib in patients with previously treated advanced renal cell carcinoma (LITESPARK-011): an open-label, randomised, controlled, phase 3 trial
Adjuvant Pembrolizumab plus Belzutifan for Renal-Cell Carcinoma
Nivolumab plus ipilimumab versus sunitinib for first-line treatment of advanced renal cell carcinoma: final analysis of efficacy and safety from the phase III CheckMate 214 trial
Belzutifan versus Everolimus for Advanced Renal-Cell Carcinoma
Read more
Related cancer types
References
20 referencesShow all references, 15 with a study cardClose the reference list
Numbers in the text, such as [1], refer to these sources. Sources with a “Study card” button are summarised in the site’s evidence library.
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- 15Lenvatinib, everolimus, and the combination in patients with metastatic renal cell carcinoma: a randomised, phase 2, open-label, multicentre trial
- 16Belzutifan versus Everolimus for Advanced Renal-Cell Carcinoma
- 17Belzutifan plus lenvatinib versus cabozantinib in patients with previously treated advanced renal cell carcinoma (LITESPARK-011): an open-label, randomised, controlled, phase 3 trial
- 18Adjuvant Pembrolizumab plus Belzutifan for Renal-Cell Carcinoma
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This page is based on reputable scientific sources and was last updated on 28 October 2026. The content of this website is for educational and informational purposes only and does not replace consultation, diagnosis or treatment by a specialist physician. Consult your treating physician about any treatment decision.
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