Renal cell carcinoma (RCC) is a common cancer affecting adults in the United States, with tens of thousands of new cases diagnosed throughout the country each year. Surgery, radiation therapy, targeted therapy, and immunotherapy are all viable options for the management of RCC, but for today’s side-by-side comparison, we’re focusing on immunotherapy.
Today's guidelines come from the Society for Immunotherapy of Cancer (SITC), National Comprehensive Cancer Network (NCCN), European Society for Medical Oncology (ESMO), and the European Association of Urology (EAU). Today's side-by-side comparison looks at adjuvant immunotherapy, first-line treatment for advanced and metastatic RCC, treatment for subtypes of RCC, and more.
Guidelines for Comparison
| Item | Immunotherapy for the Treatment of Renal Cell Carcinoma | Kidney Cancer | Diagnosis, Treatment and Follow-up of Renal Cell Carcinoma | Renal Cell Carcinoma |
|---|---|---|---|---|
| Authoring Organization | Society for Immunotherapy of Cancer (SITC) | National Comprehensive Cancer Network (NCCN) | European Society for Medical Oncology (ESMO) | European Association of Urology (EAU) |
| Publication Date | March 2026 | July 2026 | May 2024 | March 2025 |
| Links | Summary / Full Text | Full Text | Summary / Full Text | Summary / Full Text |
Guideline Scope
The four guidelines vary in scope, with the NCCN guideline covering kidney cancer broadly, the EAU guideline focusing on renal cell carcinoma, the ESMO guideline focusing on diagnosis through follow-up of RCC, and the SITC guideline focusing on immunotherapy. The categories covered below represent a fraction of the guidance provided in each of the four guidelines. To view each guideline in its entirety, refer to the full-text links in the previous table.
Side-by-Side Comparison of Recommendations
| Topic | SITC | NCCN | ESMO | EAU |
|---|---|---|---|---|
| Adjuvant Therapy | Use of validated nomograms (eg, ASSURE, Mayo Clinic, UISS) may be useful to further guide consideration for use of adjuvant pembrolizumab for patients who are eligible. For patients with resected RCC who are eligible, discussion of treatment risks and benefits of adjuvant ICI therapy is recommended. For patients with resected RCC who have pT2 with Fuhrman grade 4 or sarcomatoid differentiation, pT3 or higher, regional lymph node metastasis, or M1 NED, adjuvant pembrolizumab should be considered. For patients with resected RCC who will be receiving adjuvant pembrolizumab, treatment should be initiated within 3–4 months of surgery and should be continued for 1 year. For patients with resected RCC who experience disease progression during or within 1 year after receiving adjuvant pembrolizumab, there is currently no level one evidence to guide standard treatment. | Stage II: Adjuvant pembrolizumab or adjuvant belzutifan + pembrolizumab. Stage III: Adjuvant pembrolizumab or adjuvant belzutifan + pembrolizumab or surveillance.. Stage IV: Adjuvant pembrolizumab or adjuvant belzutifan + pembrolizumab or surveillance. | Adjuvant pembrolizumab should be considered for patients with intermediate-high- or high-risk operable ccRCC (as defined by the KEYNOTE-564 criteria) after careful patient counselling regarding potential long-term AEs. Treatment should start within 12 weeks of surgery and continue for up to one year. | Offer adjuvant pembrolizumab to ccRCC patients, preferably within 12-16 weeks post- nephrectomy, with a recurrence risk as defined in the Keynote-564 trial. If adjuvant therapy is planned: Discuss the contradictory results of the available adjuvant ICI trials with the patient to facilitate shared decision making. Inform the patient about the potential risk of overtreatment and immune related side effects if adjuvant therapy is considered. Do not offer immune checkpoint inhibitor (ICI) mono- or combination therapy in patients with recurrence during or within six months after adjuvant pembrolizumab. |
| First-Line Treatment for Advanced and Metastatic ccRCC | For patients eligible for systemic therapy, an immunotherapy-based approach is recommended. Available Immunotherapy for Treatment-Naive ccRCC: For patients with sarcomatoid features with RCC, ipilimumab plus nivolumab is a preferred option. For patients being considered for an immunotherapy-based approach, four regimens (nivolumab plus ipilimumab; pembrolizumab plus axitinib; nivolumab plus cabozantinib; pembrolizumab plus lenvatinib) have been shown to improve OS. In the absence of head-to-head comparisons any of these options is recommended. | Preferred: Axitinib + Pembrolizumab; Cabozantinib + Nivolumab; Ipilimumab + Nivolumab; Lenvatinib + Pembrolzumab. Other recommended: Axitinib + Avelumab. | Lenvatinib–pembrolizumab, axitinib–pembrolizumab, or cabozantinib–nivolumab is recommended for first-line treatment of advanced ccRCC, irrespective of IMDC risk group. There is no preferred PD-1 inhibitor–VEGFR TKI combination and indirect comparisons across trials are not recommended. Ipilimumab–nivolumab is recommended as first-line treatment for IMDC intermediate- and poor-risk disease and is an option for favourable-risk disease. Axitinib–toripalimab is an option for patients with intermediate- or poor-risk disease. Axitinib–avelumab is not associated with OS benefit compared with sunitinib and is therefore not recommended over single-agent VEGFR TKI therapy. Cessation of ICIs should be considered after 2 years. Treatment breaks from VEGFR TKI therapy do not appear to have any detrimental effect on efficacy. | Offer nivolumab plus ipilimumab, pembrolizumab plus axitinib, lenvatinib plus pembrolizumab or nivolumab and cabozantinib to patients with International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) intermediate- or poor risk-disease. Offer pembrolizumab plus axitinib, lenvatinib plus pembrolizumab or nivolumab and cabozantinib or nivolumab plus ipilimumab or sunitinib or pazopanib for IMDC favourable risk disease. Offer sunitinib or pazopanib to patients with any IMDC risk who cannot receive or tolerate immune checkpoint inhibition. Offer cabozantinib to patients with IMDC intermediate- and poor-risk clear cell metastatic renal carcinoma (cc-mRCC) who cannot receive or tolerate immune checkpoint inhibition. Patients who do not receive the full four doses of ipilimumab due to toxicity should continue on single-agent nivolumab, where safe and feasible. Re-challenge with combination therapy requires expert support after discontinuation for toxicity. |
| Second-Line Treatment for Advanced and Metastatic ccRCC | N/A | Subsequent Therapy: Prior IO Therapy (Useful in Certain Circumstances): ipilumumab + novolumab, axitinib + pembrolizumab, levantinib + pembrolizumab IO Therapy Naive: axitinib + pembrolizumab, cabozantinib + nivolumab, ipilimumab + nivolumab, lenvantinib + pembrolizumab, nivolumab. | For patients who received first-line VEGFR TKI therapy, nivolumab (if available and not contraindicated) and cabozantinib are both associated with an OS benefit. Axitinib, everolimus and lenvatinib–everolimus are also options. | N/A |
| Further-Line Treatment for Advanced and Metastatic ccRCC | N/A | N/A | The use of further PD-(L)1-targeted therapy after progression on first-line PD-1-targeted therapy is not recommended. | N/A |
| Systemic Treatment for Advanced and Metastatic pRCC | N/A | N/A | Lenvatinib–pembrolizumab and cabozantinib–nivolumab have impressive response rates but are not proven to be superior to single-agent therapy. They may be considered as alternatives to single-agent therapy. Alternative single-agent options include sunitinib and pembrolizumab. Second-line therapy may focus on agents that have not been used previously. Options include cabozantinib, sunitinib, everolimus and pembrolizumab. BSC can be considered in selected patients due to the lack of data on systemic therapy. | Offer lenvatinib plus pembrolizumab or nivolumab plus cabozantinib to patients with pRCC based on small single-arm trials. |
| Systemic Treatment of Non-Clear / Non-Papillary RCC | For patients with treatment-naïve nccRCC, enrollment on a clinical trial is recommended when available. | Preferred: Cabozantinib + nivolumab, lenvatinib + pembrolizumab. Other recommended: Ipilmumab + Nivolumab; Pembrolizumab | Sunitinib, pazopanib, lenvatinib–everolimus, everolimus and lenvatinib–pembrolizumab may be used for advanced chromophobe RCC. ICI-based therapies including ipilimumab–nivolumab, axitinib–pembrolizumab, cabozantinib–nivolumab, and lenvatinib–pembrolizumab are preferred for advanced RCC with sarcomatoid (predominant) histology. Sunitinib and pazopanib are alternative options for patients with contraindications to ICI-based therapy. | Offer lenvatinib plus pembrolizumab to patients with non-ccRCC subtypes. Offer cabozantinib and nivolumab to patients with non-ccRCC subtypes other than chromophobe RCC. Offer nivolumab plus ipilimumab in patients with non-ccRCC. |
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