SITC Immunotherapy for the Treatment of Renal Cell Carcinoma 2026 Guideline – Key Recommendations

Published: 7h 14m ago

Guideline Video

Guideline Resources

Immunotherapy for the Treatment of Renal Cell Carcinoma
Society for Immunotherapy of Cancer
March 23, 2026
Summary
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Video Transcription

Just published March 23rd, 2026, the Society for Immunotherapy of Cancer’s newest guideline on Immunotherapy for the Treatment of Renal Cell Carcinoma.

The objective of this guideline is to help improve patient care by providing evidence-based and consensus-based recommendations for the treatment of renal cell carcinoma, or RCC, using immunotherapy approaches.

In today’s rapid update, we’ll just be going over a summary of the recommendations so for the full guideline, make sure to check it out on guidelinecentral.com

Let’s get started.

Starting on the section Diagnostic Tests and Biomarkers

For patients with suspected RCC, pathology should confirm the diagnosis.
For patients with sarcomatoid/rhabdoid differentiation/features, patients may have improved outcomes to immunotherapy and should be considered for immune-based regimens.
For patients with RCC, tumor mutational burden, MSI/MMR status, PD-L1 expression, and/or specific genetic mutations are not recommended for patient selection for immunotherapy.

Next the section on Stage II, Stage III, and Stage IV RCC Amenable to Metastasis-directed Therapy

Use of validated nomograms may be useful to further guide consideration for use of adjuvant pembrolizumab for patients who are eligible.
For patients with resected RCC, clinical trial enrollment for adjuvant therapy should be offered when available.
For patients with resected RCC who are eligible, discussion of treatment risks and benefits of adjuvant immune checkpoint inhibitors, or 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 are starting adjuvant systemic therapy, imaging should be obtained within 3 months prior to initiation.
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.
For patients with resected RCC who experience disease progression during or within 1 year after receiving adjuvant pembrolizumab, although the data are limited, metastasectomy, ablation, or radiotherapy may be considered for limited recurrence.
For patients with resected nccRCC, there is no SOC adjuvant therapy, and clinical trial enrollment is recommended, when available and appropriate.
There is no standard neoadjuvant regimen for patients with non-metastatic localized RCC, and a multidisciplinary consultation should be considered to determine the best management strategy for these patients.

Next the section on Stage IV RCC

For the section on Initial Assessment

For patients who are candidates for immunotherapy with metastatic RCC, the role of cytoreductive nephrectomy or SBRT to the renal primary is under active investigation. In the absence of definitive prospective data, a multidisciplinary approach is recommended for consideration of cytoreductive nephrectomy either in an immediate or deferred fashion.
For patients eligible for systemic therapy, an immunotherapy-based approach is recommended.
A subset of patients with asymptomatic, low-volume, and slow-growing disease could be candidates for active surveillance or metastases-directed therapy.

For the section on Available Immunotherapy for Treatment-naïve 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 have been shown to improve OS. In the absence of head-to-head comparisons any of these options is recommended.
For patients with treatment-naïve metastatic RCC, clinical trial enrollment should be encouraged, when available.

For the section on Available Therapy for Previously Treated Disease

For patients with ICI-refractory metastatic RCC, a TKI-based regimen or belzutifan is recommended. If the patient previously received an ICI plus TKI combination, treatment with a different TKI should be selected.
There is no proven role for sequential anti-PD-(L)1 regimens for patients with previously treated metastatic RCC.
For patients with previously treated metastatic RCC, clinical trial enrollment should be encouraged.

For the section on Available Immunotherapy for Treatment-naïve nccRCC

For patients with treatment-naïve nccRCC, enrollment on a clinical trial is recommended when available.

Next the section on Special Considerations for ICI Treatment

Local therapy should be considered for patients with RCC with oligometastatic disease.
Local therapy for oligometastatic RCC does not require interruption of systemic immunotherapy.
For patients with RCC and brain metastases, consider local therapy with or without systemic therapy whenever feasible. Local therapy should not interrupt immunotherapy.
For patients with RCC with oligoprogressive disease, stereotactic radiation therapy should be considered.
For patients with advanced RCC with radiographic progression but who remain clinically stable and are tolerating therapy, continuation of systemic immunotherapy with close monitoring may be considered.
For patients receiving immunotherapy for metastatic RCC, the best available evidence supports 2 years of ICI treatment; however, treatment could be continued beyond 2 years as personalized to the patient.
For patients who have received local therapies to all sites of metastatic disease within 1 year of nephrectomy, adjuvant pembrolizumab treatment for 1 year can be considered .
For patients with pre-existing significant autoimmune disease or solid organ transplant, avoiding ICI therapy initially and consulting with a specialist is recommended.
For patients being considered for treatment with ICIs, HIV is not a contraindication.
For patients being considered for treatment with ICIs, older age is not a contraindication.

And last the section on Patient Education and Quality of Life, or QOL,

For patients with RCC receiving immunotherapy, providing educational materials about therapy risk and benefit is recommended.
For patients with RCC receiving immunotherapy, discussion about the risks and benefits of treatment is recommended.
For patients with a decline in QOL or physical functioning, ensure appropriate diagnostic workup for immune-mediated toxicity, disease progression, or alternative causes.
For patients with RCC receiving immunotherapy, assessment of emotional wellbeing and referral to appropriate specialists is recommended at initial diagnosis, disease progression, and for those with long-term irAEs.

And there you have it. Make sure to check out the full guideline from the Society for Immunotherapy of Cancer and other related clinical decision support tools at guidelinecentral.com.