Summary
A BMJ clinical review describes how molecular classification, kidney-sparing treatment and immune-based combinations are shaping renal cell carcinoma care. It highlights improved outcomes in some settings alongside persistent resistance and a lack of validated biomarkers to guide treatment choice.
A clinical review published in The BMJ on 26 October 2026 describes how molecular classification and newer treatments are changing the management of renal cell carcinoma (RCC), the most common form of kidney cancer. It synthesises evidence from a PubMed search covering January 2010 to February 2026, prioritising randomised trials, meta-analyses, large observational studies and clinical guidelines; it is a review, not a new treatment trial.
The authors describe a shift towards matching care to tumour subtype, stage and patient circumstances. Surgery remains central for localised disease, while immune checkpoint inhibitor combinations have extended survival for some people with metastatic cancer. Resistance to treatment and the absence of validated biomarkers to predict which therapy will work best remain important challenges.
Diagnosis and treatment of localised disease
RCC is no longer classified by appearance alone. The review notes that the World Health Organization recognises at least 24 distinct subtypes and five emerging entities, reflecting increased understanding of their molecular features. This matters because kidney tumours that look similar under a microscope can behave differently. Diagnosis generally combines CT or MRI with selective biopsy and, where needed, molecular testing.
For localised tumours, the treatment approach depends on factors including tumour size and location, kidney function and overall health. Partial nephrectomy, which removes the tumour while preserving more of the kidney, is preferred for many small renal masses. Active surveillance—monitoring a tumour rather than treating it immediately—can be considered for selected small lesions, particularly those under 2 cm. Ablation and stereotactic radiation are options for some patients who are not suited to surgery or decline it.
For some people at high risk of recurrence after surgery for clear cell RCC, pembrolizumab can be considered as adjuvant treatment. In the KEYNOTE-564 trial, which enrolled 994 patients, five-year disease-free survival was 60.9% with pembrolizumab and 52.2% with placebo. Overall survival was 87.7% and 82.3%, respectively. The review describes this as a standard-of-care option for selected patients, including those with intermediate-high or high-risk disease and some patients whose metastatic disease was resected within a year of nephrectomy.
Immune-based combinations in metastatic disease
For metastatic RCC requiring systemic treatment, combinations involving immune checkpoint inhibitors (ICIs) have become central. These medicines help the immune system recognise and attack cancer cells. Treatment may pair two ICIs or combine an ICI with a drug that blocks vascular endothelial growth factor receptors (VEGFR), which are involved in tumour blood-vessel growth. The review says choice of regimen should account for disease features, symptoms, other health conditions and treatment goals.
Long-term results from CheckMate 214 illustrate the potential benefit of dual immunotherapy. At eight-year follow-up, median overall survival was 52.7 months with nivolumab plus ipilimumab, compared with 37.8 months with sunitinib. The combination can produce durable responses, although the review notes higher rates of early immune-mediated toxicity. For selected people with slow-growing, low-volume metastatic disease and few symptoms, close monitoring before starting systemic treatment may also be reasonable.
The review describes further treatment choices after disease progression, including VEGFR-targeted drugs and, in some settings, belzutifan, which targets hypoxia-inducible factor 2α. It reports that evidence for treatment after initial therapy is more limited than for first-line treatment, so decisions need to account for previous medicines and the pace of disease.
Persistent challenges
RCC can become resistant to treatment, either from the outset or after an initial response. The review identifies the lack of validated predictive biomarkers as a barrier to selecting the most effective treatment for an individual patient. Molecular profiling has improved tumour classification, but it has not yet resolved that treatment-selection problem.
Some newer approaches remain under study. For example, the review describes circulating tumour DNA and serum kidney injury molecule-1 as potential biomarkers, while noting that they are not ready for routine clinical use. Personalised cancer vaccines and oncolytic viruses are also experimental. Overall, the evidence points to a broader set of options for RCC, but the best sequence of treatments—and how to identify who will benefit from each—remains an active clinical and research question.