Guideline Updates Offer New Strategies for Advanced Kidney Cancer Treatment

Patients with advanced kidney cancer, or renal cell carcinoma, have several new treatment paths to consider following the 2026 National Comprehensive Cancer Network (NCCN) Annual Conference. Dr. Naomi B. Haas from the Abramson Cancer Center at the University of Pennsylvania shared updates on how doctors use specific guidelines to choose the best medicine for each person. These updates focus on using the latest research to pick a treatment plan based on the specific type of cancer cells a patient has and how aggressive the cancer appears to be. By following these evidence-based steps, medical teams aim to provide more personalized care that helps patients with cancer live better lives.

How doctors choose the right medicine for your kidney cancer

The first step in planning treatment is looking at the specific type of kidney cancer cells. About 75% of patients have what is called "clear cell" kidney cancer, which is often linked to a change in a gene called VHL. Other types, such as papillary or chromophobe kidney cancer, are less common but require different approaches because they are driven by different genetic changes. For example, while the VHL gene is involved in 92% of common clear cell cases, a different gene called Met is often linked to the papillary type.

To find the best starting treatment, your healthcare team uses a "risk model" to see how the cancer might behave. They look at six specific factors, such as how long it has been since your diagnosis, your ability to do daily activities, and certain levels in your blood like calcium and hemoglobin. Based on these details, patients are placed into "favorable," "intermediate," or "poor" risk groups. Current guidelines suggest that most patients start with a combination of two medicines rather than just one. This usually involves an immunotherapy, which helps the immune system find cancer, paired with a targeted drug that blocks the blood supply to the tumor.

Results from clinical trials for kidney cancer combinations

The recommendations for these drug combinations come from large clinical trials that compared new treatments to older standards. In the CLEAR trial, a combination of lenvatinib and pembrolizumab helped keep the cancer from growing for 23.3 months, which was much longer than the 9.2 months seen with a single older drug. Another study, the CheckMate 9ER trial, showed that combining nivolumab and cabozantinib doubled the time the cancer stayed stable to 16.6 months compared to 8.3 months with the older treatment.

For patients in the intermediate or poor risk groups, a trial called CheckMate 214 looked at using two different immunotherapies together. This study found that 75% of patients using this duo were alive at the 12-month mark, compared to 60% of those using the standard single drug. For patients who have already tried a targeted drug and need a new option, a study called LITESPARK-005 found that a newer medicine called belzutifan led to a 22% response rate, which was significantly higher than the 4% response rate for the older comparison drug.

What to expect regarding side effects and safety

While these new combinations are powerful, they can cause side effects that patients and caregivers should watch for closely. When taking a combination of an immunotherapy and a targeted drug, common side effects include diarrhea, feeling very tired, high blood pressure, and skin rashes. In the CheckMate 9ER study, 7% of patients had to stop the combination treatment because the side effects became too difficult to manage.

Using two immunotherapies together can sometimes cause the immune system to become too active and attack healthy parts of the body. This might lead to inflammation in the lungs, liver, or colon. In the study for the drug belzutifan, the most common side effects reported were fatigue and anemia, which is a low red blood cell count that can make you feel weak. Your medical team will monitor you closely and can often manage these issues by changing your dose or providing supportive care to help you feel better during your treatment.

References

1. “From Guidelines to Practice: Systemic Therapy Strategies in Advanced Renal Cell Carcinoma” by Dr. Naomi B. Haas, et al., 2026 NCCN Annual Conference.

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