PATIENTS WITH KIDNEY CANCER that hasn’t spread to distant parts of their body typically undergo surgery. But even when all signs of the cancer are removed, it is estimated some 20% of people with localized kidney cancer will have a recurrence.

A study published in the April 18, 2024, issue of the New England Journal of Medicine found that the immunotherapy drug Keytruda (pembrolizumab) could increase survival for people with intermediate-to-high risk and high-risk kidney cancer. The clinical trial, called KEYNOTE-564, included 994 people who had successful surgery for clear cell renal cell carcinoma. Participants were randomly assigned to receive either Keytruda or a placebo every three weeks for about a year. After four years, those who were treated with Keytruda had a survival rate of 91% compared with 86% for those who received the placebo. Meanwhile, at the same time point, 65% were alive and free from recurrence compared with 57% for those receiving the placebo.

In 2021, the Food and Drug Administration approved Keytruda for adjuvant treatment in intermediate-high or high-risk kidney cancer. The approval was based on an earlier interim analysis from KEYNOTE-564, which showed the drug could extend the time a person lived without having a recurrence. However, these latest findings, based on more mature data from the same clinical trial, are the first to show improved patient survival with immunotherapy in this patient population, says Toni Choueiri, a medical oncologist at Dana-Farber Cancer Institute in Boston who is the lead author of the study. He says other studies on different immunotherapies did not appear to show a survival benefit in kidney cancer.

Martin Voss, a genitourinary oncologist at Memorial Sloan Kettering Cancer Center in New York City who was not involved in the study, says these results will change the way physicians think about managing people with kidney cancer after they have surgery to remove their cancer.

He notes that most patients in the study tolerated the treatment. However, 1 in 5 people who received Keytruda had serious adverse events compared with 1 in 10 who took a placebo. The most common issues were fatigue and itchiness, but some patients developed lasting immune-related problems, including Type 1 diabetes, and a condition called colitis, which is inflammation in the colon.

Explaining the benefits and risks for a person who has completed surgery and is looking to reduce recurrence “requires a tremendous amount of discussion in our clinics with our patients. And, in my opinion, shared decision-making in this space is a lot more detailed—there’s a lot more conversation that goes into it—than a patient who has overt metastatic disease,” Voss says.

These decisions are made more difficult because there’s a chance the person doesn’t need further treatment to keep their cancer from coming back. To determine whether kidney cancer has an intermediate or high risk of recurrence, physicians look at several features, including the appearance of the tumor under a microscope and the extent of the tumor’s spread to lymph nodes. Prior to successful surgery, many patients in the study had larger tumors or tumors that had spread to nearby lymph nodes, features that indicate a higher risk.

Voss hopes future research will develop tools to estimate risk of recurrence more accurately than current methods and to better identify patients who would benefit from immunotherapy.

“I do consider this a standard of care, which does not mean that every patient has to pursue it,” says Voss. “But I do think that it has to be considered in patients that fit the profile and are at increased risk for disease recurrence,” says Voss.