Breakthroughs in Kidney Cancer Research Excite Doctors

With multiple game-changing developments over the past two decades, kidney cancer patients are now living longer and better.

A big part of the reason is that many are being diagnosed at earlier stages of the disease, when it can often be more easily treated and sometimes cured. Even when cancers are caught later, advances in medications and in methods of targeting cancer cells are significantly extending survival.

“When I started two decades ago, the average survival for patients with advanced kidney cancer was one year,” says Dr. Brian Rini, a professor of medicine at the Vanderbilt University Medical Center in Nashville. “Now, the median survival is between five and six years. It’s amazing.”

The growing use of scanning technologies in medicine overall has been one of the most important changes over the last couple of decades: Tumors are being detected during scans for non-cancerous conditions.

“Most kidney cancers are found by accident quite early, because people get scans for unrelated reasons,” says Dr. William Huang, a professor of urology and radiology at the NYU Grossman School of Medicine and a urologic oncologist at NYU Langone’s Perlmutter Cancer Center in New York City. “People get scanned for almost everything now: heartburn, back pain, car accidents. Eight out of 10 newly diagnosed patients who come to see me were scanned for something completely different.”

Because these cancers are caught early, they may be “completely curable, and sometimes so early that nothing needs to be done,” Huang says. “We can just keep an eye on them, and unless they change, we don’t need to do any intervention.” Advances in imaging have also led to novel ways of determining whether a tumor is benign or malignant. Scanners allow doctors to see growths in much greater detail nowadays, which allows for diagnosis in some cases without a biopsy. For example, scans using radioactive tracers can detect fat, which can be a signal that a growth is benign, Huang says.

Here’s a look at additional kidney cancer advances that doctors are excited to see come down the pipeline.

Killing cancer without surgery
Surgeons used to remove the entire kidney when a tumor was found. “Now you can remove just part of the kidney,” Huang says. Some methods of eliminating tumors don’t even involve cutting. “You can ablate a tumor with heat or you can freeze it,” says Huang. “Right now we are involved in a clinical trial that uses a method that is completely non-invasive. There is no incision, no radiation, no needles. We just ablate the tumor using ultrasound waves, which rupture the cancer cells.”

Radiation by itself can eliminate tumors, too
For patients who aren’t good candidates for surgery because of underlying health issues, there’s another option that will eradicate the main tumor and some metastases. “This is something that has been evolving, and it’s very, very exciting,” says Dr. Catherine Spina, a kidney cancer specialist and an assistant professor of radiation oncology at Columbia University’s Vagelos College of Physicians and Surgeons in New York City. “Traditionally, radiation has been given over long courses in small doses.”

Over the years, however, specialists have discovered they could give much higher doses of radiation over a much shorter period of time, so long as the radiation was tightly targeted to hit the cancerous tissue, while giving a very low dose to the surrounding areas.

The result is that patients with a moderate-sized main tumor and cancer that has metastasized to just a few other sites can completely avoid surgery, with their cancer treated after just five or fewer radiation treatments. The technique is mostly limited to 8-centimeter main tumors, though some clinicians are also using it in tumors that are as large as 11 centimeters, Spina says.

When surgery is needed
Some patients prefer to have surgery or won’t qualify for non-invasive therapies because their cancer is too advanced. Surgical breakthroughs over the past decade or so have allowed these procedures to be more targeted and less invasive.

Many operations are now done with robotic instruments that are inserted into the body through tiny incisions, while surgeons sitting at consoles view the operation and remotely control the instruments, says Dr. George Schade, an associate professor in urology at the University of Washington and a physician with the Fred Hutchinson Cancer Center in Seattle.

Robotic surgeries are a big advance over the original minimally invasive laparoscopic operations, in which tools at the end of stiff rods were inserted through small incisions with the surgeon standing over the patient and viewing the procedure on a computer screen. The new robotic instruments, by contrast, use a jointed probe rather than a straight one, offering more mobility. “They are like tiny arms inside of the patient with wrists and fingers,” Huang says.

Fluorescent dyes can help surgeons tell the difference between healthy tissue and cancer, as well as shine a light on the location of blood vessels feeding tumors. And in what may be another big step, some specialists are using robotic equipment that allows them to have depth perception. As the surgeons peer into a patient’s body, they see a 3D image overlaying the area that they’re operating on. “This is not in wide use yet, but there are several groups working on improving the technology to bring it to the mainstream,” Schade says.

Looking forward, as high-speed internet access spreads around the country and throughout the world, it’s possible that the surgeon controlling the robot in the operating room might not even be at the same hospital. “I don’t see that as too far in the future,” Huang says.

Targeted medications
It wasn’t that long ago that specialists had little to offer cancer patients after surgery, outside of chemotherapy, which wasn’t very effective against kidney cancer. But in the past two decades, there’s been an explosion of new cancer medications. Some pump up a patient’s immune response, while others target a variety of pathways to slow or stop cancer growth and development.

Drugs known as checkpoint inhibitors stop the immune system from being fooled into quitting before the cancer is conquered, says Dr. Bobby Liaw, clinical director of genitourinary oncology for the Mount Sinai Health System and an assistant professor of medicine, hematology, and medical oncology at the Icahn School of Medicine at Mount Sinai.

Checkpoints are the part of a normally functioning immune system that act as a set of brakes to turn down the system’s response once an infection or other pathology such as cancer has been defeated. That way the immune system doesn’t start turning its attack on healthy cells.

By blocking the action of a checkpoint, these medications keep the immune system on target. There can be immune system side effects—such as skin inflammation, and less commonly, autoimmune-like effects on certain organs, as well as endocrine disturbances—from cutting one of the immune system’s brake lines.

“Any time we plan to initiate any kind of new therapy for any cancer patient, there needs to be consideration for the benefits versus the risks,” Liaw says.

In the case of serious side effects, particularly the immune system attacking healthy cells, the checkpoint inhibitor is stopped and the patient is given corticosteroids, says Dr. Toni Choueiri, director of the Lank Center for Genitourinary Cancer at the Dana Farber Cancer Institute in Boston.

A study published in April in the New England Journal of Medicine that followed patients for nearly five years showed that the checkpoint inhibitor pembrolizumab, when given after surgery, reduced the risk of death by 38%.

“Prior to the approval of pembrolizumab, there was no wide-spread accepted standard of care for patients with [the most common form of kidney cancer] after treatment with surgery,” says Choueiri, the lead author of the study. The next step, he says, is to study whether combining it with another therapy, like belzutifan, will reduce the risk of death even further.

Other drugs take aim at blood vessel formation. “Tumors are more dependent on the growth of new blood vessels than organs are,” Rini explains. “These medications choke off the blood supply to the tumor.”

One other type of drug, called a tyrosine kinase inhibitor, blocks an enzyme that’s needed for tumor cells to grow and divide. There are currently numerous tyrosine kinase inhibitors approved by the U.S. Food and Drug Administration (FDA).

At the end of 2023, kidney cancer specialists got yet another arrow to add to their quivers: The FDA approved the drug belzutifan, a medication that effectively suffocates tumors by blocking a protein involved in regulating oxygen levels.

Doctors have traditionally liked to give one cancer drug at a time, but that’s changing. Specialists believe that cancers may have a harder time surviving when multiple medications are taken at once.

A number of ongoing clinical trials are looking at the impact of this strategy and exploring which combinations work the best. “There’s absolutely an additive effect of giving more drugs at the same time,” Rini says.

A kidney cancer vaccine?
The mRNA technology that was used to create a vaccine to combat COVID-19 was initially developed as a potential way to battle cancer. Only recently has that research started to pan out.

Once a patient’s tumor has been removed, doctors identify proteins that are specific to cells in the tumor but not found anywhere else in the patient’s body. Then they determine which of those proteins are likely to be able to call the immune system’s attention to the cancer. Those proteins become the targets for the patient’s personalized mRNA vaccine.

There have already been promising results using mRNA technology to create personalized vaccines to help treat advanced melanoma. In a phase 2 trial that ended in mid-2023, researchers compared the checkpoint inhibitor pembrolizumab plus personalized vaccines to pembrolizumab alone. They found that the vaccine reduced the risk of recurrence by nearly a half.

The same strategy is being tested in a phase 2 trial that will soon be recruiting patients with advanced kidney cancer, says Choueiri, co-lead investigator of the trial.

The results of the phase 1 trial, which was testing just for safety, found “the vaccine to be well tolerated,” Choueiri says. “We and many others have been trying to do vaccines for several decades now.” The goal is to find the specific proteins in the vaccine that will be “the ones that elicit the most intense immune response that will lead to killing the cancer.”

Experts like Choueiri have high hopes for mRNA cancer vaccines. And with numerous other therapies being developed by pharmaceutical companies at the same time as others are making their way through clinical trials, the future for kidney cancer patients is getting brighter with each passing year.