circleNumerous breakthroughs over the past two decades have allowed kidney cancer patients to live longer, better lives.
This is largely because many patients are diagnosed at an early stage of the disease, when it is easier to treat and even cure, and even if cancer is detected later, advances in drugs and techniques for targeting cancer cells have significantly increased survival times.
“When I started my research 20 years ago, the average survival for patients with advanced kidney cancer was one year,” says Dr. Brian Rini, professor of medicine at Vanderbilt University Medical Center in Nashville. “Today, the average survival is five to six years. It’s astonishing.”
The increasing use of scanning technology across healthcare has been one of the most significant changes in the past few decades, with tumors now being detected during scans for non-cancerous diseases.
“Most kidney cancers are discovered incidentally quite early, because patients get tested for unrelated reasons,” says William Huang, M.D., professor of urology and radiology at NYU Grossman School of Medicine and urologic oncologist at NYU Langone Perlmutter Cancer Center in New York City. “Now, people get tested for just about anything: heartburn, back pain, car accidents. Eight out of 10 newly diagnosed patients who come into my office were getting tested for an entirely different reason.”
Because these cancers are caught early, “they’re completely curable, and sometimes so early that we don’t need to do anything,” Huang says. “We just observe, and we don’t need to intervene unless there’s a change.” Advances in imaging have also led to new ways to determine whether a tumor is benign or malignant. Today, scanners allow doctors to see tumors in much greater detail, so they may be able to diagnose them without a biopsy. For example, scans with radioactive tracers can detect fat, which can be a signal that a tumor is benign, Huang says.
Here we look at some further advances in kidney cancer treatment that doctors are excited to see coming in the future.
Cure cancer without surgery
Once a tumor was found, surgeons would remove the entire kidney. “Now we can just remove part of the kidney,” Huang says. Some methods of removing tumors don’t even involve an incision. “We can remove the tumor with heat or freeze it,” Huang says. “Right now we’re in a clinical trial that uses a completely non-invasive method. No incisions, no radiation, no needles. We just use ultrasound to remove the tumor and destroy the cancer cells.”
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Radiation alone can eliminate tumors
For patients who are not suitable for surgery because of underlying conditions, there is another option to eradicate the main tumor and some of the metastases. “This is something that is continuing to evolve, and it’s really exciting,” says Dr. Katherine Spina, a kidney cancer specialist and assistant professor of radiation oncology at Columbia University Vagelos School of Medicine in New York City. “Traditionally, radiation has been given in small doses over a long period of time.”
But over the years, experts have discovered that if the radiation is tightly targeted at the cancerous tissue and the surrounding areas receive only a very low dose, it is possible to deliver a much higher dose of radiation in a much shorter time.
As a result, patients with a medium-sized main tumor and cancer that has spread to several other places can avoid surgery altogether and treat their cancer with just five or fewer radiation treatments. The technique is primarily limited to main tumors that are 8 centimeters in size, but some clinicians are using it on tumors as large as 11 centimeters, Spina said.
When surgery is needed
Some patients prefer surgery, and others may have cancer that is too advanced to be amenable to non-invasive therapies. Advances in surgery over the past decade or so have made these procedures more targeted and less invasive.
Many surgeries are currently performed using robotic instruments that are inserted into the body through tiny incisions, with the surgeon sitting at a console watching the procedure and remotely controlling the instruments, said Dr. George Schade, an associate professor of urology at the University of Washington and a physician at the Fred Hutchinson Cancer Center in Seattle.
Robotic surgery is a big advancement over traditional minimally invasive laparoscopic surgery, in which rigid, rod-tipped instruments are inserted through small incisions while the surgeon stands beside the patient and watches the procedure on a computer screen. In contrast, the new robotic instruments use articulated probes rather than straight ones, giving them more mobility. “They’re like little arms with wrists and fingers inside the patient,” Huang says.
Fluorescent dyes not only help surgeons distinguish healthy tissue from cancer, but also illuminate the location of blood vessels that feed tumors. And in another major advancement, some specialists are using robotic devices that allow depth perception: as the surgeon peers into the patient’s body, they see a 3-D image overlaid on the area they’re operating on. “It’s not in widespread use yet, but there are several groups working to refine this technology and make it mainstream,” Schade says.
In the future, as high-speed internet connections become more widespread across the country and the world, the surgeons operating the robots in the operating room may not even be at the same hospital.
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Targeted drugs
Not so long ago, specialists had little to offer cancer patients after surgery, other than chemotherapy, which was not particularly effective against kidney cancer. But the past two decades have seen an explosion of new cancer drugs, some of which boost a patient’s immune response, while others target different pathways to slow or halt the growth and development of cancer.
The drugs, known as checkpoint inhibitors, prevent the immune system from being tricked into shutting down before the cancer can be overcome, said Dr. Bobby Liaw, clinical director of genitourinary oncology at Mount Sinai Health System and assistant professor of medicine, hematology and medical oncology at the Icahn School of Medicine at Mount Sinai.
Checkpoints are part of a normally functioning immune system and act as brakes to slow the system’s response once a disease condition, such as an infection or cancer, has been overcome, so that the immune system does not attack healthy cells.
These drugs keep the immune system targeted by blocking checkpoint activity, and cutting one of the immune system’s brake lines can lead to immune system side effects such as dermatitis, and in rare cases, autoimmune-like effects on certain organs, and endocrine disorders.
“When planning to start any new treatment for a cancer patient, we need to consider the benefits and risks,” Liaw says.
If there are severe side effects, particularly if the immune system attacks healthy cells, the checkpoint inhibitors are stopped and the patient is given corticosteroids, said Dr. Toni Choueiri, director of the Rank Genitourinary Cancer Center at the Dana-Farber Cancer Institute in Boston.
The study, published in April, New England Journal of Medicine A study that followed patients for nearly five years showed that administering the checkpoint inhibitor pembrolizumab after surgery reduced the risk of death by 38%.
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“Before pembrolizumab was approved, [the most common form of kidney cancer] “It’s possible that there may be a further reduction in the risk of death after surgical treatment,” said Choueiri, the study’s lead author. The next step, he said, will be to study whether combining the treatment with another therapy, such as verzuzifan, could further reduce the risk of death, he said.
Other drugs target angiogenesis. “Tumors depend more on the growth of new blood vessels than organs do,” Rini explains. “These drugs cut off the blood supply to the tumor.”
Another class of drugs, called tyrosine kinase inhibitors, block enzymes needed for tumor cells to grow and divide. There are currently a number of tyrosine kinase inhibitors approved by the U.S. Food and Drug Administration (FDA).
At the end of 2023, kidney cancer specialists added yet another arrow to their quiver when the FDA approved a drug called Verzucifan, which effectively suffocates tumors by blocking a protein involved in regulating oxygen levels.
Doctors have traditionally preferred to give one cancer drug at a time, but that’s changing: Experts believe that giving multiple drugs at once could make it harder for a cancer to survive.
Ongoing clinical trials are investigating the impact of this strategy and determining which combinations are most effective. “There’s definitely an additive effect when you give multiple drugs at the same time,” Rini says.
Kidney cancer vaccine?
The mRNA technology used to create vaccines to fight COVID-19 was initially developed as a potential way to fight cancer, and only recently has that research begun to bear fruit.
Once a patient’s tumor is removed, doctors will identify proteins that are unique to tumor cells and not found anywhere else in the patient’s body. They will then determine which of those proteins may draw the immune system’s attention to the cancer. Those proteins will then be targeted with a personalized mRNA vaccine.
There are already promising results using mRNA technology to create personalized vaccines to help treat advanced melanoma: A phase 2 trial that finished in mid-2023 compared the checkpoint inhibitor pembrolizumab in combination with a personalized vaccine to pembrolizumab alone, and found that the vaccine reduced the risk of recurrence by almost half.
The same strategy is also being tested in a phase 2 trial that is expected to soon recruit patients with advanced kidney cancer, says Choueiri, who is a co-principal investigator on the study.
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Phase 1 trials, which only tested for safety, found that “the vaccine was well tolerated,” Choueiri said. “We and many others have been working on vaccine development for the last few decades.” The goal is to find a specific protein in the vaccine that “will trigger the strongest immune response that will kill the cancer.”
Experts like Choueiri have high hopes for mRNA cancer vaccines, and with more treatments moving through clinical trials and being developed by pharmaceutical companies, the future for kidney cancer patients looks brighter every year.
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