Kidney cancer patients are now living longer and better, thanks to developments over the past 20 years, and the fact that many are being diagnosed earlier, when the disease 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,” said Dr Brian Rini, a professor of medicine at the Vanderbilt University Medical Centre 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 past couple of decades, reports TIME Magazine, with tumours often being detected during scans for non-cancerous conditions.
“Most kidney cancers are found by accident quite early, because people get scans for unrelated reasons,” said 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 Centre in New York City.
“People have scans 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 said. “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 tumour is benign or malignant. Scanners allow doctors to see growths in much greater detail nowadays, allowing 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 are some additional kidney cancer advances, adding to medical excitement.
Killing cancer without surgery
Surgeons used to remove the entire kidney when a tumour was found. “Now you can remove just part of the kidney,” Huang said. Some methods of eliminating tumours don’t even involve cutting.
“You can ablate a tumour with heat or freeze it,” he added. “Right now we are involved in a clinical trial using a method that is completely non-invasive. There is no incision, no radiation, no needles. We just ablate the tumour using ultrasound waves, which rupture the cancer cells.”
Radiation by itself can eliminate tumours, too.
For patients who aren’t good candidates for surgery because of underlying health issues, there’s another option that will eradicate the main tumour and some metastases. “This is something that has been evolving, and it’s very exciting,” said Dr Catherine Spina, a kidney cancer specialist and 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 shorter period of time, as 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 tumour and cancer that has metastasised 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 8cm main tumours, though some clinicians are also using it in tumours that are as large as 11cm, Spina said.
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 inserted into the body through tiny incisions, while surgeons sitting at consoles view the operation and remotely control the instruments, said Dr George Schade, an associate professor in urology at the University of Washington and a physician with the Fred Hutchinson Cancer Centre in Seattle.
Robotic surgeries are a big advance over the original minimally invasive laparoscopic operations, where 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 the patient, with wrists and fingers,” Huang said.
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 tumours. And in what may be another big step, some specialists use robotic equipment allowing them to have depth perception. As they peer into a patient’s body, they see a 3D image overlaying the area on which they’re operating.
“This is not in wide use yet, but there are several groups working on improving the technology to bring it to the mainstream,” Schade said.
In the future, as high-speed internet access spreads 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 said.
Targeted medications
Not so long ago, specialists had little to offer cancer patients after surgery, apart from chemotherapy, which wasn’t very effective against kidney cancer. But in the past two decades, there's been an explosion of new 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, said Dr Bobby Liaw, clinical director of genitourinary oncology for the Mount Sinai Health System and an assistant professor of medicine, haematology and medical oncology at the Icahn School of Medicine at Mount Sinai.
Checkpoints – part of a normally functioning immune system – act as a set of brakes to turn down the system’s response once an infection or other pathology like 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, like 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 a patient, there must be consideration for the benefits versus the risks,” Liaw said.
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, said Dr Toni Choueiri, director of the Lank Centre for Genitourinary Cancer at the Dana Farber Cancer Institute in Boston.
A study published in April this year 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%.
“Before the approval of pembrolizumab, there was no widespread accepted standard of care for patients with the most common form of kidney cancer after treatment with surgery,” said Choueiri, the lead author of the study. The next step 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. “Tumours are more dependent on the growth of new blood vessels than organs are,” Rini said. “These medications choke off the blood supply to the tumour.”
Another type of drug, called a tyrosine kinase inhibitor, blocks an enzyme that’s needed for tumour cells to grow and divide. There are currently numerous tyrosine kinase inhibitors approved by the US Food and Drug Administration (FDA).
At the end of 2023, kidney cancer specialists added yet another arrow to add to their quivers.
The FDA approved the drug belzutifan, which effectively suffocates tumours 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 cancers may have a harder time surviving when multiple medications are taken simultaneously.
A number of ongoing clinical trials are looking at the impact of this strategy and exploring which combinations work best. “There’s absolutely an additive effect of giving more drugs at the same time,” Rini said.
A kidney cancer vaccine?
The mRNA technology 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 tumour has been removed, doctors identify proteins that are specific to cells in the tumour 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 personalised mRNA vaccine.
There have already been promising results using mRNA technology to create personalised vaccines to help treat advanced melanoma.
In a phase 2 trial that ended in mid-2023, researchers compared the checkpoint inhibitor pembrolizumab plus personalised 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, said 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. “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 those 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.
Study details
Overall Survival with Adjuvant Pembrolizumab in Renal-Cell Carcinoma
Toni Choueiri, Piotr Tomczak, Jaroslav Hajek et al for the KEYNOTE-564 Investigators.
Published in NEJM on 17 April 2024
Abstract
Background
Adjuvant pembrolizumab therapy after surgery for renal-cell carcinoma was approved on the basis of a significant improvement in disease-free survival in the KEYNOTE-564 trial. Whether the results regarding overall survival from the third prespecified interim analysis of the trial would also favour pembrolizumab was uncertain.
Methods
In this phase 3, double-blind, placebo-controlled trial, we randomly assigned (in a 1:1 ratio) participants with clear-cell renal-cell carcinoma who had an increased risk of recurrence after surgery to receive pembrolizumab (at a dose of 200 mg) or placebo every 3 weeks for up to 17 cycles (approximately 1 year) or until recurrence, the occurrence of unacceptable toxic effects, or withdrawal of consent. A significant improvement in disease-free survival according to investigator assessment (the primary end point) was shown previously. Overall survival was the key secondary end point. Safety was a secondary end point.
Results
A total of 496 participants were assigned to receive pembrolizumab and 498 to receive placebo. As of September 15, 2023, the median follow-up was 57.2 months. The disease-free survival benefit was consistent with that in previous analyses (hazard ratio for recurrence or death, 0.72; 95% confidence interval [CI], 0.59 to 0.87). A significant improvement in overall survival was observed with pembrolizumab as compared with placebo (hazard ratio for death, 0.62; 95% CI, 0.44 to 0.87; P=0.005). The estimated overall survival at 48 months was 91.2% in the pembrolizumab group, as compared with 86.0% in the placebo group; the benefit was consistent across key subgroups. Pembrolizumab was associated with a higher incidence of serious adverse events of any cause (20.7%, vs. 11.5% with placebo) and of grade 3 or 4 adverse events related to pembrolizumab or placebo (18.6% vs. 1.2%). No deaths were attributed to pembrolizumab therapy.
Conclusions
Adjuvant pembrolizumab was associated with a significant and clinically meaningful improvement in overall survival, as compared with placebo, among participants with clear-cell renal-cell carcinoma at increased risk for recurrence after surgery.
NEJM article – Overall Survival with Adjuvant Pembrolizumab in Renal-Cell Carcinoma (Open access)
TIME Magazine article – What 5 doctors are excited about in kidney cancer research (Open access)
See more from MedicalBrief archives:
‘Potential new standard’ in high-risk kidney cancer — KEYNOTE-564 trial
Merck’s kidney cancer therapy approved ahead of expectations
World scientists unveil slew of new cancer treatments
Clarity on kidney cancer treatments