Sometimes numbers tell a story, but sometimes they obscure one. According to the latest figures from the National Cancer Institute, the death rate for people diagnosed with bladder cancer has hardly budged during the past 30 years. But experts who treat the disease tell a different and more hopeful tale—and they credit a surge in clinical trials for much of it. “In just the last five or six years, there has been quite a bit of work looking at new therapies for patients with bladder cancer, and we’re seeing unprecedented responses with some of these new drugs,” says Dr. Stephen A. Boorjian, professor and chair of the department of urology at Mayo Clinic in Rochester, Minn.
Some of the greatest advancements in bladder cancer treatment have involved a class of drugs called immune checkpoint inhibitors. They shift a person’s immune system activity in ways that help it fight cancer cells. “These have been paradigm-changing,” Boorjian says. “The way we treat bladder cancer is different than it was just five years ago.”
Others in his field tell a similar story. For people with both metastatic and nonmetastatic bladder cancers, the past half-decade has witnessed the introduction of dozens of promising new treatments. Some have been revolutionary, whereas others have led to incremental but important improvements in care. In every case, these advancements have depended on clinical trials and the people who take part in them.
“Clinical trials are how we got here,” says Dr. Guru Sonpavde, director of the bladder cancer program at Dana-Farber Cancer Institute and associate professor of medicine at Harvard Medical School in Boston. “All the new drugs we have coming out that have changed the outcomes for patients with bladder cancer—all of this has come from clinical trials.”
Clinical trials are carefully designed research studies, conducted in a medical setting, that help experts identify new or better ways to prevent, diagnose, or treat a disease. “Participating in a trial is often the only way to get access to new and promising drugs, or to therapeutic alternatives that may be better than standard of care,” Sonpavde explains.
Although pretty much every type of cancer is the subject of ongoing research, he says bladder cancer may be one of the hottest areas for clinical-trial work. Part of that is because of the prevalence of the cancer; bladder cancer is the sixth most common cancer in the U.S., with more than 80,000 new cases being diagnosed annually. But another factor is that, until recently, decades had passed without major breakthroughs in bladder cancer treatment. “We had some chemotherapies, but this was a cancer where we hadn’t seen many advances until about five years ago,” Sonpavde says.
Like Boorjian, he highlights the game-changing effect that immune checkpoint inhibitors have had on the treatment of bladder cancer. This and other advancements have led to an explosion in new research—and with it, a need for more people to participate in clinical trials.
Unfortunately, this need is not being met. “There are so many drugs and therapies being explored in this space that in some cases there hasn’t been enough patient participation to validate study results,” says Dr. Ashish Kamat, an endowed professor of urologic oncology and director of bladder cancer research at MD Anderson Cancer Center in Houston. “To obtain reliable results, trials need lots of patients, and until we have greater participation it’s going to be hard to move the needle as much as we’d like.”
How to find clinical trials
Part of the problem, Kamat says, is that a lot of people with bladder cancer may not be aware that they are eligible to take part in a clinical trial. Cancer doctors—especially those not affiliated with major research institutions—often fail to bring up these opportunities with their patients. “I’ve given educational talks to patient groups, and people have come up to me and said they had no idea this option existed,” he says. “In some cases they’ve ended up coming to Houston and participating.”
He recommends that patients broach the topic themselves; simply asking your doctor if clinical trials are worth exploring could be enough to get the ball rolling. Also, websites like ClinicalTrials.gov, which is maintained by the U.S. National Library of Medicine, provide up-to-date information about current research trials. You can easily search for clinical trials that are actively recruiting participants in your home state or city. Meanwhile, most major health systems and research institutions maintain their own patient-facing sites featuring clinical-trial information. For example, MD Anderson, Dana-Farber, and Mayo Clinic provide these online resources.
Not everyone with bladder cancer will be a good candidate for a clinical trial. For some, the current standard of care may provide the most effective treatment for the disease. “For a patient that has low-grade bladder cancer, a resection”—that is, surgical removal of the tumor—“has a very high cure rate,” Kamat says. “For this -patient, it may not be advisable to participate [in a trial] because the standard of care is so effective.”
On the other hand, the prognosis for those with metastatic bladder cancer—that is, a cancer that has spread to other parts of the body—may make the prospect of a trial more appealing. “Unfortunately for patients in this space, existing therapies aren’t providing durable long-term survival,” he says. Clinical trials may provide their best opportunity to beat the averages. They may also provide alternatives to invasive procedures. Kamat says that among those with non-muscle-invasive bladder cancer—a group that makes up about 75% to 80% of new bladder cancer -patients—some don’t respond well to the current drugs. These patients normally must have their bladders surgically removed. “This is a life-changing invasive procedure, and clinical trials may provide another option,” he says. Of course, every case is different and needs to be evaluated by a patient’s physician.
Some may be hesitant to sign up for what is essentially an experiment. But clinical trials are tightly regulated to ensure that those who participate are not exposed to undue risks. Dana-Farber’s Sonpavde says clinical trials are always built on a foundation of prior work that suggests the intervention—that is, the new treatment or other thing being studied—is at the very least not excessively risky compared with the current standard of care, and that there is evidence it may be beneficial. “Once a trial happens, you already have basic research showing the intervention is promising,” he says. There is always some element of risk. But with this risk comes the potential reward of gaining access to new and better cancer care, he says.
What it’s like to participate in a clinical trial
Let’s say you and your care team have identified a clinical trial that could be a good fit. You’ll next meet with someone affiliated with the trial who will make sure that you understand exactly what the experiment entails. You’ll get a thorough explanation of the study’s design, as well as any potential risks or drawbacks.
If you decide you want to proceed—that is, if you give your informed consent—you’ll likely undergo some type of screening process to ensure you meet the trial’s criteria. It may involve additional testing—scans, biopsies, blood tests—as well as an examination of your medical records. “Sometimes we start doing these evaluations and something comes out that renders the patient ineligible,” Sonpavde says. For example, the genetic makeup of your cancer may ultimately not fit the study guidelines, or you may be taking medications that would interfere with the treatment. But if screening goes well, you will likely begin the study soon—usually within one to three weeks.
It’s important to highlight that, in many clinical trials, some people do not get the new drug or novel treatment. In other words, they’re part of a “control” group that will help the study team assess whether the new intervention provides a benefit. “Generally, the trial will be comparing the new treatment to the standard-of-care treatment,” Sonpavde explains. In other words, even if you don’t get the new treatment, you’ll generally be no worse off than if you hadn’t enrolled.
Another benefit of participating in clinical research is that in some cases—whether you’re getting the new intervention or the control intervention—the cost of your treatment will be covered by the trial. Outside of a clinical-trial setting, some cutting-edge drugs would cost thousands of dollars—or they may not be accessible at all.
On the other hand, clinical trials usually will not cover the cost of lodging or transportation for those who participate. This can be a major barrier for those who don’t live in cities or near research institutions. Also, participants are typically not compensated.
What’s happening now
Almost every facet of bladder cancer is now the focus of clinical research. But several areas are the subject of particularly intense interest.
Boorjian says novel treatments for non-muscle-invasive bladder cancer are one of the most active areas of research. He recently led a trial that looked at something called adenoviral vector therapy. “This involves instilling the novel medication into the bladder to stimulate the immune system to attack the bladder cancer,” he says. His trial found promising results, and his group is now recruiting participants for some related trials. Meanwhile, Boorjian says a lot of current research is looking at new and improved ways to deliver effective treatments. For example, some trials are examining time-released delivery mechanisms for drugs, which may offer advantages over standard intravenous injections. “We’re looking at better ways to administer medications to minimize the risk of toxicity,” he says.
Another hot area of bladder cancer research is focusing on personalized therapies for metastatic cancers. These precision medicines can be directed at specific targets identified on tumors. Boorjian mentions some new classes of therapies that are designed to target specific genetic mutations within a person’s cancer cells. “We’re starting to target therapies to those tumors, and this is another move-the-field-forward change,” he says.
Changing the story
The National Cancer Institute estimates that this year alone, more than 80,000 people will be newly diagnosed with bladder cancer. More than 17,000 people with bladder cancer right now will not live to see 2023. Improving these figures will depend on clinical trials and the people who participate in them.
“The only way we make further advances is for patients to take part in this work,” Sonpavde says. Again, not everyone will be a good fit, and participating in a trial may present some risks. But you lose very little—and stand to gain a lot—by exploring your options with your care team.
September 3, 2022 at 05:18AM Markham Heid