Knowing Benefits, Risks of Bladder-Conserving Therapies in Bladder Cancer

For patients with lower- to intermediate-risk non-muscle-invasive bladder cancer, bladder-conserving treatments may be a considerable option, an expert told CURE®.

Non-muscle-invasive bladder cancer is when the tumor has not grown into the muscle layer, which may indicate an earlier stage of cancer, the American Cancer Society defines. Bladder-conserving treatments are treatments that maintain the bladder without physical alterations, such as surgery.

So, receiving treatments, such as immunotherapies or chemotherapies can be helpful, said Dr. Bogdana Schmidt, urologic surgeon at the Huntsman Cancer Institute at the University of Utah.

CURE® spoke with Schmidt about bladder-conserving treatments, patients who would benefit from this treatment, its comparison to invasive treatment and more.

LEARN MORE: Differentiating Muscle-Invasive, Non-Muscle-Invasive Bladder Cancer

CURE®: What are the risk categories for bladder cancer and how might bladder-conserving treatments play a role?

Schmidt: Non-muscle-invasive bladder cancer can be separated out into different risk categories. There’s low risk, intermediate risk and high risk. For the lower-risk patients, I generally think of them as more nuisance tumors where there’s a lot of effort on the part of the patient, where they have to come in get monitored often need additional tumor scrapings to treat the cancer, but very few of those patients progress to have deadly muscle-invasive disease.

The bulk of treatment in those patients is bladder-conserving … [and] lot of intravesical treatment (therapy administered directly into the bladder), so different immunotherapies or chemotherapies that are instilled in bladder to reduce tumor recurrence and progression (worsening or spreading).

Intermediate-risk [disease] is a mix with the higher-risk features. But [clinicians] still really want to focus on bladder-preserving treatments, so predominantly intravesical chemotherapy and sometimes intravesical immunotherapy. It’s a very exciting time right now with lots of clinical trials in the space, but those are the mainstays.

For high-risk, non-muscle-invasive cancers, those are the patients where we worry about them progressing to muscle-invasive disease or metastatic disease. For those patients, we often start by offering some intravesical bladder-preserving treatments. But know that if the first line of treatment doesn’t work, the gold standard and the standard of care is usually radical cystectomy (surgical removal of the whole bladder) in those patients.

So right now, there are clinical trials in the space where we are moving past the front line of intravesical Bacillus Calmette-Guerin (BCG; an intravesical vaccine to treat early-stage bladder cancer), which is the mainstay of treatments in the high-risk non-muscle-invasive bladder cancer space. These are the patients where we have to be much more careful about because their risk of progressing to advanced disease is a lot higher. So, there are a lot of conversations and tradeoffs and how many rounds of additional treatment we’re willing to go through to try and salvage this bladder to allow the patient to keep their bladder, which of course is very important, but balancing that with not missing an opportunity to cure a cancer.

How do doctors identify who may be eligible for bladder-conserving treatment and who may not be?

There are a lot of individual cancer characteristics that we look at there. Patients with higher-risk tumors — so lots of larger tumors —are at higher risk for recurrence. Patients who have variant histology, meaning they do not have typical urothelial carcinoma, which is the most common type of bladder cancer, often end up showing progression much faster and more aggressively, and they end up not been the best candidates for bladder-preserving treatments.

In general, I think of younger, healthier patients. They have the most to lose if this cancer becomes deadly quickly. And so, on one hand, obviously younger patients really want to preserve their bladder because that’s what they want. But on the other hand, when I have a young patient with a very aggressive tumor, that’s when I’ll often insist on earlier cystectomy and one round of intravesical treatments — I feel like everybody deserves that. But if they progress on that, then I’ll usually encourage cystectomy earlier because I really worry about that patient dying from that disease and knowing that I have a window to cure them with surgery.

What’s the difference between bladder-conserving treatment versus invasive treatment?

When we talk about whole-bladder treatments, usually we’re talking about muscle-invasive disease or patients who had a recurrence after intravesical treatments. The gold standard is a radical cystectomy and that’s as invasive as it gets. It’s basically removing the whole bladder and if the patient is a male, doctors usually remove the prostate with it. For female patients, we try to preserve organs. It’s very uncommon for bladder cancer patients to have cancer extend to the uterus or ovaries. So, we try to preserve those for patients who have them. Occasionally, if the tumor is at the bottom of the bladder near the anterior vaginal wall, that’ll be taken for some patients who can preserve the entire vagina, which is great for sexual function and just preservation of the pelvic musculature preventing prolapse or other things that can happen.

Also, urinary diversion, because once the bladder is removed, something has to be equipped to store the urine in the body. This could be an incontinent diversion (an artificial opening in the abdominal wall for urine to pass through), or a colon pouch.

Trimodality therapy — or radiation therapy — is another possible treatment for bladder cancer, usually for muscle-invasive bladder cancer, and that involves a surgical removal of the bladder tumor, coupled with chemotherapy and radiation. There’s not a lot of data using trimodality therapy and non-muscle-invasive disease. So, we try to stay away from whole-bladder treatments for non-muscle-invasive disease.

How do bladder conserving treatments affect quality of life? Does it typically make it better or worse?

That’s a really tough question, but a very important one. On one hand, a lot of people’s concepts of quality of life is really tied to having their native bladder, so they feel like losing their bladder is a really huge adjustment for their quality of life. When it comes to non-muscle-invasive treatments, obviously the goal is to preserve the bladder. With that, the bladder often suffers because whatever treatments we put in the bladder can be quite irritating. And so, people can have dysuria, or burning with urination, painful urination, urgency, urinary frequency, some blood in the urine — all of those symptoms can be quite bothersome and certainly can impact the quality of life.

When we compare some of the newer treatments to our older treatments like BCG, we’re seeing some favorable profiles, meaning that a lot of the newer drugs are not worse than what we’re used to. With BCG, some are actually better-performing with less irritation on the bladder, but they all cause some amount of bladder discomfort based on the way they work. These drugs try to irritate the bladder, they’re trying to activate the immune system to basically attack cancer cells on the bladder. So, all of that comes with some amount of quality of life.

That becomes a trade off, because I have had patients who have been through BCG, whose bladder has been causing them so much pain with painful urination, frequency, urgency, where they are ready to move on to having their bladder removed. They’re done with the quality of life, and they can move on to having their bladder removed and have less pain, less discomfort, less thought about their bladder on a day-to-day basis.

Then, you have patients on the opposite end of the spectrum who say, “Well, you just can’t take my bladder. I will get up and pee every hour. I will wear a pad I will do everything, but don’t take my bladder out,” and I think that’s very personal and certainly depends on patients’ activities, their lifestyle and what’s important to them as part of their identity and their standard of life. That’s where shared decision making comes in. Every patient should be able to make those treatment decisions for themselves.

Transcription was edited for clarity and conciseness.

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