Eric A. Singer, MD, MA, FACS, an expert urologic oncologist, discusses the use of Bacillus Calmette-Guerin (BCG) as a first-line therapy for non-muscle-invasive bladder cancer (NMIBC), and reviews subsequent treatment options for patients with high-risk NMIBC who are found to be unresponsive to BCG.
Eric A. Singer, MD, MA, FACS: My name is Eric Singer. I’m a urologic oncologist at The Ohio State University Comprehensive Cancer Center, James Cancer Hospital and Solove Research Institute in Columbus.
The use of BCG [Bacillus Calmette-Guerin] in bladder cancer is a great [topic]. BCG has been a mainstay of high-grade, non-muscle-invasive bladder cancer treatment for decades. The goal of using BCG intravesical treatment, meaning medicine that goes inside the bladder, is two-fold: to reduce the risk of recurrence, having someone’s bladder cancer come back, and to reduce the risk of progression, [which is] to have someone’s non-muscle-invasive bladder cancer get worse or become muscle invasive bladder cancer. We’ve been using that for a very long time. Of course, we want to try to continue to advance and come up with new and better treatments, so many investigators have been looking at things to add to BCG or to use after BCG is no longer effective.
Unfortunately, we don’t know how to predict responsiveness to BCG. We don’t have a great biomarker to say this patient will have a good response to BCG and this patient won’t. Usually our approach is to treat pretty much all patients [who have] high-grade non-muscle-invasive bladder cancer with BCG. It’s an induction course, meaning it’s given once a week for 6 weeks, and then we often do maintenance [doses] for several years. Many patients, fortunately, have a good response to BCG and don’t have additional recurrences, but unfortunately many patients do. Then what comes next can often be a challenging question in terms of what we should do to treat them.
For patients who are unresponsive to BCG, we have sometimes-challenging discussions, which include [deciding] do we try to give you additional medicines, whether they go inside the bladder, or one or in combination with other medicines? Or do we think about doing what’s called a radical cystectomy, where we would remove the person’s bladder, potentially some other organs as well, such as the prostate in men, and then do some type of urinary diversion? The way they hold and eliminate urine is going to be very different forever.
As you can imagine, many patients are not eager to give up the bladder they were born with. They’ve gotten quite used to having it and want to continue to use it, so patients are often very motivated, and we’re motivated as well, to try to keep using other treatments to try to delay cystectomy. But we do need to be careful that we don’t miss the window of being able to cure them and end up with them having more advanced disease through progression and having the cancer potentially spread someplace else. So we need to be careful when we’re looking at that therapeutic window in terms of using additional therapies vs going to surgery.
For patients who’ve had 1 or 2 induction courses of BCG, we’re often then thinking about other things. The KEYNOTE-057 study, which was published a couple of years ago, showed that giving patients systemic pembrolizumab, so not just inside the bladder, but through the IV, or intravenous, it goes all throughout the body and was beneficial. That drug ended up being approved by the Food and Drug Administration and is now approved and used. Other medicines that can also be considered include using different intravesical chemotherapy. BCG works through the immune system, but different chemotherapies like gemcitabine, docetaxel, mitomycin C, and valrubicin can also be used. Again, these are all intravesical chemotherapy, so medicine that’s given inside the bladder to try to kill bladder cancer and keep it from coming back or getting worse.
In terms of defining [eligibility for radical cystectomy], it’s going to be sort of a tough thing to do. Fortunately, we’ve gotten much better at the operation. It is still a morbid operation. Somewhere around 50% or more of patients who have it will have some kind of complication. Fortunately, these days, those complications are usually very manageable, but there are some patients every year who will die in the postoperative phase, the first 90 days after their radical cystectomy. So it is a serious operation, a big operation, and a morbid operation that can have a lot of adverse effects.
What I advise all patients, just like I’d advise my family, is if you’re thinking about having major surgery, go to a high-volume surgeon at a high-volume center, and do the surgery the way they do it. If it’s an open surgery with an open surgeon, go ahead and do that. If it’s someone who does a lot of robotic surgery and they feel very comfortable with their robotic skills and their robotic outcomes, I’m totally fine with that as well. For the patient population we’re talking about, ideally, it is still non-muscle-invasive bladder cancer, and the surgery would be done because they keep having recurrence and they want to avoid the potential problem of eventually getting muscle-invasive disease. That’s when we would begin to see a risk of metastasis develop as well.
I would say patient preference is going to play very heavily here. Again, we want to try to find something that is both going to be efficacious and also meet patient goals and expectations about what we’re doing. So on one hand, we may have patients who are very tired of having the frequent cystoscopies and other tests, and say, “Go ahead and do a radical cystectomy. I want a continent diversion,” meaning they would have a neobladder and would still urinate through their urethra. Other patients say they want everything possible [to be] done and they do not want to ever lose their bladder. [Those are] sort of the 2 ends of the extremes there; many patients fall in between. Again, we’re trying to make sure we’re doing things that are helping [patients] achieve their goals, but also not waiting so long that potentially something bad could end up happening in terms of disease progression. This is where it’s very important for patients to seek second opinions, to be very comfortable with their surgeons, to be working with a surgeon who understands the patient’s goals and values, and to be at a high-volume center with high-volume surgeons, so you can make sure you’re going to have the best outcome.
Transcript edited for clarity.