Dr. Jayram highlights the latest developments in bladder cancer care

In an interview during the 2023 LUGPA Annual Meeting, Gautam Jayram, MD, highlighted the latest cutting-edge developments in the treatment of patients with bladder cancer. Jayram is codirector of the Advanced Therapeutics Center at Urology Associates of Nashville in Tennessee.

Could you provide an overview of the goal of the presentation you gave at the 2023 LUGPA Annual Meeting on the facets of a successful bladder cancer program?

Many new drugs and new clinical trials are directed toward patients who are BCG unresponsive. However, there are 4 [treatment] options at this point: pembrolizumab [Keytruda]; gemcitabine/docetaxel doublet chemotherapy; nadofaragene firadenovec-vncg [Adstiladrin], which is a new option; and clinical trials, which remain an important part of this.

What’s happening in bladder cancer is somewhat similar to what was happening with prostate cancer 10 years ago, in that there’s so much out there now, in terms of new drugs, clinical trials, and diagnostics. The goal of the program was to educate our partnership on what “good” looks like. What does “good” look like in terms of diagnostics and therapeutics? [I emphasized] the importance of having a program, a centralized structure, and a couple high-volume experienced physicians in bladder cancer manage most of this work, because it’s complicated work, and bladder cancer is dangerous.

How does TURBT fit into the bladder cancer treatment paradigm?

As many new [therapies] as there are in [the paradigm], the fundamental message [regarding optimal treatment strategies] is still the same [as it has been in the past]. A good TURBT can shape a patient’s [outcome] with this disease. Our panel discussed before the session that we didn’t want to just [highlight] all these new [therapies] coming. That was part of [the goal of the presentation]. However, the fundamental message to take home for a lot of urologists is still the importance of good surgery, timely surgery, and guideline-based surgery in helping these patients get through their disease.

What treatment approaches exist for patients with Bacillus Calmette-Guérin (BCG)–unresponsive disease?

Many new drugs and new clinical trials are directed toward patients who are BCG unresponsive. However, there are 4 [treatment] options at this point: pembrolizumab [Keytruda]; gemcitabine/docetaxel doublet chemotherapy; nadofaragene firadenovec-vncg [Adstiladrin], which is a new option; and clinical trials, which remain an important part of this. [We discussed] all 4 of those options. They all have their relative pros and cons, but it was important for our partnership to understand what’s available.

What immunotherapy approaches have made their way into the paradigm?

For urologists, the [treatment option] that is important to understand is the indication for pembrolizumab in BCG-unresponsive, [high-risk, non­–muscle invasive bladder cancer with] carcinoma in situ.¹ That indication has been around [since January 2020] and is [an agent] to discuss with patients who are candidates. [Immunotherapy may also be used] post-cystectomy. After you remove a patient’s bladder, [you could potentially give them] an immuno-oncologic agent that can decrease their risk of recurrence if they’re at high risk.

There are also new data indicating that immunotherapy will now be part of the treatment for patients with metastatic disease in the first line, meaning some of these patients may not have to undergo chemotherapy. All of those [approaches] are exciting. Probably the first couple [indications] I mentioned are the most relevant to urologists.

What advice do you have for identifying and mitigating immune-related adverse effects (AEs)?

[Immunotherapy is] new for urologists. We’re not used to dealing with these types of agents. [We discussed the benefits of] implementing a structured program to monitor and manage AEs. You can do this yourself for the right patients, but you don’t need to, and probably not everybody should. However, if you don’t, you should be aware of the AE profiles [of immunotherapy agents], because you’re almost certainly going to encounter a patient who is on these treatments.

[Immunotherapy is] a pro-inflammatory treatment. It generates inflammation in any organ system. The most common [immune-related AEs] we discussed were rash, diarrhea, and cough. Those tend to [arise within a specific period] after starting the treatment. However, more severe AEs can develop. Although the AEs should not completely scare you away from giving these drugs; they certainly need to be discussed through proper patient education. If you’re going to develop a [bladder cancer] program, you need to discuss with your team that small AEs can become big AEs and that you need to monitor these.

What advances in bladder cancer treatment are on the horizon?

Four categories of clinical trial agents are being studied. The pretzel is an interesting device that you put into the bladder that [exudes] medicine and maximizes contact time with the bladder. Photodynamic therapy is basically light therapy to the bladder. There are combination treatments, where you have combinations of BCG and potentially immunotherapy or systemic agents. There is also the category of gene therapy, [which includes treatments similar to] nadofaragene firadenovec, [that generate] inflammation in the bladder. Those are 4 categories of [treatments] being studied in clinical trials. They are all interesting.

What is the importance of continuing to enroll patients to these clinical trials and encouraging community oncologists to find appropriate studies that patients may qualify for?

I’m passionate about clinical trials in bladder cancer. They can make a difference for patients, especially when the alternative is having their bladder removed and having a major, life-altering surgery. There has been a lot of movement in community urology within clinical trials. Approximately one-third of big [urology] groups have a clinical trials program. I’m a big advocate for clinical trials. They expand the menu of [treatments] you can offer [to patients]. You can give patients the opportunity to be involved with treatments that will become standard of care down the road; I’m a big proponent of that. If you have a big [urology] group with a lot of resources and patients, which most of us do, then you should strongly consider developing a trials program.

References

1. FDA approves pembrolizumab for BCG-unresponsive, high-risk non-muscle invasive bladder cancer. FDA. January 8, 2023. Accessed November 3, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-bcg-unresponsive-high-risk-non-muscle-invasive-bladder-cancer