Expert Addresses Advances and Challenges in Bladder Cancer

Mark Tyson, MD

Developments in perioperative, systemic, and immune therapies have enriched the localized bladder cancer landscape. And with more options for management, urologists must learn how to integrate these therapies, yet also know when to ask for help from medical oncologists, says Mark Tyson, MD.

In a presentation during the 2018 OncLive^® State of the Science Summit™ on Genitourinary Cancers, Tyson spoke on some of the recent data with these modalities, as well as what is on the horizon. He also touched upon the trial use of the Decipher^® Bladder Cancer Classifier (Decipher Bladder), a technology that can be used to inform treatment.

There have also been recent regulatory advances with respect to bladder cancer detection. In February 2018, the FDA approved an expansion to the label for Blue Light Cystoscopy with Cysview for surveillance of bladder cancer. This now includes use in the outpatient setting to detect the recurrence of bladder cancer using a flexible cystoscope.

OncLive: Please provide an overview of your presentation.

In an interview during the meeting, Tyson, a urologic oncologist at Mayo Clinic, discussed the management of localized advanced bladder cancer, the promise of immunotherapy, and his advice for urologists treating patients with bladder cancer. Tyson: There are a lot of exciting developments in the muscle-invasive bladder (MIBC) cancer space in the last few years. We have been giving neoadjuvant chemotherapy for a while now. One of the 2 trials I reviewed in the talk was the Medical Research Council trial that showed the benefit for 3 cycles of cisplatin, methotrexate, and vinblastine (CMV) in the neoadjuvant setting for patients receiving radiation plus surgery. There were some issues with that trial that led some to believe that the data might not be that compelling. For example, most people suggest that there should have been a benefit of 10% for it to be clinically meaningful, and at 8 years, the trial is deemed significant at 6%.

We also reviewed the SWOG 8710 trial, which was much more compelling. It was just in the surgical subset looking at methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC). The survival benefit in that trial was quite impressive at 31 months for those who received neoadjuvant chemotherapy; those in the T3 subset were also the big benefiters, with a survival benefit of almost 40 months. We do think there is a beneficial effect to neoadjuvant chemotherapy—which chemotherapy agents and for how many cycles are questions that we don't have answers to yet. In some urologists’ minds, it is still a matter of debate whether the benefit is worth toxicity, particularly with MVAC.

Some of the most exciting data that are on the frontier are from The Cancer Genome Atlas and The University of Texas MD Anderson Cancer Center. We are starting to understand the molecular phenotypes of these tumors and guide therapy on an individual basis. We are not there yet. We can't say, "This patient should get neoadjuvant chemotherapy and this patient shouldn't," but we do have an idea of who will respond.

What are other important methods of surveillance in ensuring the best perioperative care for patients?

We also reviewed our experience of using Decipher Bladder. We aren't using it in everybody, but we are using it on a trial basis in patients who cannot tolerate chemotherapy. If they are found to have a luminal subtype, then we can direct them to surgery and stop after 2 cycles.Blue Light Cystoscopy has been used in Europe for well over a decade in patients with non-muscle invasive bladder cancer (NMIBC), and for a number of years it was approved for use in the operating room. It was used in patients with suspicion of carcinoma in situ or positive cytologies, and it is beneficial in those populations. Developments with blue light were published recently with respect to office use and repeat use. More people are going to start using it, at least in the operating room, based on these data.

Other than that, most people just follow the guidelines. There is cystoscopy, and then we have used narrow band imaging for a while. The workflow for that is much better, as it does not require a catheter and installation. Narrow band imaging is fairly good, and the data supporting it are fairly good, too. They are maybe not as compelling as Blue Light Cystoscopy, but it’s helpful, at least in terms of workflow in the clinic. In the operating room, if you have a patient who has a positive cytology with no obvious source, or is a first-time diagnosis, it may be beneficial in those populations.

What advice would you give to your fellow urologists treating patients with MIBC?

Will the recent developments of immunotherapy and chemotherapy alter the role of surgery for bladder cancer? Localized bladder cancer comes in 2 forms: NMIBC and MIBC. We are enrolling in SWOG 1605. For patients with Bacillus Calmette-Guerin refractory NMIBC who are not fit or refuse to undergo cystectomy, then atezolizumab (Tecentriq) may be an option. We will have to see what the results of that phase III trial show. In terms of neoadjuvant immunotherapy, I don't think we have any trials open, but I do know that they are using checkpoint inhibitors in cisplatin-ineligible patients or for those who progress on cisplatin. For every patient with MIBC who has a good performance status and has no other obvious contraindication, they should meet with a medical oncologist in some sort of multidisciplinary setting. That is what I would encourage urologists to say. If you don't have a medical oncologist on site, find someone who you can refer to or get an opinion from, and create a good relationship with them so that they will work in your patients the same day or the next day, and then things can get started quickly. If the patient just gets a urologist’s opinion, they might not be getting all the information that they need to make an informed decision. It is important for a new patient with MIBC to see both a urologist and medical oncologist.