Expert Discusses Neoadjuvant Chemo, Cystectomy in Localized Bladder Cancer

Jonathan L. Wright, MD, MS, FACS

One of the ongoing challenges faced in localized muscle-invasive bladder cancer is determining whether or not patients are best suited for neoadjuvant chemotherapy, explained Jonathan L. Wright, MD, MS, FACS. He added that proper patient selection ultimately boils down to 2 things: disease stage and cisplatin eligibility.

“Over the past decade, we've seen a significant increase in the utilization of neoadjuvant chemotherapy,” said Wright. “We've seen the increase [in neoadjuvant chemotherapy] nationally, and we favor it for patients who are platinum-eligible.”

For those who are deemed ineligible for neoadjuvant chemotherapy, radical cystectomy is advised. Although some patients may benefit from bladder preservation, this approach should be recommended with caution, he explained.

OncLive: What factors should be considered when managing a patient with bladder cancer?

Which patients are appropriate to receive neoadjuvant chemotherapy?

Is cisplatin the preferred neoadjuvant chemotherapy?

How does your approach differ for patients who are ineligible for neoadjuvant chemotherapy?

Have approaches to radical cystectomy changed in recent years?

How do you decide who should undergo an open cystectomy versus a robotic cystectomy?

What should be emphasized about bladder conservation?

In an interview during the 2018 OncLive^® State of the Science Summit™ on Genitourinary Cancers, Wright, medical director of the University of Washington Medical Center Urology Clinic, associate professor of Urology at University of Washington, and affiliate investigator at the Fred Hutchinson Cancer Research Center, highlighted the available therapies for patients with localized muscle-invasive bladder cancer.Wright: First, [we should consider] whether or not a patient should receive neoadjuvant chemotherapy and if they are a candidate for chemotherapy. What are the appropriate choices for them? Second, [we need to look] at patients following radical cystectomy and determine the role of adjuvant chemotherapy [in these patients]. Finally, [we need to determine] who the appropriate patients are for bladder preservation and how we should recommend doing that.Ideally, we want a patient who is eligible for cisplatin with muscle-invasive or locally advanced T3, T4, and/or node-positive disease; that includes those who have adequate renal function and no significant hearing loss, peripheral neuropathy, etc. The main thing is to identify patients who are primarily eligible for cisplatin based on renal function, as that is the best treatment in the neoadjuvant setting.We looked at carboplatin, too. Although there is response, it is inferior and there's more disease progression in patients in the metastatic and neoadjuvant settings. We're now seeing immunotherapy come in with checkpoint inhibition both alone and also in combination with neoadjuvant chemotherapy. These studies are ongoing.If they’re not eligible for cisplatin-based neoadjuvant chemotherapy, we recommend upfront cystectomy. There are cases where we'll use alternative agents, but, in general, if they're not cisplatin eligible we prefer upfront cystectomy. The use of carboplatin is an inferior option for patients.Certainly—to date, more cystectomies are being done robotically. I do both robotic and open cystectomies. They are just 2 different ways to take out the bladder. Most importantly, they have similar oncologic efficacy.We have a lot of operating rooms (ORs) and only a few robots. If a patient needs to have surgery soon, I can get an OR, but I may not be able to get a robot. If they are ever going to get chemotherapy, and we can schedule it 4 months from now, it's easy to plan for a robot. It depends on what the availability is.I'm a urologist. I take out bladders for a living, but we greatly underutilize bladder preservation in appropriate patients. Bladder preservation consists of a combination of chemotherapy and radiation. Probably the majority of patients with muscle-invasive bladder cancer are not good candidates. If they have a solitary small lesion that can be completely resected, there is no extensive carcinoma in situ, there's no hydronephrosis, and they don't have significant bladder symptoms, then they may be [a candidate for bladder preservation].

What are some emerging therapies for these patients?

They may have very similar oncologic outcomes with bladder preservation as opposed to cystectomy. However, it does require close follow-up. Some of those patients will progress and need a cystectomy. Certainly, the surgery can be harder after radiation has been employed, but it's an underutilized area for the appropriate patient.Immunotherapy is a big part of bladder cancer today—–both upper tract and in the bladder; it's been used primarily upfront in the metastatic setting in patients who are ineligible for cisplatin and in those with recurrent disease. Now, we’re seeing [its use] more in clinical trials in the neoadjuvant setting and even in the nonmuscle-invasive setting. [Immunotherapy] will continue to have an important role. It has been an exciting breakthrough to have something new for our patients.

What is the biggest unmet need, and what steps are being taken to address it?

There are several agents that have been approved at different levels and there are more coming out. It's exciting because there are more options for patients. We're a little behind kidney cancer; that space has had much more of a rapid expansion of drugs, but [the bladder cancer is] very close behind. The next key is to figure out sequencing. It's an exciting time to be taking care of patients with urothelial cancer.From a clinical perspective, the biggest unmet need is determining who will respond to neoadjuvant chemotherapy. We know that it is associated with improved survival, but some patients aren't going to respond. We're focusing more on evaluating the tumor itself, the features of the tumor, and the gene expression.

Moreover, [we are also looking at] the host to see if they have specific mutations that might make them more or less sensitive to cisplatin. [That way we] can identify not only those patients who are more likely to respond, but those for whom we should avoid unnecessary treatment.

We also need to see more of a multidisciplinary approach used in the management of patients with bladder cancer. That involves not just urologists and medical oncologists, but also radiation oncologists. Additionally, [we need to work] on survivorship because bladder cancer is the most expensive cancer from diagnosis to death. There's a huge unmet need for patients and survivors, as well as for their families, to help cope with the disease and the after effects.