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Immunotherapy Emerges as Alternative to Surgery in BCG-Refractory Bladder Cancer

Gina Columbus @ginacolumbusonc
Published: Tuesday, Oct 18, 2016

Kevin Chan, MD

Kevin Chan, MD

Surgical treatment of patients with non-muscle invasive bladder cancer can be considered a curative option, but the associated risk in comorbid patients is leading researchers to further explore the option of immunotherapy.

Kevin Chan, MD, an associate clinical professor in the division of Urology and Urologic Oncology, Department of Surgery, City of Hope, explains that for patients who are refractory to the immunotherapy bacillus Calmette-Guérin (BCG), are elderly, and have several comorbidities, receiving another immunotherapy—even if it has a lower response rate—may be a more effective choice.

Currently, the PD-L1 inhibitor atezolizumab (Tecentriq) is FDA approved for the treatment of patients with locally advanced or metastatic disease, based on results from the phase II IMvigor 210 study that showed an overall response rate (ORR) of 14.8% in patients with locally advanced or metastatic disease, regardless of PD-L1 expression. Among patients with PD-L1 expression ≥5%, the ORR was 26%.

In June 2016, nivolumab (Opdivo) was granted a breakthrough therapy designation as a potential therapy for patients with unresectable locally advanced or metastatic urothelial carcinoma who have progressed on a platinum-containing regimen.

In an interview with OncLive during the 2016 OncLive State of the Science Summit on GU Cancer, Chan discussed the latest updates in BCG-refractory non-muscle invasive bladder cancer and how to decide between surgery and an alternative approach.

OncLive: What are we seeing in the space of BCG-refractory non-muscle invasive bladder cancer?

Chan: This is a common and kind of historically big problem. This is a group of patients who can be cured with surgery, but the surgery is pretty morbid and carries a lot of risks. In general, this population is elderly and has a lot of comorbidities. We are always kind of searching for alternative treatments—something simpler that doesn’t require surgery that can hopefully at least prolong life.

However, the big dilemma is that we know that surgery is curative. With these other kind of alternative therapies that are not as effective, you’re risking progression of disease. Ultimately, you can lose that window of curability as you go down this alternative treatment road.

If surgery is curative, why isn’t it the optimal option?

It carries about a 60% to 70% complication rate. The average age of patients with a muscle invasive bladder cancer, a high-risk bladder cancer, is about 73. This is an elderly population. Many of them have heart disease and these are big operations that make this surgery somewhat risky. There are people who are not candidates for surgery, but you want to be able to offer them something. Then, there’s the group of patients who adamantly refuse surgery. They don’t want to lose their bladder, they’re scared of the surgery, and they’ll do anything else—even if it means a suboptimal treatment.

How do you determine if someone is a good candidate for surgery?

I don’t think there are a lot of things stopping us from doing surgery on these patients. It really is just informing patients of what the risks are. Many times, when they have these comorbidities, they will hear that and may not want to proceed. I don’t think there’s a lot of hesitation on the clinician’s side to recommend surgery. It is just kind of weighing risks and benefits. If a patient is at a high risk for surgery and has a high chance of dying on the table, then maybe these alternative therapies that can buy you 1, 2, or 3 years of time may be worth engaging in.

There’s a lot of risk for surgery. At what point do these risks outweigh the fact that a patient may be cured of bladder cancer?

[Patients undergo] a radical cystectomy and urinary diversion, which is taking out the bladder and making a new way to urinate using a piece of intestine. That carries with it typically anywhere from a 50% to 80% complication rate. These complications commonly include infection and bowel obstruction.

View Conference Coverage
Online CME Activities
TitleExpiration DateCME Credits
Community Practice Connections™: New Directions in Advanced Cutaneous Squamous Cell Carcinoma: Emerging Evidence of ImmunotherapyAug 13, 20191.5
Clinical Practice Connections™: New York Advanced Practice CollaborativeNov 15, 20191.25
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