Brock O'Neil, MD
Better biomarkers are needed to identify which patients with localized bladder cancer are best to receive neoadjuvant chemotherapy, a treatment that is still not widespread in the community due to toxicity, explained Brock O’Neil, MD. “We need to push hard on [finding] the patients we know are going to benefit,” said O’Neil, an assistant professor in the Division of Urology at the University of Utah School of Medicine.
Beyond cisplatin-based chemotherapy, he added, researchers are beginning to explore immunotherapy in the neoadjuvant setting. Even more of a challenge is implementing adjuvant therapy into these patients with bladder cancer, which is largely due to poor accrual to clinical trials.
In an interview with O’Neil during the 2018 OncLive®
State of the Science Summit™ on Genitourinary Cancers, he shed light on the struggles with treating localized bladder cancer in both the neoadjuvant and adjuvant settings, as well as the advancements with robotic cystectomy.
OncLive: What is the standard of care for muscleinvasive bladder cancer?
In contrast to some of the other topics [discussed at this meeting], it hasn’t changed a lot recently. The data that we are going off of are really 20 years old now, which demonstrates that neoadjuvant therapy with cisplatin-based chemotherapy should be offered to all patients undergoing cystectomy. Some of the important issues with it are that we don’t do a very good job as a profession; urologists especially are highly to blame for that. We don’t do as much neoadjuvant chemotherapy as we should be doing. It is getting better, but we still have a lot to do.
Other issues are that neoadjuvant chemotherapy isn’t tolerated by everybody, especially [by] patients with bladder cancer. We run into a lot of issues with renal insufficiency; those patients are not cisplatin candidates. The clear message that we run into in the community is that there are patients who are not qualifying for cisplatin-based chemotherapy, and they end up getting carboplatin. And, we know that is a much inferior approach.
The last couple of things that we are very hopeful about is getting new markers. That will help us identify who is going to benefit from neoadjuvant chemotherapy. The benefit is relatively small to modest; that is a small survival benefit at 5 years. If we can identify patients who are less likely to benefit from that, and can move on to timely cystectomy, that would be highly beneficial.
Have biomarkers been identified?
There are a number of markers that have retrospectively been identified. There are some commercially available ones, in fact, but nothing that has been prospectively validated that has established that. There are some things that are close. One is the COXEN trial that we participated in, but results aren’t back yet. We are hopeful that will give some signals on whether this is truly a predictive marker, which will help us make these decisions. It is kind of a task among some commercial entities to try and identify prospectively some markers. As a urologic oncologist, I can’t wait for that. We are very anxiously waiting that time.
Why has there been a challenge with widespread neoadjuvant chemotherapy?
One is that the chemotherapy regimen is reasonably toxic. It is certainly not the worst out there, but it’s rough on patients. Second, we know that getting patients to timely cystectomy is really critical in terms of improving outcomes. There is a feeling that offering chemotherapy to a patient that is toxic has some benefit, [a] 5% survival benefit depending on your “glass half full, half empty” kind of view. It could be a lot or might not be. Then, we say, “Well, is that really what I want to give to my patient upfront or can I do it after surgery?” The trials have been challenging to do in the adjuvant setting, so we don’t know if there is a benefit there.
Can you expand on the state of adjuvant therapy?
There are several trials that were unsuccessful and failed due to lack of accrual. The big problem was that cystectomy is a very morbid procedure and all of the trials have a certain window in which the patients need to get enrolled on adjuvant therapy. There are a lot of challenges to get patients onto that after dealing with postsurgical complications. The trials [had very] poor accrual and eventually closed.