Researchers Aim to Further Enhance Value of RT in Prostate Cancer

Seungtaek L. Choi, MD

Researchers have long debated whether surgery or radiation therapy (RT) is a more beneficial treatment method for locally advanced prostate cancer. Seungtaek L. Choi, MD, says both are good options, but that there are definitely some patients who are more likely to benefit from RT, and researchers are exploring new approaches to enhance the benefit of the treatment.

“We are trying to figure out how to give RT better,” says Choi, an assistant professor in the Department of Radiation Oncology, and clinical Medical Director, Department of Genitourinary Medical Oncology, Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center. “More and more physicians are giving stereotactic body radiation therapy (SBRT) in the high-risk and maybe the locally advanced prostate cancer population, although that’s difficult because as soon as you need to treat more outside the prostate with these high doses, you might be increasing the risk of side effects, too.”

Combination approaches are also being explored to enhance the impact of RT, including regimens adding RT to chemotherapy, targeted therapy, and immunotherapy.

In an interview during the 2017 OncLive^® State of the Science Summit on Genitourinary Cancers, Choi discussed the latest developments with RT in prostate cancer.

OncLive: What were the highlights of your discussion on RT in prostate cancer?

Choi: The main points would be that RT is an effective method for treatment for these locally advanced cancers. These patients tend to have poorer outcomes. When you look at RT, we are getting better in terms of improving the treatments with better techniques as well as a lower risk of side effects. We still have a ways to go, but we are definitely trying to improve things by improving our treatment.

How have you seen RT evolve over the years and make a mark in this disease?

The biggest change I have seen is that the treatments have evolved to have more doses to the prostate or to the cancer. There is definitely less dose to the rectum and the bladder and I’m seeing a decreased risk of side effects.

That is what we see first. Unfortunately, with prostate cancer, it takes us a long time to see the actual cure rate. For RT, we have to wait at least 5 to 7 years to make sure we really cured the patients. However, the side effects often occur in the first 2 to 5 years, so you sort of see the side effects first and then you see the effect on the cure rate.

We have seen less rectal and bladder irritation. The risk of urinary incontinence with RT is very low—it’s usually less than 1%.

Overall, the patients have done very well. Now, we are beginning to see the patients are also cured of their cancer with very low prostate-specific antigen (PSA). When I started doing this almost 11 years ago, the PSA almost never went to 0 with RT. With surgery, you see the PSA goes to 0. With RT, it comes near baseline, but now with the higher-dose and more accurate RT delivery, the PSA is going to 0. We are doing a good job of eradicating the cancer in the prostate.

What are the considering factors for patients to receive RT for their prostate cancer?

I get that a lot. Patients often ask me, “Which treatment should I get?” Unfortunately, a lot of the patients have multiple choices. In fact, I always tell patients, “I have good news and bad news. The good news is that you have a lot of good options; the bad news is that you have to pick which one.”

However, for most patients, both surgery and RT are good options with a very high chance for cure and low risk for side effects. However, there are definitely some patients who are more likely to benefit from RT. These are the ones who have medical problems—so patients with heart disease or risk over anesthesia or surgery itself. Some other patients who might benefit better are the ones who have very aggressive disease that they might undergo RT anyway even if they had surgery. It is controversial whether RT by itself is [less effective] than RT plus surgery.

We are getting into an era of when we start talking about multimodality therapy— where we need surgery followed by RT to get the best cure rate. I am not completely sure that you need that surgery; RT by itself might be fine. In the end, in some patients, RT might be better to cover the area outside of the prostate without needing surgery.

There are some side effects that some patients want to avoid. Urinary incontinence is a risk factor with surgery and is not with RT. People say RT can cause incontinence, too, but in modern day it is very uncommon. In my practice, it is less than 1%, which means that it’s not really an issue. If that is the side effect they most want to avoid, than RT is better than surgery.

Are there any combinations with RT being explored currently?

In terms of multiple modalities, especially for locally advanced prostate cancer, you do need some combinations, such as RT with hormone therapy, for instance. The classic or standard treatment would be long-term hormone therapy defined as 24 months or longer—sometimes, even as long as 36 months. That uses the classic medication for hormone therapy, the GnRH agonist leuprolide (Lupron). We are starting to think, however, that there are more effective agents out there, such as degarelix (Firmagon).

There are some new agents, such as abiraterone acetate (Zytiga) or enzalutamide (Xtandi). Those might give more of a benefit when you add it to RT. Obviously, you have chemotherapy agents, and we are also looking at the possibility of combining RT with immunotherapy agents. I’m not sure if it’s going to be as effective in prostate cancer as we’re seeing in bladder cancer. However, it’s worth a try.

If you’re going to do RT with immunotherapy, we’re sort of looking at SBRT. That is giving a high dosage per treatment to see if that would increase the immune response that the body produces to increase the effect of the immunotherapy agents. It is all being looked at right now.

We’re actually going to start doing studies on those combinations and I am sure there are other groups doing the same, so hopefully, in a couple of years, we will have the answer.

What other studies in RT for prostate cancer do you find particularly interesting?

The most exciting trial is the ProtecT trial because that really randomized patients to RT and surgery, which we’ve never been able to do before. I was very impressed that they got that trial done. I’m a little bit biased because I’m a radiation oncologist, but the trial did show similar outcomes between surgery and RT. The survival was the same, including both overall survival and prostate cancer-specific survival.

What is really exciting is when you look at the second publication looking at the quality of life that is reported by patients, they seem to do better with RT. It was a final answer to the question of whether surgery or RT is better.

The other things we are looking at are how to combine or make RT better, in terms of both giving higher-dose RT, or adding brachytherapy or SBRT to the prostate in addition to the RT we give normally to the prostate. This will give a higher chance for cure. Once again, adding additional systemic therapy or newer agents is kind of exciting. Immunotherapy is really the buzzword right now.

What do you hope community oncologists learned from your lecture?

Locally advanced prostate cancer is aggressive, but it’s still curable. If you look at older results, the cure rate has been 75%. It can be better, but even with the older technology, it was 75%; therefore, it’s still curable and we should be aggressive. There is definitely room for improvement and the question still is, do you do RT or surgery? They are both good options for these patients, but at the same time, you have to tell a patient that they may require multiple treatments—such as both surgery and RT or RT and hormonal therapy, to get a cure. But, it’s still a highly curable cancer.