Expert Discusses Radiation Techniques, Genomic Testing in Prostate Cancer

James B. Yu, MD

Since the emergence of new data released in 2017, moderate hypofractionation has proven to be a quicker and efficacious method to administer radiation therapy to patients with prostate cancer.

The data with moderate hypofractionation from trials such as CHHiP, PROFIT, and RTOG 0415 have been compelling; guidelines from ASCO, the American Society for Radiation Oncology (ASTRO), and the American Urological Association (AUA) will soon support the use of hypofractionation in patients with prostate cancer.

In addition to moderate hypofractionation, using a hydrogel spacer has become a popular choice for prostate radiotherapy, says James B. Yu, MD. This technique has demonstrated an improved quality of life (QOL) for patients undergoing treatment for their prostate cancer, he says.

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Yu, associate professor of therapeutic oncology, and director, Prostate and Genitourinary Cancer Radiotherapy Program at Yale Cancer Center, discussed these techniques, potential roadblocks, and the importance of genomic testing in a recent interview with OncLive.Yu: The hydrogel spacer was an emerging standard last year and has spread rapidly, making it a current standard for prostate radiotherapy to space the rectum away from the prostate. Randomized studies have shown a QOL benefit for not only bowel toxicity, but also urinary and sexual toxicity.

What are some emerging techniques that seem promising?

The other standard is moderate hypofractionation. Last year, we spoke about it as an emerging standard. Although there has not been more evidence, I have a feeling that as more people start using it and get comfortable with moderate hypofractionation, it will be an excellent option for patients. Three major large randomized studies have shown that it is equivalent to standard fractionation for intermediate- and low-risk disease. Emerging standards are moderate hypofractionation, which is being investigated in the postoperative setting in the NRG GU003 study. That is accruing rapidly and is very promising; I am looking forward to seeing the results of that.

The emerging genomic tests may help differentiate between patients who need postoperative radiation versus those who would not benefit from that. The data for that are strong, and we are using genomic tests more and more to help us with therapeutic decisions. We are also beginning to bring genomic tests into the treatment intensification arena. There was an excellent study out of the University of Michigan on a clinical genomic classifier for prostate cancer rather than just a clinical classifier. [The investigators] incorporated the Decipher prostate cancer test with NCCN criteria and came up with a combined clinical genomic risk. It was very well done and is potentially practice changing.

You mentioned genomic testing. Can you expand on that?

There is also the concept of oligometastatic disease and our need to define what that is—as well as the use of molecular imaging to help detect metastatic disease that may be occult by standard imaging. We as a field are moving very rapidly in the direction of aggressively treating oligometastatic disease once it has been defined, and potentially curing patients that we previously thought were incurable. The testing that I am talking about is not germline, but testing of the tumor tissue itself. We should all be treating in a multidisciplinary way because genomic testing of the tumor tissue itself has implications for medical oncologists, surgeons, and radiation oncologists.

There are also implications for germline testing—which is testing the patients’ underlying genetics, rather than the tumor. There is a potential “can of worms” that could be opened by discussing that. There also is referral to a genetic counselor. If you are lucky enough, like I am, to have a group that does genetic testing that incorporates counselors, you should refer your patients there if you suspect that they need germline testing.

Are there any roadblocks to implementing these techniques?

Then the question is, “What do you do with that germline data once you get them?” I don't know the answer as a radiation oncologist. We think about multidisciplinary care as the radiologists, tumor board, pathologist, medical oncologist, surgical oncologist, and radiation oncologist, but we should also include a genetic counselor to that mix.When I talk about these new emerging technologies, a roadblock is always whether they get paid for by insurance or not. Typically, emerging therapies don't have a ton of comparative effectiveness data supporting them, simply because they are emerging. The question is, “What do you do for that?” Some people in the field are advocating for something called “coverage with evidence generation,” where insurance companies, Medicare, and Medicaid, will reimburse patients and pay for these new and emerging technologies as long they are being used for evidence generation in a clinical trial or prospective registry.

What do you hope that physicians take away from these advancements occurring in the radiation space?

The hard thing in medicine, a lot of the time, is getting people to pay for something you believe in, but that there isn't a lot of evidence for. The answer to that is that you have to create the evidence as you go along. You can't just say, "I believe it. It works. Let's just do it." Those days are over. Good clinical trials and prospective registries, or retrospective comparative effectiveness studies, would be very helpful. I try to be very forward thinking. I hope that they take away the notion that things are changing very rapidly, and that they need to learn about these genomic tests, molecular imaging, and this concept of oligometastases. These are 3 areas that practicing radiation oncologists have not had a lot of time to look at since they are so inundated with the “nitty gritty” of radiation treatment. But these things are coming, and we are going to be talking about them more and more in the years to come.