In Prostate Cancer, Moderate Hypofractionation Could Be New Standard

James B. Yu, MD

A recent emergence of data is showcasing the efficacy of moderate hypofractionation as a quicker way to administer radiation therapy in patients with prostate cancer, compared with the conventional radiation treatment. The novel method, according to James B. Yu, MD, may very well be on its way to an adoption as the new standard of care.

However, he adds, many clinicians will likely wait a few more years for additional data to read out before making this switch in practice.

OncLive: Can you give an overview of your talk on current and emerging standards in radiation therapy for prostate cancer?

In an interview with OncLive during the 10th Annual Interdisciplinary Prostate Cancer Congress^®, Yu, associate professor of therapeutic oncology, and director, Prostate and Genitourinary Cancer Radiotherapy Program, at Yale Cancer Center, discussed the current data in support of using moderate hypofractionation in prostate cancer, as well as recent data showing how genomic testing can help with treatment decision making postoperatively.Yu: I talked about both current and emerging standards. Currently, the new standard with the most evidence behind it is something called moderate hypofractionation for prostate cancer. There’s been 3 randomized trials now showing that you can speed up the radiation treatment with equivalent cancer control.

What data has there been so far in support of moderate hypofractionation?

The other topics I talked about were proton radiation, high-dose rate brachytherapy, prostate rectum spacing using something called a hydrogel gel, and finally, I talked briefly about genomic tests and their ability to help with decision making postoperatively—whether you should give radiation or not.There have been multiple randomized trials. The key trials are what is called noninferiority trials, which are trials that are trying to show that this new treatment is not inferior to the control treatment. These noninferiority trials need a lot more patients [than usual], so kudos to them for finishing them.

The US studies, including RTOG 0415, which was presented by W. Robert Lee, MD, [during the 2016 Genitourinary Cancers Symposium] showed equivalent, noninferior cancer control, and basically equivalent side effects, and maybe a slight increase in moderate side effects.¹

In your opinion, will everyone adopt moderate hypofractionation as the new standard?

What did you discuss in terms of genomic tests and their ability to help with decision making postoperatively?

Recently, the PROFIT study came out, by Charles N. Catton, MD, and team, also showing the same thing that RTOG 0415 showed, with a slightly different fractionation scheme. Then the CHIPS study out of the United Kingdom also showed the same thing. Basically, everyone’s showing maybe a little more toxicity, acutely, mainly because you’re giving the radiation faster, but noninferior cancer control.Moderate hypofractionation will be adopted across the country to replace hypofractionation if there’s a couple more years of data. I think the comparison is with breast cancer where they took 8 to 10 years of follow-up, even sometimes 12 years of follow-up, before the community accepted this faster radiation treatment. It looks like it’s on the way. I think many academics are of the opinion that moderate hypofractionation is the new standard, but there’s always many academics and people in the community who I think will still wait for more data to accrue.I mentioned the University of Michigan’s PORTOS test and the Decipher test. The one with more data right now is Decipher. A paper that came out in the Journal of Clinical Oncology, the first author was Robert Den, MD, showed that this score can prognosticate about whether someone will benefit from radiation or not in the postoperative setting.² That’s a big deal because when we radiate people postoperatively, it’s a little bit of a gamble because we’re hoping that there is cancer in the treatment volume you’re radiating. If the cancer is away from what you’re radiating, no amount of radiation in the world is going to help because you’re not radiating in the right spot.

What would you say are the main takeaways from your presentation?

What else is important to highlight in radiation news?

I think what Den and his team’s data showed was that this genomic test can help you figure out if the disease is going to be in the area that you radiate, but also if it will respond to radiation. Hopefully, it will help the people who will benefit to get the treatment and the people who won’t benefit to think long and hard about whether they want to go through the treatment.The main takeaways from my talk are that moderate hypofractionation is coming and if it’s not already adopted in someone’s practice, in a couple more years I have a feeling it will be as more data comes out. Proton radiotherapy is also being rapidly adopted, although evidence is still being sought on whether it’s better than photon radiation therapy. There have been randomized trials showing that a rectal spacer, or hydrogel in between the rectum and prostate, improves a patient’s quality of life if they go through radiation treatment.The other big news this past year is the ProtecT study, which came out in the New England Journal of Medicine.³ The press, I think, picked up on the idea that there isn’t a huge survival difference, or no survival difference, between active surveillance and local therapy, such as surgery and radiation. I think a lot of radiation oncologists were very interested in the quality-of-life idea that also came out, showing that there’s better genitourinary and sexual function with 6 months of radiotherapy compared to surgery. That’s the first randomized data that we have comparing those 2 quality-of-life factors. GI function was worse for patients who underwent surgery. My response to that is that we now also have this randomized trial showing that a rectal spacer can decrease your gastrointestinal side effects almost 3-fold.

Those 2 randomized trials in combination, to me, say that radiation therapy is the quality-of-life choice, compared to surgery. I think the debate continues to rage about which treatment is ultimately better for patients, and usually it depends on which type of physician you are. I think that side of the PROTECT study has been underdiscussed outside of radiation circles and should be made aware to everybody.

References

1. Lee WR, Dignam JJ, Amin M, et al. NRG Oncology RTOG 0415: A randomized phase III non-inferiority study comparing two fractionation schedules in patients with low-risk prostate cancer. J Clin Oncol. 2016;34(suppl 2S; abstr 1).
2. Den RB, Yousefi K, Trabulsi EJ, et al. Genomic classifier identifies men with adverse pathology after radical prostatectomy who benefit from adjuvant radiation therapy. J Clin Oncol. 2015;33(8):944-951. doi: 10.1200/JCO.2014.59.0026.
3. Hamdy FC, Donovan JL, Lane A, et al. 10-year outcomes after monitoring, surgery, or radiotherapy for localized prostate cancer. N Engl J Med. 2016;375:1415-1424. doi: 10.1056/NEJMoa1606220.