Comparing RT Schedules in Prostate Ca

High doses of external-beam radiotherapy delivered in a very short fractionation schedule were as effective as conventional fractionation in controlling intermediate-risk prostate cancer, although early toxicity was more pronounced with the ultra-hypofractionated approach, the prospective Scandinavian HYPO-RT-PC study indicated.

At a median follow-up of 5 years (interquartile range of 3.1-7 years), failure-free survival rates were identical at 84% (95% CI 80%-87%) for patients treated with either approach, indicating that the ultra-hypofractionation regimen was non-inferior to conventional fractionation, at an adjusted hazard ratio of 1.002 (95% CI 0.758-1.325), Anders Widmark, MD, of Umea University in Sweden, and colleagues reported.

As shown in their study online in The Lancet, there was also no difference in overall survival at 5 years, with 94% of patients still alive in the ultra-hypofractionation group (95% CI 92%-96%) compared with 96% in the conventional fractional group (95% CI 95%-98%).

However, the frequency of acute grade 2 or worse urinary toxicity was higher at the end of the treatment schedule at 28% in the ultra-fractionation group compared with 23% in the conventional fractionation group.

"To our knowledge, the present study is the first randomized trial to report on the efficacy and side effects of ultra-hypofractionation compared with convention fractionation for prostate cancer," Widmark and colleagues observed. "Introduction of ultra-hypofractionation with image-guided radiotherapy techniques would offer added patient convenience and significantly reduce radiotherapy department workloads."

The non-inferiority, phase III trial, randomized 589 patients to ultra-hypofractionation and 591 to conventional fractionation from July 2005 through November 2015. A total of 89% of the men had intermediate-risk prostate cancer, while 11% had high-risk prostate cancer.

Patients assigned to the ultra-hypofractionation radiotherapy schedule received 42.7 Gy in seven fractions delivered on 3 days a week for 2.5 weeks including 2 weekends.

Patients assigned to the conventional fractionation arm received a standard regimen of 78.0 Gy in 39 fractions delivered on 5 days a week for 8 weeks.

"No androgen-deprivation therapy was allowed, and the primary endpoint was time to biochemical or clinical failure, analyzed in the per-protocol population," the researchers said.

Writing in an accompanying editorial, Charles Catton, MD, of the University of Toronto, and Himu Lukka, MD, of McMaster University in Hamilton, Ontario, explained that the main concern with hypofractionated regimens is a greater risk of reversible mucosal injury during and immediately after treatment. This can be followed, however, by progressive irreversible bowel and urinary symptoms later on. The study, however, found no significant differences in grade 2 or greater urinary or bowel late toxicity between the two treatment groups, with the exception of a slightly greater increase in urinary toxicity at 1 year in the ultra-hypofractionation group; grade 3 toxicity was not common in either group.

"Notably, 80% of patients were treated with three-dimensional conformal therapy, and use of more modern techniques might further reduce normal tissue doses and consequent toxicity for either fractionation technique," Catton and Lukka continued.

They agreed with Widmark and colleagues that the results should not be extended to patients with high-risk prostate cancer, since that may well behave differently than intermediate-risk disease. "The median follow-up of 5 years is [also] relatively short, and reporting with longer follow-up data is awaited," the editorialists wrote.

Nevertheless, they said the study provides "the strongest data to date supporting the use of ultra-hypofractionation for intermediate-risk prostate cancer."

'Share Best Practices for the Procedure'

Also commenting on the findings, Matthew Katz, MD, a radiation oncologist at Lowell General Hospital in Massachusetts and a spokesperson for the American Society for Radiation Oncology, called the ultra-hypofractionation approach very appealing, since it allows men to finish their treatment in a much shorter time than the conventional approach.

"I think the side effects may be a consideration if men are at higher risk for side effects, so it's an important discussion to have with your patients," Katz told MedPage Today. However, given that the urinary toxicity reported in the trial was largely grade 2, "the symptoms can usually be managed with a prescription medication," and taking a medication to relieve symptoms may well be worth the trade-off if men can complete their treatment in an average of 16 days rather than the typical 57 days for conventional fractionation, he said.

Katz noted that the ultra-hypofractionation regimen is not as widely offered in the U.S. as it might be -- not because U.S. hospitals don't have the technology needed, since they usually do, but because the experts publishing their results often fail to share best practices with colleagues elsewhere, so other radiation oncologists are uncertain as to how to administer the ultra-hypofractionation regimen safely and effectively.

"Many of us are generalists, so we don't treat only prostate cancer," Katz observed. "So having the experts give us details about the procedure and not just publish a paper showing good results would accelerate adoption of this practice, and with that, I think, more community and non-academic doctors would be able to offer this approach more widely."