Trial Results Illustrate Efficacy of Moderate Hypofractionation

Whether hypofractionated radiotherapy should replace conventional radiotherapy as the standard of care for prostate cancer has been the subject of much debate. The results of 2 large, randomized, phase 3 trials of moderate hypofractionation for prostate cancer, recently published in The Lancet Oncology, led trial investigators to draw opposite conclusions.

In an accompanying commentary piece, W. Robert Lee, MD, of Duke Health argues that the explanation for the seemingly contradictory results lies largely in the differing hypotheses of the 2 studies—noninferiority vs superiority—and the amount of radiation administered per fraction.

In the Conventional or Hypofractionated High-Dose Intensity Modulated Radiotherapy in Prostate Cancer (CHHiP) trial, 5-year relapse-free survival was assessed in 3,216 men with prostate cancer receiving either 1 of 2 hypofractionation regimens (60 Gy in 20 fractions of 3 Gy for 4 weeks or 57 Gy in 19 fractions of 3 Gy for 3.8 weeks) or a conventionally fractionated regimen (74 Gy in 37 fractions of 2 Gy for 7.4 weeks). Trial investigators hypothesized that moderate hypofractionation is not inferior to conventional fractionation.

By contrast, the Hypofractionated Irradiation for Prostate Cancer (HYPRO) trial, which included 804 men, examined whether hypofractionation (64.6 Gy in 19 fractions of 3.4 Gy for 6.5 weeks) is superior to conventional fractionation (78 Gy in 39 fractions of 2 Gy for 8 weeks) in terms of 5-year relapse rates.

The results of the CHHiP trial indicate that hypofractionation is not worse than conventional fractionation, and the study authors recommend using hypofractionation because of its financial and logistical advantages. However, the researchers of the HYPRO trial found that hypofractionation is not superior to conventional fractionation and is accompanied by greater acute and late gastrointestinal and genitourinary toxic effects.

Despite the differing hypotheses, Lee notes that it is clear that the hypofractionation regimen used in the CHHiP trial has a rate of efficacy comparable to the conventional approach. However, he agrees with the HYPRO researchers that the higher-dose fractions used in their study should not be adopted—primarily because of the increased rates of toxicity.

“Based on the results of these studies, radiation oncologists now have evidence to offer a shorter course, making treatment more convenient for patients and their families,” Lee says.

“The CHHiP trial and a previously published NRG Oncology trial have demonstrated that moderate hypofractionation (daily dose of 2.5-3.0 Gy over 4-5 weeks) is safe and effective,” he adds. “In the next few years, we need to test whether extreme hypofractionation schedules (4-5 fractions in 1-2 weeks) are as effective as more extended schedules.”