A hypofractionated radiotherapy regimen was found to be noninferior to conventional fractionation for low-risk prostate cancer patients in a new randomized phase III trial.
A hypofractionated radiotherapy regimen was found to be noninferior to conventional fractionation for low-risk prostate cancer patients in a new randomized phase III trial. Results were presented at the 2016 American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium, held January 7–9 in San Francisco (abstract 1).
“In the last 15 years, low-level evidence has accumulated suggesting that the fractionation sensitivity of prostate cancer may favor hypofractionation-that is, fewer, larger fractions,” said W. Robert Lee, MD, of Duke University School of Medicine in Durham, who led the new trial. Randomized trials, however, have not confirmed that finding. The new study was intended to test noninferiority of the hypofractionated regimen rather than proving superiority.
The trial included 1,092 evaluable patients; 542 patients were randomized to receive conventional fractionation consisting of 41 fractions of 1.8 Gy, 5 days a week for 8.2 weeks for a total dose of 73.8 Gy. The experimental group (550 patients) received 28 fractions of 2.5 Gy over 5.6 weeks, for a total dose of 70 Gy. Performance status was generally very good in these patients, and 80% of men had a PSA between 4 and 10.
After a median follow-up of 5.8 years, the trial’s results were reported early following a third planned interim analysis. The disease-free survival rate at 5 years was 85% with conventional fractionation and 86% with hypofractionation, for a hazard ratio (HR) of 0.85 (95% CI, 0.64–1.14). Lee said this met the predefined criteria for noninferiority.
The 5-year biochemical recurrence rate was 8% with conventional fractionation and 6% with hypofractionation, for an HR of 0.77 (95% CI, 0.51–1.17). This again met the noninferiority criteria.
Acute gastrointestinal (GI) and genitourinary (GU) adverse events were similar between the groups, but there was an increase in late GI and GU adverse events. An increase in grade 2 toxicities in the hypofractionation group is what drove that overall increase.
“In men with low-risk prostate cancer, 70 Gy in 28 fractions is noninferior to 73.8 Gy in 41 fractions, albeit with a slight increase in grade 2 GI/GU toxicity,” Lee concluded. “It would be of great interest to determine if the small increase in grade 2 toxicity is manifest in patient-reported quality of life.” A quality-of-life analysis will be reported at a later date, he said.
The discussion for the session, Daniel Hamstra, MD, PhD, of the Texas Center for Proton Therapy in Irving, said that these and other results “now clearly establish that modest hypofractionated regimens are noninferior for biochemical failure with modest to no change to toxicity. This is probably ready for prime time.”