Hypofractionation of intensity-modulated radiation therapy failed to reduce treatment failure rates in a study of 303 men with prostate cancer.
The combined biochemical and clinical failure rate was comparable between men randomly assigned to receive conventionally fractionated IMRT (76 Gy in 38 fractions of 2.0 Gy per fraction) and those assigned to receive hypofractionated IMRT (70.2 Gy in 26 fractions of 2.7 Gy per fraction), reported Dr. Alan Pollack, of the University of Miami, and his associates in the Journal of Clinical Oncology (2013 Oct. 7; published online ahead of print [doi: 10.1200/JCO.2013.51.1972]).
At the time the trial was designed, preliminary data indicated that hypofractionation (a higher radiation dose per fraction) carried a therapeutic advantage without increasing toxicity. The researchers estimated that by using hypofractionation, they would raise the cumulative dose from 76 Gy to the equivalent of 84.4 Gy, which they hoped would result in 15% fewer treatment failures.
The study subjects were men who had moderate- to high-risk prostate cancer. A total of 152 patients were randomly assigned to receive conventionally fractionated IMRT and 151 to receive hypofractionated IMRT. The two study groups were well balanced with regard to patient age, tumor T category and Gleason score, and initial prostate-specific antigen (PSA) level.
Men considered high risk received 2 years of androgen deprivation therapy; those at moderate risk received up to 4 months of androgen deprivation therapy. The proportion of patients in the moderate- and high-risk categories was similar between the two study groups.
At 5 years, biochemical and clinical failure rates did not differ significantly between the men who received conventionally fractionated IMRT (21.4%) and those who received hypofractionated IMRT (23.3%). These results were unchanged in two further analyses that used slightly different definitions of biochemical and clinical treatment failure, the investigators said.
Also, the two study groups did not differ in overall survival, prostate cancer–specific mortality, or rates of death from any cause.
Rates of local and distant treatment failure also were comparable: three cases of local failure and six of distant failure with conventionally fractionated IMRT, compared with five cases of local failure and eight of distant failure with hypofractionated IMRT.
Tumor T category, Gleason score, initial PSA level, and duration of androgen deprivation therapy were significant predictors of treatment failure. Treatment assignment was not a significant predictor of treatment failure.
The rates and severity of toxicity also were similar between the two study groups. Overall rates of gastrointestinal adverse events were comparable, as were the rates of each grade of severity of GI adverse events.
Rates of genitourinary dysfunction were high in both groups at baseline, mainly because many of the patients reported already having urinary frequency and urgency. Still, these rates increased substantially during follow-up in both groups. By the end of the study, 14.6% of men who received conventionally fractionated IMRT and 15.3% of those who received hypofractionated IMRT reported adverse genitourinary effects of grade 2 or higher.
Using a slightly different definition of genitourinary toxicity, the investigators found that 5-year cumulative risks of grade 2 or higher adverse effects were 37.9% for conventionally fractionated IMRT and 39.1% for hypofractionated IMRT, which also was not a significant difference.
This study was supported by the National Cancer Institute and Florida Biomed. Dr. Pollack and his associates reported ties to GE Healthcare, Calypso, and other companies.