Hypofractionated Radiation Trial Results Comparable to Standard in Intermediate - and High-Risk Patients

Delivering higher doses of external beam radiation in a shorter period of time (ie, hypofractionated radiation) was as effective as conventional radiation in preventing treatment failure in men with intermediate- to high-risk prostate cancer, according to results of a Phase III trial reported at the 2011 Annual Meeting of the American Society for Radiation Oncology (ASTRO) in Miami, Florida, in October.

At 5 years, the cumulative incidence of treatment failure, defined as a risk in the prostate-specific antigen (PSA) score of >2 ng/mL from the lowest value, was 13.9% in the group treated with hypofractionated radiation versus 14.4% in the conventional radiotherapy group.

The 5-year risk of failure, according to PSA rise or clinical failure (local failure, distant metastasis, or death), was 15.3% for the hypofractionated radiation group versus 15.4% for conventional radiation. “Hypofractionated radiation is a reasonable option for men with intermediate- to high-risk prostate cancer,” stated Alan Pollack, MD, PhD, chair of Radiation Oncology at the University of Miami Miller School of Medicine, Florida.

The current standard of care for prostate cancer radiotherapy is intensity-modulated radiation therapy using 76 Gy in 2-Gy daily fractions over 7.5 weeks (conventional radiotherapy). The hypofractionated regimen entails giving 70.2 Gy in 2.7-Gy fractions over 5.1 weeks, and is more convenient for patients and less costly, Pollack noted.

Alan Pollack, MD, PhD

The study enrolled 303 men with intermediate (two-thirds of the population) or high-risk (one-third) prostate cancer. At baseline, treatment groups were similar with regard to Gleason score, pretreatment PSA, T-category, or use or duration of androgen deprivation therapy (ADT). Forty-five percent received previous ADT.

Overall, 61 patients had biochemical failure, with no significant difference in failure rate between the 2 arms. The 5-year rates of local regional failure or distant metastasis for the 2 arms were 1.3% for the hypofractionated arm and 1% for conventional radiation.

Hypofractionation incurred much higher rates of grade 2 and higher genitourinary toxicity: 18.3% for hypofractionation versus 8.3% for conventional radiotherapy. The rate of grade 2 or higher gastrointestinal toxicity was 6.8% versus 5%, respectively. “Urinary incontinence was the most frequent genitourinary adverse event, and the rate of late urinary problems was rather low and favorable with both arms compared with previous studies,” Pollack said. The long-term rates of bowel/rectal adverse events and erectile dysfunction were identical for the 2 arms.

The study hypothesis was that hypofractionation would be superior to conventional radiotherapy in terms of biochemical failure and would not cause greater toxicity, but the study failed to show this.

A post hoc analysis found that American Urological Association (AUA) symptom score related to pretreatment urinary function was the strongest predictor of genitourinary adverse events in the hypofractionated group. The median AUA score in the study population was 5, and when patients were divided at the 10 cut point, at 5 years, the rate of genitourinary adverse events was 34.8% in those with a score of >10 versus 11.3% in those with a score of <10.

Pollack suggested that the ratio for equivalence of radiation doses given at different rates may need to be adjusted to improve these results. It is possible that higher radiation doses per fraction may be needed to obtain better outcomes.