Hypofractionated Radiation Compares to Conventional Course for Prostate Cancer



A shorter, more intense course of radiotherapy was as effective as conventional intensity-modulated radiation therapy for the treatment of intermediate- to high-risk prostate cancer in a randomized, controlled, phase III dose-escalation trial involving 303 patients.

At 5 years of follow-up, outcomes were similar whether men received hypofractionated intensity-modulated radiation therapy (hIMRT) or conventional IMRT (cIMRT), Dr. Alan Pollack reported during a press conference sponsored by the American Society for Radiation Oncology (ASTRO).

The hypofractionated approach – which compresses the standard prostate cancer treatment schedule by delivering a higher dose of radiation for fewer days – shortened treatment duration to 5.1 weeks without increasing long-term toxicity, he said. Radiotherapy lasted 7.5 weeks with conventional IMRT.

The findings will be presented on Oct. 3 at the ASTRO annual meeting in Miami Beach.

The approach is based on extensive data indicating that hypofractionation confers radiobiological advantages, according to Dr. Pollack, professor and chair of radiation oncology at the University of Miami.

The 151 patients who were randomized to receive hIMRT (70.2 Gy in 27.2 Gy fractions) had a 5-year cumulative incidence rate of biochemical failure of 13.9%, compared with 14.4% in the 152 patients randomized to receive cIMRT (76 Gy in 2.0 Gy fractions).

Clinical failure rates (defined as local/regional failure or distant metastases) were 1.3% in the hIMRT group and 1.0% in the cIMRT groups, Dr. Pollack said. The rates of "any failure" were 15.3% and 15.4% in the groups, respectively.

Dr. Pollack and his colleagues had hypothesized correctly that hIMRT would have a failure rate in the 15% range, but they also hypothesized that it would be superior to cIMRT. Conventional IMRT performed better than expected, he said.

As for side effects, grade 2 or higher genitourinary toxicities occurred in 13.8% and 8.9% of patients in the hIMRT and cIMRT groups, respectively (P = 0.2), and gastrointestinal toxicities occurred in 5.9% and 4.1% of the patients in the groups, respectively (P = 0.5).

More bladder control problems in the men who had received hIMRT accounted for the difference in genitourinary effects, as the frequency of unsatisfactory erections in the groups were similar. However, the rates of persistent urinary symptoms were less than 10% in both groups, which is still less than the 15% typically reported in the literature, Dr. Pollack noted.

"We did find that in general, the side effects were low," said Dr. Pollack, who described HIMRT as "a more sophisticated way of administering radiation."

CIMRT and HIMRT patients, all of whom were treated in 2002-2006, were similar in regard to T categories, Gleason scores, pretreatment initial prostate-specific antigen levels, and use of – and length of – androgen deprivation therapy. Biochemical failure was assessed using the Phoenix definition (PSA nadir + 2 ng/mL), and clinical failure was defined as either locoregional failure or distant metastases, he noted.

"Hypofractionation for prostate cancer does show promise," Dr. Pollack said, noting that work is ongoing to identify the limits and best approaches for applying hypofractionation while limiting side effects – particularly urinary side effects, which tend to cause the greatest amount of problems following most types of treatment for prostate cancer.

The approach has not been broadly adopted, because long-term follow-up and greater understanding of the risks are needed, but Dr. Michael L. Steinberg, professor and chair of radiation oncology at the University of California, Los Angeles, and ASTRO’s president-elect, agreed that hypofractionation represents an emerging trend in the treatment of prostate and other cancers.

It will also likely represent a cost benefit, Dr. Pollack added. The current study did not include a cost-benefit analysis, but the shorter treatment duration should translate into significant savings both in up-front costs and in terms of time away from work, he said.

Dr. Pollack had no relevant disclosures. Dr. Steinberg serves in a leadership position on the American College of Radiology Economics Committee.

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