Hypofractionated Radiotherapy for Prostate Cancer: So Far, So Good

Nick Mulcahy

November 12, 2009

November 12, 2009 (Chicago, Illinois) — Hypofractionated radiotherapy, which delivers higher doses of radiation in fewer treatments than conventional radiotherapy, appears to give comparable or better results, according to 2 studies presented here at the American Society for Radiation Oncology (ASTRO) 51st Annual Meeting.

One of the studies showed a statistically significant reduction in biochemical recurrence at 3 years in high-risk prostate patients, compared with conventional treatment. The other study showed biochemical recurrence at 5 years in men with intermediate- and high-risk prostate cancer that was comparable to that of conventional radiotherapy.

There was no significant increase in toxicity with the hypofractionation in either trial. The treatments were also delivered 2.5 to 3 weeks faster than conventional therapy in both studies.

Everyone has been very, very nervous about hypofractionation.

"Everyone has been very, very nervous about hypofractionation," said incoming ASTRO president Anthony Zietman, MD, who moderated a press conference on the new studies, both of which are phase 3 trials.

"Radiation has been given the same way for 70 years until this change," observed Dr. Zietman, who is from Harvard Medical School in Boston, Massachusetts. "We have had a great fear about giving radiation in large doses. Giving a lot in a short time has always been an anathema," he continued.

In accordance with these fears, radiation oncologists have been extending the duration of treatment in prostate cancer. "Treatment goes on longer now — sometimes up until 9 weeks," Dr. Zietman said.

Dr. Allan Pollack (Courtesy of ASTRO)

"The more radiation you give, the more likely you are to eradicate the cancer," he explained.

The 2 reports on hypofractionated radiotherapy highlighted at ASTRO are "somewhat preliminary but very encouraging," said Allan Pollack, MD, from the University of Miami Miller School of Medicine in Florida, at the press conference. He is lead author of the study reporting 5-year results in intermediate- and high-risk men.

"It will be a few more years until we know that hypofractionation is equally effective and a few more still before we know if it is equally safe," summarized Dr. Zietman.

High-Risk Men Benefit

The 3-year study with significantly better results was based in Italy. It compared the efficacy and toxicity of hypofractionated and conventional fractionation radiotherapy (62 Gy in 20 fractions over 5 weeks vs 80 Gy in 40 fractions over 8 weeks) in patients with high-risk prostate cancer. A total of 168 patients were enrolled and randomized from 2003 to 2007.

All men in the study were treated with 3-dimensional conformal radiation therapy.

To be eligible, patients had to be younger than 80 years and have histologically proven prostate adenocarcinoma with a prostate-specific antigen (PSA) test score higher than 20 ng/mL, a Gleason score higher than 7, or tumor stage T3 or higher. Patients who had 2 of the following 3 characteristics were also eligible: a Gleason score of 7, a PSA level of 11 to 20 ng/mL, and stage T2c disease. All patients received a 9-month course of androgen-deprivation therapy.

Dr. Giorgio Arcangeli (Courtesy of ASTRO)

The 3-year freedom from biochemical failure rates were 87% and 79% in the hypofractionated and conventional fractionation groups, respectively. The difference was statistically significant (P = .035).

This is an important benefit for these high-risk patients.

"The study not only shows that hypofractionated radiation improves the control of prostate cancer, but it also cuts the number of treatment visits in half for patients. This is an important benefit for these high-risk patients, who are typically an older, less mobile population," said study lead author Giorgio Arcangeli, MD, from the Regina Elena National Cancer Institute in Rome, Italy, in a press statement. "It's also especially helpful for those living a long distance from radiation treatment centers," he added.

In terms of adverse effects, no patient experienced a grade 4 acute toxicity, and grade 3 toxicity was observed in only 1 patient, said Dr. Arcangeli.

No difference was found for late toxicity between the 2 treatment groups, with 3-year grade 2 rates of 17% and 16% for gastrointestinal complications and 14% and 11% for genitourinary complications in hypofractionated and conventional fractionation groups, respectively.

Intermediate- and High-Risk Men: Biochemical Failure Rates Comparable

The 5-year results come from a study that Dr. Pollack presented earlier this year at the 2009 Genitourinary Cancers Symposium. The results show that a 5-week course of hypofractionated radiotherapy is as effective and well tolerated as the standard 7.5-week course in reducing the risk for prostate cancer recurrence.

This study involved 303 men with intermediate- and high-risk disease and compared treatment with standard intensity-modulated radiotherapy (SIMRT) and hypofractionated intensity-modulated radiotherapy (HIMRT).

Dr. Pollack and his colleagues compared biochemical failure rates in 152 men with prostate cancer randomly assigned to 38 SIMRT treatments over 7.5 weeks (2.0 Gy per treatment; 76 Gy total dose) and 151 men randomly assigned to 26 HIMRT treatments over 5.1 weeks (2.7 Gy per treatment; 70.2 Gy total dose, but biologically equivalent to 84.4 Gy).

The study design also involved 34 intermediate-risk patients in the SIMRT group who received short-term androgen-deprivation therapy for a median of 4 months and 102 high-risk patients in the HIMRT group who received long-term androgen-deprivation therapy for a median of 24.5 months.

After a median follow-up of 39 months, 17% of the HIMRT group and 21% of the SIMRT group experienced a biochemical recurrence using the "nadir+2" definition (P = .7); the difference was not statistically significant.

Longer follow-up is needed and a final analysis is planned for 2011.

For the SIMRT and HIMRT groups, 5-year grade 2 or higher gastrointestinal toxicity was 8% and 6%, respectively (= .5), and genitourinary toxicity was 17% and 25% (P = 0.2).

"Although these are significant findings, longer follow-up is needed and a final analysis is planned for 2011," Dr. Pollack said in a press statement. "Other clinical trials are exploring hypofractionation and I encourage men with prostate cancer interested in shorter treatments to talk to their radiation oncologist about joining a study."

The researchers have disclosed no relevant financial relationships.

American Society for Radiation Oncology (ASTRO) 51st Annual Meeting: Abstracts 168 and 172. Presented November 4, 2009.

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