Prostate Cancer Radiation in 2.5 Weeks: 'Extreme' but Safe

Phase 3 Clinical Trial

Nick Mulcahy

September 27, 2016

BOSTON — Radiation oncologists in Scandinavia are experimenting with the boundaries of delivering radiation therapy for the treatment of intermediate-risk prostate cancer.

In an ongoing open randomized phase 3 trial, they are comparing "extreme" hypofractionation, which was delivered in seven fractions across 2.5 weeks, with conventional treatment of 39 fractions across 8 weeks, said Anders Widmark, MD, a professor of radiation sciences at Umeå University in Sweden.

Dr. Widmark presented 2-year toxicity results from the HYPO-RT-PC Trial at a press conference here at the American Society for Radiation Oncology (ASTRO) 2016 Annual Meeting.

In the trial, extreme hypofractionation was similar to the conventional approach in terms of urinary and bowel toxicities and sexual function, he reported.

The trial will produce data on its primary endpoint, biochemical failure-free survival, in about 1 year.

Dr Widmark explained that the rationale behind the acceleration was that prostate cancer is postulated as having a "high radiation-fractionation sensitivity" with potential therapeutic benefit for hypofractionation.

Indeed, outcomes with moderately hypofractionated schedules (3 Gy per fraction over 4 weeks) have been found to be similar to or better than those seen with longer conventional fractionation.

But there was a concern that toxicity might be worse with the extreme hypofractionation, which consists of seven fractions of 6.1 Gy each.

"It's going to be a more intensive, a more hot treatment," explained Dr Widmark.

It's going to be a more intensive, a more hot treatment. Dr Anders Widmark

Clinicians in North America might not recognize the term "extreme hypofractionation," said George Rodrigues, MD, PhD, from the London Health Sciences Centre, Ontario, Canada, who moderated the press conference.

In the context of treating prostate cancer, "extreme hypofractionation" is interchangeable with "stereotactic body radiotherapy" (SBRT), which is used in North America to deliver abbreviated, more intense radiation.

However, older radiotherapy technology can also be used. In the Scandinavian trial, most of the patients (90%) were treated with conventional three-dimensional conformal radiotherapy and only 10% with an SBRT-type technology.

The treatment of intermediate-risk prostate cancer is in the midst of change, Dr Rodrigues further commented.

While 7 to 8 weeks of radiotherapy has been the standard approach in this setting, clinical trials have now shown that moderate hypofractionation of 4 weeks' length is comparable, he said. Dr Rodrigues' London Health Sciences Centre is changing its standard, default treatment to that shorter schedule, he told Medscape Medical News.

Extreme hypofractionation for intermediate-risk prostate cancer is still experimental and is the subject of the now-underway PACE trial in the United Kingdom and a planned NRG Oncology trial in North America.

Study Details

The investigators enrolled 1200 men with intermediate-risk prostate cancer (T1c-T3a and prostate-specific antigen [PSA] level ≤20 with one or two of the following risk factors: T3a or Gleason score ≥ 7 or PSA >10) into the noninferiority trial between 2005 and 2015. Androgen deprivation therapy was not allowed among study participants.

Median follow-up time from randomization for the entire patient population was 4.2 years, and the findings are from 866 patients who reached 2-year follow-up at the time of reporting in May 2016.

Adverse events were measured at baseline, at the end of radiotherapy, and at 3, 6, 12, 18, and 24 months after treatment.

Primary outcomes included both physician- and patient-reported adverse events.

Rates of physician-reported grade 2+ toxicities at 2 years after treatment did not differ significantly between treatment groups. Urinary side effects were reported for 5.4% of patients receiving extreme hypofractionation and 4.6% for those receiving conventional fractionation (P = .59). Bowel adverse events were reported for 2.2% of the extreme hypofractionation group and 3.7% of the conventional fractionation group (P = .20).

Impotence at 2 years after treatment was reported in 34% of both groups, compared with 16% among all participants at baseline.

Patient-reported outcomes at 2 years after treatment also did not differ significantly between treatment groups for overall bother from urinary (P = .17), bowel (P = .12), or sexual function (P = .71) symptoms.

Although the two treatments did not show much difference in terms of toxicity at 2 years, some statistically significant differences emerged between the treatment groups in shorter-term bowel and urinary side effects.

For example, acute urinary toxicity immediately after treatment was similar for both treatment groups (27.6% for the extreme group vs 22.8% for the conventional group; P = .11). But at the end of radiotherapy, acute bowel toxicity was higher for the the extreme group (9.4% vs 5.3%; P = .023).

But over time, equal late toxicity emerged between the two treatment groups, leaving behind the differences in shorter-term side effects.

Dr Widmark and Dr Rodrigues have disclosed no relevant financial relationships.

American Society for Radiation Oncology (ASTRO) 2016 Annual Meeting. Abstract LBA-5. To be presented September 27.

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