Prostate Cancer Study Shows Hypofractionation Comparable to Standard Radiation in Low-risk Patients

Hypofractionated radiotherapy can achieve similar cure rates with similar side effects compared with conventional radiotherapy for men with low-risk, early prostate cancer, according to a recent study.

Hypofractionated radiotherapy can achieve similar cure rates with similar side effects compared with conventional radiotherapy for men with low-risk, early prostate cancer, according to follow-up RTOG 0415 study data presented October 20, 2015, during a scientific session at the 2015 ASTRO Annual Meeting.

Hypofractionated radiotherapy is delivered in larger doses over 5.5 weeks whereas conventional radiotherapy requires 8 weeks of treatment. “Results of our study demonstrate that for men with low-risk prostate cancer, hypofractionated radiotherapy offers a shorter, more convenient treatment schedule without compromising cure or causing additional side effects,” said lead author W. Robert Lee, MD, professor of radiation oncology at Duke University School of Medicine, Durham, NC.

Senior author of the study, Howard Sandler, MD, professor and chair of radiation oncology at Cedars Sinai Medical Center, Los Angeles, CA, said, “This is the first large-scale, randomized study demonstrating the value of a shorter course of radiotherapy for low-risk prostate cancer. The results are not surprising; however, given that studies of the effects of hypofractionated radiation therapy in patients with early-stage breast cancer, which is similar to early-stage prostate cancer, have demonstrated similar outcomes.”

Study Details

The phase III RTOG 0415 study, conducted from April 2006 to December 2009 in the United States and Canada, enrolled 1115 men with low-risk prostate cancer and randomized them to receive either hypofractionated radiotherapy or a conventional radiotherapy schedule. Baseline demographic and disease characteristics were comparable between the two groups. Mean age was about 65 years and pretreatment prostate specific antigen (PSA) score was 5.4 ng/mL.

RTOG 0415 was designed as a noninferiority study for the two techniques, as reflected by a 5-year disease-free survival (DFS) rate not lower by more than 7% compared with conventional radiotherapy.

A total of 1105 men with low-risk prostate cancer were randomized 1:1 to conventional radiotherapy (73.8 Gy in 41 fractions delivered over 8.2 weeks) or hypofractionated radiotherapy (70 Gy in 28 fractions delivered over 5.6 weeks). Low risk was defined as not palpable, PSA <10 ng/mL, or Gleason score of 6 or lower.

At a median follow-up of 5.9 years, DFS rates were similar for both groups of men. In more than 300 men followed for more than 5 years, 82% in the hypofractionated group and 76% in the conventional radiotherapy group were alive with no evidence of disease. This demonstrates noninferiority, Sandler said.

Biochemical recurrence and overall survival also met noninferiority criteria.

Toxicity is important to assess in these men, Sandler continued. Grade 3 or higher gastrointestinal toxicity was slightly higher with hypofractionation: 3% for conventional radiotherapy versus 4.6% for hypofractionation. Grade 3 or higher genitourinary toxicity was 3.5% versus 2.3%, respectively.

“These are small absolute differences, with a possible increase in late side effects,” Sandler noted. “Both techniques are very well tolerated. If there is a difference between them, that difference is very small. Results suggest that this shorter regimen is a treatment regimen that physicians can be comfortable discussing and prescribing for their patients.”

“Standard radiotherapy for prostate cancer takes 8 to 9 weeks. It is a long time commitment and somewhat daunting to patients. Shorter radiotherapy treatments may be a better way to treat prostate cancer,” Sandler said.

During the discussion following this presentation at a press conference, Sandler commented that many patients with low-risk disease, such as those included in this trial are now managed with active surveillance, moving on to treatment if there is an indication that the disease has progressed.

“We carefully monitor these patients. Some will progress. I would recommend active surveillance as the first option, and move on to hypofractionated radiotherapy if and when it is needed,” he stated.

Lee, RW. NRG Oncology RTOG 0415: A randomized phase III non-inferiority study comparing 2 fractionation schedules in patients with low-risk prostate cancer. Presented at the 2015 ASTRO Annual Meeting: San Antonio, TX; Abstract LBA 6.