1. Susman, Ed

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SAN FRANCISCO-A prostate cancer radiation regimen that delivers less radiation over a shorter period of time still provides equivalent oncologic control for low-risk patients as does conventional radiation schemes, researchers reported here at the 2016 Genitourinary Cancers Symposium (Abstract 1).

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About 86.3 percent of patients achieved an estimated five-year disease-free survival if they were in the 550-patient cohort receiving a hypofractionated radiation program that consisted of a cumulative 70 Gray dose delivered in 28 fractions over 5.6 weeks, said W. Robert Lee, MD, Professor of Radiation Oncology at Duke University Medical Center, Durham, North Carolina. Each fraction was 2.5 Gray.


Among the 542 patient receiving the conventional 73.8 Gray in 41 fractions over 8.2 weeks, the estimated disease-free survival at five years was 85.3 percent, Lee reported at his poster presentation. Each fraction was 1.8 Gray.


"The hypofractionated regimen is not inferior to the conventional treatment," he told OT. The difference in outcome in the NRG Oncology RTOG 0415 trial was not statistically significant.


Seeing a Pattern

Other outcomes showed the same pattern:


* Biochemical recurrence was observed in 8.1 percent (or 50 men in the conventional radiation cohort) and in 6.3 percent (39 men in the hypofractionated group), a non-significant difference; and


* Overall survival at five years was 93.2 percent in the patients treated with the conventional radiation regimen and 92.5 percent in patients who were given the hypofractionated radiation therapy, also a non-significant difference, Lee said.



Median follow-up for the study is 5.9 years, the researchers reported.


"I am using this schedule now but most people are not," Lee said. "I think that is because our results have not yet been published. I have been using hypofractionated radiation therapy at the Durham VA for seven years."


'Practice Changing' Data

In commenting on the study, Sumanta Pal, MD, Assistant Professor of Medical Oncology at City of Hope, Duarte, Calif., told OT, "In my opinion, this rises to the level of practice changing data. This is Level 1 evidence in the form of a Phase III clinical trial that has been done by one of our most respected, cooperative groups in the domain of radiation treatment and it would mandate a change in clinical practice...and perhaps a change in clinical guidelines."


Study Details

To be eligible for the study, patients were required to be diagnosed with histologically confirmed prostate adenocarcinoma within 180 days prior to randomization to either the conventional treatment or the hypofractionated therapy arm. All the patients had Stage 1 to Stage 2c. Their pre-treatment prostate specific antigen (PSA) level had to have been less than 10 ng/mL and the Gleason score of the tumor had to be less than 7. Prior-or planned-androgen deprivation therapy or bilateral orchiectomy was not allowed. They were recruited between April 2006 and December 2009.


About 16 percent of the men in the study receiving the conventional treatment were 59 years of age or less compared with 17 percent of the men who were getting hypofractionated therapy; 44.1 percent of the men receiving conventional therapy were ages 60 to 69 compared with 45.6 percent of the men who were treated with hypofractionated therapy; and 39.9 percent of men in the conventional cohort were 70 years of age or older, as were 37.1 percent of the men in the hypofractionated therapy group.


Lee reported that 75.8 percent of the patients in the conventional treatment arm of the study were diagnosed with Stage T1 prostate cancer compared, with 80.4 percent of the men in the hypofractionated therapy arm. The remaining patients were diagnosed with Stage 2 prostate cancer. More than 90 percent of the patients were in the Zubrod Performance Status of 0. Only two patients in the study-both in the conventional treatment arm-had Gleason scores less than 4. The others all had scores of 5 or 6.


Late Grade 3 and 4 adverse events were uncommon in the study. Late gastrointestinal Grade 3 adverse events were observed among 2.4 percent of the patients who underwent conventional radiation treatment compared with 4.1 percent of the patients who had hypofractionated radiation therapy. There was one Grade 4 adverse event that occurred to a patient in the conventional treatment arm.


Late genitourinary Grade 3 adverse events were observed among 2.1 percent of the patients in the conventional therapy arm compared with 3.5 percent of men in the hypofractionated radiation therapy group. The only Stage 4 adverse genitourinary event was in the conventional treatment cohort.


Impact of Results

"Rectal bleeding is what is driving the Grade 2 and Grade 3 adverse events in this study," Lee noted. "The rating scales in this area are not that great. They say 'mild' or 'moderate' but there is not good definition of what is meant."


Grade 3 bleeding events required some interventions, he said. Grade 2 adverse events-also mainly reported rectal bleeding-were seen in as many as 20 percent of patients on conventional treatment and in 26 percent of those patients who received the short course of radiation.


"A lot of the Grade 2 rectal bleeding was occasional spotting," he said, but those cases did not require interventions.


"The benefit of this demonstration is that we shorten the duration of therapy by more than two weeks," said Pal. "And that may relieve many burdens, including economic costs and time costs to the patient. One of the traditional challenges with radiation therapy in prostate cancer is that it is administered over such an extended period of time. It becomes a real challenge for patients who come from long distances for their radiation treatment and certainly might compromise compliance."


Lee said his patients have been very accepting of the shorter course of therapy. "When you present the two regimens to a patient, very few of them select the longer treatment option," he said.


The conference is co-sponsored by the American Society of Clinical Oncology, American Society for Radiation Oncology and Society of Urologic Oncology.