Newer Radiotherapy for Prostate Cancer Less Harmful to Rectum

Men with localized prostate cancer had fewer acute and late side effects in the bowel and rectum when they were treated with a newer, more targeted form of radiotherapy in a phase III dose-escalation trial conducted by the Radiation Therapy Oncology Group.

The newer procedure, intensity-modulated radiation therapy (IMRT), was associated with 26% fewer late rectal and bowel toxicities, compared with three-dimensional conformal radiation therapy (3D-CRT) in an analysis of men with localized prostate cancer who were part of the study’s high-dose treatment arm.

Although the difference in late toxicity was not statistically significant, acute grade 2 or higher rectal, bowel, and bladder toxicities were significantly fewer, and radiation doses to the bladder and rectum were significantly reduced as well.

Patients in the RTOG 0126 trial were initially treated with 3D-CRT, but the trial protocol was amended after 1 year to allow IMRT, which is a newer, specialized form of 3D-CRT that allows more precise delivery of radiation to the tumor.

The current study represents a preliminary analysis of acute and late toxicities in 491 patients treated with 3D-CRT and 257 patients treated with IMRT. The findings will be presented on Oct. 3 at the annual meeting of the American Society for Radiation Oncology (ASTRO).

Acute grade 2 toxicities occurred in 16.9% in the 3D-CRT arm and 13.9% of patients in the IMRT groups. Acute grade 3 toxicities occurred in 2.5% and 2.4% of patients in the groups, respectively, Dr. Jeff Michalski reported during a press conference held in advance of the ASTRO meeting.

No acute grade 4 toxicities occurred in the 3D-CRT group, but 0.4% of patients in the IMRT group experienced grade 4 toxicities, according to Dr. Michalski, professor and vice chair of radiation oncology at Washington University Medical Center in St. Louis.

Univariate and multivariate analyses demonstrated a significant decrease in acute collective genitourinary and gastrointestinal toxicity for IMRT, but there were no significant differences for acute grade 2 or higher genitourinary toxicities alone, he noted.

As for late toxicities – which are particularly important to control because they can be irreversible – 23.6% and 19.9% of patients in the 3D-CRT and IMRT groups, respectively, experienced grade 2 toxicities; 8.9% and 4.7%, respectively, experienced grade 3 toxicities; 0.4% of patients in both groups experienced grade 4 toxicities, Dr. Michalski said. Although 0.2% of the 3D-CRT group had a late grade 5 toxicity, none was reported in men receiving IMRT.

The difference between 3D-CRT and IMRT in late toxicities did not reach statistical significance, but there was a trend toward a "clinically meaningful" 26% reduction in grade 2 or higher late toxicities with IMRT, he said.

Notably, there was a significant 15% increase in grade 2 or higher rectal toxicity in white men vs. men of other races, regardless of treatment type. The causes of this finding are unclear, but may be associated with differences in treatment tolerance or cultural differences in the reporting of side effects, he suggested.

"IMRT is a safe and very well-tolerated therapy associated with many fewer acute and late complications than 3D-CRT," Dr. Michalski said, adding, "I believe this study supports the use of IMRT in the management of localized prostate cancer."

Although prior findings have supported the notion of a technical advantage with IMRT in terms of delivering a higher dose of radiation to the tumor without increasing toxicity to the bladder and rectum, a good data set allowing direct comparisons of 3D-CRT and IMRT was lacking, he said.

"This is the first contemporary group of patients that demonstrates a benefit," he said.

This study was supported the ASTRO Radiation Oncology Institute and by several grants from the National Cancer Institute. Dr. Michalski reported receiving funding from Augmenix, Elekta, and Viewray.

Men with localized prostate cancer had fewer acute and late side effects in the bowel and rectum when they were treated with a newer, more targeted form of radiotherapy in a phase III dose-escalation trial conducted by the Radiation Therapy Oncology Group.

The newer procedure, intensity-modulated radiation therapy (IMRT), was associated with 26% fewer late rectal and bowel toxicities, compared with three-dimensional conformal radiation therapy (3D-CRT) in an analysis of men with localized prostate cancer who were part of the study’s high-dose treatment arm.

Although the difference in late toxicity was not statistically significant, acute grade 2 or higher rectal, bowel, and bladder toxicities were significantly fewer, and radiation doses to the bladder and rectum were significantly reduced as well.

Patients in the RTOG 0126 trial were initially treated with 3D-CRT, but the trial protocol was amended after 1 year to allow IMRT, which is a newer, specialized form of 3D-CRT that allows more precise delivery of radiation to the tumor.

The current study represents a preliminary analysis of acute and late toxicities in 491 patients treated with 3D-CRT and 257 patients treated with IMRT. The findings will be presented on Oct. 3 at the annual meeting of the American Society for Radiation Oncology (ASTRO).

Acute grade 2 toxicities occurred in 16.9% in the 3D-CRT arm and 13.9% of patients in the IMRT groups. Acute grade 3 toxicities occurred in 2.5% and 2.4% of patients in the groups, respectively, Dr. Jeff Michalski reported during a press conference held in advance of the ASTRO meeting.

No acute grade 4 toxicities occurred in the 3D-CRT group, but 0.4% of patients in the IMRT group experienced grade 4 toxicities, according to Dr. Michalski, professor and vice chair of radiation oncology at Washington University Medical Center in St. Louis.

Univariate and multivariate analyses demonstrated a significant decrease in acute collective genitourinary and gastrointestinal toxicity for IMRT, but there were no significant differences for acute grade 2 or higher genitourinary toxicities alone, he noted.

As for late toxicities – which are particularly important to control because they can be irreversible – 23.6% and 19.9% of patients in the 3D-CRT and IMRT groups, respectively, experienced grade 2 toxicities; 8.9% and 4.7%, respectively, experienced grade 3 toxicities; 0.4% of patients in both groups experienced grade 4 toxicities, Dr. Michalski said. Although 0.2% of the 3D-CRT group had a late grade 5 toxicity, none was reported in men receiving IMRT.

The difference between 3D-CRT and IMRT in late toxicities did not reach statistical significance, but there was a trend toward a "clinically meaningful" 26% reduction in grade 2 or higher late toxicities with IMRT, he said.

Notably, there was a significant 15% increase in grade 2 or higher rectal toxicity in white men vs. men of other races, regardless of treatment type. The causes of this finding are unclear, but may be associated with differences in treatment tolerance or cultural differences in the reporting of side effects, he suggested.

"IMRT is a safe and very well-tolerated therapy associated with many fewer acute and late complications than 3D-CRT," Dr. Michalski said, adding, "I believe this study supports the use of IMRT in the management of localized prostate cancer."

Although prior findings have supported the notion of a technical advantage with IMRT in terms of delivering a higher dose of radiation to the tumor without increasing toxicity to the bladder and rectum, a good data set allowing direct comparisons of 3D-CRT and IMRT was lacking, he said.

"This is the first contemporary group of patients that demonstrates a benefit," he said.

This study was supported the ASTRO Radiation Oncology Institute and by several grants from the National Cancer Institute. Dr. Michalski reported receiving funding from Augmenix, Elekta, and Viewray.

Men with localized prostate cancer had fewer acute and late side effects in the bowel and rectum when they were treated with a newer, more targeted form of radiotherapy in a phase III dose-escalation trial conducted by the Radiation Therapy Oncology Group.

The newer procedure, intensity-modulated radiation therapy (IMRT), was associated with 26% fewer late rectal and bowel toxicities, compared with three-dimensional conformal radiation therapy (3D-CRT) in an analysis of men with localized prostate cancer who were part of the study’s high-dose treatment arm.

Although the difference in late toxicity was not statistically significant, acute grade 2 or higher rectal, bowel, and bladder toxicities were significantly fewer, and radiation doses to the bladder and rectum were significantly reduced as well.

Patients in the RTOG 0126 trial were initially treated with 3D-CRT, but the trial protocol was amended after 1 year to allow IMRT, which is a newer, specialized form of 3D-CRT that allows more precise delivery of radiation to the tumor.

The current study represents a preliminary analysis of acute and late toxicities in 491 patients treated with 3D-CRT and 257 patients treated with IMRT. The findings will be presented on Oct. 3 at the annual meeting of the American Society for Radiation Oncology (ASTRO).

Acute grade 2 toxicities occurred in 16.9% in the 3D-CRT arm and 13.9% of patients in the IMRT groups. Acute grade 3 toxicities occurred in 2.5% and 2.4% of patients in the groups, respectively, Dr. Jeff Michalski reported during a press conference held in advance of the ASTRO meeting.

No acute grade 4 toxicities occurred in the 3D-CRT group, but 0.4% of patients in the IMRT group experienced grade 4 toxicities, according to Dr. Michalski, professor and vice chair of radiation oncology at Washington University Medical Center in St. Louis.

Univariate and multivariate analyses demonstrated a significant decrease in acute collective genitourinary and gastrointestinal toxicity for IMRT, but there were no significant differences for acute grade 2 or higher genitourinary toxicities alone, he noted.

As for late toxicities – which are particularly important to control because they can be irreversible – 23.6% and 19.9% of patients in the 3D-CRT and IMRT groups, respectively, experienced grade 2 toxicities; 8.9% and 4.7%, respectively, experienced grade 3 toxicities; 0.4% of patients in both groups experienced grade 4 toxicities, Dr. Michalski said. Although 0.2% of the 3D-CRT group had a late grade 5 toxicity, none was reported in men receiving IMRT.

The difference between 3D-CRT and IMRT in late toxicities did not reach statistical significance, but there was a trend toward a "clinically meaningful" 26% reduction in grade 2 or higher late toxicities with IMRT, he said.

Notably, there was a significant 15% increase in grade 2 or higher rectal toxicity in white men vs. men of other races, regardless of treatment type. The causes of this finding are unclear, but may be associated with differences in treatment tolerance or cultural differences in the reporting of side effects, he suggested.

"IMRT is a safe and very well-tolerated therapy associated with many fewer acute and late complications than 3D-CRT," Dr. Michalski said, adding, "I believe this study supports the use of IMRT in the management of localized prostate cancer."

Although prior findings have supported the notion of a technical advantage with IMRT in terms of delivering a higher dose of radiation to the tumor without increasing toxicity to the bladder and rectum, a good data set allowing direct comparisons of 3D-CRT and IMRT was lacking, he said.

"This is the first contemporary group of patients that demonstrates a benefit," he said.

This study was supported the ASTRO Radiation Oncology Institute and by several grants from the National Cancer Institute. Dr. Michalski reported receiving funding from Augmenix, Elekta, and Viewray.