Hypofractionated radiation regimen noninferior for low-risk prostate cancer

Hypofractionated radiation therapy, which delivers fewer, larger fractions than conventional radiation therapy, is no less efficacious for treating low-risk prostate cancer, although it does yield somewhat more late toxicity, according to results of the Radiation Therapy Oncology Group 0415 trial.

Investigators led by Dr. W. Robert Lee, a radiation oncologist with Duke Medicine in Durham, N.C., enrolled 1,115 men with low-risk disease in the phase III trial and randomized them to a hypofractionated regimen or a conventionally fractionated regimen.

An estimated 85%-86% of the men were alive and free of prostate cancer at 5 years regardless of regimen, they reported online in the Journal of Clinical Oncology. The difference between the two regimens fell well within the predefined margin for noninferiority.

At the same time, the hypofractionated regimen was associated with higher rates of late gastrointestinal and genitourinary toxicity, although the excess events were mainly grade 2 in severity.

“If disease control is similar, reducing the number of treatments from 41 to 28 and reducing the duration of therapy by 2.5 weeks (a nearly one-third reduction) provides greater patient convenience and reduced cost,” the investigators maintain. “The observed increase in late GI and GU adverse events in patients assigned to treatment with [hypofractionated radiation], however, suggests that increased convenience leads to more treatment-related toxicity.”

They stress that, in contrast to some other noninferiority trials, this trial included only men with low-risk disease, and the planning treatment volume included only the prostate (and not the seminal vesicles and pelvic lymph nodes). Additionally, men in the trial underwent radiation therapy immediately, so findings may not apply to those who experience progression of low-risk disease during a period of active surveillance.

“Several patient-reported outcomes, including health-related quality of life, anxiety, and depression, were collected as a component of this study but have not been analyzed to date,” the investigators note. “It will be of great interest to determine whether patients themselves report differences according to assigned treatment.”

Trial participants had clinical stage T1b-T2c disease, a Gleason score of 2-6, and a prostate-specific antigen level of less than 10 ng/mL. They could not have nodal or distant metastatic disease, among other exclusion criteria.

The men were randomized evenly to a hypofractionated regimen (70 Gy in 28 fractions over 5.6 weeks) or a conventionally fractionated regimen (73.8 Gy in 41 fractions over 8.2 weeks). Androgen suppression was not allowed.

With a modified intent-to-treat analysis and a median follow-up of 5.8 years, the 5-year rate of disease-free survival (the trial’s primary endpoint) was 85.3% with the conventional regimen and 86.3% with the hypofractionated regimen (J Clin Oncol. 2016. doi: 10.1200/JCO.2016.67.0448). The hazard ratio of 0.85 in favor of hypofractionation fell within the predefined noninferiority margin of 1.52 (P less than .001).

Findings were similar for the 5-year rates of biochemical recurrence (8.1% vs. 6.3%; HR, 0.77) and overall survival (93.2% vs. 92.5%; HR, 0.95), with differences in both outcomes falling within noninferiority margins. The main causes of death were cardiovascular disease and second cancers.

The two regimens did not differ significantly with respect to the rates of early gastrointestinal and genitourinary adverse events. But the hypofractionated regimen was associated with a higher rate of late gastrointestinal adverse events (P = .002), driven by more grade 2 events (18.3% vs. 11.4%), and a trend toward a higher rate of late genitourinary adverse events (P = .06), also driven mainly by more grade 2 events (26.2% vs. 20.5%).

“The increased late toxicity after treatment with [hypofractionated radiation] in this study is somewhat surprising as most of the [randomized controlled trials] have not observed excess GI and GU toxicity with hypofractionation. … although the power of these studies to detect a small difference is limited,” the investigators note.

The investigators disclosed potential conflicts of interest with Varian Medical Systems, Siemens, ViewRay, and General Electric, among others.

These study results were presented at the Genitourinary Cancers Symposium in January.

Hypofractionated radiation therapy, which delivers fewer, larger fractions than conventional radiation therapy, is no less efficacious for treating low-risk prostate cancer, although it does yield somewhat more late toxicity, according to results of the Radiation Therapy Oncology Group 0415 trial.

Investigators led by Dr. W. Robert Lee, a radiation oncologist with Duke Medicine in Durham, N.C., enrolled 1,115 men with low-risk disease in the phase III trial and randomized them to a hypofractionated regimen or a conventionally fractionated regimen.

An estimated 85%-86% of the men were alive and free of prostate cancer at 5 years regardless of regimen, they reported online in the Journal of Clinical Oncology. The difference between the two regimens fell well within the predefined margin for noninferiority.

At the same time, the hypofractionated regimen was associated with higher rates of late gastrointestinal and genitourinary toxicity, although the excess events were mainly grade 2 in severity.

“If disease control is similar, reducing the number of treatments from 41 to 28 and reducing the duration of therapy by 2.5 weeks (a nearly one-third reduction) provides greater patient convenience and reduced cost,” the investigators maintain. “The observed increase in late GI and GU adverse events in patients assigned to treatment with [hypofractionated radiation], however, suggests that increased convenience leads to more treatment-related toxicity.”

They stress that, in contrast to some other noninferiority trials, this trial included only men with low-risk disease, and the planning treatment volume included only the prostate (and not the seminal vesicles and pelvic lymph nodes). Additionally, men in the trial underwent radiation therapy immediately, so findings may not apply to those who experience progression of low-risk disease during a period of active surveillance.

“Several patient-reported outcomes, including health-related quality of life, anxiety, and depression, were collected as a component of this study but have not been analyzed to date,” the investigators note. “It will be of great interest to determine whether patients themselves report differences according to assigned treatment.”

Trial participants had clinical stage T1b-T2c disease, a Gleason score of 2-6, and a prostate-specific antigen level of less than 10 ng/mL. They could not have nodal or distant metastatic disease, among other exclusion criteria.

The men were randomized evenly to a hypofractionated regimen (70 Gy in 28 fractions over 5.6 weeks) or a conventionally fractionated regimen (73.8 Gy in 41 fractions over 8.2 weeks). Androgen suppression was not allowed.

With a modified intent-to-treat analysis and a median follow-up of 5.8 years, the 5-year rate of disease-free survival (the trial’s primary endpoint) was 85.3% with the conventional regimen and 86.3% with the hypofractionated regimen (J Clin Oncol. 2016. doi: 10.1200/JCO.2016.67.0448). The hazard ratio of 0.85 in favor of hypofractionation fell within the predefined noninferiority margin of 1.52 (P less than .001).

Findings were similar for the 5-year rates of biochemical recurrence (8.1% vs. 6.3%; HR, 0.77) and overall survival (93.2% vs. 92.5%; HR, 0.95), with differences in both outcomes falling within noninferiority margins. The main causes of death were cardiovascular disease and second cancers.

The two regimens did not differ significantly with respect to the rates of early gastrointestinal and genitourinary adverse events. But the hypofractionated regimen was associated with a higher rate of late gastrointestinal adverse events (P = .002), driven by more grade 2 events (18.3% vs. 11.4%), and a trend toward a higher rate of late genitourinary adverse events (P = .06), also driven mainly by more grade 2 events (26.2% vs. 20.5%).

“The increased late toxicity after treatment with [hypofractionated radiation] in this study is somewhat surprising as most of the [randomized controlled trials] have not observed excess GI and GU toxicity with hypofractionation. … although the power of these studies to detect a small difference is limited,” the investigators note.

The investigators disclosed potential conflicts of interest with Varian Medical Systems, Siemens, ViewRay, and General Electric, among others.

These study results were presented at the Genitourinary Cancers Symposium in January.

Hypofractionated radiation therapy, which delivers fewer, larger fractions than conventional radiation therapy, is no less efficacious for treating low-risk prostate cancer, although it does yield somewhat more late toxicity, according to results of the Radiation Therapy Oncology Group 0415 trial.

Investigators led by Dr. W. Robert Lee, a radiation oncologist with Duke Medicine in Durham, N.C., enrolled 1,115 men with low-risk disease in the phase III trial and randomized them to a hypofractionated regimen or a conventionally fractionated regimen.

An estimated 85%-86% of the men were alive and free of prostate cancer at 5 years regardless of regimen, they reported online in the Journal of Clinical Oncology. The difference between the two regimens fell well within the predefined margin for noninferiority.

At the same time, the hypofractionated regimen was associated with higher rates of late gastrointestinal and genitourinary toxicity, although the excess events were mainly grade 2 in severity.

“If disease control is similar, reducing the number of treatments from 41 to 28 and reducing the duration of therapy by 2.5 weeks (a nearly one-third reduction) provides greater patient convenience and reduced cost,” the investigators maintain. “The observed increase in late GI and GU adverse events in patients assigned to treatment with [hypofractionated radiation], however, suggests that increased convenience leads to more treatment-related toxicity.”

They stress that, in contrast to some other noninferiority trials, this trial included only men with low-risk disease, and the planning treatment volume included only the prostate (and not the seminal vesicles and pelvic lymph nodes). Additionally, men in the trial underwent radiation therapy immediately, so findings may not apply to those who experience progression of low-risk disease during a period of active surveillance.

“Several patient-reported outcomes, including health-related quality of life, anxiety, and depression, were collected as a component of this study but have not been analyzed to date,” the investigators note. “It will be of great interest to determine whether patients themselves report differences according to assigned treatment.”

Trial participants had clinical stage T1b-T2c disease, a Gleason score of 2-6, and a prostate-specific antigen level of less than 10 ng/mL. They could not have nodal or distant metastatic disease, among other exclusion criteria.

The men were randomized evenly to a hypofractionated regimen (70 Gy in 28 fractions over 5.6 weeks) or a conventionally fractionated regimen (73.8 Gy in 41 fractions over 8.2 weeks). Androgen suppression was not allowed.

With a modified intent-to-treat analysis and a median follow-up of 5.8 years, the 5-year rate of disease-free survival (the trial’s primary endpoint) was 85.3% with the conventional regimen and 86.3% with the hypofractionated regimen (J Clin Oncol. 2016. doi: 10.1200/JCO.2016.67.0448). The hazard ratio of 0.85 in favor of hypofractionation fell within the predefined noninferiority margin of 1.52 (P less than .001).

Findings were similar for the 5-year rates of biochemical recurrence (8.1% vs. 6.3%; HR, 0.77) and overall survival (93.2% vs. 92.5%; HR, 0.95), with differences in both outcomes falling within noninferiority margins. The main causes of death were cardiovascular disease and second cancers.

The two regimens did not differ significantly with respect to the rates of early gastrointestinal and genitourinary adverse events. But the hypofractionated regimen was associated with a higher rate of late gastrointestinal adverse events (P = .002), driven by more grade 2 events (18.3% vs. 11.4%), and a trend toward a higher rate of late genitourinary adverse events (P = .06), also driven mainly by more grade 2 events (26.2% vs. 20.5%).

“The increased late toxicity after treatment with [hypofractionated radiation] in this study is somewhat surprising as most of the [randomized controlled trials] have not observed excess GI and GU toxicity with hypofractionation. … although the power of these studies to detect a small difference is limited,” the investigators note.

The investigators disclosed potential conflicts of interest with Varian Medical Systems, Siemens, ViewRay, and General Electric, among others.

These study results were presented at the Genitourinary Cancers Symposium in January.