Dose-escalated radiation therapy brings mixed results in prostate cancer

 

Dose-escalated radiation therapy reduced the need for subsequent therapy in patients with intermediate-risk prostate cancer but did not improve overall survival, according to results of a large, randomized clinical trial.

The absence of a survival benefit compared with standard radiation therapy was seen despite a reduction in rates of both biochemical failure and distant metastases, Jeff M. Michalski, MD, and his associates reported in JAMA Oncology.

Negative overall survival results may be attributable to the growing availability of systemic salvage therapies that have prolonged the natural history of this disease, said Dr. Michalski, MD, of the department of radiation oncology at Washington University in St. Louis.

“Patients experiencing a biochemical or clinical failure may go on to receive several life-prolonging systemic agents, which may negate any clinical advantage from a more effective primary local therapy,” Dr. Michalski and associates wrote.

 

Results of the study support that hypothesis. Patients who received the standard dose radiotherapy were significantly more likely to go on to salvage therapy, compared with patients in the dose-escalation arm.

Dr. Michalski and his associated reported on the randomized NRG Oncology/RTOG 0126 clinical trial, which included 1,532 patients with intermediate-risk cancer enrolled between March 2002 and August 2008 at one of 104 North American sites.

In the trial, patients with intermediate-risk prostate cancer were randomized to receive three-dimensional conformal radiation therapy or intensity-modulated radiation therapy to 79.2 Gy in 44 fractions or 70.2 Gy in 39 fractions, the study said.

With a median follow-up of 8.4 years for 1,499 patients, there was no difference in overall survival between arms, study results show. The 8-year rates of overall survival were 76% for dose-escalated radiotherapy and 75% for standard radiotherapy (hazard ratio, 1.00; 95% confidence interval, 0.83-1.20; P = .98).

Otherwise, patients in the dose-escalated radiotherapy arm had significantly lower rates of distant metastases (4% vs. 6%; P = 0.05), and lower rates of biochemical failure rates at both 5 and 8 years, investigators said.

 

Patients in the high-dose arm less often went on to salvage therapy; however, investigators noted that they also had more toxic effects. compared with patients in the standard radiotherapy arm.

“The advantage of avoiding or delaying the adverse effects of these therapies has to be weighed against the increased rate of RT-related morbidity with dose escalation,” Dr. Michalski and his associates wrote.

Dr. Michalski reported no conflicts of interest. The co-authors reported several conflicts of interest, including ties to ViewRay, Augmenix, Sanofi, AstraZeneca, AbbVie, and other companies.

[email protected]

SOURCE: Michalsky Jeff M et al. JAMA Oncol. 2018 Mar 15. doi: 10.1001/jamaoncol.2018.0039.

 

Dose-escalated radiation therapy reduced the need for subsequent therapy in patients with intermediate-risk prostate cancer but did not improve overall survival, according to results of a large, randomized clinical trial.

The absence of a survival benefit compared with standard radiation therapy was seen despite a reduction in rates of both biochemical failure and distant metastases, Jeff M. Michalski, MD, and his associates reported in JAMA Oncology.

Negative overall survival results may be attributable to the growing availability of systemic salvage therapies that have prolonged the natural history of this disease, said Dr. Michalski, MD, of the department of radiation oncology at Washington University in St. Louis.

“Patients experiencing a biochemical or clinical failure may go on to receive several life-prolonging systemic agents, which may negate any clinical advantage from a more effective primary local therapy,” Dr. Michalski and associates wrote.

 

Results of the study support that hypothesis. Patients who received the standard dose radiotherapy were significantly more likely to go on to salvage therapy, compared with patients in the dose-escalation arm.

Dr. Michalski and his associated reported on the randomized NRG Oncology/RTOG 0126 clinical trial, which included 1,532 patients with intermediate-risk cancer enrolled between March 2002 and August 2008 at one of 104 North American sites.

In the trial, patients with intermediate-risk prostate cancer were randomized to receive three-dimensional conformal radiation therapy or intensity-modulated radiation therapy to 79.2 Gy in 44 fractions or 70.2 Gy in 39 fractions, the study said.

With a median follow-up of 8.4 years for 1,499 patients, there was no difference in overall survival between arms, study results show. The 8-year rates of overall survival were 76% for dose-escalated radiotherapy and 75% for standard radiotherapy (hazard ratio, 1.00; 95% confidence interval, 0.83-1.20; P = .98).

Otherwise, patients in the dose-escalated radiotherapy arm had significantly lower rates of distant metastases (4% vs. 6%; P = 0.05), and lower rates of biochemical failure rates at both 5 and 8 years, investigators said.

 

Patients in the high-dose arm less often went on to salvage therapy; however, investigators noted that they also had more toxic effects. compared with patients in the standard radiotherapy arm.

“The advantage of avoiding or delaying the adverse effects of these therapies has to be weighed against the increased rate of RT-related morbidity with dose escalation,” Dr. Michalski and his associates wrote.

Dr. Michalski reported no conflicts of interest. The co-authors reported several conflicts of interest, including ties to ViewRay, Augmenix, Sanofi, AstraZeneca, AbbVie, and other companies.

[email protected]

SOURCE: Michalsky Jeff M et al. JAMA Oncol. 2018 Mar 15. doi: 10.1001/jamaoncol.2018.0039.

 

Dose-escalated radiation therapy reduced the need for subsequent therapy in patients with intermediate-risk prostate cancer but did not improve overall survival, according to results of a large, randomized clinical trial.

The absence of a survival benefit compared with standard radiation therapy was seen despite a reduction in rates of both biochemical failure and distant metastases, Jeff M. Michalski, MD, and his associates reported in JAMA Oncology.

Negative overall survival results may be attributable to the growing availability of systemic salvage therapies that have prolonged the natural history of this disease, said Dr. Michalski, MD, of the department of radiation oncology at Washington University in St. Louis.

“Patients experiencing a biochemical or clinical failure may go on to receive several life-prolonging systemic agents, which may negate any clinical advantage from a more effective primary local therapy,” Dr. Michalski and associates wrote.

 

Results of the study support that hypothesis. Patients who received the standard dose radiotherapy were significantly more likely to go on to salvage therapy, compared with patients in the dose-escalation arm.

Dr. Michalski and his associated reported on the randomized NRG Oncology/RTOG 0126 clinical trial, which included 1,532 patients with intermediate-risk cancer enrolled between March 2002 and August 2008 at one of 104 North American sites.

In the trial, patients with intermediate-risk prostate cancer were randomized to receive three-dimensional conformal radiation therapy or intensity-modulated radiation therapy to 79.2 Gy in 44 fractions or 70.2 Gy in 39 fractions, the study said.

With a median follow-up of 8.4 years for 1,499 patients, there was no difference in overall survival between arms, study results show. The 8-year rates of overall survival were 76% for dose-escalated radiotherapy and 75% for standard radiotherapy (hazard ratio, 1.00; 95% confidence interval, 0.83-1.20; P = .98).

Otherwise, patients in the dose-escalated radiotherapy arm had significantly lower rates of distant metastases (4% vs. 6%; P = 0.05), and lower rates of biochemical failure rates at both 5 and 8 years, investigators said.

 

Patients in the high-dose arm less often went on to salvage therapy; however, investigators noted that they also had more toxic effects. compared with patients in the standard radiotherapy arm.

“The advantage of avoiding or delaying the adverse effects of these therapies has to be weighed against the increased rate of RT-related morbidity with dose escalation,” Dr. Michalski and his associates wrote.

Dr. Michalski reported no conflicts of interest. The co-authors reported several conflicts of interest, including ties to ViewRay, Augmenix, Sanofi, AstraZeneca, AbbVie, and other companies.

[email protected]

SOURCE: Michalsky Jeff M et al. JAMA Oncol. 2018 Mar 15. doi: 10.1001/jamaoncol.2018.0039.