Dose escalation does not improve overall survival among patients with intermediate-risk prostate cancer, according to a new study looking at outcomes from 104 radiation therapy oncology groups in the U.S.
“We had hoped that by better controlling the primary tumor it would translate into an improvement in overall survival. But it did not,” according to study author Jeff M. Michalski, MD, MBA, of Washington University School of Medicine in St. Louis.
However, there were significant improvements among those studied on the higher radiation dose in terms of biochemical failure and distant metastases. And while high radiation doses caused more late toxic effects, patients in the standard dose arm of the study had lower rates of salvage therapy.
For the research, which was published in JAMA Oncology (March 15, 2018 [Epub ahead of print]), the authors studied about 1,500 patients with intermediate-risk prostate cancer, who received 3-dimensional conformal radiation therapy or intensity-modulated radiation therapy. Among those, 748 men received the standard 70.2 Gy in 39 fractions, while 751—the investigational group—received increasing doses up to 79.2 Gy in 44 fractions.
Three quarters of the men in the standard group survived after a median 8.4-year follow-up, versus 76% in the investigational group. At 8 years, rates of mortality from prostate cancer were not statistically different, at 4% in the standard radiation dose group, compared to 2% among those receiving the escalated dose.
Secondary outcomes included the 8-year cumulative rate of distant metastases, which was 4% in the 79.2-Gy arm, versus 6% in the 70.2-Gy group. Biochemical failure at 8 years was 20% with 79.2 Gy and 35% with 70.2 Gy—a statistically significant difference. The rate of salvage therapy was significantly reduced with the use of the higher dose of radiation. But high doses caused more late toxic effects.
Today, urologists and other providers measure the success of radiation treatment by PSA outcome, according to Dr. Michalski.
In two biochemical control measures used in this study—the Phoenix definition, a PSA >nadir+2ng/mL and the older American Society for Radiation Oncology definition, which is three consecutive rises in PSA after nadir—Dr. Michalski and colleagues found a rather large improvement in outcome with dose escalation.
“While biochemical control doesn’t mean differences in survival, it does mean a lot to the emotional well-being of the patient to know that their PSA is maintaining a very low level. If the PSA rises, oftentimes, patients will undergo additional investigations or additional therapies that have considerable side effects and toxicity,” he said.