Dose-escalated radiation therapy (RT) does not increase overall survival compared with standard RT in men with localized, intermediate-risk prostate cancer (PCa), a new study finds.
Since previous trials were underpowered to detect survival differences, the NRG Oncology/RTOG 0126 randomized clinical trial (NCT00033631) was designed to test 2 levels of RT exposure. Investigators randomly assigned 1532 patients from 104 institutions to 3-dimensional conformal RT or intensity-modulated RT administered at 79.2 Gy in 44 fractions or 70.2 Gy in 39 fractions. The patients, who were previously untreated, had cT1b to T2b PCa with either a Gleason score of 2 to 6 and PSA level of 10 to 20 ng/mL or a Gleason score of 7 and PSA level less than 15 ng/mL.
At 8 years, the overall survival (OS) rates were 76% for the 79.2 Gy group and 75% for the 70.2 Gy group, a non-significant difference between the groups, Jeff Michalski, MD, MBA, of the Washington University School of Medicine in St. Louis, Missouri, and his colleagues reported in JAMA Oncology.
Biochemical failure, local progression, and distant metastasis rates did improve with RT dose escalation, however. By both the ASTRO and Phoenix definitions, biochemical failure rates at 5 and 8 years were 31% and 20%, respectively, in the 79.2 Gy group compared with 47% and 35%, respectively, in the 70.2 Gy group. The 8-year rates of distant metastasis were 4% in the 79.2 Gy group compared with 6% in the 70.2 Gy group. In addition, fewer high-dose RT patients required salvage therapy: 14.8% vs 22.5%.
As expected, more high-dose RT patients experienced late toxic effects. At 5 years, the rates of late grade 2 or greater gastrointestinal and genitourinary toxic effects were 21% and 12% with 79.2 Gy, respectively, and 15% and 7% with 70.2 Gy, respectively.
“Dose escalation has several clinical advantages including improved rates of biochemical and clinical cancer control. These benefits do not translate into improved OS,” Dr Michalski’s team concluded. “The decision to deliver high radiation dose must be balanced against the risk of morbidity in the individual patient.” To minimize late toxicity, the researchers recommended intensity-modulated RT for select patients and exposing less than 15% of the rectum to more than 70 Gy.
The team acknowledged that notable advances in PCa staging and systemic salvage therapies occurred during the study period (March 2002 to August 2008), which could have influenced survival rates above RT dose.
Michalski JM, Moughan J, Purdy J, et al. Effect of standard vs dose-escalated radiation therapy for patients with intermediate-risk prostate cancer The NRG Oncology RTOG 0126 Randomized Clinical Trial. JAMA Oncol. doi:10.1001/jamaoncol.2018.0039. [Published online March 15, 2018]