New research suggests that a shortened course of radiation therapy is safe and effective for men with high-risk prostate cancer. Presented at the recent American Society for Radiation Oncology (ASTRO) Annual Meeting, findings from the randomized study confirmed that men with high-risk prostate cancer can be treated with 5 versus 8 weeks of radiation therapy, according to the authors (Abstract 4). They noted that the Phase III clinical trial is the first to substantiate the safety and efficacy of a moderately shortened course of radiation exclusively for patients with high-risk disease.
"Large, randomized studies have confirmed the safety and efficacy of moderately shortened, or hypofractionated, radiation therapy for patients with low-, intermediate-, or mixed-risk prostate cancer," according to an ASTRO statement. "The PCS5 trial is the first to show the same results specifically for men with high-risk disease."
High-risk disease makes up about 15 percent of prostate cancer diagnoses, with high-risk prostate cancers having the potential "to progress to a lethal phenotype that can be fatal," according to past research, "in marked contrast to low-risk tumors deemed suitable for active surveillance" (Nat Rev Clin Oncol 2014; doi: 10.1038/nrclinonc.2014.68).
These patients face a higher likelihood than the lower-risk groups of their cancer recurring and/or spreading. In those instances, they are more likely to die, noted the authors of the study presented at ASTRO, adding that the radiobiological properties of prostate cancer cells make them particularly sensitive to changes in radiation therapy fraction size. The idea behind this study-delivering moderately higher doses of radiation therapy per day in conjunction with long-term androgen deprivation therapy (ADT)-was that it's possible to maintain the same prostate cancer control rates as with standard fractionation, but in a shorter period of time.
Study Details
In this multi-center Canadian trial, 329 patients were randomized to receive either standard/conventionally fractionated prostate radiation (76 Gy in 38 daily sessions) or moderately hypofractionated radiation (68 Gy in 25 daily sessions). Patients had to have high-risk disease, indicated by a higher Gleason score (8-10), Stage T3a or higher, or PSA above 20 to be eligible for the study. All patients also received radiation to the pelvic lymph nodes and long-term ADT before, during, and after radiation. The median duration was 24 months.
Seven years after completing radiation therapy, the men who received hypofractionated or standard treatment had similar rates of recurrence and survival. Comparing patients who received accelerated versus standard treatment, researchers found no differences in overall survival (81% vs. 82%), prostate cancer-specific mortality (94.9% vs. 96.4%), biochemical recurrence (87.4% vs. 85.1%), distant metastatic recurrence (91.5% vs. 91.8%), or disease-free survival (86.5% vs. 83.4%).
Side effects were also similar between the treatment arms. There were no Grade 4 toxicities in either arm, and no significant differences in severe short-term or long-term genitourinary and gastrointestinal toxicities. The research team was "pleasantly surprised" that side effects were not significantly more pronounced with accelerated treatment, according to ASTRO.
While most patients with high-risk prostate cancer can benefit from the shorter course of radiation therapy, some patients, such as those who previously had prostate treatment (focal therapy), remote pelvic radiation therapy for other reasons or those with active inflammatory bowel disease, among other reasons, were excluded from the trial and should still be treated with 8 weeks of radiation, according to the researchers.
Lead author Tamim M. Niazi, MD, Associate Professor of Oncology at McGill University and a radiation oncologist at Jewish General Hospital in Montreal, Canada, attributes the key finding to the lower alpha/beta ratio of the prostate compared to the surrounding organs at risk (the bladder and rectum), which allows for larger doses of therapeutic radiation to prostate tumors.
"The efficacy and toxicities were rather similar in both arms," Niazi noted. "And, as such, patients in both arms tolerated the treatment well."
Looking ahead at how these results could impact the way care teams approach the treatment and management of high-risk prostate cancer patients, Niazi stated that "high-risk prostate cancer patients who choose treatment with external beam radiation therapy with long-term androgen deprivation therapy can be offered moderately hypofractionated radiation therapy (68 Gy in 25 fractions) with long-term ADT as a standard option."
Mark McGraw is a contributing writer.