Five-session SBRT reduces side effects in intermediate-risk prostate cancer

Five-session SBRT reduces side effects in intermediate-risk prostate cancer

In patients with intermediate-risk localized prostate cancer, five-session radiation therapy reduced patient-reported side effects compared with longer courses of radiation, according to results of a large, randomized phase III trial. Patients treated with stereotactic body radiation therapy (SBRT) reported fewer deteriorations in bowel, urinary and sexual function, but were more likely to have an increase in prostate-specific antigen (PSA). Initial results from the NRG Oncology GU005 trial will be presented today at the American Society for Radiation Oncology (ASTRO) Annual Meeting.

These results provide important new insights that may aid treatment decisions for patients with localized prostate cancer, a disease with typically high cure rates and long life expectancy. The results help clarify what patients can expect from shorter or longer courses of radiotherapy and enable more personalized treatment decisions based on individual priorities.”

Rodney Ellis, MD, principal investigator of the study and professor of radiation oncology at the University of South Florida/Tampa General Hospital

Prostate cancer is the most common solid tumor in male patients. Approximately 70,000 adults in the United States are diagnosed each year with an intermediate-risk disease limited to the prostate for which radiation therapy is a standard treatment option. Historically, patients received external beam radiation therapy in 35 to 45 daily sessions over a period of seven to nine weeks. However, research over the last decade has shown that moderately hypofractionated courses of 20 to 28 sessions over four to six weeks are equally effective.

More recently, researchers have been testing whether SBRT, which delivers higher doses in just five sessions, can further shorten the course of therapy while maintaining high cure rates. SBRT uses advanced imaging and treatment planning techniques to target tumors with extreme precision and minimize radiation exposure to nearby organs such as the bladder and rectum. The approach offers practical benefits, including fewer visits, fewer trips and lower average costs, but requires specialized technology and expertise that may not be widely available.

The NRG-GU005 trial was designed to test whether SBRT would outperform moderately hypofractionated radiation in both cancer control and patient-reported outcomes. Researchers recruited 698 patients with previously untreated intermediate-risk localized prostate cancer at multiple international centers between 2017 and 2022.

Participants were randomly assigned to either SBRT (36.25 Gy in five fractions, n = 353) or moderately hypofractionated intensity-modulated radiotherapy (MH-IMRT, 70 Gy in 28 fractions or 60 Gy in 20 fractions, n = 345). Co-primary endpoints combined clinical measures of disease control with patient-reported outcomes collected via questionnaires at baseline, 12 months and 24 months post-treatment to track whether patients experienced clinically meaningful declines in bowel, urinary or sexual function.

Fewer patients treated with SBRT reported clinically meaningful decline in bowel function at two years (34.9% vs. 43.8% with MH-IMRT, p = 0.034). Overall, urinary quality of life was similar between groups, but urinary incontinence was less common two years after SBRT (decrease of 25.9% vs. 34.7% with MH-IMRT, p = 0.023). Sexual function scores favored SBRT at one year (34% vs. 44%, p = 0.026) but were similar at two years (43 vs. 41%, p = 0.67).

In terms of disease-free survival, 88.6% of patients in the SBRT group were free of disease progression at three years, compared to 92.1% who received longer courses of radiation. The difference was primarily due to higher rates of biochemical failure or increasing PSA after treatment in the SBRT arm (7.8% vs. 4.2%, p = 0.037).

“The PSA findings require careful interpretation,” noted Dr. Ellis. “When treated with higher doses per fraction, patients may experience transient PSA elevations or “benign bounces” that resolve over time. We need five years of follow-up to determine whether these increases result in actual disease progression.”

The GU005 study used a lower total SBRT dose than other recent studies (36.25 vs. 40 Gy), which, according to Dr. Ellis could alternatively explain the higher PSA progression rate. In comparison, the PACE-B trial reported at ASTRO in 2023 found equivalent cancer control with the higher dose, but with increased intestinal side effects. Longer follow-up of GU005 will help clarify whether the lower dose has an impact on long-term outcomes.

Local recurrence rates did not differ between arms (1.2% SBRT vs. 1.0% MH-IMRT at 3 years, p = 0.97), and three-year overall survival was similar at 97% in each group (p = 0.62). Severe genitourinary complications were rare with both treatments but less common with SBRT (0.6% vs. 2.5%, p = 0.04).

The study also found that rectal spacers, gel-like devices that temporarily separate the rectum from the radiation field, appeared to reduce intestinal side effects when used in both treatment groups (in 56% of patients in the SBRT arm and 55% in the IMRT arm).

Dr. Ellis said future research will look at the potential of SBRT for patients with higher-risk conditions and test additional strategies to further reduce side effects while maintaining survival outcomes. He said for now, patients with intermediate-risk prostate cancer have clearer information to help guide their treatment decisions: more convenient treatment with better quality-of-life outcomes, or longer courses of therapy with potentially greater biochemical cancer control.

“Patients have different priorities and values ​​when it comes to their care,” noted Dr. Ellis. "Some may value convenience and minimizing impact on daily life, while others may be primarily focused on achieving the best possible cancer control measures. These findings help inform these deeply personal decisions."

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