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In men with localized, intermediate-risk prostate cancer, stereotactic body radiation therapy (SBRT) was associated with less toxicity at 2 years but a higher rate of biochemical failure at 3 years than moderately hypofractionated intensity-modulated radiation therapy (IMRT), a recent phase 3 trial found.

“Patients have different priorities and values when it comes to their care. Some may prioritize convenience and minimizing impact on daily life, while others focus primarily on achieving the strongest possible cancer control,” said GU005’s principal investigator Rodney Ellis, MD, radiation oncologist at the University of South Florida, Tampa, Florida. “These results [can] help inform those deeply personal decisions.”

The NRG-GU005 trial, presented at the American Society for Radiation Oncology (ASTRO) 2025 Annual Meeting in San Francisco, addressed a long-standing question in prostate radiotherapy: Can men safely opt for a shorter, lower-dose SBRT regimen instead of the more traditional longer, higher-dose IMRT regimen?

To evaluate this, 698 patients were randomized to receive SBRT (n = 353) or IMRT (n = 345). The SBRT arm received 36.25 Gy in five fractions over about 2 weeks, while the IMRT group received 70 Gy in 28 fractions or 60 Gy in 20 fractions over about 4-6 weeks.

The researchers found that SBRT came with a better side-effect profile. At 2 years, almost 44% of men in the IMRT arm reported a decline in bowel function compared with nearly 35% of men in the SBRT arm (P = .034). Overall urinary irritation or obstruction was less common after SBRT but not significantly so (33.7% vs 34.7%; P = .68); however, significantly fewer patients in the SBRT group experienced urinary incontinence 2 years post-treatment (26% vs 35%; P = .023). And fewer in the SBRT arm had sexual issues 1 year after treatment (34% vs 44%; P = .026).

The use of rectal spacers — injectable hydrogel that temporarily separates the prostate from the rectum — could also help reduce radiation-related bowel injury. More than half of the men in both treatment arms opted for rectal spacers, which was associated with a modest but consistent reduction in bowel toxicity.

That rectal spacers “showed consistent reductions in toxicity in both arms is noteworthy,” commented trial discussant Matthew Abramowitz, MD, a radiation oncologist at the University of Miami, Coral Gables, Florida.

As for local recurrence and overall survival, the researchers found no statistically significant difference between the two groups at 3 years. Disease-free survival modestly favored IMRT (92.1% vs 88.6%), driven primarily by a higher biochemical failure rate in the SBRT arm (7.8% vs 4.2%; P = .0367).

Abramowitz thought that underdosing was the most plausible explanation for the disease control outcomes in the SBRT arm. He pointed to the UK’s PACE-B trial — the only other large randomized comparison of SBRT and IMRT for localized prostate cancer — which enrolled 874 mostly intermediate-risk men and used a higher SBRT dose of 40 Gy in five fractions to the clinical target volume.

In contrast to the current analysis, PACE-B found no difference in disease control at 5 years between SBRT and IMRT. However, genitourinary toxicity favored IMRT: 26.9% of SBRT patients vs 18.3% of IMRT patients had grade 2 or higher GU side effects at 5 years.

“I think SBRT for low- and intermediate-risk prostate cancer is clearly here to stay based on the convenience and the potential for reduced toxicity,” Abramowitz said. “However, I think 36.25 [Gy] in five [fractions] is inadequate,” noting that the PACE-B dose of 40 Gy in five fractions should be the standard for SBRT.

Both Ellis and Abramowitz also suggested a potential middle ground that could preserve quality-of-life benefits with SBRT while addressing concerns about cancer control.

In his own practice, Ellis noted that he treats the entire prostate with SBRT — the standard of care — and boosts the dose directly to the tumor, something not done in either GU005 or PACE-B.

“When I see a tumor buried in the prostate, I’ll circle and mark that area and dose-paint it to a higher level. I’m getting the same results I think you’d expect to see on PACE-B while trying to match the lower toxicity seen in GU005,” he told Medscape Medical News.

Abramowitz concurred, noting that “the integration of a flame-style micro-boost to SBRT may be a solution to further dose escalation.”

GU005 was funded by the National Institutes of Health. Ellis and Abramowitz reported having no disclosures.

M. Alexander Otto is a physician assistant with a master’s degree in medical science and a journalism degree from Newhouse. He is an award-winning medical journalist who worked for several major news outlets before joining Medscape Medical News. Alex is also an MIT Knight Science Journalism fellow. Email: aotto@mdedge.com.