Top Line: We learned at ASTRO that relatively lower-dose ultra-hypofractionated prostate radiation results in less bowel effects at the expense of biochemical control when compared to the more established moderate hypofractionation.
The Study: We now have the full manuscript of NRG-GU005, a phase 3 trial randomizing 698 men with localized favorable intermediate-risk prostate cancer to ultra- (36.25 Gy/5 fractions) versus moderately (70 Gy/28 fractions or 60 Gy/20 fractions) hypofractionated intensity-modulated radiotherapy (IMRT). Conspicuously missing here was any focal microboost which has since become mainstream. At 2 years, there was no difference in clinically meaningful declines in urinary irritative/obstructive quality-of-life (35% with ultra vs 34% with moderate) while ultra-hypofractionation did produce fewer declines in bowel quality-of-life (35% vs 44%). However, the prespecified goal of demonstrating superior disease control with ultra-hypofractionation failed with disease-free survival rates at 3 years of 88.6% versus 92.1%, respectively. Once again, included is a prespecified analysis of non-randomized rectal spacer use which was associated with a higher (+2.8) average bowel function score than non-use, though it is unclear if this was clinically meaningful considering the threshold for a clinically meaningful decline in an individual was defined as -4 points.
TBL: This phase 3 trial doesn't give us a reason to abandon established moderate hypofractionation, and a focal microboost +/- selective use of a rectal spacer for those at highest risk of rectal side effects may expand the therapeutic window of both fractionation schema. | Ellis, JAMA 2026
The Study: We now have the full manuscript of NRG-GU005, a phase 3 trial randomizing 698 men with localized favorable intermediate-risk prostate cancer to ultra- (36.25 Gy/5 fractions) versus moderately (70 Gy/28 fractions or 60 Gy/20 fractions) hypofractionated intensity-modulated radiotherapy (IMRT). Conspicuously missing here was any focal microboost which has since become mainstream. At 2 years, there was no difference in clinically meaningful declines in urinary irritative/obstructive quality-of-life (35% with ultra vs 34% with moderate) while ultra-hypofractionation did produce fewer declines in bowel quality-of-life (35% vs 44%). However, the prespecified goal of demonstrating superior disease control with ultra-hypofractionation failed with disease-free survival rates at 3 years of 88.6% versus 92.1%, respectively. Once again, included is a prespecified analysis of non-randomized rectal spacer use which was associated with a higher (+2.8) average bowel function score than non-use, though it is unclear if this was clinically meaningful considering the threshold for a clinically meaningful decline in an individual was defined as -4 points.
TBL: This phase 3 trial doesn't give us a reason to abandon established moderate hypofractionation, and a focal microboost +/- selective use of a rectal spacer for those at highest risk of rectal side effects may expand the therapeutic window of both fractionation schema. | Ellis, JAMA 2026