This meta-analysis pooled 25 randomized trials (n=12,479) comparing definitive prostate radiation dose regimen. Dose-escalation strategies (i.e., using brachytherapy or focal external beam simultaneous integrate boosts) delivered a statistically significant improvement in metastasis-free survival (HR 0.76) and biochemical control (HR 0.43), with a signal toward improved overall survival emerging after excluding shorter follow-up data. In contrast, hypofractionation showed a modest improvement in biochemical control (HR 0.88), reaching significance only after removing lower-dose outliers. On the flip-side, hypofractionation increased acute grade 2+ GI events (RR 1.43), with a small bump in acute GU grade 3+ events in ultra-hypo regimens, while dose-escalation carried a higher risk of late GU grade 3+ events, largely driven by ASCENDE-RT. With all of that said, EQD2 modeling didn’t convincingly explain these differences so a convincing ������/������ assignment for prostate cancer remains elusive. | Marcin Miszczyk, Radiother Oncol 2026
