Background: Prostate cancer (PCa) is a leading global malignancy, with unfavorable intermediate‑risk (UIR) and high‑risk (HR) disease requiring optimized treatment strategies. Hypo fractionated intensity‑modulated radiotherapy (HF IMRT) has gained attention due to the low α/β ratio of prostate cancer, suggesting enhanced sensitivity to larger fraction sizes. This study compares PSA kinetics, dosimetric and toxicity outcomes between HF IMRT and conventional fractionated IMRT (CF IMRT).

Methods: In this prospective phase II study, 60 patients with UIR or HR localized PCa were enrolled. 30 patients received HF IMRT (60 Gy in 20 fractions over 4 weeks), while 30 underwent CF IMRT (74–80 Gy in 37–40 fractions over 7.4–8 weeks). All patients received androgen deprivation therapy. PSA levels were monitored regularly, and biochemical relapse‑free survival (BRFS) was defined by the Phoenix criterion. Dosimetric parameters for bladder, rectum, femoral heads, bowel, and penile bulb were analyzed.

Results: After a median follow‑up of 17 months, 2.5‑year BRFS was 96.7% in the HF IMRT group versus 90% in the CF IMRT group (p =0.612). PSA nadir values were comparable, but time to nadir was significantly shorter with HF IMRT (12.8 vs. 17.1 months, p = 0.019), indicating a more rapid biochemical response. Dosimetric analysis revealed significantly lower bladder and rectal dose‑volume exposures (p < 0.001) and reduced femoral head maximum dose with HF IMRT. Target coverage metrics (D95, CI, HI) were similar between groups, confirming oncologic equivalence.

Conclusion: Hypo fractionated IMRT demonstrates durable PSA control with greater treatment efficiency and improved dosimetric safety compared to CF IMRT. As a phase II study, these findings are preliminary and subject to inherent limitations; therefore, definitive conclusions cannot be drawn. Nonetheless, they provide a strong rationale for appropriately designed phase III trials to validate the benefits of hypofractionation in unfavorable intermediate- and high-risk prostate cancer.