Hypofractionated versus conventional IMRT in unfavorable intermediate- and high-risk prostate cancer: A phase II comparative study of PSA kinetics, dosimetric and toxicity outcomes.

Abstract

Background: Prostate cancer (PCa) is a leading global malignancy, with unfavorable intermediate-risk (UIR) and high-risk (HR) disease requiring optimized treatment strategies. Hypofractionated 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. Thirty patients received HF IMRT (60Gy in 20 fractions over 4 weeks) while 30 underwent CF IMRT (74-80Gy 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: Hypofractionated 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.

Level of evidence: Evidence from multiple phase III randomized controlled trials and meta-analyses (Level 1) supports the non-inferiority of HF IMRT compared to CF IMRT, confirming equivalent biochemical control and toxicity outcomes.