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

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.