Hypofractionated Dose Escalation Versus Conventionally Fractionated Radiation Therapy for Patients With Intermediate-...

The HYpofractionated irradiation for PROstate cancer trial was a multicenter, randomized, phase 3, superiority trial comparing dose escalated hypofractionation (HF) with conventional fractionation (CF) for the treatment of localized intermediate- and high-risk prostate cancer. This trial aimed to demonstrate equivalent toxicity of HF. In prior publications, noninferiority of acute and late toxicity could not be established. Here, we report the long-term survival outcomes.

We randomly assigned patients (1:1) with intermediate- to high-risk T1b-T4NX-N0MX-M0 localized prostate cancer to receive either HF (64.4 Gy in 19 fractions of 3.4 Gy, 3 fractions per week) or CF (78.0 Gy in 39 fractions of 2 Gy, 5 fractions per week) radiation therapy. The HF schedule was a dose escalation compared with CF, based on a α/β ratio of prostate cancer of ∼1.5 Gy, the equivalent total dose in fractions of 2 Gy is 90.4 Gy for HF versus 78.0 Gy for CF. The primary endpoint of this paper was relapse-free survival at 10 years and secondary outcome was overall survival.

Of the 820 patients, 804 were included in the current evaluation, 407 patients received HF and 397 CF radiation therapy. The 10-year relapse-free survival was 64.5% (95% CI, 58.6-69.7) in the HF arm compared with 60.1% (95% CI, 53.9-65.8) in the CF arm (hazard ratio, 0.89; 95% CI, 0.69-1.14; P = .35). The 10-year overall survival in the HF arm was 69.2% (95% CI, 64.1-73.7) versus 61.2% (95% CI, 55.7-66.2) in the CF arm (hazard ratio, 0.82; 95% CI, 0.65-1.05; P = .11).

In the updated findings, we could not demonstrate a statistically significant improvement in 10-year relapse-free survival following dose escalated HF compared with CF. Although patients in the HF arm showed a favorable 10-year overall survival, this difference did not remain statistically significant in the multivariable analysis.