Every-Other-Day Versus Once-a-Week Urethra-Sparing Prostate Stereotactic Body Radiation Therapy: 5-Year Results of a Randomized Phase 2 Trial

Abstract

To present the 5-year results from a prospective multicenter phase II randomized trial of every-other-day (EOD) vs. once-a-week (QW) urethra-sparing stereotactic body radiotherapy (SBRT) for localized prostate cancer. Between 2012 and 2015, 170 patients from nine European institutions with cT1c-3aN0M0 prostate cancer were randomized to 36.25 Gy in 5 fractions (6.5 Gy/fraction to the urethra) delivered either EOD (arm A, n=84), or QW (arm B, n=86). The median follow-up was 78 months (interquartile range, IQR 23 months) and 77 months (IQR 16 months) for arms A and B, respectively. Among the 165 patients treated and retained for the final analysis (arm A, n=82; arm B= 83), acute toxicity (CTCAE v4.03 scale) was mild or absent with no differences between arms. The 5-year ≥ grade-2 genitourinary (GU) toxicity-free survival was 75.9% and 76.1% for arms A and B, respectively (p=0.945), while the 5-year ≥ grade-2 gastrointestinal (GI) toxicity-free survival was 89% and 92% for arms A and B, respectively (p=0.596). No changes in EORTC QLQ-PR25 scores were observed in both arms for GU, GI, and sexual domains at 5-year follow-up compared to baseline. At the last follow-up, biochemical failure was observed in 14 patients in the EOD arm and in 7 patients in the QW arm with a 5-year biochemical relapse-free survival rate of 92.2% and 93% for arms A and B, respectively (p=0.13). Prostate cancer SBRT with a 10% dose reduction to urethra was associated with a minimal impact on urinary function and quality of life regardless of a EOD or QW fractionation schedule. Biochemical control so far, has been encouraging and much alike in both study arms, though longer follow-up is probably needed to assess the true value of overall treatment time on disease outcome.