Phase 2 Multicenter Trial of Heterogeneous-dosing Stereotactic Body Radiotherapy for Low- and Intermediate-risk Prostate Cancer: 5-year Outcomes

Stereotactic body radiation therapy is an emerging treatment for prostate cancer (PC), with potential biological and oncologic advantages. A well-established radiation dosing schedule (38Gy in 4 fractions) has shown excellent long-term efficacy in high-dose-rate (HDR) brachytherapy. To report 5-yr efficacy, toxicity, and quality-of-life (QOL) outcomes of a novel 4-d SBRT regimen. This was a single-arm prospective phase 2 trial involving 259 patients with low- or intermediate-risk PC treated at 18 US centers from December 2007 to February 2012. The median follow-up was 5yr (interquartile range 37–85mo). SBRT with 38Gy in four fractions; radiation plans mimicked HDR brachytherapy dosimetry. We measured freedom from biochemical recurrence (BCR) and assessed toxicities using the Common Terminology Criteria for Adverse Events v3.0 and QOL using the Expanded Prostate Cancer Index Composite. The 5-yr BCR-free rates were 100% and 88.5% for patients with low- and intermediate-risk PC, respectively. The cumulative 5-yr grade 2, 3, and 4 toxicity rates were 12.4%, 1.9%, and 0.4% for urinary, and 3.4%, 0%, and 0% for gastrointestinal toxicities, respectively. The median baseline prostate-specific antigen (PSA) level of 5.12ng/ml decreased to 0.1ng/ml by ≥42mo. QOL scores decreased at 1mo but returned to baseline by 6mo, with a later decline (≥24mo) in the urinary continence domain (pad use was 2% at baseline and 10% at 5yr), and lower sexual potency over time. Comparative outcomes versus other types of radiotherapy are difficult because the trial was not randomized. This regimen yields a high rate of BCR-free survival, with a very low median PSA nadir suggesting prostate ablation. For properly selected patients with low- or intermediate-risk PC who choose SBRT, this treatment regimen is effective. This potent four-treatment stereotactic body radiotherapy regimen appears to be effective for patients with early prostate cancer. The 5-yr results from this multicenter phase 2 trial show that a novel four-fraction stereotactic body radiotherapy regimen is safe and effective for properly selected patients with low- or intermediate-risk prostate cancer.