Stereotactic Ablative Radiotherapy for High-Risk Prostate Cancer-a Prospective Multi-level MRI-based Dose Escalation Trial.

Purpose Radiation dose intensification improves outcome in men with high-risk prostate cancer (HR-PCa). A prospective trial was conducted to determine safety, feasibility, and maximal tolerated dose (MTD) of multi-level MRI-based 5-fraction stereotactic radiation (SAbR) in patients with HR-PCa. Methods and Materials This phase I clinical trial enrolled HR-PCa patients with grade group ≥4, PSA ≥ 20ng/ml, or radiographic ≥T3, and well-defined prostatic lesions on multi-parametric MRI (mpMRI) into 4 dose-escalation cohorts. The initial cohort received 47.5Gy to the prostate, 50Gy to mpMRI-defined intra-prostatic lesion(s), and 22.5Gy to pelvic lymph nodes in 5 fractions. Radiation doses were escalated for pelvic nodes to 25Gy and mpMRI lesion(s) to 52.5Gy and then 55Gy. Escalation was performed sequentially according to rule-based trial design with 7-15 patients per cohort and a 90-day observation period. All men received peri-rectal hydrogel spacer, intra-prostatic fiducial placement, and 2 years of androgen deprivation. The primary endpoint was MTD according to a 90-day acute dose-limiting toxicity (DLT) rate Results Fifty-five of the 62 enrolled patients were included in the analysis. Dose was escalated through all 4 cohorts without observing any DLTs. Median overall follow-up was 18 months, with a median follow-up of 42, 24, 12, and 7.5 months for cohorts 1-4 respectively. Acute and late grade 2 GU toxicities were 25% and 20%, while GI were 13% and 7%, respectively. Late grade 3 GU & GI toxicities were 2% and 0%, respectively. Conclusions SAbR dose for HR-PCa was safely escalated with multi-level dose painting of 47.5Gy to prostate, 55Gy to mpMRI-defined intra-prostatic lesions, and 25Gy to pelvic nodal region in 5 fractions. Longer and ongoing follow-up will be required to assess late toxicity.