A Prospective, Single-Arm, Phase II, Multi-Center Study of Stereotactic Body Radiation Therapy for Low- and Intermediate-Risk Prostate Cancer

Abstract

To measure the biochemical disease-free survival (bDFS) & the rates of acute & late gastrointestinal (GI) or genitourinary toxicity (GU) following stereotactic body radiation therapy (SBRT) for clinically localized prostate adenocarcinoma.Eligible men aged 18 years & older with NCCN low- & intermediate-risk prostate cancer & ECOG performance status 0-1 were enrolled at two institutions. Participants were simulated with a Foley catheter to visualize the prostatic urethra. All patients received MRI. Participants received 36.25 Gy in 5 fractions on non-consecutive days to the planning target volume (PTV) with a simultaneous boost of 40 Gy to the entire prostate. Treatment was performed on a linear accelerator or frameless robotic radiosurgery system. Androgen deprivation therapy & hydrogel spacer placement were not permitted. The coprimary endpoints were grade 3 or higher GI or GU toxicity as measured by CTCAE v3.0 & bDFS using the Phoenix criteria. This study was designed to test the null hypothesis that the cumulative incidence of Grade 3 or higher GI/GU toxicity rate at 2 years was less than 10%. With n = 200 eligible patients, there was 99% power of identifying an unacceptable toxicity rate if the true toxicity rate was 20% with a one-sided significance level of 0.05. Assuming a 2-year bDFS rate of 97% for SBRT, a sample size of 200 patients also provided 92% power to determine if SBRT was superior to a historical bDFS control rate of 92%. Secondary endpoints were quality of life (QoL), prostate cancer-specific mortality, & overall survival.From January 2011 to July 2020, we enrolled 163 men. The trial was stopped early due to slow accrual. Two men were deemed ineligible & one man withdrew consent leaving 160 evaluable men. Median age was 67.9 years (IQR 62.6-73.2), 60 men (37.5%) were low risk, and 100 (62.5%) were intermediate risk. Median prostate volume was 41.5 cm3 (IQR 35.0-59.2), median baseline IPSS was 7 (IQR 3-12), and median baseline SHIM was 15 (IQR 3-23). Median PTV coverage was 96.9%. With a median follow-up of 2.2 years, the worst acute GU toxicity proportions were grade 2 in 51 (31.9%) & grade 1 in 66 (41.2%) patients, and the worst acute GI toxicity proportions were grade 2 in 7 (4.3%) and grade 1 in 30 (18.8%) patients. The cumulative incidence of late GI and GU grade 2 adverse events were 3.1% and 20.6%, respectively. No acute or late grade 3 or higher GI or GU toxicities were reported, meeting the co-primary safety endpoint (P < 0.001). 2-year bDFS was 98%, significantly higher than historical control (P < 0.01). Dosimetric correlates for toxicities and QoL will be reported separately.In one of the largest prospective series to date, prostate SBRT for low- and intermediate-risk prostate cancer is efficacious and well tolerated, with high rates of early biochemical control and low rates of clinically significant toxicity. Long-term outcomes will be reported with longer follow-up.