Stereotactic Ablative Radiation And Short-Term Androgen Ablation For Intermediate-Risk Localized Prostate Adenocarcinoma: Safety And Toxicity From A Prospective Single-Arm Phase Ii Trial (Nct01517451)

Stereotactic ablative radiation (SABR) is a safe, effective, and convenient treatment for localized prostate cancer. Short-term androgen deprivation therapy (STADT) is the standard of care for men with intermediate-risk prostate cancer treated with conventionally fractionated RT but the majority of SABR data in men with intermediate-risk prostate cancer is without ADT and no prospective trials have exclusively examined STADT with prostate SABR in intermediate-risk men. We hypothesized STADT would enhance the efficacy without significantly worsening toxicity or quality of life (QOL). Eligible patients were >18 years old with histologically and radiologically confirmed localized prostate cancer meeting D’Amico intermediate-risk criteria (T2b-T2c, PSA 10-20 ng/mL, Gleason 7). Exclusion criteria included International Prostate Symptom Score (IPSS) > 15, prior radical prostatectomy or pelvic RT, chemotherapy within 5 years, inflammatory bowel disease, and significant comorbidity. Patients received 5 fractions of 7.25 Gy over 2 weeks via volumetric modulated arc therapy (VMAT) with daily cone-beam CT (n = 45) or robotic radiosurgery (n = 1). Gold fiducials were used in 36 patients. STADT was 4 months LHRH agonist plus ≥2 weeks bicalutamide beginning at least 1 month prior to radiotherapy. The primary objective is 5-year biochemical failure free rate with failure defined as nadir + 2 ng/mL. Secondary objectives include CTCAE v4.0 adverse events (AEs) and self-reported QOL data including IPSS, Sexual Health Inventory for Men (SHIM), and Extended Prostate Cancer Index Composite (EPIC-26) bowel domain. From 8/2013 and 10/2017, 45 patients were treated across 3 institutional sites (1 lost to follow-up). Median follow-up is 23 months. Eight patients experienced grade 2 hot flashes and 2 experienced grade 2 diarrhea on treatment; 2 experienced grade 2 urinary frequency/urgency at 3 months post-treatment. No other grade 2 AEs occurred in more than one patient per time point. One patient experienced a grade 3 myocardial infarction at 4 months post-treatment; no other grade 3 or higher AEs were noted. There were two patient deaths not attributable to prostate cancer or study interventions. Median IPSS at baseline was 7 (IQR 3.75-10) which increased to a maximum of 10 (IQR 7-15) at 8 months and was 7 (IQR 3.75-9) at most recent follow-up. Median SHIM at baseline was 5.5 (IQR 2-19.5) which decreased to a minimum of 1 (IQR 1-2.25) at 7.5 months and was 2 (IQR 1-15) at most recent follow-up. Among 23 evaluable patients, median EPIC-26 bowel domain at baseline was 100 (IQR 87.5-100) which decreased to a minimum of 87.5 (IQR 81.25-95.8) at 11 months and returned to 100 (IQR 91.7-100) at most recent follow-up. SABR to the prostate with STADT is safe and well-tolerated with toxicity comparable to conventionally fractionated regimens.