Phase I Trial of Stereotactic Radiotherapy Prior to Robotic Prostatectomy in High Risk Prostate Cancer

Abstract

Standard therapies for patients with high risk prostate cancer (HR-CaP) include radiotherapy (RT) with hormonal therapy and radical prostatectomy (RP), usually followed by 6-7 weeks of local RT. Given recent data in the breast and pancreas cancer literature about the feasibility of preoperative stereotactic body RT (SBRT), we developed a prospective phase I trial investigating pre-operative SBRT dose escalation in patients with HR-CaP. Patients were eligible if they had HR-CaP, defined as a Gleason Score (GS) 8-10 on biopsy specimen. Patients received a total of 25 Gy or 30 Gy in 5 daily fractions of SBRT to the prostate and proximal seminal vesicles. Patients underwent robotic RP with pelvic lymph node dissection approximately 5 weeks after completion of RT. Primary outcomes were physician-reported genitourinary (GU) and gastrointestinal (GI) toxicities (CTCAE v4). Secondary outcomes were patient-reported quality of life (QoL) on AUA and EPIC questionnaires and biochemical recurrence (BcR), defined as PSA ≥0.2ng/mL. PSA was monitored every 3-6 months. Three patients received SBRT to 25 Gy in 5 fractions and four patients received 30 Gy in 5 fractions. Median time to RP after SBRT was 35 days (range 31-45). Median follow-up was 18 months. Patient characteristics are summarized in the accompanying table. Each patient experienced at least one Grade 2 GU event; most commonly erectile dysfunction (100%) and urinary incontinence (57%). One patient experienced Grade 3 urinary incontinence, but there were no Grade ≥4 GU toxicities. Two patients experienced GI toxicity which were one Grade 1 and one Grade 2 hemorrhoidal hemorrhage. On QoL surveys, acute GU complaints were common and peaked at 3 months (mean AUA total score 14.2, mean EPIC overall urinary function score 3). Acute bowel complaints were mild and uncommon, with only one patient reporting a score of ≥3 on EPIC overall bowel function score. Two patients experienced BcR; both had GS 4 + 5 with ypN1 disease at the time of RP, while one of the two was ypT3b and the other was ypT3a. Neither had evidence of distant metastasis on CT or bone scans. Both BcR were salvaged with leuprolide and bicalutamide with subsequent decrease in PSA. Pre-operative SBRT followed by RP in HR-CaP is feasible and safe. It is associated with moderate GU toxicity and rare GI toxicity. Phase II trials evaluating this treatment paradigm should exclude patients with GS 5, and those with clinically or radiographically T3b or node positive disease. A prospective trial is ongoing to determine the efficacy of pre-operative SBRT in selected patients with HR-CaP.Abstract 4112; TableCaseAge (y)SBRT Dose (Gy)GS (pre-op)PSA (pre-op)PSA (post-op)Stage (post-op)Surgical MarginsF/U (m)1**62254 + 525.330.59ypT3bN1+34254254 + 47.91<0.02ypT3aN0+26358254 + 48.40<0.02ypT2cN0-10464304 + 48.66<0.02ypT3aN0+24564304 + 45.93<0.02ypT2aN0-17658304 + 45.94<0.02ypT3aN0-187**66304 + 551.703.69ypT3aN1-12**Patient experienced biochemical recurrence Open table in a new tab