Stereotactic Body Radiotherapy for High-Risk Prostate Cancer: Preliminary Toxicity Results of a Phase 2 Trial

Abstract

Stereotactic body radiotherapy (SBRT) for high-risk prostate cancer (CaP) remains investigational not only due to undetermined efficacy but also due to concerns for the potential toxicity when the treatment volumes extend beyond the prostate gland itself. Herein we present the preliminary toxicity results of a phase II trial evaluating a five fraction SBRT regimen for high-risk CaP that allows for the integration pelvic nodal radiation (RT) and androgen deprivation therapy (ADT). Men with high-risk CaP, as defined by Gleason score >= 8, clinical stage T3-T4, or initial PSA >= 20 ng/mL, were enrolled on a multicenter phase II trial and were treated with 40 Gy to prostate. Radiation to the pelvic nodes with 25 Gy in a simultaneous integrated boost plan (5 Gy per fraction) and/or a nine months neoadjuvant and concurrent androgen deprivation therapy (ADT) could be integrated with prostate SBRT at the discretion of the treating physician. Follow-up assessment was with CTCAE v4 and Expanded Prostate Composite Index (EPIC). SBRT was delivered with a linear accelerator using volumetric modulated arc therapy or with a CyberKnife system. A total of 73 patients have been treated on this protocol, with a median follow-up of 13.8 months. Forty-six (63%) received ADT and 23 (32%) received nodal RT. The median initial PSA was 8.8 ng/mL and 11% of patients had clinical T3-T4 disease; 48% and 33% had Gleason score 8 and 9-10 disease, respectively. No grade 3 or higher genitourinary (GU) or gastrointestinal (GI) toxicities were seen. For patients receiving nodal radiation, rates of acute grade 1 and 2 GU toxicities were 18.2% and 4.5%; for those not receiving nodal RT, they were 23.5% and 17.6%. Rates of acute grade 1 and 2 GI toxicities were 9.1% and 9.1% with and 11.8% and 3.9% without nodal RT. Late grade 1 and 2 GU toxicities rates with nodal RT were 27.3% and 4.5%; without nodal RT, the rates were 18.6% and 7.0%. Late grade 1 and 2 GI rates were 13.6% and 13.6% with nodal radiation and 11.6% and 4.7% without it. Mean changes in EPIC urinary and bowel domain scores at 4 months were +0.13 and -4.17 with nodal RT, and +0.79 and -2.97 without it. Mean changes in EPIC urinary and bowel domain scores at 12 months were -1.52 and -5.12 with nodal RT and -1.71 and -5.67 without it. Overall, the receipt of nodal RT had no significant association with either physician- or patient-reported toxicity profiles (p > 0.1, Fisher’s exact test). Similarly, the receipt of ADT had no significant association with any toxicity parameter. Two patients (2.7%) experienced biochemical failure; in both cases, the PSA never decreased after SBRT. SBRT regimens can be safely utilized to deliver the entire course in 5 treatment days in patients with high-risk localized CaP, with or without the integration of nodal RT and/or short-course ADT. Despite the short followup, the low rate of biochemical failure is encouraging.