Management of Unfavorable Intermediate and High Risk Prostate Cancer with Stereotactic Body Radiation Therapy as Monotherapy Versus Boost: A Ten Year Study

Abstract

The use of stereotactic body radiotherapy (SBRT) in prostate cancer has been increasing in recent years. However, management of high-risk prostate cancer with SBRT remains controversial, in part due to the limited number of reports published and lack of long-term data. In this present study, we add to the existing body of literature by reporting 10-year outcomes for high-risk patients treated with SBRT alone or as a boost to external beam radiotherapy(EBRT). We studied 130 patients with organ-confined prostate cancer, treated between 2006-2009, with robotic arm SBRT (35-36.25 Gy in 5 fx, n=85) or EBRT followed by SBRT boost (45 Gy plus 18-21 Gy boost, n=45). EBRT was delivered as a four field box with 3D planning. SBRT dose was defined to cover a PTV created by a 5mm expansion of the prostate (3mm posteriorly). All patients had NCCN high- (n=73) or unfavorable intermediate-risk disease (n=57; defined as Gleason 4+3=7, or more than 1 intermediate risk factor). Median PSA was 12; median Grade Group of 4; 61 patients received ADT up to 6 months. Biochemical failure was defined using Phoenix criterion. Survival estimates were determined using Kaplan-Meier methods. The 10y biochemical recurrence free survival (bRFS) was 63.0% for both unfavorable intermediate and high-risk patients, with no significant difference between the two groups. Overall local control was 91% and median PSA nadir was 0.12 ng/ml. There was no significant difference in 10y bRFS amongst patients treated with SBRT monotherapy versus SBRT boost (65.0 versus 60.4%), or ADT versus no ADT (62.8 vs 63.3%). On multivariate analysis, PSA was significant for bRFS (P=0.006), whereas ADT, EBRT and Gleason score were not. Toxicity was overall mild. There was no significant difference in G2-3 GU toxicity between patients treated with SBRT boost vs SBRT alone (5.4 vs 9.4%, P=0.29), but a higher (P=0.042) incidence of G2 GI toxicity was noted after EBRT + SBRT boost compared to SBRT alone (13.3% vs 3.5%). There was no G3 GI toxicity. Mean EPIC QOL urinary and bowel domains for all patients declined during the first 3 months and then returned to baseline. Mean sexual QOL scores declined by 40% at 10 years. In conclusion, prostate SBRT appears to be a safe and effective approach for high risk prostate cancer, with biochemical outcomes comparable to HDR brachytherapy and IMRT. The addition of pelvic EBRT or ADT fails to demonstrate clinical benefit with now up to 10 years of follow up. Mature results of prospective studies are awaited to validate these findings.