While IMRT and brachytherapy are the most commonly used radiation therapy modalities for clinically localized prostate cancer, SBRT utilization is increasing . The accuracy assured by intra-fraction image guidance, which allows the use of smaller CTV-PTV margins, may allow safe prostate treatment in four or five large (e.g., 7–9.5 Gy) radiation fractions. Emerging data from single institutional series [6–8] and a small multi-institutional Phase I study  suggest that this approach may provide similar clinical outcomes as other radiation modalities with high rates of biochemical control and low rates of grade 3 and higher toxicities. A recent update of grouped series confirmed SBRT achieved 5-year biochemical disease-free survival of 93% in patients with favorable prognosis . Based on these reports, as well as patient preference for a shorter treatment course, SBRT utilization is likely to continue to increase.
Our institutional experience adds to the growing body of evidence supporting the effectiveness and safety of SBRT. Our early PSA outcomes have been favorable. The two-year post-treatment PSA nadir of 0.49 ng/mL predicts a high rate of long-term disease control . This PSA response is unlikely due to declines in testosterone since the majority of patients had stable testosterone over time. As with other SBRT series [6, 7, 20] and other radiation therapy modalities [23, 24], benign PSA bounces were common and transient. Considering that our series includes a higher percentage of intermediate- and high-risk patients than others [6–8, 20], our 99% actuarial 2-year biochemical failure-free survival rate is reassuring.
There is limited data on the use of SBRT for unfavorable patients (6). To date, SBRT studies have included mostly favorable patients due to the concern over limited coverage of potential extracapsular extension and seminal vesicle invasion. A recent dosimetric study suggest that SBRT delivers adequate dose to areas of potential extracapsular extension and the proximal seminal vesicles in unfavorable patients . Although prospective studies are needed to confirm long-term tumor control, currently available data are comparable to results reported for brachytherapy and conventional external beam radiotherapy  .
Toxicity following SBRT was similar to that following external beam radiation therapy or brachytherapy . Late Grade 2 and Grade 3 GU toxicity were observed in 30% and 1% of patients, respectively (Figure 3). Alpha antagonist utilization was the most common grade 2 toxicity, but similar to brachytherapy treatment, it returned to baseline one to two years post-treatment . To maximize patient comfort, it is currently our institutional policy to initiate prophylactic alpha antagonist use prior to initiating treatment. The single grade 3 toxicity was hematuria requiring a TURP. This patient had a history of benign prostatic hypertrophy with a large prostate and two prior TURP procedures and was dependent on intermittent catheterization prior to receiving SBRT. As others have, we recommend that urethral instrumentation following treatment should be limited in patients treated with SBRT . The SF-12 scores showed no significant change throughout the follow-up period suggesting that toxicities did not significantly adversely affect the patients' perceptions of their health.
As seen by other SBRT series , our mean AUA scores returned to baseline by three months post treatment. However, a minority of patients experienced a clinically meaningful increase in their urinary symptoms greater than six months after the completion of treatment. To our knowledge this is the first reported series to characterize late urinary symptom flare [17, 29–32] in patients receiving SBRT. Like conventionally fractionated external beam radiation therapy and brachytherapy, late urinary toxicity occurred in a minority of our patients and resolved with conservative management (urinary anesthetics, alpha-blockers and/or brief steroid tapers). Endoscopic evaluation of these patients has suggested that this may be caused by urethritis (unpublished data). Knowledge of these late urinary toxicities and their resolution with conservative management will enable clinicians to relieve patient concerns and prevent unnecessary invasive procedures such as cystoscopy and/or TURP.
In our opinion, late urinary symptom flare may be exacerbated by the high central doses in our relatively inhomogeneous plans (Figure 1a). With the aim of reducing urinary symptoms, we have modified our institutional protocol. Specifically, we have reduced the anterior/superior PTV expansion to 3 mm to reduce the bladder neck dose. In addition, it is now our practice to prescribe to ≥ 80% isodose line to reduce the dose delivered to the prostatic urethra. Finally, to further reduce the prostatic urethral dose, we have restricted the maximum prostatic urethral dose to 110% of the prescription dose. We believe that such modifications will reduce the incidence and severity of late urinary symptom flare without increasing the risk of local failures [9, 10].
As in other radiation therapy series, our patients were elderly with poor baseline erectile function and high PDE5 inhibitor utilization prior to treatment [33–35]. Similar to other SBRT series [8, 36], 79% of patients who were sexually potent prior to treatment maintained potency at two years’ post-treatment. These results are comparable to results with conventionally fractionated EBRT or brachytherapy [37, 38]. Interestingly, as observed by others, the greatest decline in SHIM occurred in the first year with sexual function stabilization afterwards . The etiology of this early decline in SHIM is uncertain. Fifty-one percent of patients utilized PDE5 inhibitors in follow-up. It is not clear why utilization was not higher following treatment. Potential explanations include patient indifference , limited effectiveness  or the high cost of such medications.
Our study should be examined in the context of the study design. Our study is limited by the retrospective nature of the analysis. However, subjects were accrued consecutively and all data were collected prospectively in a centralized database, therefore limiting selection and reporting bias present in pure retrospective studies. In addition, the narrow focus of the AUA on obstructive symptoms and SHIM on erectile function is another limitation of our study . Future studies should employ more comprehensive instruments to assess the effect of prostate SBRT on overall urinary and sexual function in this elderly patient population.