Stereotactic Body Radiation Therapy for Prostate Cancer: Review of Experience of a Multicenter Phase I/II Dose-Escalation Study

The effectiveness of stereotactic body radiotherapy (SBRT) for localized prostate cancer is tested. A total of 1100 patients with clinically localized prostate cancer were enrolled in separate prospective phase 2 clinical trials of SBRT from 8 institutions during 2003-11 and pooled for analysis. SBRT using the CyberKnife delivered a median dose of 36.25Gy in 4-5 fractions. Patients were low-risk (58%), intermediate-risk (30%) and high-risk (11%). A short-course of androgen deprivation therapy (ADT) was given to 14%. PSA relapse defined as a rise >2ng/ml above nadir was analyzed with the Kaplan Meier method. With a median follow-up of 36months there were 49 patients with PSA failure (4.5%), 9 of whom were subsequently determined to be benign PSA bounces. The 5-year biochemical relapse free survival (bRFS) rate was 93% for all patients; 95%, 83% and 78% for GS ⩽6, 7 and ⩾8, respectively (p=0.001), and 95%, 84% and 81% for low-, intermediate- and high-risk patients, respectively (p 0.2ng/ml was noted among 16% of patients. For 135 patients possessing a minimum of 5years follow-up, the 5-year bRFS rate for low- and intermediate-risk patients was 99% and 93%, respectively. PSA relapse-free survival rates after SBRT compare favorably with other definitive treatments for low and intermediate risk patients. The current evidence supports consideration of SBRT among the therapeutic options for these patients. Copyright © 2013 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Background Stereotactic body radiation therapy (SBRT) delivers fewer high-dose fractions of radiation which may be radiobiologically favorable to conventional low-dose fractions commonly used for prostate cancer radiotherapy. We report our early experience using SBRT for localized prostate cancer. Methods Patients treated with SBRT from June 2008 to May 2010 at Georgetown University Hospital for localized prostate carcinoma, with or without the use of androgen deprivation therapy (ADT), were included in this retrospective review of data that was prospectively collected in an institutional database. Treatment was delivered using the CyberKnife® with doses of 35 Gy or 36.25 Gy in 5 fractions. Biochemical control was assessed using the Phoenix definition. Toxicities were recorded and scored using the CTCAE v.3. Quality of life was assessed before and after treatment using the Short Form-12 Health Survey (SF-12), the American Urological Association Symptom Score (AUA) and Sexual Health Inventory for Men (SHIM) questionnaires. Late urinary symptom flare was defined as an AUA score ≥ 15 with an increase of ≥ 5 points above baseline six months after the completion of SBRT. Results One hundred patients (37 low-, 55 intermediate- and 8 high-risk according to the D’Amico classification) at a median age of 69 years (range, 48–90 years) received SBRT, with 11 patients receiving ADT. The median pre-treatment prostate-specific antigen (PSA) was 6.2 ng/ml (range, 1.9-31.6 ng/ml) and the median follow-up was 2.3 years (range, 1.4-3.5 years). At 2 years, median PSA decreased to 0.49 ng/ml (range, 0.1-1.9 ng/ml). Benign PSA bounce occurred in 31% of patients. There was one biochemical failure in a high-risk patient, yielding a two-year actuarial biochemical relapse free survival of 99%. The 2-year actuarial incidence rates of GI and GU toxicity ≥ grade 2 were 1% and 31%, respectively. A median baseline AUA symptom score of 8 significantly increased to 11 at 1 month (p = 0.001), however returned to baseline at 3 months (p = 0.60). Twenty one percent of patients experienced a late transient urinary symptom flare in the first two years following treatment. Of patients who were sexually potent prior to treatment, 79% maintained potency at 2 years post-treatment. Conclusions SBRT for clinically localized prostate cancer was well tolerated, with an early biochemical response similar to other radiation therapy treatments. Benign PSA bounces were common. Late GI and GU toxicity rates were comparable to conventionally fractionated radiation therapy and brachytherapy. Late urinary symptom flares were observed but the majority resolved with conservative management. A high percentage of men who were potent prior to treatment remained potent two years following treatment.

Recent reports using extreme hypofractionated regimens in the treatment of low-risk prostate adenocarcinoma have been encouraging. Here, the authors report on their own multi-institutional experience with extreme hypofractionated stereotactic radiotherapy for early stage disease. In total, at 4 centers, 45 patients with National Comprehensive Cancer Network-defined, low-risk prostate adenocarcinoma were enrolled in a phase 1, multi-institutional trial of hypofractionated radiosurgery with a proprietary radiosurgical device (CyberKnife). Thirty-four patients received 7.5 grays (Gy) delivered in 5 fractions, 9 patients received 7.25 Gy delivered in 5 fractions, and 2 patients received other regimens. The variables evaluated were biochemical progression-free survival (bPFS), prostate-specific antigen (PSA) bounce, and toxicities. Health-related quality of life was evaluated using the Sexual Health Inventory for Men (SHIM), American Urological Association (AUA), and Expanded Prostate Cancer Index Composite (EPIC) questionnaires. The median follow-up for surviving patients was 44.5 months (range, 0-62 months). The bPFS rate at 3 years was 97.7%. The median PSA declined from 4.9 ng/mL at diagnosis to 0.2 ng/mL at last follow-up, and the median percentage PSA decline at 12 months was 80%. Nine patients experienced at least 1 PSA bounce ≥0.4 ng/mL, and 4 patients experienced 2 PSA bounces. The median time to first PSA bounce was 11.6 months (range, 7.2-18.2 months), and the mean percentage PSA bounce was 1.07 ng/mL. There was 1 episode of late grade 3 urinary obstruction, and there were 2 episodes of late grade 3 proctitis. There was a significant late decline in SHIM and EPIC sexual scores and a small, late decline in the EPIC Bowel domain score. In a select population, extreme hypofractionation with stereotactic radiosurgery was safe and effective for the treatment of low-risk prostate adenocarcinoma. Copyright © 2011 American Cancer Society.