Stereotactic body radiation therapy (SBRT) for clinically localized prostate cancer: the Georgetown University experience

Abstract

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.

Figure 1

(a) Treatment planning axial computed tomography images demonstrating the prostate (red line) and rectum (brown line). Isodose lines shown as follows: 115% of the prescription dose, yellow line; 100% of the prescription dose, light blue line: 75% of the prescription dose, dark blue line; and 50% of the prescription dose, green line. (b) A typical dose–volume histogram for CyberKnife treatment of a prostate cancer patient.

Figure 2

Pre- and post-treatment PSA and testosterone levels: (a). PSA levels for all patients (error bars indicate interquartile intervals) and (b). Box-and-Whisker plot of total testosterone levels. Only patients who did not receive androgen deprivation therapy (ADT) were included in the testosterone diagram. The p values were from χ²-analysis with baseline testosterone levels.

Figure 3

Cumulative late urinary toxicity (grades 2 and 3).

Figure 4

Short Form-12 (SF-12) Health Survey quality of life: (a) SF-12 physical component score (PCS) and (b) SF-12 mental component score (MCS). The graphs show unadjusted changes in average scores over time. The scores range from 0–100 with higher values representing improved health status. Numbers above each time point indicate the number of observations contributing to the average.

Figure 5

Urinary quality of life: (a) AUA score, (b) alpha antagonist utilization and (c) urinary symptom flare. The graphs show unadjusted changes in average scores over time for each domain. AUA scores range from 0–35 with higher values representing worsening urinary symptoms. Numbers above each time point indicate the number of observations contributing to the average. The thresholds for clinically significant changes in scores (½ standard deviation above and below the baseline) are marked with dashed lines. Error bars indicate 95% confidence intervals.

Figure 6

Sexual quality of life: (a) SHIM and (b) PDE5 utilization. The graphs show unadjusted changes in average scores over time for each domain among men who were potent at baseline (N = 57). SHIM scores range from 0–25 with lower values representing worsening sexual symptoms. Numbers above each time point indicate the number of observations contributing to the average.