Low incidence of new biochemical and clinical hypogonadism following hypofractionated stereotactic body radiation therapy (SBRT) monotherapy for low- to intermediate-risk prostate cancer

Abstract

Background: The CyberKnife is an appealing delivery system for hypofractionated stereotactic body radiation therapy (SBRT) because of its ability to deliver highly conformal radiation therapy to moving targets. This conformity is achieved via 100s of non-coplanar radiation beams, which could potentially increase transitory testicular irradiation and result in post-therapy hypogonadism. We report on our early experience with CyberKnife SBRT for low- to intermediate-risk prostate cancer patients and assess the rate of inducing biochemical and clinical hypogonadism.

Methods: Twenty-six patients were treated with hypofractionated SBRT to a dose of 36.25 Gy in 5 fractions. All patients had histologically confirmed low- to intermediate-risk prostate adenocarcinoma (clinical stage ≤ T2b, Gleason score ≤ 7, PSA ≤ 20 ng/ml). PSA and total testosterone levels were obtained pre-treatment, 1 month post-treatment and every 3 months thereafter, for 1 year. Biochemical hypogonadism was defined as a total serum testosterone level below 8 nmol/L. Urinary and gastrointestinal toxicity was assessed using Common Toxicity Criteria v3; quality of life was assessed using the American Urological Association Symptom Score, Sexual Health Inventory for Men and Expanded Prostate Cancer Index Composite questionnaires.

Results: All 26 patients completed the treatment with a median 15 months (range, 13-19 months) follow-up. Median pre-treatment PSA was 5.75 ng/ml (range, 2.3-10.3 ng/ml), and a decrease to a median of 0.7 ng/ml (range, 0.2-1.8 ng/ml) was observed by one year post-treatment. The median pre-treatment total serum testosterone level was 13.81 nmol/L (range, 5.55 - 39.87 nmol/L). Post-treatment testosterone levels slowly decreased with the median value at one year follow-up of 10.53 nmol/L, significantly lower than the pre-treatment value (p < 0.013). The median absolute fall was 3.28 nmol/L and the median percent fall was 23.75%. There was no increase in biochemical hypogonadism at one year post-treatment. Average EPIC sexual and hormonal scores were not significantly changed by one year post-treatment.

Conclusions: Hypofractionated SBRT offers the radiobiological benefit of a large fraction size and is well-tolerated by men with low- to intermediate-risk prostate cancer. Early results are encouraging with an excellent biochemical response. The rate of new biochemical and clinical hypogonadism was low one year after treatment.

Figure 1

Treatment planning axial (A) and sagittal (B) computed tomography images demonstrating the GTV (red), CTV and PTV expansion (dark blue), bladder (orange), rectum (green), bowel (yellow), membranous urethra (pink) and penile bulb (light blue). Isodose lines shown as follows: Blue 79% (prescription), white 70% and purple 50%.

Figure 2

Pre- and post-treatment (A) PSA levels, (B) total testosterone levels, and (C) PSA/testosterone ratios for all patients. Error bars indicate 95% confidence intervals.

Figure 3

Comparison of pre-treatment biochemical hypogonadism rates to those at up to 1 year following treatment.

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 and bowel quality of life using the American Urology Association (AUA) score and the Expanded Prostate Cancer Index Composite (EPIC): (A) AUA score, (B) EPIC urinary and (C) EPIC bowel. 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. EPIC scores range from 0 - 100 with higher values representing a more favorable health-related QOL. Numbers above each time point indicate the number of observations contributing to the average. Error bars indicate 95% confidence intervals.

Figure 6

Sexual quality of life using the Health Inventory for Men (SHIM) and Expanded Prostate Cancer Index Composite (EPIC): (A) SHIM, (B) EPIC sexual and (C) EPIC hormonal scores. The graphs show unadjusted changes in average scores over time for each domain. SHIM scores range from 0 - 25 with lower values representing worsening sexual symptoms. EPIC scores range from 0 - 100 with higher values representing a more favorable health-related QOL. The graphs show unadjusted changes in average toxicity and QOL scores over time. Numbers above each time point indicate the number of observations contributing to the average.