Virtual HDR CyberKnife SBRT for Localized Prostatic Carcinoma: 5-Year Disease-Free Survival and Toxicity Observations

Abstract

Purpose: Prostate stereotactic body radiotherapy (SBRT) may substantially recapitulate the dose distribution of high-dose-rate (HDR) brachytherapy, representing an externally delivered "Virtual HDR" treatment method. Herein, we present 5-year outcomes from a cohort of consecutively treated virtual HDR SBRT prostate cancer patients.

Methods: Seventy-nine patients were treated from 2006 to 2009, 40 low-risk, and 39 intermediate-risk, under IRB-approved clinical trial, to 38 Gy in four fractions. The planning target volume (PTV) included prostate plus a 2-mm volume expansion in all directions, with selective use of a 5-mm prostate-to-PTV expansion and proximal seminal vesicle coverage in intermediate-risk patients, to better cover potential extraprostatic disease; rectal PTV margin reduced to zero in all cases. The prescription dose covered >95% of the PTV (V100 ≥95%), with a minimum 150% PTV dose escalation to create "HDR-like" PTV dose distribution.

Results: Median pre-SBRT PSA level of 5.6 ng/mL decreased to 0.05 ng/mL 5 years out and 0.02 ng/mL 6 years out. At least one PSA bounce was seen in 55 patients (70%) but only 3 of them subsequently relapsed, biochemical-relapse-free survival was 100 and 92% for low-risk and intermediate-risk patients, respectively, by ASTRO definition (98 and 92% by Phoenix definition). Local relapse did not occur, distant metastasis-free survival was 100 and 95% by risk-group, and disease-specific survival was 100%. Acute and late grade 2 GU toxicity incidence was 10 and 9%, respectively; with 6% late grade 3 GU toxicity. Acute urinary retention did not occur. Acute and late grade 2 GI toxicity was 0 and 1%, respectively, with no grade 3 or higher toxicity. Of patient's potent pre-SBRT, 65% remained so at 5 years.

Conclusion: Virtual HDR prostate SBRT creates a very low PSA nadir, a high rate of 5-year disease-free survival and an acceptable toxicity incidence, with results closely resembling those reported post-HDR brachytherapy.

Keywords: CyberKnife; HDR; brachytherapy; dosimetry; image guided; prostate cancer; stereotactic body radiotherapy.

Figure 1

Typical PTV margins used in this protocol for low-risk (left panel) and intermediate-risk (right panel) cases. The protocol calls for Prostate + 2 mm CTV to PTV expansion margins (low-risk disease) and prostate + 5 mm unilaterally or bilaterally if Gleason 7 disease or PSA >10 ng/mL is present (intermediate-risk disease). Note “shaving” of the GTV to PTV margin to zero against the rectum in the midline for both risk-groups. Also note that a 2-mm PTV expansion tends to “split” the NVB (delineated by white ovoid contour) while a 5-mm PTV expansion tends to fully encompass it.

Figure 2

This is an example of an intermediate-risk case with L-sided Gleason score 7 disease present. Note the asymmetric GTV to PTV expansion margins (L Panel) (2 mm around the R lobe versus 5 mm around the L lobe) to more widely encompass the possibility of significant extracapsular extension on the side with the higher Gleason score. This creates wider prescription (yellow line) isodose coverage on the higher-risk side, and also tends to create larger volumes of dose escalation within the prostate on the more heavily involved side (center panel). Finally, note full prescription isodose coverage (yellow line) encompassing at least 1 cm of adjacent seminal vesicle on the sagittal image, required for intermediate-risk cases only (SV/prostate junction denoted by the oblique black line)(R panel).

Figure 3

Entire study population: median PSA at presentation and at annual follow-up intervals post-SBRT.

Figure 4

Biochemical-relapse-free survival post-SBRT stratified by risk-group: Phoenix definition.

Figure 5

Biochemical-relapse-free survival post-SBRT stratified by risk-group: ASTRO definition.

Figure 6

Cumulative incidence of long-term grade 2 or higher GU or GI morbidity, annualized to 5 years. There were no further events beyond 5 years in this study.

Figure 7

Percent of patients with preserved potency – analysis limited to those who were potent pre-SBRT. Note that virtually the entire loss incidence occurs within year one post-SBRT, with relatively stable rates thereafter.