Abstract

Background: CyberKnife SBRT is capable of producing dosimetry comparable to that created by HDR brachytherapy. Our original CyberKnife prostate SBRT schedule of 3,800 cGy/4 fractions (“high dose”) was based upon favorable published prostate HDR brachytherapy experience. Subsequently, our trial was modified to allow a lower dose of 3,400 cGy/5 fractions (“moderate dose”) in selected cases.Methods: Two hundred eighty-nine low and intermediate-risk patients were treated to either high dose (178 pts) or moderate dose (111 pts). The dose selection was individualized; high dose more commonly used in younger, intermediate-risk patients, and moderate dose more commonly used in older, low-risk patients.Results: Median PSA reached 5-year nadir levels of 0.034 ng/mL in the high dose, vs. 0.1 ng/mL in the moderate dose groups, respectively (p = 0.044 by year 4), with 62 vs. 44% reaching an ablation PSA nadir (<0.1 ng/mL) by year 5, respectively. Five year biochemical relapse free survival rates measured 98.3% for moderate dose and 94.3% for high dose groups, respectively (p = 0.1946). Five-year actuarial grade 2 genitourinary (GU) toxicity rates measured 11.6 vs. 8.7% for high dose vs. moderate dose groups, respectively, with a far lower incidence of grade ≥3 GU and grade ≥2 GI toxicity rates in both groups.Conclusions: Both regimens are efficacious in their respective, selected groups. Both arms have low grade ≥3 GU toxicity and ≥grade 2 GI toxicity. In favor of the original high dose regimen, it has longer follow-up, produces a lower PSA nadir value and is more likely to eventually produce an ablation PSA nadir (<0.1 ng/mL). In favor of the lower dose regimen, it also produces a low PSA nadir, and does so with a slightly lower grade 2 GU toxicity rate. As a lower PSA nadir could be the initial predictor a lower clinical relapse rate far beyond 5 years, even if no difference is apparent within that time frame, a practical strategy could be to more strongly consider the high dose regimen in those with the greatest potential longevity, while for those with a more limited longevity, particularly if they have minimal negative prognostic factors, the moderate dose regimen could be more attractive.

Highlights

  • High dose rate (HDR) brachytherapy, using a dose of 3,800 cGy/4 fractions, has shown high efficacy and acceptable toxicity for localized low to intermediate-risk prostate cancer [1]

  • In the initial creation of our “Virtual HDR” prostate stereotactic body radiotherapy (SBRT) protocol, we chose to emulate a specific effective published HDR brachytherapy regimen of 3,800 cGy/4 fractions [1]. We did this after demonstrating that an “HDR-like” dose distribution could reasonably recapitulated on the CyberKnife SBRT planning computer, escalating the intraprostatic dose to 125–200% of prescribed, while maintaining comparable bladder, rectum, bladder, and urethra Dmax limitation metrics vs. simulated actual HDR brachytherapy [9]

  • High efficacy and reasonable safety are demonstrated to 5 years with each of the two different prostate SBRT dose fractionation regimens in this protocol, though this conclusion remains more tempered for the moderate dose regimen, due to its smaller sample size, and shorter median follow-up

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Summary

Introduction

High dose rate (HDR) brachytherapy, using a dose of 3,800 cGy/4 fractions, has shown high efficacy and acceptable toxicity for localized low to intermediate-risk prostate cancer [1]. Favorable prostate cancer biochemical relapse free rates using lower SBRT doses in the range of 3,500–3,750 cGy/5 fractions have been reported [5,6,7]. A larger pooled analysis of 2,142 men from 10 institutions, treated with 33.5–40 Gy/4–5 fx, demonstrated high 7-year efficacy for low-risk and intermediaterisk disease, with no discernible effect of specific EQD2 on the DFS outcome [8]. Until there are a larger volume of long term efficacy data available the optimal prostate SBRT dose fractionation schedule will remain unsettled. Our original CyberKnife prostate SBRT schedule of 3,800 cGy/4 fractions (“high dose”) was based upon favorable published prostate HDR brachytherapy experience. Our trial was modified to allow a lower dose of 3,400 cGy/5 fractions (“moderate dose”) in selected cases

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