A prospective dose escalation trial of high-dose-rate brachytherapy boost for prostate cancer: Evidence of hypofractionation efficacy?

Abstract 

Purpose

The study aimed to evaluate mature outcomes of a Phase I/II high-dose-rate brachytherapy (HDRB) boost protocol.

Methods and materials

We analyzed data from 88 patients with T1a–T3a, N0, M0 prostate adenocarcinoma treated on a prospective Phase I/II HDRB boost protocol of 16 (n=47) or 20Gy (n=41) in four fractions, without planned androgen deprivation therapy. HDRB was added to 46Gy of external beam radiotherapy (EBRT). Outcomes were compared to a contemporaneous retrospective cohort of 104 patients receiving 66Gy EBRT monotherapy. The primary endpoint was freedom from biochemical failure, defined as a 2ng/mL rise above the lowest prostate-specific antigen (PSA) (FFbFn2), whereas the American Society of Therapeutic Radiology and Oncology consensus definition (ACD) was used for comparative purposes.

Results

For the HDRB cohort, the overall actuarial 5-year FFbFn2 was 67.4% (95% CI: 58.2–75.5%). For the HDRB doses of 16 and 20Gy, the 5-year FFbFn2 rates were 58.8% (95% CI: 41.9–72.5%) and 77.3% (95% CI: 64.4–88.3%), respectively (log-rank test p=0.07). Compared to men treated with 66Gy EBRT, using multivariate analysis, there was no significant benefit to using HDRB with the FFbFn2 outcome (p=0.52), yet the ACD suggested a significant advantage (hazard ratio 0.50, 95% CI: 0.29–0.86, p=0.011). There was a trend to better FFbFn2 outcomes with increasing biologically effective doses (p=0.09), which was significant using the ACD (p=0.0003).

Conclusions

The data support HDRB boost as a potential means of dose escalation in prostate cancer. Significant findings using the ACD need to be validated with contemporary biochemical failure definitions. Prospective trials to optimize fractionation and evaluate outcomes in comparison to contemporary EBRT techniques are warranted.

Keywords: Prostate cancer, Brachytherapy, α/β ratio