International Journal of Radiation Oncology*Biology*Physics
Clinical InvestigationDirect 2-Arm Comparison Shows Benefit of High-Dose-Rate Brachytherapy Boost vs External Beam Radiation Therapy Alone for Prostate Cancer
Introduction
Patients receiving radical treatment for intermediate- and high-risk prostate cancer have been shown to benefit from radiation dose escalation 1, 2. High-dose-rate brachytherapy (HDRB) boost in combination with conventional external beam radiation therapy (EBRT) is now a generally accepted method of delivering a conformal high biological radiation dose, although high level evidence to support its use remains sparse. The hypofractionated nature of HDR brachytherapy uses the concept of high fraction size sensitivity of prostate cancer (3), allowing for delivery of a high biologically effective dose (BED) to the target. Superior biochemical progression-free survival has been demonstrated in 2 randomized studies 4, 5.
The evidence base supporting the use of HDRB can be difficult to interpret in the context of modern RT practice. Existing randomized studies 4, 5 used implant techniques and radiation doses which do not readily extrapolate to contemporary practice in many institutions. Similarly, most published retrospective data report the summary data of several dose fractionation schedules of HDRB boost, in which the magnitude of benefit from an individual HDRB approach is difficult to ascertain.
In our institution, men with intermediate- or high-risk prostate cancer are offered combination HDRB as an alternative to EBRT monotherapy. Using a large cohort of men treated with uniform dose fractionation schedules of EBRT (74 Gy) and EBRT with HDRB boost (46 Gy with HDRB boost of 19.5 Gy in 3 fractions), we compared the biochemical outcomes achieved with these approaches. A matched pair analysis incorporating tumor characteristics, patient comorbidity indices, and treatment contemporaneity was used.
Section snippets
Patient cohort
Sequential patients were treated with radical intent RT at the Peter MacCallum Cancer Centre during the period 2001-2006 inclusive, using either EBRT or HDRB. Eligible patients were those with histological evidence of adenocarcinoma of the prostate, with a clinical stage T1-3b Nx/0 M0 (American Joint Committee on Cancer Staging System, 2002) and intermediate- or high-risk disease according to National Comprehensive Cancer Network (NCCN) risk group criteria (6). These criteria identified 344
Results
We identified 1107 patients who received EBRT and 344 patients who received HDRB in the same time period who were eligible for analysis. In the unmatched cohorts, significant differences were observed between the 2 cohorts (Table 1).
Discussion
We demonstrate the superiority of an additional HDRB boost compared to EBRT alone in preventing biochemical recurrence, with a relative recurrence reduction of 41% at 5 years. This finding is consistent with previous reports demonstrating superiority of HDRB over EBRT when various pooled dose schedules were compared 14, 15, 16. Many such studies have been highly informative and have contributed to the ongoing interest in HDRB as a therapeutic option for prostate cancer. Several of these studies
Conclusions
In conclusion, this retrospective single-institution study demonstrates HDR EBRT improves biochemical control compared to conventional EBRT dose when accounting for known prognostic covariates. HDR EBRT is an effective method of biological dose escalation, albeit with a significantly higher rate of urethral toxicity. These results add further weight to the proposed low α/β ratio observed in carcinoma of the prostate.
References (20)
- et al.
Prostate cancer radiation dose response: results of the M. D. Anderson phase III randomized trial
Int J Radiat Oncol Biol Phys
(2002) - et al.
Confirmation of a low alpha/beta ratio for prostate cancer treated by external beam radiation therapy alone using a post-treatment repeated-measures model for PSA dynamics
Int J Radiat Oncol Biol Phys
(2011) - et al.
Randomised trial of external beam radiotherapy alone or combined with high-dose-rate brachytherapy boost for localised prostate cancer
Radiother Oncol
(2012) - et al.
Urethral stricture following high dose rate brachytherapy for prostate cancer
Radiother Oncol
(2009) - et al.
A new method for synthesizing radiation dose-response data from multiple trials applied to prostate cancer
Int J Radiat Oncol Biol Phys
(2010) - et al.
A multicenter study demonstrating discordant results from electronic prostate-specific antigen biochemical failure calculation systems
Int J Radiat Oncol Biol Phys
(2006) - et al.
A note on quantifying follow-up in studies of failure time
Control Clin Trials
(1996) - et al.
A prospective dose escalation trial of high-dose-rate brachytherapy boost for prostate cancer: evidence of hypofractionation efficacy?
Brachytherapy
(2006) - et al.
Comparison of PSA relapse-free survival in patients treated with ultra-high-dose IMRT versus combination HDR brachytherapy and IMRT
Brachytherapy
(2010) - et al.
Is alpha/beta for prostate tumors really low?
Int J Radiat Oncol Biol Phys
(2001)
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Conflict of interest: none.