Clinical Investigation
Direct 2-Arm Comparison Shows Benefit of High-Dose-Rate Brachytherapy Boost vs External Beam Radiation Therapy Alone for Prostate Cancer

https://doi.org/10.1016/j.ijrobp.2012.07.006Get rights and content

Purpose

To evaluate the outcomes of patients treated for intermediate- and high-risk prostate cancer with a single schedule of either external beam radiation therapy (EBRT) and high-dose-rate brachytherapy (HDRB) boost or EBRT alone.

Methods and Materials

From 2001-2006, 344 patients received EBRT with HDRB boost for definitive treatment of intermediate- or high-risk prostate cancer. The prescribed EBRT dose was 46 Gy in 23 fractions, with a HDR boost of 19.5 Gy in 3 fractions. This cohort was compared to a contemporaneously treated cohort who received EBRT to 74 Gy in 37 fractions, using a matched pair analysis. Three-dimensional conformal EBRT was used. Matching was performed using a propensity score matching technique. High-risk patients constituted 41% of the matched cohorts. Five-year clinical and biochemical outcomes were analyzed.

Results

Initial significant differences in prognostic indicators between the unmatched treatment cohorts were rendered negligible after matching, providing a total of 688 patients. Median biochemical follow-up was 60.5 months. The 5-year freedom from biochemical failure was 79.8% (95% confidence interval [CI], 74.3%-85.0%) and 70.9% (95% CI, 65.4%-76.0%) for the HDRB and EBRT groups, respectively, equating to a hazard ratio of 0.59 (95% CI, 0.43-0.81, P=.0011). Interaction analyses showed no alteration in HDR efficacy when planned androgen deprivation therapy was administered (P=.95), but a strong trend toward reduced efficacy was shown compared to EBRT in high-risk cases (P=.06). Rates of grade 3 urethral stricture were 0.3% (95% CI, 0%-0.9%) and 11.8% (95% CI, 8.1%-16.5%) for EBRT and HDRB, respectively (P<.0001). No differences in clinical outcomes were observed.

Conclusions

This comparison of 2 individual contemporaneously treated HDRB and EBRT approaches showed improved freedom from biochemical progression with the HDR approach. The benefit was more pronounced in intermediate- risk patients but needs to be weighed against an increased risk of urethral toxicity.

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.

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Conflict of interest: none.

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