Role of Androgen Ablation with Low-Dose-Rate Brachytherapy in the Treatment of Prostate Cancer

Ashesh B. Jani; Asal Shoushtari; Jeffrey M. Feinstein


Clin Drug Invest. 2006;26(12):723-731. 

In This Article

Abstract and Introduction

Background: Androgen ablation is often used in addition to low-dose-rate brachytherapy in the treatment of prostate cancer, particularly for disease with adverse features. We report a single-institution experience and analysis of the role of androgen ablation with brachytherapy in patients with prostate cancer.
Methods: A cohort of 189 consecutive patients receiving low-dose-rate brachytherapy for prostate cancer at our institution who had demographic, disease and treatment information and a minimum of 2 years of follow-up available, constituted the analysis study group. This cohort was divided into two major categories based on the use of androgen ablation. Using two successive prostate- specific antigen (PSA) rises above 1 ng/mL as the definition of failure, biochemical failure-free survival (BFFS) curves were constructed for the androgen ablation and no-androgen ablation groups and compared using the log rank test; additionally, a multivariate analysis of all major disease and treatment factors was performed using the Cox proportional hazards model. These analyses were conducted for the whole cohort as well as for subgroups defined by the use of external beam radiotherapy (EBRT).
Results: The 4-year BFFS in the androgen ablation versus no-androgen ablation groups was 76% versus 70% (p = 0.230) for the whole cohort, 75% versus 62% (p = 0.182) for EBRT patients, and 75% versus 82% (p = 0.764) for no-EBRT patients. For the whole cohort, the use of EBRT was the only factor reaching significance on multivariate analysis (p = 0.040). When analysing the EBRT and no-EBRT subgroups separately, no factor, including androgen ablation, reached significance on multivariate analysis.
Conclusion: In our study, addition of androgen ablation conferred no biochemical control advantage when added to low-dose-rate brachytherapy for the treatment of patients with prostate cancer.

Prostate cancer, particularly early- and intermediate-stage prostate cancer, is one of the most common malignancies and can be treated successfully using many different modalities, with radical prostatectomy and radiotherapy each having firmly established roles.[1,2] Radiotherapy can consist of brachytherapy (high-dose rate[3] or low-dose rate[4,5] ), external beam radiotherapy (EBRT),[6] or both.

As the prostate is hormonally sensitive to testosterone level, the role of androgen ablation in prostatic neoplasms has been well studied.[6] Androgen ablation has a proven role in the management of metastatic disease[7] and in the management of locally advanced and localised/intermediate-risk disease when EBRT is used as the radiation modality.[8,9] The role of androgen ablation with brachytherapy is, however, a matter of considerable controversy.

One use of androgen ablation is for cytoreduction to reduce the number of needles/seeds required when performing the brachytherapy procedure;[10] in some cases, this downsizing is absolutely necessary to permit implantation. The impact of androgen ablation on biochemical control in patients treated with brachytherapy (the subject of the current investigation) is, however, unclear. Many studies formally examining the use of androgen ablation have not found a biochemical control advantage with its use,[11,12,13,14] whereas some studies do suggest such an advantage,[15,16,17,18,19] particularly in intermediate- and high-risk disease. Most of these studies (both positive and negative) have shortcomings, such as short follow-up, lack of correction for imbalanced prognostic factors, and, perhaps most importantly, the potential confounding biases associated with use of supplemental EBRT.

Several collaborative studies have examined or are continuing to examine the role of androgen ablation with brachytherapy. A Cancer and Leukemia Group B phase II study is examining the role of EBRT and hormone therapy with brachytherapy[20] – however, this study, while important, will not clarify the role of androgen ablation on biochemical control because there is no control group in which androgen ablation is not administered. Two Radiation Therapy Oncology Group (RTOG) studies, RTOG P-0019[21] (a phase II study examining EBRT + brachytherapy) and RTOG 98-05[22] (a phase II study examining brachytherapy alone) did not incorporate androgen ablation into the treatment plan. Two additional studies, RTOG 0321[23] (a phase II study evaluating the use of high-dose-rate brachytherapy and EBRT) and RTOG 0232[24] (a phase III study comparing low-dose-rate brachytherapy + EBRT with brachytherapy alone) are not designed specifically to determine if there is any benefit of androgen ablation, but will report outcomes stratified by androgen ablation status.

It will be several years, however, before these studies have reached their accrual goals and the data have been analysed and made available. In the interim, the practising physician is often faced with the decision of whether to offer androgen ablation. In this communication we report a single-institutional experience/analysis of the role of androgen ablation in patients receiving low-dose-rate brachytherapy for prostate cancer.


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