What is the efficacy of combined radiotherapy and androgen ablation for the treatment of prostate cancer?

Updated: Nov 29, 2018
  • Author: Isamettin Andrew Aral, MD, MS; Chief Editor: Edward David Kim, MD, FACS  more...
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Answer

Answer

The 5-year results of the RTOG 86-10 trial in patients with bilobar and more severe prostate carcinoma demonstrated that 4 months of total androgen blockade (TAB) in conjunction with conventional external beam radiotherapy (EBRT) was more beneficial than radiotherapy alone. Specifically, improved prostate-specific antigen (PSA) relapse-free survival, disease-free survival (DFS), and local control were observed. Overall survival rate was not better in the neoadjuvant androgen ablation arm; however, this may be because of the lack of protracted follow-up.

The 5-year results from the European Organization for Research and Treatment of Cancer (EORTC) trial that compared radiotherapy alone for locally advanced disease (T1, T2 grade 3 disease, any T-T4 without pelvic lymph node involvement) with radiotherapy followed by adjuvant androgen ablation for 3 years demonstrated improved outcome, including a survival advantage for the combined modality arm.

RTOG trial 92-02, which evaluated the role of continued androgen blockade for 2 years, found that PSA relapse-free survival, DFS, and local control were better with combined therapy (ie, TAB and radiotherapy) than with radiotherapy alone. However, it did not prove that combined therapy conferred an overall survival advantage. As the data mature, a demonstrable survival advantage to combined therapy may be anticipated.

Preliminary analysis of a trial by Laverdiere et al showed a potential for marked improvement in outcome when patients with early-stage prostate cancer are offered combined therapy. [29] In this prospective study, more than 120 patients with early-stage prostate carcinoma were divided into the following 3 treatment arms:

  • Radiotherapy alone

  • 3 months of neoadjuvant antiandrogen therapy, followed by radiotherapy

  • 3 months of neoadjuvant antiandrogen therapy, followed by combined therapy (ie, radiotherapy and TAB) and then by 6 months of TAB (post radiotherapy)

The study followed both posttreatment PSA and gland biopsy. [29] As expected, patients receiving TAB reached lower PSA nadirs. In addition, at 1 year posttherapy, the rate of repeat prostate biopsy was twice as high in patients not receiving TAB.

The RTOG 94-08 trial demonstrated definitively that the addition of short-term TAB to radiation therapy does not improve survival in patients with low-risk prostate cancer (T1/T2a). However, a subgroup analysis of the trial, presented at the 2010 Genitourinary Cancers Symposium in San Francisco, showed that patients with intermediate-risk prostate cancer obtained a significant survival benefit from TAB. [30]

Nevertheless, full determination of the benefits of TAB for this group of patients may require more study. For example, RTOG 94-08 employed lower doses of radiation than are currently used.

At present, TAB is used primarily for volume reduction in early-stage disease. This can be of great importance for patients undergoing either brachytherapy or 3-dimensional conformal radiotherapy (3D-CRT).

Although the results of combined therapy continue to offer encouraging results, each component of therapy (TAB and EBRT) is associated with its own potential morbidity. Adverse effects of androgen ablation include anemia, decreased muscle tone, gynecomastia, hepatotoxicity, hot flashes, impotence, osteoporosis, and loss of libido. These effects rarely necessitate termination of therapy.


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