NHS Evidence Health Information Resources formerly National Library for Health

An early short course of hormone treatment can slow the spread of prostate cancer by up to eight years, reported two newspapers (3 January 2008). The newspapers briefly summarised the findings of a well conducted randomised trial, which found adding four months' hormone therapy to radiotherapy improved disease-specific outcomes in men with advanced prostate cancer.

Prostate cancer can be held back for up to eight years by an early short course of hormone treatment, reported two newspaper articles on 3 January 2008 (1,2).
The reports were based on a randomised trial (3) that evaluated the longer-term effects of adding four months of androgen deprivation therapy (ADT) to radiotherapy in the treatment of advanced prostate cancer. The trial showed that, after ten years, addition of ADT did not significantly influence overall survival or local tumour progression. However, 10-year estimates of disease specific mortality, distant metastases, biochemical failure, and disease-free survival significantly favoured combined therapy.
Both newspapers provide concise reports of what appears to be a well conducted study. However, it should be noted that the Telegraph's (1) statement that prostate cancer "can be held back for up to eight years" refers specifically to the difference in time between treatment groups for 40% of men to be diagnosed with bone metastases.

Evaluation of the evidence base for short-term neoadjuvant androgen deprivation therapy and external beam radiotherapy for locally advanced prostate cancer

Where does the evidence come from?

The research was conducted by Dr Mack Roach of the Departments of Radiation Oncology and Urology, University of California San Francisco and colleagues.

What were the authors' objectives?

To evaluate the longer-term effects of androgen deprivation therapy (ADT) combined with external-beam radiotherapy (EBRT) against EBRT alone in men with locally advanced prostate cancer.

What was the nature of the evidence?

The evidence came from a prospective randomised trial of 456 men aged between 49 and 88 years (median age 70 years) with bulky tumours of the prostate. This paper discussed outcomes after patients were followed up for an average of 11.9 years in combined therapy group and 13.2 years in the EBRT alone group. Outcomes measured included 10-year estimates of: overall survival, disease-specific mortality, local tumour progression, distant metastasis, disease-free survival and fatal cardiac events.

What interventions were examined in the research?

Patients were randomised to receive either four months of ADT (goserelin and flutamide) before and concurrent with EBRT or two months of EBRT alone.

What were the findings?

There were no differences between the groups in terms of 10-year estimates of overall survival or local progression.

A statistically significant advantage was found for combined ADT-EBRT therapy over EBRT therapy alone in terms of 10-year estimates of disease specific mortality (23% vs. 36% respectively), distant metastases (35% vs. 47%), biochemical failure (65% vs. 80%) and disease-free survival (11% vs. 3.2%).

There was no significant difference between the groups in terms of the frequency of fatal cardiac events.

What were the authors' conclusions?

The addition of four months of ADT to EBRT appears to have a dramatic impact on clinically meaningful end points in men with locally advanced disease with no statistically significant impact on the risk of fatal cardiac events.

How reliable are the conclusions?

Based on the information available in this follow-up report, the authors' conclusions are derived from what appears to be a generally well conducted randomised trial. The two intervention groups were comparable at baseline in terms of important characteristics that could influence the results. The report does not indicate whether the investigators were blinded to which treatment patients received, but the statistical analysis appears appropriate and the results as presented appear to support the authors' main conclusions. However, the trial did not measure certain adverse outcomes which have previously been associated with ADT, such as metabolic changes, osteoporosis, and depression.

Systematic reviews

Information staff at CRD searched for systematic reviews relevant to this topic. Systematic reviews are valuable sources of evidence as they locate, appraise and synthesize all available evidence on a particular topic.

There was one related systematic review identified on the Cochrane Database of Systematic Reviews (CDSR) (4) and one review which is currently being undertaken and will be available in the future (5). One related systematic review was identified on the Database of Abstracts of Reviews of Effects (DARE) (6).

References and resources

1. Hormone help for prostate cancer. Daily Telegraph, 3 January 2008, p2.

2. Early therapy 'delays prostate cancer'. The Times, 3 January 2008, p21.

3. Roach M, Bae K, Speight J, Wolkov HB, Rubin P, Lee RJ, et al. Short-term neoadjuvant androgen deprivation therapy and external-beam radiotherapy for locally advanced prostate cancer: long-term results of RTOG 8610. Journal of Clinical Oncology online publication 2 January 2008; doi: 10.1200/JCO.2007.13.9881.

4. Kumar S, Shelley M, Harrison C, Coles B, Wilt TJ, Mason MD. Neo-adjuvant and adjuvant hormone therapy for localised and locally advanced prostate cancer. Cochrane Database of Systematic Reviews 2006, Issue 4. Art. No.: CD006019. DOI: 10.1002/14651858.CD006019.pub2.

5. Gryn S, Winquist E. Effects of the duration of androgen deprivation therapy for localized or locally advanced prostate cancer in patients treated with radiotherapy. (Protocol) Cochrane Database of Systematic Reviews 2007, Issue 4. Art. No.: CD006773. DOI: 10.1002/14651858.CD006773.

6. Vicini FA, Kini VR, Spencer W, Diokno A, Martinez AA. The role of androgen deprivation in the definitive management of clinically localized prostate cancer treated with radiation therapy. International Journal of Radiation Oncology, Biology, Physics 1999;43(4):707-13. [DARE Abstract]