NHS Evidence Health Information Resources formerly National Library for Health

Hormone therapy could cure prostate cancer, reported two newspapers (6 August 2007). The newspaper articles are based on a poorly reported review of the literature and as such, the review conclusions should be treated with caution.

On 6th August 2007, two newspapers reported that hormone therapy with drugs such as Zoladex (goserelin) could cure prostate cancer (1, 2), with a third of men with prostate cancer considered to be cured after taking hormone therapy.
The newspaper reports were based on a non systematic review of the literature published in the journal Prostate Cancer and Prostatic Diseases. The review reported that goserelin improved survival in men with poor-prognosis, non-metastatic prostate cancer when administered alongside surgery or radiotherapy (3).
The newspapers appear to overstate the results of a poorly reported review. Neither newspaper highlighted that the review was based on results for men with a poor prognosis. Both newspapers report that the review was based on four trials. Although these were the focus of the review, it is clear that other studies were referred to, for which sufficient details were not provided. One newspaper (1) reported that the review was funded by the manufacturers of goserelin. Given the poor reporting of the review process, and the potential for missing studies, error and bias, the conclusions should be treated with caution.

Evaluation of the evidence base for adjuvant androgen deprivation therapy for the treatment of non-metastatic prostate cancer.

Where does the evidence come from?

The review was a collaborative project by researchers from six universities and hospitals in the USA, Canada, UK, and the Netherlands, led by Dr N Fleshner from the Division of Urology, Princess Margaret Hospital, Toronto, Canada. Funding was provided by AstraZeneca, manufacturers of goserelin.

What were the authors' objectives?

To determine whether androgen deprivation therapy given adjuvant to radical prostectomy or radiotherapy should be classified as a treatment of curative intent in men with poor-prognosis, non-metastatic prostate cancer.

What was the nature of the evidence?

The article seems to be a review of the literature. Randomised controlled trials (RCTs) that enrolled men with non-metastatic prostate cancer who met specified criteria signifying poor-prognosis and who were followed-up for at least five years were reviewed. Further selection criteria were not specified, and the search strategy was not reported. The number of relevant studies retrieved was unclear, and the review methodology was not reported. Details of five of the included studies were provided.

What interventions were examined in the research?

The review evaluated adjuvant androgen deprivation therapy. Where details were provided, the included studies evaluated goserelin, compared to either standard therapy alone, or observation.

What were the findings?

One study reported that fewer men died after radical prostatectomy when given goserelin as an adjuvant. The review reported that survival curves in these men may be approaching that of the general population. Two studies reported that survival was significantly improved with goserelin plus radiotherapy compared to radiotherapy alone. One study reported no significant difference in overall survival between goserelin plus radiotherapy and neoadjuvant hormonal therapy, however those with a poor prognosis had an increased survival with goserelin plus radiotherapy. The authors state that several trials reported adjuvant castration including goserelin and orchiectomy prevents the relapse of prostate cancer; study details were not provided.

What were the authors' conclusions?

Goserelin can control disease for a long period of time, and adjuvant goserelin should be reclassified as a treatment of curative intent in men with poor-prognosis, non-metastatic prostate cancer.

How reliable are the conclusions?

This is a poorly reported review. The authors did not report a search strategy, the number of relevant studies retrieved, or the method used to select studies for inclusion in the review, therefore there is a potential for missed studies and selection bias. Other review methods were not reported, therefore the potential for error and bias can not be ruled out. The authors do not appear to have undertaken a quality assessment of the included studies, and details for all included studies were not provided. The authors state that patients with prostate cancer given adjuvant goserelin have a mortality risk similar to that of the general population, however they do not provide comparative data from the general population to support this. Given the lack of reporting of the review process, and the potential for missing studies, and error and bias, the conclusions should be treated with caution.

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 were two related systematic reviews identified on the Cochrane Database of Systematic Reviews (CDSR) (4-5) and five related reviews on the Database of Abstracts of Reviews of Effects (DARE) (6-10).

References and resources

1. Hormones 'can cure a third of all prostate cancer victims'. Daily Mail, 6 August 2007, p8.

2. 'Cure' for prostate victims. Daily Express, 6 August 2007, p2.

3. Fleshner N, Keane TE, Lawton CA, Mulders PF, Payne H, Taneja SS, Morris T. Adjuvant androgen deprivation therapy augments cure and long-term cancer control in men with poor prognosis, nonmetastatic prostate cancer. Prostate Cancer and Prostatic Diseases Advance online publication 3 July 2007; doi: 10.1038/sj.pcan.4500982.

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. Schmitt B, Bennett C, Seidenfeld J, Samson D, Wilt T. Maximal androgen blockade for advanced prostate cancer. Cochrane Database of Systematic Reviews 1999, Issue 2. Art. No.: CD001526. DOI: 10.1002/14651858.CD001526.

6. Prostate Cancer Trialists' Collaborative Group. Maximum androgen blockade in advanced prostate cancer: an overview of the randomised trials. Lancet 2000;355:1491-1498. [DARE Abstract]

7. Bonney W W, Schned A R, Timberlake D S. Neoadjuvant androgen ablation for localized prostatic cancer: pathology methods, surgical end points and meta-analysis of randomized trials. Journal of Urology 1998;160(5):1754-1760. [DARE Abstract]

8. Caubet J F, Tosteson T D, Dong E W, Naylon E M, Whiting G W, Ernstoff M S, Ross S D. Maximum androgen blockade in advanced prostate cancer: a meta-analysis of published randomized controlled trials using nonsteroidal antiandrogens. Urology 1997;49(1):71-78. [DARE Abstract]

9. Blue Cross and Blue Shield Association, Aronson N, Seidenfeld J. Relative effectiveness and cost-effectiveness of methods of androgen suppression in the treatment of advanced prostate cancer. Rockville, MD, USA: Agency for Health Care Policy and Research; 1999. [DARE Abstract]

10. Vicini F A, Kini V R, Spencer W, Diokno A, Martinez A A. 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):707-713. [DARE Abstract]