Can hormone drug treatment cure prostate cancer?

Taking “hormone drugs such as Zoladex” can cure up to a third of British men diagnosed with prostate cancer the Daily Ma il reported on July 6 2007.

The newspaper went on to report that researchers said “more than 10,000 men can be effectively cured of prostate cancer every year by taking hormone therapy”.

The story was about a review that reassessed the evidence from previous studies examining the effect of ‘adjuvant’ hormonal therapy (hormone therapy given alongside either radical prostatectomy or radiotherapy) in men with non-metastatic prostate cancer with a poor-prognosis.

It is, however, important to note that treatment in prostate cancer is targeted to the individual, guided by the degree of cancer spread (stage) and other medical factors. Therefore, hormone treatment may not be appropriate or required for all cases of prostate cancer.

The study considers only one type of hormone treatment in prostate cancer, Zoladex, a drug made by the company that funded the research. Other hormones are used to treat prostate cancer, depending on the clinical need, and these have different mechanisms of action. These other hormones have not been assessed by this review.

Care is needed when interpreting the news reports that “hormones can cure prostate cancer victims” as reported in the Daily Mail . This review does not suggest in any way that hormonal treatment be considered instead of radical prostatectomy or radiotherapy for localised high-risk prostate cancer.

Where did the story come from?

Doctors from Princess Margaret Hospital and other medical institutions in America, Holland and the UK conducted this review. This review of research was funded by the pharmaceutical company AstraZeneca. The study was published in the peer-reviewed journal, Nature .

What kind of scientific study was this?

The researchers collected research information from four randomised controlled trials (RCTs). They discussed the results of each of these studies separately, applying their definition of cure (disease control at 10-15 years) to see how adjuvant hormonal therapy affects long-term disease-free survival. The researchers then summarised these discussions by comparing the life expectancy with men of comparable age in the general population without prostate cancer.

There is no indication that the researchers used systematic methods (i.e. thorough methods to search for all research trials relevant to the study of hormone treatment in prostate cancer) to identify the RCTs they discuss. All four identified RCTs appear to be studies of Zoladex, a hormonal treatment manufactured by AstraZeneca. The drug’s generic name is goserelin. There is no methods section in this publication.

What were the results of the study?

The researchers report that the survival curves for the hormone-treated population became “indefinitely flat after long-term follow up”. They say  this flattening represents a mortality risk that is similar in the population without prostate cancer.

What interpretations did the researchers draw from these results?

The researchers conclude that by applying their revised definition of "cure" to the findings from four randomised controlled trials, adjuvant hormonal therapy appears to “augment cure in a sizeable proportion of men with poor-prognosis non-metastatic prostate cancer when given adjuvant to radical prostatectomy or radiotherapy”.

What does the NHS Knowledge Service make of this study?

This review of existing studies raises some important points. The following issues concerning the conduct of this study must be kept in mind when considering how to interpret these results:

• The researchers here are putting forward a proposal to reclassify treatments to reduce the levels of testosterone in the body as curative rather than palliative. They do this by revisiting the results of four randomised controlled trials and interpreting them in light of their new definition of "cure" as 10-15-year disease-free survival.
• Three of the four studies that the researchers discuss did not follow up their participants for long enough to be eligible for this revised definition of "cure". For these, the researchers have the opinion that hormonal treatment may achieve sufficiently long-term control of disease to be considered curative.
• This review of the research was not systematic (as was reported in the news article). The absence of systematic methods means that studies with negative results may have been excluded.
• The usefulness of a narrative comparison (i.e. without statistical testing) of the "flattening of the survival curve" in men given hormonal treatment with survival curves in the general population could be questioned.

Hormonal treatment is already a fairly well established adjuvant treatment for men with advanced prostate cancer. It may not be appropriate for all cases of prostate cancer however, and treatment options are clinically targeted as to what is most appropriate for the individual. Other clinical issues to consider when interpreting the news report that has resulted from this study include:

• Not all men with prostate will require immediate treatment at all, for some with low-risk localised prostate cancer, a careful period of “watch and wait” surveillance may be considered most appropriate depending on age and other medical factors.
• Men with high-risk localised prostate cancer (as considered by this research) will usually be treated with surgical removal of the prostate (prostatectomy) or radiotherapy in an attempt to cure the disease completely. Whilst concurrent hormone treatment is a common therapy for such men undergoing radiotherapy, it is not currently routinely considered for men undergoing prostatectomy. 
• This study considered the use of hormone treatment in men whose prostate cancer has not spread. The situation is different in men with metastatic prostate cancer for whom hormone treatment may be a first-line option.
• Zoladex is a type of hormone treatment that blocks the production of testosterone, and is associated with several important side effects that have not been considered. For example, it can cause osteoporosis, hot flushes and other symptoms similar to the female menopause. There may also be initial worsening of prostate cancer symptoms, as testosterone levels rise prior to decreasing.
• Labelling the results of this study as “hormone treatment” may imply that this includes all hormone therapies used in prostate cancer. This isn’t the case; others are used with different clinical indications.

An important message is that this review is not suggesting in any way that hormonal treatment be considered instead of radical prostatectomy or radiotherapy for localised high-risk prostate cancer.