Tuesday, 4 November 2008

When it's best to do nothing - Prostate cancer

If we knew which prostate tumours will not kill, men could avoid risky treatment
Sometimes, the best way to deal with cancer is to leave well alone. Tests for specific gene mutations promise not only to turn many deadly cancers into diseases that people can live with, they could also help to address another problem: the harm done by needlessly treating tumours that are never going to kill.
Take prostate cancer. The number of reported cases in the US jumped sharply after the introduction in 1986 of a blood test for a protein called the prostate specific antigen, or PSA (see graph). While death rates have fallen somewhat, the decline began too quickly to be clearly attributable to screening; it seems likely that it was more to do with improved treatments for tumours that have spread around the body.
PSA screening is not even specific for cancer, as levels of the protein are also elevated in men with benign enlargement of the prostate. The main reason for its failure to put a big dent in the death rate, though, is that most prostate tumours grow relatively slowly. Combined with the fact that men with prostate cancer are usually elderly, this means that many more with the disease die from other causes than die from it.
Still, in line with the received wisdom that early detection has to be a good thing, men with elevated PSA are given biopsies to look for cancerous cells. If these are found - and the tumour doesn't seem to have spread beyond the prostate gland itself - the most common treatments are radiation therapy or surgical removal of the gland.
While this intervention may prevent thousands of deaths from aggressive forms of the disease, the gains come at a huge cost. Aside from the billions of dollars spent on screening and treatment each year, surgical removal frequently leaves men impotent or incontinent. "What we really have now is a problem of over-treating people," says John Semmes of the Eastern Virginia Medical School in Norfolk.
No wonder, then, that this August the US Preventive Services Task Force recommended against PSA screening in men over 75. For younger men, it concluded that there was not enough evidence to urge for or against.
What's needed is some way to tell the difference between slow-growing tumours and life-threatening ones. Among the most promising candidates is a test for a genetic mutation that fuses a "promoter" sequence called TMPRSS2, which boosts gene activity, with a gene called ERG. Prostate cancer cells with this mutation respond to male hormones by becoming more invasive.
Ventana Medical Systems of Tucson, Arizona, is now developing a test for the TMPRSS2-ERG mutation in biopsied tissues, while Gen-Probe, based in San Diego, California, hopes to detect the RNA copies of this and other dangerous mutations in urine. Such tests could spare many men from unnecessary treatments, costs and stress.
Peter Aldhous

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