The role of 5-ARIs in cancer prevention: controversy not resolved

Monday, 29 June 2009- Urologists must exercise caution when considering the use of 5-alpha-reductase inhibitors as a PCa prevention measure, was the key message of a lecture by Dr. Nicolas Mottet, presented at the 4th ESU Masterclass on Medical treatment of urological cancer.

The role of 5-ARIs in cancer prevention has been a subject of heated discussions since the Prostate Cancer Prevention Trial (PCPT) of more than ten yeas ago, the results of which have been confirmed and improved by the still ongoing REDUCE trial. The 23% reduction of PCa incidence at four years (REDUCE) -  a promising conclusion – resulted in the recent AUA/ASCO statement recommending both finasteride and dutasteride for cancer prevention in men, who have a high risk of developing this condition.

During his lecture, Dr. Nicolas Mottet reviewed the exiting evidence, pointing to the significance of these findings as well as the numerous limitations (PCPT). He pointed out that the efficacy of 5-alpha-reductase inhibitors can only be seen in the decrease of Gleason 6 tumour detection, which “might be related to the fact that the bio-chemistry of more advanced cancer is actually different from that of G6 and lower.”

“It is disappointing that no such impact was observed for more advanced forms of cancer,” he said.

Talking about the drawbacks of this drug used for preventive purposes, he warned about the significant side effects on the sexual function which need to be weighed against the potential benefit.

“When we talk about a 23% decrease in cancer detection, we really mean a relative risk reduction which leads to much lower absolute figures -1,4 %,” said Dr. Mottet. “Furthermore, little is known about the ‘real life’ efficacy of the drug, as there is little or no observance outside clinical studies.”

"At this stage I would recommend all practitioners to be very, very careful, when it comes to using 5ARIs as a PCa preventive measure,” he told Urosource. “There are also financial implications to consider. A wide-spread finasteride prescription would cost an incredible $3 billion per year in the US alone.”

In his lecture Dr Mottet also reviewed the potential of other prostate cancer prevention measures, such as the use of statins, anti- oestrogens, anti-inflammatory drugs, as well as vitamin E alone and in combination with selenium. He said that none of these measures seem to show any significant reduction in risk, leaving the scientists with the only potentially viable option, the 5-alpha-reductase inhibitors, the benefit of which still needs to be clarified.

“I believe that the future of prostate cancer prevention will lie with a completely different field and a completely different technology. There is certainly a lot of potential in the genetics of this pathology, especially considering the fact that preventive measures are recommended for men with a family history of this disease. ”

By Evgenia Starkova

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