John Libbey Eurotext

Bulletin du Cancer

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Keyrole of endocrinology in the victory against prostate cancer Volume 93, issue 9, Septembre 2006

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Centre de recherche du Centre hospitalier de l’Université Laval, 2705 boulevard Laurier, Québec, Québec, G1V 4G2, Canada

The most significant discovery of the last quarter of the XXth century in the field of prostate cancer is probably the observation that the human prostate synthesizes locally an amount of androgens from the inactive steroid precursors dehydroepiandrosterone (DHEA) and its sulfate DHEA-S that is approximately equivalent to the androgens made in the testis. Based upon this observation, two important discoveries also made by our group are applied worlwide, namely the use of GnRH (gonadotropin -releasing hormone) agonists that completely block testicular androgen secretion, while, simultaneously, the androgens made locally in the prostate from DHEA are blocked in their access to the androgen receptor by a pure antiandrogen (flutamide, bicalutamide or nilutamide). This treatment, called combined androgen blockade, has been the first treatment demonstrated to prolong life in prostate cancer in prospective and randomized studies. While the first studies were performed in patients with advanced and metastatic disease, our recent data indicate a much higher efficacy of the same treatment applied to localized prostate cancer, thus leading to an at least 90 % possibility of cure. In fact, the lifesaving benefits of androgen blockade in prostate cancer have been largely underestimated. When compared to other cancer therapies, the results obtained are quite remarkable. A recent metaanalysis of all clinical trial data mostly gives the credit to follow-up hormone therapy. « Hormonal treatment as a whole works ridiculously well », as reported by Arnst. In fact, while death rates decreased by 1.1 % per year from 1993 to 2001 for all cancers combined, prostate cancer showed a larger decrease at 3.6 %. Although improvements in surgery and radiotherapy are likely to play a role, a study by Frank R. Lichtenberg using National Cancer Institute data obtained from 2.1 million cancer patients, has concluded that « cancer-fighting drugs improved survival rates, especially for cancer of the prostate, where drug innovations have been the greatest ». The knowledge about the absence of development of resistance to androgen blockade in localized prostate cancer is extremely important. In fact, it is often erroneously believed that androgen blockade should not be administered early because resistance to treatment will develop and one might as well wait to use androgen blockade at a later stage of the disease. In fact, deferring treatment implies that, very often, it will then be too late, because after the cancer has migrated to the bones, resistance to treatment can no more be avoided. It should be realized that when prostate cancer is first detected, even by screening, the cancer is not small since its diameter is of the order of 1 cm or more. This is the most appropriate time to treat with the strong hope of a cure. With the presently available techniques, screening can diagnose prostate cancer at a clinically localized stage in 99 % of cases. Such an early diagnosis permits immediate treatment with a curative intent, combined androgen blockade (CAB) being a truly efficient alternative especially in older patients. Most importantly, CAB must be used immediately in patients who fail radical prostatectomy, radiotherapy of brachytherapy. When androgen blockade is used, it should always be combined androgen blockade. Using this strategy, based upon today’s available diagnostic and therapeutic approaches, death from prostate cancer can be an exception, confirming that victory against prostate cancer is achieved.