04:02am Monday 20 November 2017

European Urology: Editorial about REDUCE trial underlines value of dutasteride

The long-expected final report of the REDUCE trial appeared on April 1, 2010 in the New England Journal of Medicine [1] together with a commentary entitled ‘Chemoprevention of prostate cancer’ by Dr Patrick Walsh. What were the noteworthy items of the editorial?

* The REDUCE trial, contrary to the Prostate Cancer Prevention Trial (PCPT) [2], is performed in men who would have been candidates for biopsy anyway because of PSA values of 2.5 – 10 ng/ml, making the reduction of the chance of a positive biopsy of 23% clinically relevant.

* The mechanism of dutasteride is not primarily prevention but the inhibition of growth of small, well differentiated cancers as a result of the intracellular reduction of 5a-dihydrotestosterone (DHT). This mechanism which results in the prevention of disease progression is called ‘tertiary prevention’ and in this setting can be seen as treatment of minimal disease. This effect is seen in spite of the simultaneous, up to 40 times increase in testosterone (T) [3]. It remains unclear why the rise in T does not prevent the effect of the reduction in DHT.

* The report indicates a small difference in cardiovascular side effects in disadvantage of dutasteride. The long-term general health effects obviously remain unknown at this time.

* Unanswered issues: is dutasteride useful in reducing unnecessary biopsies and does it help to selectively identify aggressive disease? The reported data show that in men with an indication of periodic biopsies the reduction in the detection of potentially over-diagnosed cancers is 28.2% (table 3 in [1]).

* More detailed analyses are warranted. Extended follow-up to monitor, for example, the outcome of relevant endpoints such as delayed diagnosis of aggressive cancers, progression to metastatic disease and disease-specific mortality in comparison to the control population will be of great scientific value in spite of the unblinding of the trial and should therefore have top priority.

References:

1. Andriole GL, Bostwick DG, Brawley OW, Gomella LG, Marberger M, Montorsi F, Pettaway CA, Tammela TL, Teloken C, Tindall DJ, Somerville MC, Wilson TH, Fowler IL, Rittmaster RS, for the REDUCE Study Group. Effect of Dutasteride on the risk of prostate cancer. N Eng J Med. 2010 April 1 362;13. 2.Thompson IM, Goodman PJ, Tangen CM, Lucia MS, Miller GJ, Ford GJ, Lieber MM, Cespedes RD, Atkins JN, Lippman SM, Carlin SM, Ryan A, Szczepanek CM, Crowley JJ, Coltman CA Jr. The influence of finasteride on the development of prostate cancer. N Engl J Med. 2003 Jul 17;349(3):215-24. 3.Gleave M, Qian J, Andreou C, Pommerville P, Chin J, Casey R, Steinhoff G, Fleshner N, Bostwick D, Thomas L, Rittmaster R. The effects of the dual 5alpha-reductase inhibitor dutasteride on localized prostate cancer–results from a 4-month pre-radical prostatectomy study. Prostate. 2006 Nov 1;66(15):1674-85. Schröder FH, Roobol MJ. The REDUCE Trial. Eur Urol (2010), doi:10.1016/j.eururo.2010.04.031, http://www.europeanurology.com
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About the European Association of Urology (EAU) The European Association of Urology (EAU) represents more than 16,000 urology professionals across Europe and worldwide. Its mission is to raise the level of urological care in Europe. The EAU Annual Congress is the second largest urological congress in the world. Education and postgraduate training are essential tasks of the EAU and aims at promoting quality urological education across Europe and worldwide. Providing effective communication links to promote and disseminate scientific results and information amongst European urologists through e.g. European Urology and European Urology Today remains vital. The EAU has special sections on the Internet, such as Uroweb (www.uroweb.org) and Urosource (www.urosource.com), which allows for direct communication.
For more information, please contact Lindy Brouwer, EAU Communication Officer, at l.brouwer@uroweb.org.


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