The Effect of Dutasteride on Magnetic Resonance Imaging Defined Prostate Cancer: MAPPED-A Randomized, Placebo Controlled, Double-Blind Clinical Trial

Caroline M. Moore (1, 2) , Nicola L. Robertson (1, 2) , Fatima Jichi (3) , Adebiyi Damola (1, 2) , Gareth Ambler (3) , Francesco Giganti (4) , Ashley J. Ridout (1, 2) , Simon R. J. Bott (5) , Mathias Winkler (6) , Hashim U. Ahmed (1, 2) , Manit Arya (1, 2) , Anita V. Mitra (7) , Neil Mccartan (2) , Alex Freeman (8) , Charles Jameson (8) , Ramiro Castro (9) , Giulio Gambarota (10) , Brandon Whitcher (11, 12) , Clare Allen (4) , Alex Kirkham (4) , Mark Emberton (1, 2)

1 Division of Surgery and Interventional Science [London, UK]
2 King's College Hospital NHS Foundation Trust - Department of Urology [London, UK]
3 Biostatistics Group [London, UK]
4 Department of Radiology [London, UK]
5 Department of Urology [Surrey, UK]
6 Charing Cross Hospital - Department of Urology [London, UK]
7 Department of Clinical Oncology [London, UK]
8 Department of Pathology [London, UK]
9 GlaxoSmithKline Research and Development [Philadelphia, USA]
10 LTSI - Laboratoire Traitement du Signal et de l'Image
11 Department of Mathematics [Imperial College London]
12 Klarismo [London, UK]

PURPOSE: Dutasteride, which is licensed for symptomatic benign prostatic hyperplasia, has been associated with a lower progression rate of low risk prostate cancer. We evaluated the effect of dutasteride on prostate cancer volume as assessed by T2-weighted magnetic resonance imaging.MATERIALS AND METHODS: In this randomized, double-blind, placebo controlled trial, men with biopsy proven, low-intermediate risk prostate cancer (up to Gleason 3 + 4 and PSA up to 15 ng/ml) who had visible lesion of 0.2 ml or greater on T2-weighted magnetic resonance imaging sequences were randomized to daily dutasteride 0.5 mg or placebo for 6 months. Lesion volume was assessed at baseline, and 3 and 6 months with image guided biopsy to the lesion at study exit. The primary end point was the percent reduction in lesion volume over 6 months. This trial was registered with the European Clinical Trials register (EudraCT 2009-102405-18).RESULTS: A total of 42 men were recruited between June 2010 and January 2012. In the dutasteride group, the average volumes at baseline and 6 months were 0.55 and 0.38 ml, respectively and the average reduction was 36%. In the placebo group, the average volumes at baseline and 6 months were 0.65 and 0.76 ml, respectively, and the average reduction was -12%. The difference in percent reductions between the groups was 48% (95% CI 27.4-68.3, p <0.0001). The most common adverse event was deterioration in erectile function, which was 25% in men randomized to dutasteride and 16% in men randomized to placebo.CONCLUSIONS: Dutasteride was associated with a significant reduction in prostate cancer volume on T2-weighted magnetic resonance imaging compared to placebo.

Keywords: dutasteride; Magnetic Resonance Imaging; Prostatic Neoplasms; Biopsy; watchful waiting

Domains: Life Sciences [q-bio]; Human health and pathology; Urology and Nephrology; Life Sciences [q-bio]; Cancer; Life Sciences [q-bio]; Pharmaceutical sciences; Pharmacology; Life Sciences [q-bio]; Bioengineering; Imaging

Caroline M. Moore, Nicola L. Robertson, Fatima Jichi, Adebiyi Damola, Gareth Ambler, et al.. The Effect of Dutasteride on Magnetic Resonance Imaging Defined Prostate Cancer: MAPPED-A Randomized, Placebo Controlled, Double-Blind Clinical Trial. Journal of Urology, 2017, 197 (4), pp.1006-1013. ⟨10.1016/j.juro.2016.11.090⟩. ⟨hal-01518408⟩