Avodart for low risk patients on active surveillance,

Below are studies that I have come across, both pro and con for the use of avodart for low risk patients who are on Active Surveillance......any thoughts on this million dollar question


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Avodart discussion pro and con jan 2012

pro

Lancet. 2012 Mar 24;379(9821):1103-11. Epub 2012 Jan 24.
Dutasteride in localised prostate cancer management: the REDEEM randomised, double-blind, placebo-controlled trial.
Fleshner NE, Lucia MS, Egerdie B, Aaron L, Eure G, Nandy I, Black L, Rittmaster RS.
Source
Princess Margaret Hospital, University of Toronto, Toronto, Ontario, Canada. neil.fleshner@utoronto.ca
Abstract
BACKGROUND:
We aimed to investigate the safety and efficacy of dutasteride, a 5α-reductase inhibitor, on prostate cancer progression in men with low-risk disease who chose to be followed up with active surveillance.
METHODS:
In our 3 year, randomised, double-blind, placebo-controlled study, undertaken at 65 academic medical centres or outpatient clinics in North America, we enrolled men aged 48-82 years who had low-volume, Gleason score 5-6 prostate cancer and had chosen to be followed up with active surveillance. We randomly allocated participants in a one-to-one ratio, stratified by site and in block sizes of four, to receive once-daily dutasteride 0•5 mg or matching placebo. Participants were followed up for 3 years, with 12-core prostate biopsy samples obtained after 18 months and 3 years. The primary endpoint was time to prostate cancer progression, defined as the number of days between the start of study treatment and the earlier of either pathological progression (in patients with ≥1 biopsy assessment after baseline) or therapeutic progression (start of medical therapy). This trial is registered with ClinicalTrials.gov, number NCT00363311.
FINDINGS:
Between Aug 10, 2006, and March 26, 2007, we randomly allocated 302 participants, of whom 289 (96%) had at least one biopsy procedure after baseline and were included in the primary analysis. By 3 years, 54 (38%) of 144 men in the dutasteride group and 70 (48%) of 145 controls had prostate cancer progression (pathological or therapeutic; hazard ratio 0•62, 95% CI 0•43-0•89; p=0•009). Incidence of adverse events was much the same between treatment groups. 35 (24%) men in the dutasteride group and 23 (15%) controls had sexual adverse events or breast enlargement or tenderness. Eight (5%) men in the dutasteride group and seven (5%) controls had cardiovascular adverse events, but there were no prostate cancer-related deaths or instances of metastatic disease.
INTERPRETATION:
Dutasteride could provide a beneficial adjunct to active surveillance for men with low-risk prostate cancer.
FUNDING:
GlaxoSmithKline.
Copyright © 2012 Elsevier Ltd. All rights reserved

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pro

1. Urology. 2010 Nov;76(5):1067-71. Epub 2010 May 15.
The effect of short-term dutasteride intake in early-stage prostate cancer: analysis of 148 patients who underwent three-dimensional prostate mapping biopsy.
Barqawi AB, O'Donnell CI, Siomos VJ, Hou AH.
Source
Department of Surgery, Division of Urology, University of Colorado Denver, Aurora, CO 80045, USA. al.barqawi@ucdenver.edu
Abstract
OBJECTIVES:
The effect of dutasteride on existing prostate cancer volume is largely unknown. In this study, we assessed the impact of dutasteride on tumor burden and Gleason score.
METHODS:
A retrospective review of patients from our institution was performed, examining men interested in surveillance for prostate cancer, who underwent transperineal three-dimensional mapping (TP-3DM) biopsy within 3-6 months after their initial cancer diagnosis. The criteria to qualify for TP-3DM biopsy included prostate-specific antigen < 10 ng/mL, Gleason score ≤ 7, ≤ 2 positive cores out of 12. There were 2 cohorts of men--those who took dutasteride daily before the TP-3DM biopsy and those who did not receive any 5ARIs. Upstaging of prostate cancer diagnosis was defined as an increase in one or more positive cores or a change from unilateral to bilateral disease.
RESULTS:
From 2006-2008, a cohort of 148 men underwent TP-3DM biopsy of the prostate. Ninety-one men received a treatment regime of dutasteride at least 3 months before TP-3DM biopsy. Fifty-seven men did not receive dutasteride or any other 5ARI. Approximately 74% of men who did not take dutasteride were upstaged and/or upgraded compared with 49.4% of men who received dutasteride (P = .0038).
CONCLUSIONS:
We observed a 24.3% decrease in the proportion of upstaging and/or upgrading of prostate cancer in men who received dutasteride at least 3 months before 3D prostate TP-3DM biopsy. Thus, the effect of dutasteride on prostate cancer may have implications for its potential use as a secondary chemoprevention agent.
Copyright © 2010 Elsevier Inc. All rights reserved.
PMID: 20472268 [PubMed - indexed for MEDLINE

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con

1. BJU Int. 2012 Jan 30. doi: 10.1111/j.1464-410X.2011.10875.x. [Epub ahead of print]
Effect of treatment with 5-α reductase inhibitors on progression in monitored men with favourable-risk prostate cancer.
Ross AE, Feng Z, Pierorazio PM, Landis P, Walsh PC, Carter HB, Trock BJ,Schaeffer EM.
Source
James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins Medicinal Institutions, Baltimore, MD, USA.
Abstract
Study Type - Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Finasteride (Proscar) and dutasteride (Avodart) are 5-α reductase inhibitors (5-ARIs) used to treat LUTS in men with benign prostatic enlargement. Because these drugs suppress androgens, the theory has been put forward that 5-ARIs might prevent the development of prostate cancer. Careful analysis of two randomized controlled trials, however, showed that, in the clinical setting, this was not the case, and that these drugs can increase the occurrence of more aggressive high-grade disease. Because of this, the U.S. Food and Drug Administration did not approve 5-ARIs for the primary prevention of prostate cancer and notified healthcare professionals about a change in the 'Warnings and Precautions' for these drugs. Interest remains among some for using 5-ARIs in men diagnosed with very low-risk prostate cancer to delay the progression from clinically indolent disease to clinically significant disease requiring treatment. The present study investigated whether 5-ARI use among men with very low-risk prostate cancer in an active surveillance (AS) programme would reduce the number of cancers reclassified to clinically significant disease on surveillance biopsy. Our results do not support the use of 5-ARIs for slowing or preventing cancer progression in men with low-risk prostate cancer, but do suggest that men with very low-risk prostate cancer who take 5-ARIs for LUTS are unlikely to be at increased risk for the development of high grade disease during AS.
OBJECTIVE:
•  To determine whether 5-α reductase inhibitor (5-ARI) use delays cancer reclassification in an active surveillance (AS) cohort.
PATIENTS AND METHODS:
•  We performed a retrospective study of 587 men enrolled in an AS programme, who had no history of 5-ARI use. •  Chi-squared and t-tests were used to compare characteristics of 5-ARI users and non-users. •  Univariable and multivariable proportional hazards models, treating 5-ARI use as a time-dependent covariate, were used to evaluate the influence of 5-ARIs on the risk of a subsequent biopsy no longer meeting criteria for continued AS (i.e. reclassification).
RESULTS:
•  5-ARI use was initiated in 47 men while on AS. •  Men using 5-ARIs had larger prostates and higher PSA levels at diagnosis. •  During 5-ARI use, PSA levels and prostate volume deceased by mean values of 47% and 11%, respectively. •  Men using 5-ARIs had a mean of 2.5 surveillance biopsies while on the drug. Reclassification occurred in 17% of 5-ARI users compared with 31% of non-users (P= 0.04). •  Multivariable models (adjusting for age, α-blocker use, PSA level, %free PSA, PSA density, prostate volume and number/percent biopsy core involvement at diagnosis) showed nonsignificant risk reductions for reclassification in 5-ARI users as determined by either tumour extent (hazard ratio [HR]= 0.37 (95% confidence interval [CI] 0.12 to 1.13), P= 0.08) or grade (HR = 0.8 (95% CI 0.25-2.59), P= 0.7).
CONCLUSION:
•  Treatment with 5-ARIs did not significantly alter the outcome of biopsy reclassification by grade in men with very low-risk prostate cancer.
© 2012 THE AUTHORS. BJU INTERNATIONAL © 2012 BJU INTERNATIONAL.
PMID: 22289613 [PubMed - as supplied by publisher]