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Clinical Practice Guideline on the Use of5-alpha Reductase Inhibitors or Prostate

Cancer Chemoprevention

American Society of Clinical

American Society of Clinical Oncology 2008

nco ogy mer can ro og ca ssoc at on

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ASCO Health Services Committee, ASCO Cancer

,

Urological Association (AUA) Practice Guidelines

American Urological Association (AUA) and ASCO

commissioned a S stematic Review Wilt et al. 5-alpha reductase inhibitors for prostate cancerchemoprevention: a systematic review of the

evidence regarding effectiveness and adverseeffects. (Cochrane Database of Systematic


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Systematic Review

Wilt et al. completed a review and analysis of data publishedthrough December 2006

9MEDLINE

9PreMedlineoc rane o a ora on rary

9Reviews

9Personal files

*Additional search in April 2007 of MEDLINE/PreMEDLINE (yielded no relevant results)


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Guideline Methodology(contd): Panel Members

Barnett Kramer, MD, Co-Chair National Institutes of Health

Paul Schellhammer, MD, Co-Chair Eastern Virginia Medical School

Stewart Justman, Ph.D., PatientRepresentative

University of Montana Liberal Studies

Peter C. Albertsen, MD University of Connecticut Health Center

William J. Blot, PhD International Epidemiology Institute

H. Ballentine Carter, MD Johns Hopkins University

Joseph P. Costantino, PhD National Surgical Adjuvant Breast and Bowel

Project

Jonathan I. Epstein, MD Johns Hopkins University


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Guideline Methodology(contd): Panel Members

Paul Godley, MD, PhD University of North Carolina Chapel Hill

usse . arr s, n vers y o or aro na a ape

Timothy J. Wilt, M.D., MPH University of Minnesota School of

Medicine, v

Robin Zon, MD Michiana Hematology Oncology


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2008 Recommendations for Use of 5- Reductase Inhibitors for

Prostate Cancer Chemoprevention

OverarchingClinical Question

Should men routinely be offered a 5-Alphae uc ase n or or e

chemoprevention of prostate cancer?


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-Prostate Cancer Chemoprevention

Clinical Questions

A. What is the impact of 5--reductase inhibitors on the risk

of incident prostate cancer, prostate cancer mortality, and

overall mortality? Do benefits and harms of 5--re uc ase n ors vary among en a e

subpopulations (e.g., age, race/ethnicity, family history,

baseline risk for rostate cancer and b t e of 5--

reductase inhibitor?


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2008 Recommendations for Use of 5- Reductase Inhibitors for

Prostate Cancer Chemoprevention

C. What is the impact of 5--reductase inhibitors on theneed for treatment for benign prostatic disease?

D. What is the impact of 5--reductase inhibitors on qualityof life? What are other potential harms and side effects

of 5--reductase inhibitors? What are other potentialene s o , an n ca ons or, --re uc ase n or

use (e.g., benign prostatic hyperplasia, male baldness)?

E. How long should treatment continue for the best outcome

per o vs. e ongF. What are the future directions of research regarding 5--

reductase inhibitors for the prevention of prostate


cancer

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Primary Source of Evidence rostate ancer revent on r a

N = 18,882

Design endpoint of period prevalence* Finasteride administered for 7 years

Participant characteristics

No prior prostate cancer Asymptomatic or, at most, mild lower urologic

symptoms

< ng m Normal DRE*


prostate cancer over trial period

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In a group of 1000 men, treatment with finasteride

decrease of 15 cases ,

increased cases of high-grade (Gleason score 8-

10) from 18 to 21; an increase of 3 cases Both courses above are seven years

NNT to revent one case of rostate cancer b

treating for 7 years with finasteride = 71


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Question A: What is impact on risk of incident prostate cancer,

prostate cancer morta ty, an or overa morta ty re t ere

differences by identifiable subpopulations?

esponse v ence

Relative decrease in period prevalence = 26%

Absolute risk reduction = 1.4%

Trials not powered to show mortality difference, no difference found

o erences oun among eren races e n c es , ages,baseline risks or family histories of prostate cancer

* -


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Clinical Questions and

Findings Question B: Are there differential effects on

differences in grades/stages? What is applicability ofGleason histologic grading system?

Secondary analysis of PCPT found increase of 3cases of hi h- rade rostate cancer er 1000 men

Difference of opinion on explanation of this finding

Until the explanation of finding known, decisions

regarding the natural history of the disease anddecisions regarding treatment interventions shouldbe based on the histolo ic information obtained on


biopsy regardless of 5-ARI status

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Findings

benign prostatic disease

5-ARIs are established, FDA-approved treatments for

From PCPT

Reduces urinary retention RR = .67

Reduces transurethral resection of the prostate (TURP)


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Findings uestion D: What is im act on QOL? What are other

potential benefits/harms, other indications

Response/evidence:

Erectile Dysfunction 2-4% increase

Decreases in ejaculate volume 1.3-2.9% Gynecomastia 1.6-3.11%

Decreased libido 1-4%

Decrease in PSA

Male Pattern Baldness 50 years, 50% decrease in PSA


an mg s m ar o mgs a year o ow-up s ng estudy).

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Findings uestion E: What is o timal treatment duration?

Response/evidence: Guideline recommends seven year duration for primary

prevention for Finasteride (PCPT)

Trial using four year administration of dutasteride is


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regular screening for prostate cancer. The- ,

including finasteride, on the risk of

not being actively screened is therefore not

.


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Future Directions of Research

- Establish effect on prostate cancer morbidity and

Establishing optimal dose 1 mg versus 5 mg - -

ARIs which would trigger a biopsy

Establish the role of 5-ARIs for men not activelyreceiving screening

Establish the most effectivene means of

commun ca on or men cons er ng e use o a -ARI


molecular data

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, .

oug e ma or y o e ane u ge a e

observed higher incidence of high-grade (Gleason8-10 cancer in the finasteride rou is likel dueto confounding factors, the increased incidence of

high-grade cancer as a result of induction by the.benefits accruing from the drug are reduction ofthe risk of urinar retention and need for sur ical

intervention. Harms include sexual side effects,which usually diminish with time.


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Strategies to Improve Doctor-

Patient Communication-.

these agents reduce the incidence of prostatecancer and be sure to be clear that these

agents do not reduce the risk of prostate

cancer to zero;

2. Discuss the elevated rate of high-grade cancer

observed in the PCPT and inform men of thepotential explanations;


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Strate ies to Im rove Doctor-Patient Communication, contd..

term effects of 5-ARIs on prostate cancerincidence exists beyond about seven years-

prostate cancer mortality or increases life

expectancy remains unknown;

4. Inform men of possible but reversible sexual

5. Inform men of the likely improvement in lower


.

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This full text of the guideline, this slide set, and a doctor-

patient discussion guide are available at:http://www.asco.org/guidelines/5ari/

Access the cancer.net website for a Patient Guide and

other patient-friendly information at http://www.cancer.net


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Documents

5 ARI Slides 2.10.09