Originally published as JCO Early Release 10.1200/JCO.2009.22.9997 on June 1 2009

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Reply to P.C. Walsh

National Institutes of Health, Bethesda, MD

Karen L. Hagerty, Mark R. Somerfield

American Society of Clinical Oncology, Alexandria, VA

Paul Schellhammer

Eastern Virginia Medical School/Sentara Medical Group, Norfolk, VA

We thank Dr Walsh¹ for his comments on the American Society of Clinical Oncology/American Urological Association guideline² on the use of 5-alpha-reductase inhibitors for prostate cancer chemoprevention. Dr Walsh raises important points that the panel discussed in depth during their deliberations while working on the guideline, and we are pleased, on behalf of the panel, to take this opportunity to clarify those discussions in responding to Dr Walsh's comments.

Dr Walsh contends that "5-alpha-reductase inhibitors do not prevent prostate cancer, they just prevent men from undergoing diagnostic biopsies."¹ The panel was aware of Dr Walsh's arguments against the use of finasteride in the setting of prostate cancer chemoprevention, including his concern about the potential for differential biopsy rates between men taking finasteride versus placebo. The panel was also aware of responses from the Prostate Cancer Prevention Trial (PCPT) investigators³ to those concerns. Nevertheless, with one exception, the panel felt that the observed decrease in period prevalence in the finasteride arm was unlikely to be due to differential biopsy rates. This has been subsequently reinforced by an analysis, published by PCPT investigators, which addresses the issue of between-arm imbalance of prostate biopsies by calculating estimates of overall prostate cancer prevalence had all subjects been biopsied.⁴ The relative risk and statistical significance for a reduced period prevalence of prostate cancer remained virtually unchanged.

We agree with Dr Walsh's underlying point that regular prostate-specific antigen (PSA) screening will increase the chance that a man will receive a diagnosis of prostate cancer. Despite lack of proof that PSA screening reduces prostate cancer mortality,^5–7 it is actively recommended by many physicians and is in common use. Given current evidence, the panel emphasized that finasteride specifically and 5-alpha-reductase inhibitors in general have been tested for chemoprevention only in men who choose to undergo regular PSA screening and that these are the only men for whom a discussion of the pros and cons of finasteride for prostate cancer chemoprevention is appropriate.

Finally, off-label use of many medications is common medical practice and well accepted by the US Food and Drug Administration.⁸ It has been estimated that at least 50%, and as much as 75%, of the use of oncologic agents is off-label.⁹ Physicians have long been authorized to use US Food and Drug Administration–approved agents, such as finasteride, in off-label settings when such use is based on peer-reviewed medical studies.

AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The author(s) indicated no potential conflicts of interest.

REFERENCES

1. Walsh PC: Three considerations before advising 5--reductase inhibitors for chemoprevention. J Clin Oncol 27:e22; 2009.[Free Full Text]

2. Kramer BS, Hagerty KL, Justman S, et al: Use of 5-alpha-reductase inhibitors for prostate cancer chemoprevention: American Society of Clinical Oncology/American Urological Association 2008 Clinical Practice Guideline. J Clin Oncol 27:1502–1516, 2009.[Abstract/Free Full Text]

3. Thompson I, Walsh P: The prostate cancer prevention trial: point/counterpoint. AUA News, 8–10, 2007.

4. Redman MW, Tangen CM, Goodman PJ, et al: Finasteride does not increase the risk of high-grade prostate cancer: A bias-adjusted modeling approach. Cancer Prev Res (Phila Pa) 1:174–181, 2008.[Medline]

5. US Preventive Services Task Force. Screening for prostate cancer: US Preventive Services Task Force recommendation statement. Ann Intern Med 149:185–191, 2008.[Abstract/Free Full Text]

6. Andriole GL, Grubb RL III, Buys SS, et al: Mortality results from a randomized prostate-cancer screening trial. N Engl J Med 360:1310–1319, 2009.[Abstract/Free Full Text]

7. Schröder FH, Hugosson J, Roobol MJ, et al: Screening and prostate-cancer mortality in a randomized European study. N Engl J Med 360:1320–1328, 2009.[Abstract/Free Full Text]

8. US Food and Drug Administration. Investigational New Drug Application, General Provisions, Applicability: Title 21, Vol 5, Code of Federal Regulations 312.2, Washington, DC, Government Printing Office, Washington, DC: 2008 https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm? fr=312.2 2008.

9. Soares M: "Off-label" indications for oncology drug use and drug compendia: History and current status. J Oncol Pract 1:102–105, 2005.[Free Full Text]

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