Originally published as JCO Early Release 10.1200/JCO.2009.22.9070 on June 1 2009

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Three Considerations Before Advising 5--Reductase Inhibitors for Chemoprevention

The James Buchanan Brady Urological Institute, Johns Hopkins Medicine, Baltimore, MD

To the Editor:

Kramer et al¹ omitted three important considerations that strongly influence the decision about the use of 5--reductase inhibitors (5-ARIs) for the chemoprevention of prostate cancer.

First, 5-ARIs do not prevent prostate cancer, they just prevent men from undergoing diagnostic biopsies. Because 5-ARIs reduce prostate-specific antigen (PSA) levels by at least 50%, patients and their physicians can be lulled into a false sense of security. In the first seven years of the Prostate Cancer Prevention Trial (PCPT), although 25% fewer men on finasteride were diagnosed with prostate cancer, this occurred largely because 15% fewer men underwent a diagnostic biopsy. In the men on finasteride who actually underwent a biopsy, the risk of a positive biopsy was reduced by only 10% (biopsies were positive in 26.5% of men on finasteride and in 29.5% of men on placebo; a 3% absolute difference which was not statistically significant [95% CI, 0.81 to 1.0]).² Thus, finasteride will have no significant effect on reducing the risk of cancer in men who are followed closely and undergo a biopsy because of an elevated PSA or abnormal digital rectal examination, which is the exact setting where it would be used for prevention. For the patient who watched his father die from prostate cancer and who does not want to have a similar fate, treatment with a 5-ARI is the last thing he should do because all it will do is prevent him from knowing that he might have cancer until it may be too late to cure. Kramer et al, in their section on physician-patient communication, state, "5-ARIs do not eliminate the risk of developing prostate cancer; they reduce its clinical incidence. This distinction should be made clear."¹ How would anyone understand what those words mean without the data presented above?²

Second, for patients on a 5-ARI, there are guidelines for monitoring their PSA. Based on data from the randomized PCPT, when PSA levels increased in men who were on finasteride, their risk of having cancer was three-fold higher than in men without a rise and six-fold higher for being diagnosed with high-grade disease.³ I believe that this is important information that the treating physician needs. Although this cut point has not been prospectively validated, it was based on a secondary analysis of data from the PCPT, and has similar validity to other conclusions derived from post hoc analyses that were used by the authors to support other recommendations. Kramer et al¹ state, "even if 5-ARI treatment never translates into reduced overall or prostate cancer-specific mortality, reduction in risk of prostate cancer diagnosis with the consequent morbidity of treatment is a clinically beneficial end point in and of itself." I would view it another way. If men do not want to know if they have prostate cancer, why don't they just avoid PSA testing? This will save them $700 to $1,000 a year (ie, the cost of finasteride that is not likely to be covered by insurance), the possibility of being diagnosed with high-grade disease, and potential adverse effects.

Third, the authors are advocating the off-label use of a drug that is not approved by the US Food and Drug Administration as safe or effective in preventing prostate cancer.

AUTHOR'S DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

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

REFERENCES

1. Kramer BS, Hagerty KL, Justman S, et al: Use of 5--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]

2. Wilt T, MacDonald R, Hagerty K, et al: 5--Reductase Inhibitors for prostate cancer prevention. Cochrane Database Syst Rev 2:CD007091; 2008.[Medline]

3. Thompson IM, Pauler AD, Chi C, et al: Prediction of prostate cancer for patients receiving finasteride: Results from the Prostate Cancer Prevention Trial. J Clin Oncol 25:3076–3081, 2007.[Abstract/Free Full Text]

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