Originally published as JCO Early Release 10.1200/JCO.2009.25.0886 on September 8 2009

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Reply to P.H. Frankel et al

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 agree with Frankel et al¹ that there is no evidence that healthy men live longer with the use of 5--reductase inhibitors (5-ARIs), as we stated explicitly in our joint American Society of Clinical Oncology/American Urological Association clinical practice guideline on the use of 5-ARIs for prostate cancer chemoprevention.² However, it is clear that 5-ARIs have clinically meaningful benefits on urinary function, including reduction in risk for acute urinary retention as well as the need for transurethral resection of the prostate for lower urinary tract symptoms due to benign prostatic hyperplasia. Most importantly, 5-ARIs clearly reduce the period prevalence of prostate cancer in men who routinely undergo screening for prostate cancer. This effect of 5-ARIs leads to a clinically important reduction in the major (and common) complications of therapy for prostate cancer: urinary incontinence (that may require the use of diapers or pads), significant erectile dysfunction after surgery or radiation, and rectal injury. These are meaningful outcomes even if 5-ARIs are never shown to decrease the risk of dying of prostate cancer. We were equally explicit about the adverse effects of 5-ARIs, which include a 2% to 4% increase in reported erectile dysfunction and gynecomastia, and a decrease in ejaculate volume.

Frankel et al¹ focus on the upper bound of a CI for overall mortality in the 5-ARI trials. Stated more neutrally, the full range of the CI based on all of the randomized trials is consistent with no effect on overall mortality. The trials were not powered to show a difference in overall mortality, and to focus on the upper bound of the range—or on the lower bound, for that matter–risks misleading the man facing the decision about whether to take 5-ARIs.

Finally, the statement by Frankel et al¹ that the guideline conclusion "men may benefit from a discussion" of 5-ARIs may be interpreted as an implicit endorsement of a drug is itself a misinterpretation of the explicit language in the guideline, which states "...it is essential that the physician present the available data and highlight the remaining uncertainty."² Nevertheless, this exchange serves to emphasize Frankel et al's point that people can examine the same data and yet have divergent opinions. Why impose, as they suggest, one viewpoint, "a clear recommendation against use of 5-ARIs in otherwise healthy men?" Some men may look at the same information made available to Frankel et al in the American Society of Clinical Oncology/American Urological Association guideline and come to a different conclusion.

AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

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

REFERENCES

1. Frankel PH, Twardowski P: Guideline for 5--reductase inhibitors in the prevention of prostate cancer is premature. J Clin Oncol 27:e164; 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]

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