Finasteride does not hike risk of high-grade tumors, new findings show.


Contrary to original findings from the Prostate Cancer Prevention Trial (PCPT), finasteride does not increase the risk of high-grade prostate cancer, according to a new analysis.

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In fact, according to investigators, the medication may even decrease the risk.


The trial, which examined finasteride’s ability to lower prostate cancer risk, involved 18,822 men aged 55 and older who were randomized to receive either finasteride or placebo for seven years.


The original PCPT results, published in 2003, showed that finasteride cut overall prostate cancer risk by 25% compared with placebo, but apparently increased the risk of high-grade disease. T


he new analysis, which adjusted for various biases, revealed a 30% reduction in overall prostate cancer risk and a nonsignificant 14% increase in high-grade malignancy. A review of grading information from 500 radical prostatectomy specimens showed that the rates of high-grade disease were 8.2% in placebo-treated patients compared with 6% in finasteride recipients, a significant 27% risk reduction.


The new findings appear in Cancer Prevention Research (2008; online ahead of print).


“We found no evidence that finasteride increased the risk of high-grade prostate cancer in the PCPT,” the authors wrote. “Therefore, we conclude that men 55 years and older have no need to be concerned about an increased risk of high-grade prostate cancer with finasteride.”


The new study, led by Mary Redman, PhD, a biostatistician at Fred Hutchinson Cancer Research Center in Seattle, suggests that the greater risk of high-grade disease originally observed with finasteride treatment appears to have been due to facilitated diagnosis resulting mainly from increased prostatic biopsy sensitivity in finasteride recipients, the authors noted.


“Therefore, men who are undergoing regular prostate cancer screening or who express an interest in cancer prevention should be informed of the opportunity to take finasteride for preventing prostate cancer,” the researchers stated.


In another recent analysis of PCPT data published online in the same journal, M. Scott Lucia, MD, of the University of Colorado Health Sciences Center in Denver, and colleagues concluded that no clear PSA threshold can be considered normal and cutoff values for PSA screening should be individualized.


The analysis of prostate biopsy characteristics of men in the finasteride and placebo arms showed that 75% of all detected tumors and 62% of tumors with a Gleason score of 6 or less met biopsy criteria for clinical significance. Tumors in men treated with the drug were smaller and had less aggressive characteristics, the researchers reported.


Moreover, as PSA levels increased, the likelihood of insignificant cancer decreased. PSA levels of 0-1.0, 1.1-2.5, 2.6-4.0, and 4.1-10 ng/mL were associated with a 51.7%, 33.7%, 17.8%, and 11.7% risk of insignificant cancer, respectively. Conversely, the risk of high-grade tumors associated with the same PSA levels was 15.6%, 37.9%, 49.1%, and 52.4%.


The investigators observed: “These data highlight the dilemma of PSA when used for screening: Lower cutoff levels increase detection of insignificant disease, but cure is more likely, whereas higher cutoff levels make detection of significant cancer more likely but cure is less likely.”


In the initial PCPT report, researchers observed a higher incidence of high-grade tumors among men taking finasteride who under-went biopsies because of an abnormal PSA level or digital rectal examination, but not among those biopsied without clinical cause at the end of the seven-year study, observed Eric A. Klein, MD, head of the section of urologic oncology at the Cleveland Clinic.


Although this finding inhibited the use of finasteride to prevent prostate cancer, the results suggested that finasteride somehow affected the detection of cancer in those taking it, Dr. Klein said. Indeed, subsequent studies demonstrated that finasteride increases the diagnostic accuracy of both PSA and DRE, so high-grade cancers are more likely to be found in screened men taking finasteride. The new studies, for the first time, account for this effect, which was unknown when PCPT findings initially were reported.


“The results clearly suggest that finasteride does not cause and might even prevent high-grade disease,” Dr. Klein told Renal & Urology News. “These articles should diminish concerns about potential deleterious biologic effects of finasteride and encourage its more widespread use for prevention of prostate cancer.”


Laurence Klotz, MD, chief of the division of urology at Sunnybrook Health Sciences Centre in Toronto and professor of surgery at the University of Toronto, called the two new studies “a major contribution to our understanding of the effect of finasteride on prostate cancer prevention.”


He noted that critics will argue that the study by Dr. Redman’s group is a modeling exercise and thus inherently suspect. “However, in the context of what we know about finasteride’s effects, this modeling seems eminently reasonable.”


Regarding the study by Dr. Lucia and colleagues, Dr. Klotz explained that if finasteride simply prevented development or progression of low-grade insignificant tumors and had no effect on the serious cancers, the finasteride-treated patients would be expected to have more high-grade tumors compared with placebo re-cipients. “The observation that the opposite is true bolsters the concept that the effect [of finasteride] is broad, across all grades,” he said.


With respect to the clinical implications of the latest findings, Dr. Klotz observed: “Practice should change, with an emphasis on risk reduction. For men at high risk, the benefit and appeal are obvious. For men at lower risk, it is a matter of balancing benefits and costs.”


Even though finasteride has the dual benefit of lowering cancer risk while concurrently managing BPH, he said, “not all men will embrace the opportunity to prevent prostate cancer. The modest risk of loss of libido will deter some, and cost will be a barrier to others. For the cancer-phobic, however, this well-tolerated drug should be embraced.”