Should You Be Taking 5-Alpha-Reductase Inhibitors For Prostate Cancer Prevention – Dr. Pazdur et al’s Study

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5 alpha reductase inhibitor and prostate cancer

Can 5 alpha reductase inhibitors prevent prostate cancer?

A direct answer to this could be a, NO, 5-alpha reductase inhibitors have not yet been proved to protect against aggressive prostate cancers.

The issue of 5 α reductase is a hot topic among the medical and scientific community ever since the Food and Drug Administration (FDA) have begun evaluating the benefits of 5 α reductase inhibitors and their potential risk increase for high-grade prostate cancer in lieu of two large randomized, placebo controlled trials. These were the Prostate Cancer Prevention Trial (PCPT) that used the drug finasteride and the Reduction by Dutasteride of Prostate Cancer Events (REDUCE). Both trials indicated a decrease of almost 23% to 25% of low-grade prostate cancer (Gleason score ≤ 6). However, the trial results also indicated an increased incidence of high-grade prostate cancer in the group taking chemopreventive drugs.

FDA Analysis and Assessment on Use of 5α Reductase Inhibitors

The FDA assessed potential risks and benefits of chemopreventive drugs.

The participants of the trials did not have prostate cancer at the beginning of study.
There was 25% reduction in overall prostate cancer incidence as reported.
There was also an increase in occurrence of high-grade prostate cancers.
Since the REDUCE trial results did not report the use of modified Gleason scores (mGS), the FDA review reassessed biopsy specimens collected in the REDUCE trial. An independent pathologist, who was not aware of the previous scores, conducted the reassessment.
Reassessment too revealed that there was no reduction in occurrence of prostate cancer having modified Gleason Scores of 7 to 10. However, there was a 0.5% increase in incidence of prostate cancer having mGS of 8 to 10 in the dutasteride group.
Detection bias was suggested to be the cause of increased incidence of high-grade prostate cancer in the finasteride group. 5 α reductase inhibitors reduce levels of serum prostate specific antigen as well as prostate volume, hence, there arises an increased sensitivity to PSA values even slightly above the normal. However, when the biopsies were analyzed independent of the PSA values, the observation of increased incidence of high-grade prostate cancer persisted in both finasteride and dutasteride trials. This analysis, thus, does not comply with the detection bias suggestion.
Another suggestion for increased incidence of high-grade prostate cancer was increased sampling density. When the prostate volume decreases on taking 5 α reductase inhibitors, core needle biopsies might uncover cancers due to higher density of cancerous cells in a smaller prostate. This suggestion was dismissed, as in spite of adjusting prostate volume and mGS as 8 to 10, there was evidence of increased incidence of high-grade prostate cancer.

Conclusions of the FDA Assessment and the Advisory Committee

Analyses of both trials indicate that observed reduction in prostate cancer risk on taking finasteride and dutasteride was limited to tumors that had mGS of ≤ 6.
Data collected in REDUCE trial indicates that 80% of these cancers belong to ‘very low risk’ category (Epstein pathological criteria) and hence, their clinical significance is negligible.
Use of 5 α reductase inhibitor drugs may hence prevent 3 to 4 low-grade cancers at the expense of one high-grade prostate cancer.
The committee concluded that both drugs do not have significant risk-benefit profile for preventing prostate cancer in healthy men.

The labels of 5 α-reductase inhibitors would now include information about observation of high-grade prostate cancers in clinical trials.