The effect of finasteride on the risk of acute urinary retention and the need for surgical treatment among men with benign prostatic hyperplasia 

Comment

Only men with enlarged prostates on rectal examination and moderate to severe symptoms were included in this study. This is important to note, since previous studies of finasteride vs. alpha-blockers for symptoms of obstructive uropathy indicate that finasteride's effect may be limited to men with enlarged prostate glands. A study published in the NEJM in 1996, which did not require evidence of prostatic enlargement on physical exam, found no benefit for finasteride, but a significant benefit of terazosin. In an editorial published along with that study, Walsh hypothesizes that obstructive symptoms may be due to smooth muscle hyperplasia or to glandular hyperplasia. Men with smaller prostates and obstructive symptoms are more likely to suffer from smooth muscle hyperplasia and would not be expected to benefit from finasteride but would benefit from an alpha blocker. Men with large prostates are more likely to have glandular hyperplasia, which would be expected to respond to an anti-testosterone agent such as finasteride. Thus, the results presented here cannot be automatically extrapolated to all men with obstructive uropathy symptoms, only to those with clinically enlarged prostates. 

One point not addressed in the article is the serum PSA level. In this study, men with mildly elevated PSA levels were required to undergo a prostate biopsy in order to participate in the study. This probably caused a bias towards lower PSA levels among study patients, since many patients with only mildly elevated PSA levels would be reluctant to undergo this procedure. In fact, despite the fact that the average prostate volume was elevated (55 ml), the average serum PSA was only 2.8 ng/ml. This could conceivably have biased the results, possibly against finasteride, since an elevated PSA level could be a marker for glandular tissue responsive to the drug. It would have been instructive to know the effect of serum PSA levels on the study results. 

It is interesting that the primary endpoint of this study was the improvement in symptoms with finasteride, whereas the most important results were represented by the secondary endpoints (surgery and urinary retention). At the time the study was initiated, it was already known that finasteride significantly improved symptoms in men with enlarged prostate glands. Thus, the choice of primary endpoint was presumably made to ensure a positive result of the trial, while leaving open the possibility of emphasizing the importance of the secondary endpoints if they turned out to be significant, as was the case. Although this is not a major problem, the primary endpoints of a study are those upon which sample size determinations are usually made, and should represent the main topic being studied. 
 

March 9, 1998 

References

Reader Comments

 The article posted was very interesting. I have even found finasteride produced some symptomatic improvement in what turned out to be a definite carcinoma. I don't think its use should mask the diagnosis as I usually, as a general practitioner, take a PSA before starting treatment. I also usually refer to a urologist for biopsy etc. In my experience finasteride is well tolerated.

John Warre. (UK) 
 
 
 

The problem of finasteride potentially masking symptoms of prostate cancer (and thus delaying diagnosis) would also apply to alpha-blockers. The importance of evaluating urinary obstructive symptoms for potential prostate cancer should be borne in mind. --mj 

Thu, 26 Mar 1998
From: sachin dave <sdave@musom.marshall.edu>

I have two comments:

How sensitive is digital prostatic examination (DPE) to identify an enlarged prostate gland? Are there any studies available? If not, then the decision to include patients in the study should have been based on objectively (sonogram/MRI) documented gland size enlargement instead of DPE i.e. any patient with symptoms of prostatism should have been subjected to these exams before inclusion in the study. Because we often encounter patients with normal prostate size (muscular component predominence hypothetically) who may have an enlarged prostate missed by DPE. That would have helped in assesing sensitivity and specificity of DPE as well, considering Sonogram/MRI as gold standard.

How long does it take for finasteride to become effective once we start it on a patient with Benign Prostatic Hypertrophy (BPH) ( given the hypothesis that it decreases glandular component of Prostate)? What should be done for patients with symptoms of prostatism meanwhile? Use alphablockers? We may have to reconsider our options. Is finasteride overrated for BPH? I am glad it has found another medical use [for baldness. mj]. 
 
 
 

This study (together with others) suggests that finasteride is more likely to be efficacious in patients with an enlarged prostate and obstructive symptoms than in patients whose gland is not enlarged. It is true that gland size can be more accurately assessed using imaging techniques than by digital examination alone, and many patients will end up undergoing imaging for the purpose of cancer screening, but it does not seem reasonable to require every patient with obstructive symptoms to undergo imaging solely to decide on the appropriateness of finasteride therapy. This study was designed to look at the utility of finasteride in patients with clinically enlarged glands, without requiring confirmatory imaging (although many patients did, in fact, undergo MRI).

Alpha blockers are likely to be effective more rapidly than finasteride, and may need to be given initially along with finasteride if rapid symptomatic improvement is desired. --mj 

Mon, 22 Feb 1999
From: Amit Ghosh <ghosh004@maroon.tc.umn.edu>
 

Evidence based medicine uses the term number needed to treat (NNT) very often to discuss the clinical significance of a therapy. It is defined as the number of patients needed to be treated in order to obtain one benefit. NNT is calculated as 100 / (absolute risk reduction). In the Study by McConnell et. al the absolute risk reduction due to the use of finasteride was 7%-4%= 3%, and the NNT is 100/3=33. Despite the statistical significance, one needs to treat 33 patients with finasteride to get 1 fewer episode of urinary retention.  The NNT for prostate surgery was 20, which seemed to be clinically more relevant information. The NNH (number needed to harm) was about 23 for impotence during the first year of treatment. One needs to use these numbers when discussing the risks versus benefit of finasteride therapy with patients. Both groups were equally affected by prostate cancer.
 

Amit Ghosh, MD
University of Minnesota
Minneapolis, MN 55455
 
 
 
 

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