The 5-alpha reductase inhibitor for prostate cancer myth clarified

If a man with prostate cancer is given a LHRH agonist (namely Lupron, Eligard, Zoladex, Trelstar etc) the result of treatment (depending on the timing and cancer agressivity) is a reduction of the patient’s PSA and potentially an improvement of lesions on imaging tests. The reduction of the patient’s testosterone and metabolites (DHT among them) that cause a PSA reduction is never identified as a false value. There is no question of the PSA being masked. A PSA test level at that point is considered to be what it is. In most cases a reduction in PSA is considered valuable because it is related to a tumor volume reduction caused by the lack of androgen.

If such is the case, imagine giving the same prostate cancer patient only a 5-alpha reductase inhibitor (Proscar or Avodart). These chemical are considered "light androgen deprivation" because they inhibit the formation of testosterone’s metabolite dihydrotestosterone. Why would a PSA reduction in such patient be considered to be a false level? It is not a false or a mask level. The PSA test measures PSA in blood and doesn’t know if the patient is on LHRH therapy of on a 5-AR inhibitor alone. The biologic effect of such chemicals is to reduce dihydrotestosterone formation and to cause the cancer cells to undergo cell death. The fact is that DHT is the most potent androgen and recognized as the androgen that has the greatest affinity for the androgen receptor. This to a lesser degree is the same effect of the LHRH agonist reducing testosterone and DHT because testosterone is not affected.

Why is this myth so pervasive? The reason is that 5-AR inhibitors were developed to treat prostate enlargement(BPH). Since both BPH and prostate cancer are common in older men, the manufacturers of these chemicals, in marketing their products, wanted to avoid the secret development of PCa in the patients treated for BPH. They advised such users to double their PSA to trigger a PSA test to detect PCa. In the case of a patient with prostate cancer there is no need to double their PSA because a PSA level in them is what it is. In simpler words, the manufacturers of a drug used to treat a condition wanted to avoid being sued for masking the development of PCa in men treated for BPH. Hence the recommended to double their PSA levels.

RalphV

Hi SecialLady,

Your first question was answered by Rittmaster et al years ago. Finasteride, by inhibiting the formation of dihydrotestosterone (which as the most potent androgen that drives cell growth).This inhibition of DHT will cause prostate gland atrophy and cell death. This reduction in prostate volume is correlated to a reduction in PSA. This is why in the case of treating PCa with a 5-AR inhibitor the reduction in PSA is real and a sign of activity against the cancer.

Furthermore, these 5-AR inhibitors by reducing DHT inhibit a vascular growth factor (VEGF) that promotes tumor vascularity. These two known mechanisms are the ones that make these chemicals valuable in the treatment of PCa. Unfortunately, interpretation of trials to prevent PCa are complex and resulted in the failure to the FDA approval of these inhibitors as chemopreventive in prostate cancer. Many physicians still use these for the benefit of their patient's quality of life.

RalphV

Source:

Rittmaster RS, Norman RW, Thomas LN, Rowden G. Evidence for atrophy and apoptosis in the prostates of men given finasteride. J Clin Endocrinol Metab. 1996 Feb;81(2):814-9. PubMed PMID: 8636309.

Donohue JF, Hayne D, Karnik U, Thomas DR, Foster MC. Randomized,placebo-controlled trial showing that finasteride reduces prostatic vascularity rapidly within 2 weeks. BJU Int. 2005 Dec;96(9):1319-22. PubMed PMID: 16287453.

It's there but the addition does not appear when I choose include signature.

Anyway, latest PSA, 3/23/12 is 2.28.

Another one in 10 days

Mel

Good questions. I have no answers, but I hope you will report here on what Myers says.

Mel

That's great news.

My next PSA will be in 1 month.

I just got my latest results.

After a 33% drop, it is now up 7%.

Still hopeful that it will stay at this pace.

My PSADT was 3 months before avodart

Mel