"The Finasteride PCa prevention trial [PCPT] - Last Word?" ... More Words.

[pjoshea13]

Some might remember this thread from January:

healthunlocked.com/advanced...

The following comments by Patrick Walsh have just appeared in Practice Update:

Written by Patrick C Walsh MD

This is an important warning for every physician who prescribes 5α-reductase inhibitors (5-ARIs) for the treatment of BPH (finasteride 5 mg and dutasteride) or male pattern baldness (finasteride 1 mg). If PSA levels are not monitored or adjusted properly for the effect of the drug, this can spell disaster. In this study by Sarkar et al, patients who were taking 5-ARIs at the time of their diagnosis of prostate cancer presented with more high-grade, lymph node–positive, metastatic disease and had worse prostate cancer–specific and all-cause mortality.

We have been told that 5-ARIs prevent prostate cancer and do not increase the risk of high-grade disease.1 If this were true, why did the men in this study develop high-grade disease and die from it? Sadly, because we have not been told the full truth. There is no 5α-reductase enzyme in normal or malignant prostatic epithelial cells; it is located in the stroma. Because higher-grade cancers (Gleason >6) have little stroma, 5-ARIs have no effect in reducing Gleason 7–10 disease.2 Treatment with a 5-ARI reduces the production of PSA by stromal cells in BPH. To correct for this effect, men treated with a 5-ARI must multiply their level by 2.0 for the first 2 years, by 2.3 for years 2 to 7, and after year 7, by 2.5.3 If patients do not know this, they will not realize they may need a biopsy and may miss the opportunity of being diagnosed with curable disease. This explains the findings in this study. It may also reinforce the findings of the FDA, which concluded that the increase in high-grade disease was real and that, for every 200 patients treated with a 5-ARI, there would be 1 new case of Gleason 8–10 disease.2

When I first prescribe 5-ARIs, I explain to patients the importance of having their PSA measured regularly for as long as they are taking the drug. I tell them why they need to know these numbers and that, if their PSA ever increases, they need a biopsy. In patients taking a 5-ARI, PSA levels should continue to go down for as long as they are taking them. If their PSA ever goes up at all, the risk of cancer is increased by a factor of 3 ,and the risk of high-grade disease by a factor of 6.4

I wonder how many of the patients in this study who died from prostate cancer were told by their well-meaning, but misinformed, urologists that this drug would prevent their disease. If that is what you believe, it’s time to understand the truth.

References

Goodman PJ, Tangen CM, Darke AK, et al. Long-term effects of finasteride on prostate cancer mortality. N Engl J Med. 2019;380(4):393-394. nejm.org/doi/full/10.1056/N...

Theoret MR, Ning YM, Zhang JJ, et al. The risks and benefits of 5α-reductase inhibitors for prostate-cancer prevention. N Engl J Med. 2011;365(2):97-99. nejm.org/doi/full/10.1056/N...

Etzioni RD, Howlader N, Shaw PA, et al. Long-term effects of finasteride on prostate specific antigen levels: results from the prostate cancer prevention trial. J Urol. 2005;174(3):877-881. auajournals.org/doi/10.1097...

Thompson IM, Pauler AD, Chi C, et al. Prediction of prostate cancer for patients receiving finasteride: results from the Prostate Cancer Prevention Trial. J Clin Oncol. 2007;25(21):3076-3081. ascopubs.org/doi/full/10.12...

***

-Patrick

[Hidden]

Would that mean that having high gleason score already beforehand (so little stroma), taking finasteride (triple blockade for instance) would not be of any help?

And again the idea that there are "false" PSA readings.... and also somewhat contradictory: if there is little stroma in higher Gleason scores, why should you still you have to ajust PSA readings...

[pjoshea13 in reply to Hidden]

At age 51 & again at age 54, I was told that I had the prostate of a man in his early 20's. This was actually presented to me as being abnormal. It is normal to have some BPH at those ages. The PSA cutoff for biopsy is based on that, with no adjustment for having no BPH.

The second comment was made while I was having a biopsy. My PSA was only 0.8. The procedure was because of a nodule. Without a DRE detecting the nodule, PSA screening would not have been much use for me.

So, imagine a Finasteride (Proscar) or Dutasteride (Avodart) user who no longer has BPH noise & has a PSA of only 2.5, say, but serious PCa - his cancer will be discovered later than a similar case: a non-user who has a lot of BPH noise.

It's merely a detection issue.

There are no "false" readings. The creator of the PSA test envisaged it as being used to detect biorecurrence after primary curative treatment. We have misused the PSA test as a screening tool for ~30 years. When a PSA > 4.0 is used as the criterion for a biopsy, 80% will be negative. For men with PCa detected when the PSA is <4.0, the cancers are no less serious.

Why does Walsh rattle on about stromal cells when PCa occurs in epithelial cells? Finasteride targets 5α-reductase-2, which is mostly present in the stroma. Dutasteride targets 5α-reductase-1 & 5α-reductase-2. 5α-reductase-1 is present mostly in the epithelium.

Strangely, Dr. Myers, who favored Avodart because it is, both, a 5AR1I & a 5AR2I, doesn't point out the importance of the 5AR1I aspect in his vlog posts. Proscar wouldn't be very effective in men who have had a prostatectomy - no stromal cells.

-Patrick

[HOPEFULSPOUSE in reply to pjoshea13]

Thanks for the post and clarification. Great info.

[Break60 in reply to pjoshea13]

PJ

I had bph and took finasteride for many years. My psa never moved above .4. Then it suddenly doubled and doubled again . I had a bx which found Gleason 4/5 PCa and stage pt3b at RP. Since ‘15 I’ve been stage 4 with pelvic lymph node mets then bone mets. I’ve been taking dutasteride since ‘15 inasmuch as I put was on ADT3 plus metformin then. Since December I’ve dropped casodex and trelstar and use estradiol patches plus dutasteride and a statin. I dropped metformin a couple months ago.

I was not happy when I learned that finasteride had cut my Psa in half and may have contributed to my high risk PCa. Is it a good idea to continue to take dutasteride?

Bob

[pjoshea13 in reply to Break60]

Bob,

There are two situations where Dutasteride [Avodart] would be beneficial.

1] According to Dr. Myers, some men produce dihydrotestosterone [DHT] even though T is at castrate levels. The purpose of ADT is to deprive PCa of DHT - not T - but doctors typically measure T rather than DHT. A blood test will determine if one needs Avodart for this reason.

2] There are various ways in which PCa can become resistant to ADT. One such is by creating DHT via a pathway that does not involve T. A blood test will not detect this, since it happens within the cell, for use by the cell. The probability may be low, but Avodart is used by some as a safety play. I use it. Nalakrats too.

-Patrick

[Break60 in reply to pjoshea13]

Well it doesn’t seem to have side effects so I’ll stay on it as safety valve . My RO prescribed it as a disciple of Snuffy .

[larry_dammit]

Men beware, I was on it for several years, it artificially keeps the PSA numbers low. Went from a PSA of 3 to 11 and stage 4 cancer in 6 months