Quick question on Avodart and PSA

3.5 yrs after RP my psa has gone up to .36. Been reading old threads on here about using Avodart. Here is my understanding about Avodart. If you have growing benign prostate cells, Avodart will lower and stop the rise of psa. If you have prostate cancer cells left in there, Avodart will not lower psa and it will continue to rise. Am I correct???
I'm trying to avoid RT. My Decipher score indicates a low risk for metastisis in 5 yrs.
More info later.
Steve

Hi Steve,

There is evidence that 5-alpha reductase inhibitors (Proscar, Avodart) reduce the incidence of PCa by some 25% and although not FDA approved for the disease they have a place in the treatment of prostate cancer.

What is the evidence?:

1. The PCPT trial demostrated a 25% PCa prevention benefit. The implication is that inhibiting DHT is men older than 50 can have a protective effect. Also that these inhivitors are active compounds in PCa. The increase in aggressive cancers in the PCPT has been a red herring, but several explanations seem to agree that it was an artifactual finding. After 18 years those participants with more "aggressive disease" have not experienced a higher mortality rate.

2. In the Dominican Republic there are several families of men born with a genetic disorder by which they do not convert testosterone to dihydrotestosterone (DHT). These men all have prostate atrophy, do not experience either BPH or prostate cancer and are capable of procreation. It is a medical fact that DHT is recognized as the androgen involved in the development of the prostate gland.

3. Finasteride was developed by Merck to treat BPH. Since BPH and PCa are two diseases that could cause a PSA elevation and those prostate conditions can and do coexist in many males, Merck promoted studies known as The Finasteride Group Study to ensure that men treated with finasteride for BPH would not be at increased risk of PCa by having reduced levels of PSA. In those studies, men treated with Proscar for prostate enlargement experienced a blood serum PSA reduction of approximately 50%. There is ample evidence that this PSA reduction is related to a reduction in gland volume (maximized by one year of treatment) caused by cell death and reduced cell proliferation. In other words, the PSA reduction is not an artifact causing a masking effect on the measuring test, but simply an effect caused by definitive biological factors (gland volume reduction)induced by the inhibition of DHT.

4. The use of Proscar to treat prostate cancer is not a recognized label use for this product. In spite of this, Proscar is used in hormone suppression protocols when maximal suppression is intended. It is used in intermittent androgen suppression during the off-cycle period to extend the time off medications. Drs. Leibowitz, Strum/Scholz and Bruchovsky have successfully used Proscar to effectively extend the off-cycle period.

5. Dr. William Fair studied the use of Proscar in treating stage D PCa and concluded that a decrease inserum PSA in the finasteride treatment group suggests that finasteride exerts a minor effect in patients with prostate cancer. This effect does not approach that seen with medical or surgical castration, but it is important because finasteride's lack of toxicity.

6. E Damber and coworkers in Sweden showed that finasteride treatment decreases VEGF expression in the human prostate. Vascular endothelial growth factor (VEGF) is a potent regulatory factor of angiogenesis in human prostate tissue. Also Wang and coworkers at New York University demonstrated that the level of androgen receptor was dramatically decreased in the cells treated with finasteride.

7. In hematuria cases caused by TURP procedures, finasteride has been proven effective in reducing or preventing the event by reducing the flow of blood to the prostate. Also in bleeding caused by radiation treatment, finasteride is effective in managing this complication. Finasteride's action in reducing blood flow to prostate tissues indicates that the action mechanism is antiangiogenic and explains its value in promoting longer off-cycle periods in an intermittent hormonal suppression protocol.

Why would Merck invest so heavily in the PCPT trial knowing that finasteride does not affect prostate cancer cells? In my view, item 2 above is a clear indication that early on in men's lives a lack of DHT causes a reduced (undeveloped) size prostate gland and prevents the incidence of prostate cancer in men genetically deficient in 5-alpha reductase (5-AR) production.

In summary, Proscar and Avodart have a place in the treatment of PCa. These drugs are a milder form of hormone suppression and yet have an important place in this treatment. Many men on active surveillance use 5-AR inhibitors to slow down disease progression. In men with more advanced disease the major benefit is the prolongation of hormone suppression off-cycles that is an improvement in patient's quality of life. Unfortunately there is resistance in the use of these drugs in the treatment of prostate cancer. Go figure!

RalphV

I've put more info in my signature. Also I include this link for reference.
https://askdrmyers.wordpress.com/
Watch the video on Avodart.

Hello LoneRyder,

I had my RALP surgery in June, 2011. Prior to my operation, my biopsy suggested a gleason score of 7 (3+4). After surgery, that gleason was down-graded to 6 (3+3) but unfortunately I had a single, focal positive margin.

The only time my PSA was truly "undetectable" was 6 weeks after surgery. Three months later, my PSA came back at .01. Thus began my slow PSA rise, tracked every three months. You can click on the link in my signature and see my entire PSA history since my surgery.

In January, 2014 (33 months after surgery), my PSA had progressed to just shy of .08 and I was ready to initiate salvage radiation. But I thought I would try one more thing in hopes of delaying that radiation for as long as possible. Enter Avodart.

I talked to my Urologist about it and although he was on the fence about it's usefulness in my particular case, he agreed with me in that there would be no harm in trying it for three months to see what happens, and I immediately started a daily regimen of 5mg of Avodart.

Three months later, I went in for my scheduled PSA test. Imagine my surprise when my PSA came back at .024, a decrease of almost 70%. To be honest, I was expecting some drop in my PSA but nowhere close to that much. Needless to say, I was ecstatic and told the radiation oncologist that SRT was on hold until further notice.

Now, here I am a bit over four years since my surgery. My PSA has continued to show a slow, upward trend to it's current value of .048.

So did the Avodart have an effect on my PSA ? The answer to that is obvious. But why my PSA went down is not completely clear to me. I see a couple of possibilities:

(1) Benign prostate tissue left behind from the surgery was shrunk by the Avodart, resulting in the PSA drop.
(2) Since I had a positive margin, the cancerous tissue left behind after the surgery no longer had DHT to feed on and suffered a "shock" of sorts, resulting in the PSA drop.

I know my PSA numbers are almost infinitely low, but based on a recent study suggesting that SRT success rates can be improved by starting early (three consecutive PSA rises after .030), I will most likely move forward with SRT later this year if my PSA shows another rise when I have my next quarterly test in July.

John, Towing my Ultraglide Ltd. to the Black Hills, Wy. and N. Utah with my motorhome. Love riding in the west!

So it sounds like you did have multiple focal positive margins, and some of them may have been of the Gleason grade 4 variety. I think that explains where your PSA is coming from, and perhaps give you some assurance that it is localized and perhaps curable by salvage radiation.