Effect of Avodart on BCR / PSA progression - Help me understand

Hey folks,

I'm hoping I can get some help in understanding what is going on with my PSA.

I had my RALP surgery in June, 2011. The only time my PSA was truly "undetectable" was 6 weeks after my surgery. Since then, my PSA has been slowly increasing until three months ago when my PSA had gone up to .08.

It was at that time that I started Avodart daily. I know that Avodart is used primarily to treat BPH by preventing the conversion of regular testosterone to dihydrotestosterone (DHT). But what I've also read is that sometimes Avodart can slow down PSA progression by removing its primary fuel for growth, DHT.
I just got my results for my April PSA test and I was shocked to see my PSA had dropped to .024 !! You can see my entire PSA history by clicking on the link in my signature below.

So now my head is swimming with questions. I was hoping my PSA progression would slow down, but I simply did not expect it to drop so much.

So what do you suppose is happening here? Does Avodart affect PCa cells differently from benign prostate cells? I've read that when using Avodart, you need to double your PSA test results to get a correct PSA reading for your blood, but even doing that, my PSA would still be less than .05.

Does Avodart also reduce the volume of prostate cancer cells in the same way that it reduces the volume of benign cells ? Does Avodart have any effect on the production of PSA from cancer cells, or is the PSA production from the cancer go on unchanged ? If PSA produced by the cancer is the same after taking Avodart, then it can be presumed that someone who has a significant proportion of their PSA coming from cancer cells, won't have a 50% reduction in PSA, but a lesser percentage due to their prostate volume reduction.

I've also read (here on this forum), that cancerous prostate cells can give off much more PSA than benign normal cells relative to their volume. Benign cells give off .66 PSA per cc and G6 can give off as much as 3 or 4 PSA per cc. Thus, reducing the level of DHT can help shrink cancerous cells and have a greater proportionate PSA reduction than the shrinking of the benign cells. This reduction is less as the Gleason score increases so the effect is not as pronounced in someone with a higher Gleason.

I'm not scheduled to see my urologist until later this month. But I'm starting this thread here in hopes that some of you might be able to help me understand what exactly is happening here.

Avodart has been known to cause regression of GS6 cancer in untreated men on AS. In one study I read, more than half the men with very low risk PC and BPH were devoid of cancer after a year on Avodart. In a randomized controlled trial of Avodart vs placebo in low-risk men, there was 38% less PC progression among men taking Avodart. Whether the therapy killed off all the cancer is impossible to say at this time, although that is indeed a possibility. This is exactly what happened to a friend of mine. And he had a saturation biopsy to hunt for any possible bits of cancer - they found none. Needless to say, he is thrilled.

It's possible that a bit of GS6 was left behind by your surgeon, and the Avodart is killing it off. It's also possible that some of the PSA is from left-behind benign hyperplastic cells and the Avodart is shrinking them. Either way, it is great news for you - keep up what you're doing!

BTW - the "doubling" of PSA is just a rough rule of thumb and only applies to untreated PC. It's not useful in your case.

- Allen

HDRIDER QUOTE: "I've also read (here on this forum), that cancerous prostate cells can give off much more PSA than benign normal cells relative to their volume. Benign cells give off .66 PSA per cc and G6 can give off as much as 3 or 4 PSA per cc."
--------------------------------------------------------------------------------------------
HI HDRIDER, - One of the dangers of the internet, including Boards such as this one, is that information posted is often accepted as "fact" when, actually, the information is inaccurate. Then, it gets repeated from a memory that cites their source as "I read (or heard) it somewhere". In fact you DID read it on this Board, and so did I, in a Post from an often-credible source on some PCa subjects,

BUT, in this case, whether due to a typo or an incorrect understanding, the conversion factor of .66 contained in the quoted Post above is erroneous and should NOT be perpetuated.

The Prostate Cancer Research Institute (PCRI) states that: " - - - gland volume in cubic centimeters (cc) multiplied by 0.066 yields the amount of PSA produced by the benign-related epithelial cell population of prostate cells." - - - and this is the original source of this calculation by Medical Oncologist Stephen Strum, MD.. But Dr. "Duke" Bahn, another touted PCa "expert", reportedly promotes 0.1 per cc of tissue volume as the appropriate multiplier, but PSA is not an exact science and so both are approximations. This range of .066 to 0.1, however, is probably a pragmatic basis for such calculations and is helpful in estimating the amount of PSA usually attributable to normal benign tissue in an individual elevated PSA reading. Obviously, the proper placing of the decimal point is CRUCIAL to accuracy in such calculations.

The LIKELY cause of any additional PSA yield must then be attempted to be determined, with the full recognition that the other two main sources, other than PCa, would likely be cells affected by BPH (Benign Prostate Hyperplasia or Hypertrophy (natural benign growth with advancing age) and/or Inflammation, which is known as Prostatitis. Any of the 3 sources, or all three, MAY be contributors to any excess PSA present. At the present time, direct examination of Biopsy tissue samples by a qualified Pathologist, is the ONLY widely accepted method of identifying PCa, although advancing imaging can sometimes identify "suspicious" lesions, they need to be confirmed by Biopsy to legitimize an individual Prostate Cancer diagnosis.

Re: Reported “ZERO” PSA
TECHNICALLY, there is no such thing as a real zero reading. Each and every PSA assay (test) has a known limitation to its sensitivity, below which readings are not reliable. This reliability threshold varies with the individual assay used, but exists in each.

ACTUAL results, if any, below the reliable sensitivity level of the assay involved, are usually reported as LESS THAN (<) the specific known limitation. In the Standard PSA test, this is usually 0.1 ng/ml (<0.1), but there is at least one that is 0.2 ng/ml. Hyper-sensitive and Ultra-sensitive PSA assays have sensitivity reliability that can go as low as 0.01 and/or even 0.001 ng/ml (not taking into account electrical interference=”noise”) that can sometimes artificially alter such highly sensitivity results

This said, the casual term "zero" is often used in the verbal reporting of a result when it is below the stated reliability thresholds, even though, TECHNICALLY, it is not the actual reading, which would contain the < icon, before the numerical identification. The term "undetectable" is even more often used as a substitute for the actual reading but, obviously, that meaning varies with the sensitivity of the result, as does it’s clinical significance.

There is only one way to get a formal, printed "zero" report, and that would be to employ an assay material with sensitivity that is below the amount actually reported. Example: If I would use an assay with sensitivity to 0.001 (1/1000th) to OBTAIN my PSA reading, but only REPORTED to 1/100th of a nanogram it would read 0.00, BUT technically, that would not accurately report the true reading actually obtained.

As you can see, this gets quite complicated and such broad terms as "undetectable" can mean different things to different individuals. Generally, it refers to "CLINICALLY" undetectable, which is WIDELY accepted to be anything LESS than 0.1 (<0.1 ng/ml) in the routine monitoring of post-surgical PCa patients, although certain exceptions are possible in individually advanced cases.

I appreciate this is a lot of explanation for something that is mostly inconsequential to patients who have had successful treatment results, but to those that are interested in the technical determinations and their true meaning and significance, I hope it has been both explanatory and beneficial.

I feel that of the confusion in accurately addressing this disease is often a direct result of NOT knowing and/or UNDERSTANDING the subtle differences found in communicated PCa terminology. - [email protected] (aka) az4peaks

You can trust these big human trial studies. There are too many people involved for the companies to fudge, even if they wanted to. And, as further proof, Glaxo Smith Kline got murdered by a study they did on Avodart a couple years back. They were looking at Avodart for preventing prostate cancer and they found that while it reduced the total number of cancers diagnosed in the treatment arm there were more high-gleason, aggressive cancers. Yikes!

Since then they've been digging and they have pretty much gotten themselves out of that hole. But that study cost them big time. The confounding factor was that Avodart shrinks the prostate but does not shrink high-grade tumors. Even though it didn't cause the high-risk cancers it did make them more likely to be diagnosed in a biopsy -- same needle, less haystack. And it did prevent quite a few low-grade cancers. Pretty good stuff, actually, but GSK took a big hit.

Hi folks,

Just thought I'd bump this thread with my latest PSA results.

To recap, I’ve been experiencing a slow PSA rise since my robotic prostatectomy a bit over three years ago. In February, my PSA had reached .08 when I started taking Avodart. In the three months that followed, my PSA had dropped to .024, a reduction of almost 75%. I was elated.

I just had my quarterly follow-up with my urologist yesterday and got my latest PSA results. My PSA is currently at .035, an increase of .011. A complete history of my PSA can be viewed using the link in my signature.

I am still taking Avodart but have decreased the dosage to one capsule every other day. I will continue to do so and we'll see how my PSA looks in October.