There are a lot of questions about this topic on this board, and it's helpful to learn what our doctors are learning about it.
I'm still surprised by the amount, quality and timeliness of information available to us patients from the medical community. This is a good example. The following information is my version of the published highlights from a presentation just last Friday, August 1, 2008, at the "Masters in Urology 2008" Conference at the Elbow Beach Resort, Bermuda. (Wish I had been there!
The presenters were Michelle L. Ramirez, DO, William J. Catalona, MD, and Christopher P. Evans, MD. I have not heard of Drs. Ramirez and Evans, but Dr. Catalona is world famous both as a prostate cancer surgeon and as a prostate cancer researcher, especially regarding both surgery and PSA. That makes me believe this information is authoritative (though my account is not). I'm not trying to be comprehensive but have tried to hit the high points.
- PSA in prostatic fluid is about a million times higher than in serum! That was news to me.
- There are both lot-to-lot PSA test material differences for the same brand of test as well as differences between different brands of PSA tests (Lehman 1994). My own experience with many PSA tests of several different brands for more than eight years is that the results seem to line up very well, but with at least one disturbing exception that was the result of a test processing error.
- Variation in consecutive PSA tests within a short time span: one study found that PSA results varied by about 15% for total PSA when three tests were run with two weeks in between each; the variation for free PSA was 17%, and the free to total percentage varied by 14% (Ornstein 1997, with Catalona as senior author). Say your true PSA was 3.0; the study shows that your PSA test could come out to be 2.55 to 3.45. The percentage appeared to be unaffected by either PSA level or age. Therefore, if your true PSA were 10, your PSA result might turn out to be as high as 11.5 or as low as 8.5. (If I were being screened for prostate cancer, I'd want another test quickly if I got a result over the 10 level because of the significance of that level in making predictions! Of course, if I were not even a PC patient yet, I would not know enough to ask for it.
- The average PSA for a completely healthy (I think - probably minimal BPH, no infection, no prostate cancer) prostate is 0.7 for men in their fifties, 0.9 for men in their sixties, 1.3 for men in their sixties, and 1.7 for men in their seventies, according to Dr. Catalona.
- Year-to-year variation in PSAs: one study found that 26 to 37% of men with elevated PSA levels returned to normal the next year, with 45 to 55% returning to normal within four years. For 65 to 83%, the PSA remained normal for years afterward. "For those who had a prostate biopsy recommended for abnormal PSA levels, 40 to 55% would have had their PSA paramaters fall below the biopsy criteria during the four years of follow-up." (Eastham 2005)
- Dehydration can affect the PSA level. That was a new insight to me, but it's easy to see why. The amount of PSA in the blood will be a smaller percentage per unit of blood if the blood is diluted with extra water, and it will be a higher percentage if the body is dehydrated. I'm guessing the impact would be small; the text did not say.
- Seasonal variations in PSA level. A large French PC screening study collected data over years and found that PSA was highest in the summer. Here are their results by season:
The bottom line here is to try to have annual screening tests done in the same season each year. This had a practical impact, as 23% more men screened for the study in the summer would have been referred for a biopsy based on a trigger PSA score of 3.0. (Salama 2007) Wow! That's a half point difference between the winter/spring versus the summer!
Mixing up seasons, especially spring and summer, which are close to each other of course, could throw off PSA velocity indicator also. That's a good reason not to procrastinate in setting the date for that annual test!
- Finasteride, formerly marketed as Proscar before going generic, cuts the PSA score about 50% - no news there, but I was surprised that Propecia, a 1 mg, 1/5 dose of finasteride, sold for hair restoration, also cut PSA by 40% for men aged 40 to 49 and 50% in men 50 to 59. Use of these medications shouldn't be a problem, I've heard, as long as the appropriate adjustments are made in figuring trigger points and trends. Finasteride also cuts free PSA by about the same percentage, which makes the free to total PSA percentage stay about the same as it would have been without the drug. (Espana 2002)
- Saw palmetto did not alter PSA levels in a large, gold-standard type trial. While many saw palmetto trial failures can be excused based on use of a suspect brand of the herb, this study used Permixon, which has an excellent reputation for quality. (Habib 2005) It makes you wonder if it's helping any against prostate cancer!
- Antibiotic therapy: one study showed that a 28 day course of fluoroquinolone for chronic prostatitis patients reduced average PSA from 8.3 to 5.3, including decreasing PSA below the 4.0 cut-off for 42%. (Schaeffer 2005) Ciprofloxacin, used in another study for three weeks, decreased PSA in 59% of patients; prostate cancer was detected in 40% with unchanged PSA contrasted to detection in just 20.2% with decreased PSA, and in this study no prostate cancer was detected when the PSA fell below 4.0 or was reduced by 70%. (Seretta 2008)
- Increasing drug resistance: a problem with antibiotic therapy that probably many of do not consider (me included) is increasing. It's still apparently pretty low for fluoroquinolone, just 2.6% in 2006, but that's a disturbing increase from 0.8% in 2005 and 0.6% in 2004. E-coli is the bacterium most responsible for prostatitis; it was found in 91% of patients having a positive urine culture or infection complications after a biopsy; unfortunately, 86% of these men were resistant to fluoroquinolones (and 94% to ampicillin, 44% to bactrim, 72% to piperacillin, and 22% to gentrimicillin (spelling?). That illustrates why it can be hard to eliminate prostatitis.
- Recommendations for using antibiotics to clarify the PSA picture: The authors suggest not using them for an isolated increase without any evidence of an infection. They recommend using them based on either an above threshold result from a certain urological test result or if there are large PSA fluctuations. They also recommended allowing a month after antibiotic treatment to let the intestinal environment normalize before having a repeat PSA test or biopsy to reduce the risk of infection.
- PSA velocity: Dr. Catalona is convinced that the traditional warning sign of an increase of 0.75 in a year is okay for men with a PSA above 4.0 but that it should be 0.3 to 0.5 for men with a PSA less than 4.0. The presenters noted that guidelines from the National Comprehensive Cancer Network now suggest a PSA velocity trigger for biopsy of an increase of 0.35 per year.
Please remember that this is my summary as a layman with no enrolled medical education. I hope this post provides leads and a basis for better communication with physicians, but please don't take it as authoritatitive. I hope it helps.