The PCA3 Test
I'm one of the few that on the Peak Testosterone Forum that still believe there is considerable
value in the PSA test. Even so, I will freely admit that there is a lot to be desired with the PSA. One of the issues is that it picks up on other conditions, such as the prostate growing in volume, increased inflammation, prostatis, etc. So wouldn't it be a great idea if they came up with a test that specifically targeted just prostate cancer? Well, that is exactly what the new PCA3 test does. The test is not perfect, but it does give good additional information that I believe can help in the diagnosis and treatment of prostate issues. (I have read that it is about 70% accurate.)
NEWS FLASH: There is now a significantly more accurate test out of the market called the 4Kscore. I recently took this test and here is my story with it:
My 4kScore to Test for Aggressive Prostate Cancer.
I urge you to read that page first.
I am particularly interested in this topic, because I myself had a high PSA and was kicked off of HRT. "Never again" is my motto now. Urologists have not begun using this test, but a few naturopaths that specialize in men's health issues have and below is my interview with one of them, Dr. Eric Yarnell. You will be fascinated with the Doctor Horror Story that drove him to become a naturopath and a discussion as to how he has healed a few men of their low testosterone. He also discusses a fascinating (and scary of course) research link between varicoceles and prostate cancer. Most of the interview below, though, is a discussion of the PCA3 test and how he uses it in his practice.
CAUTION: Please do not alter your treatment plan or medications based on anything in this article without discussing it first the urological physician, naturopathic or allopathic, first.
Q. I think it's great that you're a naturopathic doctor. Can you let us know what drove you to take this route with your career?
A. My displeasure with the conventional medical system combined with my general interest in healthy eating (I became vegetarian as a teenager, though
ultimately found that diet wasn't the best for me) and helping people. I'll give an example: I developed otitis media in college. I went to the
emergency room as I was very dizzy and disoriented. I sat naked except for a hospital gown in a freezing cold room (to this day I have no idea why
they wanted all my clothes off for an ear problem) for over 2 hours before I was seen by an intern who was super rushed and fairly disoriented himself. He
did look in my ear and pronounced that I had an "ear infection." When I expressed skepticism about his plan to give me antibiotics, he eventually brought
in the senior doctor who seconded his opinion without looking in my ears. I was prescribed the antibiotics and sent on my way. I did not fill the
prescription; I found a naturopathic doctor in Colorado Springs who instead gave me some herbs to take, explained that usually otitis media was due
to allergies, and had me do hot compresses over my ear and to rest. She took her time, really listened to me, didn't have me sit and freeze naked and
exposed for 2 hours, and was just generally very pleasant. In a day I was feeling much better without drugs and really feeling encouraged that there were
One thing that I know some men will be interested in: do you handle HRT in your current practice? If you want to say a bit about that, I know some
men are always looking for good practitioners.
I have chosen not to prescribe testosterone in my practice. I am working hard to figure out why testosterone levels fall in some men and correct
the underlying causes. In some cases where testosterone has been clearly indicated I have referred to colleagues who do prescribe it. I am
concerned that we are headed down a similar path as what happened with estrogen in women: an uncritical treatment of the lab numbers instead
of the person, a failure to ask why the process was happening, and a failure to then do something about the underlying causes. And we have the
added difficulty that the "normal range" for testosterone is extremely wide and no one can really explain why or how one man with a serum total
T of 300 feels completely fine when another with a serum total T of 400 feels awful with classic hypogonadism symptoms. And I've seen both situations!
it seems clear to me we are in a new era of understanding men have hormonal changes, but they are complicated and I don't believe they just happen out of nowhere. I
believe obesity, sedentariness, poor diet, stress, environmental toxins, and probably many other factors play a role in causing this (based on my observation that
very often I can get patients feeling better and their levels will go up if they are able to make major changes in their lifestyles).
Q. The PCA-3 test is a topic of great interest to me. As you know, I had a high PSA read (6.3) and I am still above my old baseline values of about 1.4. I
had a biopsy and they found no cancer or precancer (PIN) and found inflammation. So, supposedly, I have no PC, but the bioposies are not perfect. Would
I be a good candidate for the PCA-3 test and, if so, why?
A. In my opinion you would be a good candidate, though having more information about your case would be necessary to say for certain (including results of past prostate exams, urinalyses if any, and any other symptoms you might have in the area). One of the main problems with biopsy is sampling error: at some level the needles are stuck in randomly (ultrasound does try to identify the most likely areas of problem to target, but often doesn't see any). PCA-3 is much better at overcoming this (but not perfect) as it is dealing with cells shedding from throughout the prostate. Anyhow, the test is also relevant because it is very safe (no needles, just a digital rectal exam/brief massage of the prostate required) and either of its results could really change the course of your case. If it were positive, I would strongly consider imaging the prostate with color Doppler ultrasound or endorectal MRI. If it were negative, I would be thinking much more about chronic prostatitis.
Q. Where you do you stand on the subject of testosterone and prostate cancer? Do you feel that well-managed HRT can fuel prostate cancer, etc.?
A. I am following closely the publications by Gat and Goren out of Israel and their studies on local vs. systemic testosterone and prostate cancer. This is my current working model (which is subject to change and isn't perfect I'm sure, but does a better job than existing models of explaining what we see clinically):
1. Testosterone normally produced by the testes circulates through the body becoming highly dilute, delivering only a small amount to the prostate in normal circumstances.
2. This level of testosterone is permissive for normal and neoplastic prostate cell growth. Without it, they won't grow; but it doesn't trigger them to grow or cause cancer.
3. With age, men develop varicoceles (varicosities of the testicular venous plexus as well as the internal spermatic veins). This is due to gravity acting on venous valves. It is more-or-less inevitable though the degree of varicosity is variable depending on diet, exercise levels, etc.
4. As varicoceles progress, they cause more and more blood to pool in the testicular venous plexi. As a result, androgen levels go up in this blood to something like 100 times greater than the levels found in the peripheral blood (like drawing blood out of your arm vein).
5. There are one or more tiny deferential veins connecting the venous plexi of the testicles to the venous drainage of the prostate. The blood backs up from the varicoceles into the prostate via these veins. Now there is a super physiological level of androgens (again, up to 100 x normal) in the prostate, and this does have a direct stimulating effect.
6. Treating the varicoceles eliminates early-stage prostate cancer.
Gat Y, Joshua S, Gornish MG. Prostate cancer: a newly discovered route for testosterone to reach the prostate : Treatment by super-selective intraprostatic androgen deprivation. Andrologia 2009 Oct;41(5):305-15.
Based on this theory and the evidence we have so far, systemic testosterone therapy does not affect prostate cancer in most cases. And to be sure, one can simply take a 5-alpha-reductase inhibitor drug at the same time to be super safe. The androgen problem is with this venous problem causing massive buildup in the prostate, far beyond what any dose of testosterone you can give without seriously and acutely hurting a patient.
Q. How accurate do you feel the test is both on the false positive and false negative side of the equation?
A. Very good on false negatives front, moderately good on the false positives front.
False negatives: so far I haven't seen any of these and the test numbers look pretty good. We'll need a lot more data to be really sure. But I suspect due to sampling error problems we will see false negatives. We may also see some due to mutational differences between prostate cancer strains that the test can't identify (yet).
False positives: I have not seen this be thrown off by prostatitis or BPH which is a big step up over PSA. However, I have seen several positive tests where biopsy showed low-grade, minimal cancer (Gleason 3+3 in 1-2 cores only) or imaging (if the patient refused biopsy) showed only what seem to be very mild problems.
So like practically every test we have for prostate cancer, this test is still limited by its inability to distinguish aggressive from non-aggressive prostate cancer. This is huge because most prostate cancer is non-aggressive and doesn't need to be treated with surgery, radiation, or drugs (the major exception would be for those patients who are so very anxious they can't stand living with even this low-grade cancer in their body). All patients with prostate cancer have to be monitored lest they have early aggressive forms and we can catch them as they start to look more aggressive as early as possible.
Q. Is the PCA-3 test FDA-approved yet? If not, do you think it ever will be?
A. It is approved (well at least one testing kit for it by Gen-Probe is approved): http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/DeviceApprovalsandClearances/Recently-ApprovedDevices/ucm294907.htm
Q. What are the rough costs for the test itself? And are you seeing other naturopaths and/or traditional urologists making it a part of their regular practice?
A. I have seen some pretty crazy differences in prices between labs. I talked the current lab down to $432 (used to be several hundred dollars more). The lab they bought out used to charge $250.
I am not seeing urologists use it much at all. They seem to feel that it is biopsy or nothing. But I see it occasionally. And more naturopaths are definitely starting to use it, though I still get a lot of referrals. Part of the problem is, it doesn't warrant keeping the kits around if you don't do a lot of them, so most NDs are just not seeing enough patients with this problem to warrant it. I do, so it makes a lot of sense for me.
I also tend to see those patients who refuse a prostate biopsy no matter what, and conventional urologists get frustrated and angry and can't work with these patients. Rather than writing them off as "kooks" or whatever, I have come up with other ways to help them the best I can. PCA-3 and imaging are part of this, as they avoid the needles but can still help us know pretty well (nothing is perfect) whether they have aggressive cancer that really needs conventional and natural medicine combined, or if they have low-grade cancer which just natural medicine can help, or no cancer at all.
Q. Do you think the PCA-3 should be used in conjunction with the PSA or in place of it or neither?
In conjunction, with careful education and preparation of the patient to understand what the tests can and cannot do, and how to interpret them. I also emphasize
that if they are positive it means more testing is going to be necessary.
Q. Do you feel that the PCA-3 is as accurate as the standard 12-point biopsy? And, if so, could it ever replace the biopsy?
A. In terms of detecting prostate cancer in general, it gives the biopsy a run for its money.
In terms of differentiating aggressive from non-aggressive cancer, biopsy is way, way better.
So it is not really an issue of replacement, and I don't think it ever will be. PCA-3 should be a tool to decide whether a patient should undergo a
biopsy or more intensive imaging; if it is negative, then we can just wait and retest in a year or two.
Q. One of the things we really need to know is if one has aggressive prostate cancer. Does the PCA-3 test help with that at all?
A. Nope. See discussion above.
Q. Finally, can you tell us a little bit your practice and give men some contact information if they have further questions for you?
A. DrYarnell.com has all the information. I do a lot of things so I only practice one or two days a week
depending on my teaching and writing schedules.
Eric Yarnell, ND