What to do if your PSA test is abnormal | Peter Attia & Ted Schaeffer

let's talk about the PSA a little bit because we've alluded to it a number of times so let's explain what it is where it comes from and and more importantly of course how we use it yeah so PSA is a is a protein it exists to Aid in the liquefication of semen so it's produced by the prostate and if one were to um measure PSA in semen it would be very very high I always tell people if you looked at PSA and the cement it would be I don't know 100,000 nanograms from of PSA and semen it's designed to be there and it exists there to liquefy the semen to help in the process of fertilization it is not designed and it should not exist in the blood but a certain percentage of PSA made in prostatic epithelial cells leaks into the bloodstream and when we do a PSA blood test we're measuring the PSA that has leaked into the bloodstream from a prostatic epithelial cell now most of the PSA that leaks into the bloodstream is bound to other proteins a certain percentage is that like albumin mostly or sex Alpha kyot tripin oh so it's its own separate binding protein yeah it has that's the most common protein that PSA binds to but it can bind to a family of three or four four or five different but these are prostatic proteins yeah yep it's bound now how much it's processed because as you know protein so don't come out finished they grow into the their final State and they grow by shrinking right they get things snipped off of them as they're maturing and and going through that process as PSA is evolving in the normal kind of development of its exocrine function it gets snipped into smaller and smaller States fully fully processed PSA can float around in the bloodstream freely that's free PSA so if you have a benign prosthetic epithelial cell a lot of its PSA will be fully processed and ready to go in the ejaculate let's just say and if it leaks into the bloodstream it can float around freely you can measure it in an assay and it's what we call free PSA a lot of the unprocessed or incompletely processed PSA bound to protein Alpha kimot tripon is the most common one and that is what we would consider to be when we do a measurement of when we looking at total PSA you're measur ing mostly bound PSA and some free PSA and that ratio we use you and I use in our practices to help discriminate against PSA that's in the bloodstream that may have leaked from a cancer cell or may have leaked from a benign epithelial cell now there are other siblings of PSA that are also produced in prosthetic epithelial cells of course all in response to androgens they're produced in those cells and they can also leak into the bloodstream and we use those in some Advanced PSA based blood testing as well but in general when we are measuring PSA we are measuring the amount of PSA this Protein that's leaked from an prostatic epithelial cell into the bloodstream we can refine that value by saying how much of it is how much is there and how much is free if we have high amounts of free PSA 30% for example then we can have good reassurance that most of the PSA in the blood that you're detecting is from benign cells when most of the PSA that you have in your blood is um bound very limited amounts of free PSA that's a strong marker that there's something going on I. E that cancer cells are leaking the PSA into the bloodstream now as I mentioned you can also measure other byproducts um other other types of free PSA or other sibling molecules to PSA PSA is called hk3 or human caline 3 you can measure for example how much of human caline 2 is in the blood and these are part of it more advanced PSA tests like the 4K score or for example the prostate health index these are both mathematical equations that predict probability of aggressive cancers but they're built off of looking at not just the PSA itself but the PSA and how much other types of processed PSA exist as well let's go back and talk a little bit about the free PSA um does the amount of free PSA that we would want to see to be more assured of a benign nature of the PSA vary by age and absolute PSA level yes it does um so we begin to use the kind of free PSAs and the free PSA ratios and all those things when PSAs have crossed over certain threshold right because yeah typically a lab if you if your PSA is one we can't even get a lab to check a free PSA that's that's right because we know if your P if you're screening someone and your PSA is one then the chances you the probability of a prostate cancer that's lethal is incredibly low right so that's why they they just don't they don't have the ass set up to check it and often times or some Labs will not that you know secondary default testing unless it's over four for example or over 2. 5 we our lab set up to do everything at low levels as low as two so you can get them at lower levels but in general the idea is well if your PSA is below two the probability you have a lethal prostate cancer is you know less than one in a million so we don't have to worry about that individual and we really want to use the percent free PSA to discriminate y individuals who have elevated PSAs and having to discriminate between elevated because of BPH and elevated because of a cancer so yes as you get older your prostate enlarges as we talked about metabolic syndrome causes your prostate in large part to grow all you know just because of the tte ratios um as it gets as you get older your prostate gets bigger so you we begin to use that in in as you get older and your prostate gets bigger you can have a proportional rise in total PSA in your blood stream just because your prostate is bigger and it's leakier but you can easily tease that out by looking at the percent free PSA so if the percent free PSA is over 18 to 20 then you can be rest pretty well assured that that's likely not coming from some aggressive bulky tumor what about with prostatitis when we see these huge spikes everything goes up in thosea in those cases but but does the free still remain disproportionately high to well it's a good question I don't use free PSA in people because I'm I'm tracking it I'm L looking for trends for coming back down to a new Baseline so yeah okay um let's talk about two other ways we use the PSA the density and the velocity how do those work yeah so um as I mentioned as you get older your prostate on average gets bigger not for all men but for many men and when that happens your PSA can concordantly rise because it's just your prostate gets bigger and gets equ it's equally Le so the PSA can kind of go up now what we look at is the ratio of the prostate the PSA value to the prostate volume and that as you alluded to is called PSA density and in general when I when I educate patients I tell them well we want a a PSA to be about 10% of the volume of the prostate or less to kind of be in a safe range so if your PSA is four and your prostates 40 grams which is about average size for a 60 65 year old guy that's a PSA density of 0.

1 we know that that is correlated with a low risk of having an aggressive prostate cancer so when when I'm looking at someone's case I want to know what their PSA density is if the PSA density in a young man frankly is more than 0. 1 I get a little worried if on an average age person if the PSA density is more than 0. 15 I also get I start saying let's do some additional test so I put you put everything but yes PSA density predicts likelihood that you'd ever be diagnosed with prostate cancer it predicts aggressiveness of a cancer If you're diagnosed with it and it actually predicts your outcome if you have a prostate cancer so the higher your PSA density the more significant your disease will be so the faster it increases and the faster that your PSA Rises it is a canary in the coal mine to say hey you need to do some additional evaluation now it doesn't mean you have prostate cancer because I often have we share patients where their PSA went from 1 to 5 but they had we we we tracked it and it came back down because they had a flare up or inflammation in their prostate that made their PSA go sometimes we don't know why often we don't know why but if you track it you can see that so whenever somebody in general comes to see me with an elevated PSA the first thing I always do is just recheck it because there can be transient rises in the PSA now as you know we have very similar practice I don't just recheck the PSA I always order Advanced PSA based testing what does that mean that is testing that involves looking at the percent free PSA and then other things like minus two pro PSA for the prostate health index test or the 4K score which basically will looks at different calres and their ratios so and you and I discussed these tests in great detail in the first podcast so we can also refer people back to those um so that I won't make you re-explain them but um it does surprise me that the official screening guidelines for prostate cancer uh don't make any recommendation on the use of PSA testing other than something benign like discussed every patient should discuss this with their physician which is a a real copout in my view of what we should be doing is that still is that well it depends on which guideline you're looking at so the American urolog this was the this is the guideline preventive this is the US preventative task force and the CDC um and there's one other that is yeah the American Cancer Society uh the American neurology Society the national Comprehensive Cancer Network they're a little bit more Progressive they really suggest that you should talk about the risk and the benefits of screening they kind of screed around the idea of well how do you properly screen for well AUA and and and and American Cancer Society don't get into details up front they say start the discussion with like what's your potential risk for developing prostate cancer you can ascertain that with the family history again if you're reading the AA guidelines of the American Cancer Society guidelines you already have a leg up on the average internist because an average internist is just looking at General things they learned in med school or the US preventative Services Task Force which is too General and too vague so I totally agree with you I like and personally reference everybody to the National Comprehensive Cancer Network's prostate cancer screening guideline that basically says that every man at age 45 should have a baseline PSA because as you mentioned changes over time are key they're critical and you want to know where you are in relationship to the median right so a 45y old man's median PSA between 05 and7 somewhere around there understand your median PSA and then if your PSA is below one you could just get re you can get rechecked in two to four years if your PS but Ted isn't I mean the test is free it doesn't cost anything to do a PSA why wouldn't we do this every single year you I guess the argument against it is that um there can be natural variations in P again if you're a smart physician you're going to pick up that hey there's natural variations and if it goes up from 7 to 1.