In part II of our discussion around what is deemed to be new or updated for 2024, we are going to look at what lab-based tools are interesting, or at least of interest to the experts. As stated in my last post, and it is very frustrating but true, most of these tests still revolve around the PSA test. Thus, I will report them to you, and we can, together, decide.
At this point it is worth it to take a step back and review the facts around the PSA test. From earlier posts we learned that PSA is Prostate Specific Antigen. When measured it is stated in nanograms per milliliter (ng/ml) which for those of us not from a scientific background is one- billionth of a gram per one-thousandth of a liter. Thus, a PSA test is designed to determine the level of PSA in one’s blood. That is all it does, no more and no less!! Got the basics??
The basics are what makes the dependence on PSA so frustrating. What is the value of this test? Ask 10 experts and get 12 answers, because I do not think they really know but there has to be some kind of starting point, right?? It is also well documented that PSA is a nonspecific marker. It just tells us that we have PSA because we have a Prostate. Remember from Dr. Ablin’s early work when he discovered the existence of an antigen specific to the Prostate, he planned to only use a PSA test for men who previously had a prostatectomy. The simple logic was and still should be, if you do not have a Prostate there should be no PSA present. If there is PSA present then call Houston because we probably have a problem!!
Also, remember historically a PSA level of 4.0 or less was and is considered normal. There have been some institutions that have made some adjustments in the “normal” range to account for age (but ask your doctor and 5 will get you 10 he will say normal is 4.0!!. Again the challenge here is that there is NO science that says 4.0 is normal. It is an arbitrary number picked out of the air when PSA was in front of the FDA for the first approval (as documented in an earlier post here). One can have a high grade aggressive cancer that does not produce much PSA, which can manifest in a low PSA number but one still has cancer. Conversely, one can have a high (or what is considered above normal) PSA but no cancer is present. Again I( ask the simple question, can anyone tell me the value of a PSA test when it is really a nonspecific marker and not a diagnostic tool at all since there really is no such thing as a normal PSA! Let’s just move on then.
Lab Based Diagnostic tools in 2024.
PSA Test. We will not waste any more time on this test as it has been well documented here and in other posts on my blog and in the literature around Prostate Cancer and screening.
Free PSA Test. Your doctor may consider a Free PSA test to determine what the amount of PSA in the blood is floating free on its own or is attached to a protein molecule. Benign conditions tend to produce more free PSA whereas cancer tends to produce the form that is attached to a protein molecule. By measuring the ratio of free versus attached PSA your doctor may be able to get a better clue about what has caused an elevated PSA. According to the experts a lower percent of free PSA can suggest the presence of cancer in the Prostate.
PSA Velocity. A test to measure the change in your PSA levels over time. There is some evidence to suggest that PSA Velocity may aid in screening for Prostate Cancer and help identify men who may need quicker and more aggressive therapy. As always there is a caution that this test may not be very accurate since it is a PSA based test!!
PSA Density. If you have an enlarged Prostate, our doctor may use this test. The logic for this test is that an enlarged Prostate may cause higher PSA levels. PSA density is determined by dividing the PSA level by the size of the Prostate. A higher PSA Density may suggest an increased risk of Prostate Cancer.
ISOPSA Test. This is a test pioneered by researchers from The Cleveland Clinic. It is a test designed to assess the risk of high-grade Prostate Cancer. Unlike normal PSA tests, the ISOPSA test examines various isoforms of PSA to identify molecular changes that indicate whether these proteins are produced by cancerous or benign cells. The ISOPSA index is calculated to gauge a man’s risk of having high-grade Prostate Cancer. The ISOPSA test is indicated to assess the risk of high-grade Prostate cancer for men over 50 years of age with a total PSA of 4 ng/ml or greater.
Prostate Health Index and [-2] pro-PSA test. One isoform (protein variant) of free PSA, [-2] pro-PSA may predict early-stage Prostate Cancer and is related to the risk of aggressive disease. Studies of this led to the creation of the Prostate Health Index (PHI). PHI is a mathematical calculation incorporating [-2] pro-PSA , other forms of free PSA and PSA. Research suggests that PHI is more effective than total PSA or free PSA at detecting Prostate cancer at initial and repeat biopsy and that it can help predict clinically significant Prostate cancer and reduce the number of unnecessary biopsies (someone smarter than me is going to have to explain that one to us because if you are still doing a biopsy, define unnecessary for me)!!
4 K Score. This test may help predict who may have more aggressive Prostate cancer on biopsy which may reduce unnecessary biopsies (there is that statement again).This test measures blood levels of four Prostate-derived proteins: total PSA, free PSA, intact PSA and human kallikrein 2. These biomarkers are combined with a patient’s age, digital rectal exam and biopsy history to calculate the likelihood of finding a high-grade Prostate Cancer on biopsy.
Liquid Biopsy. These tests have come into being because of Researchers looking at genetics to determine the possibility of genetics causing Prostate cancer. These new tests examine an array of genetic markers in addition to PSA and individual clinical characteristics in blood and urine samples to assess a man’s likelihood of having Prostate cancer but also of his odds of having high-grade cancer on initial biopsy. 4 of these new tests are listed here with a brief description: ExoDx Prostate Intelliscore (EPI). This test examines urine samples for Prostate cancer antigen 3 (PCA3), which is a gene specific to Prostate cancer and other exosomes (chemical messengers) that are expressed in men with high-grade Prostate cancer. This test is used to determine if a man with a PSA between 2.0 and 10 ng/ml presenting for an initial biopsy has high-grade cancer and whether he can forgo the initial biopsy and continued to be monitored. This could help reduce the number of unnecessary biopsies.
MyProstateScore (MPS). This test was created by researchers at the University of Michigan. It is a urine test designed to measure PCA3, PSA and the TMPRSS2:ERG gene fusion (NOTE: fusion in the TMPRSS2, ETS and other gene families are found in high levels in the urine of SOME (caps for emphasis) Prostate cancer patients). The test is designed to predict a man’s risk of having cancer on biopsy.
SelectMDX®. This test is also a urine-based test. It measures messenger RNA (mRNA) levels of 2 genes, DLX1 HOXC6, that at higher expression levels, have been associated with a GREATER (Caps for emphasis) likelihood for high-grade Prostate Cancer. The test has mixed results. In one study of 599 men scheduled for initial Prostate biopsy, the test found that 38% of the men had negative SELECTMDX results and could avoid an unnecessary biopsy. On the other hand the test missed high-grade Prostate Cancer in 10% of the participants.
Stockholm3. Swedish scientists have developed the Stockholm3 model, which screens for Prostate Cancer using multiple forms of PSA and other protein biomarkers in the blood as well as HOXB13 and other germline genetic markers and clinical variables. This test is only available in Scandinavian countries at present.
The above 4 tests all fall in the category of “Liquid Biopsy.” There are also other tests undergoing clinical trials that also fall in this category. We will report on these as data becomes available.
One last point on Prostate screening. Experts from the Cleveland Clinic and other medical centers have proposed an algorithm that can be used by Primary-Care Physicians (PCP’s) to reduce the number of men referred to urologists for more advanced Prostate Cancer testing, such as the tests covered in this post. This screening guide has 4 import points covered: 1. Screening should be done for men with at least a 10-year life expectancy, 2. Men with a PSA level of 1.5ng/ml or lower could be rescreened in 5 years, 3. If PSA levels were higher than 1.5 ng/ml or abnormalities were found on digital rectal exam (DRE), the PCP would CONSIDER (caps for emphasis) referring the patient to a urologist for further testing and evaluation, 4. Patients suspected of having Prostate Cancer could then undergo more advanced testing like some of the tests covered in this post.
Closing comment. None of the tests covered in this post, whether a diagnostic lab test or a “Liquid Biopsy” can yet replace the biopsy. They all still lead to a biopsy if the results of the test are unfavorable. Hopefully as science progresses in the detection and treatment of Prostate Cancer we will soon have a test that can eliminate the need for a biopsy rather than simply confirming the need to have a biopsy. Remember, having a Prostate biopsy is not the end of the world but trust me from experience, it can be a bit of a discomfort!!
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