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Prostate Cancer Testing


Prostate Cancer Testing: Navigating The Maze

By: John King



September was Prostate Cancer Awareness Month.  If you’ve been on social media then you probably have seen at least one advertisement reminding men to get their prostates checked. But what does this entail? Usually, just a simple blood test and a physical exam. But what if you require additional testing? Knowing your testing options is vital to gathering all of the required data to properly access your prostate health.


In this article I will describe testing methods used to detect prostate cancer.  The order in which I list the various tests is similar to how they may be performed in real life by your doctor.  If you are having trouble with your prostate, suspect that you may have prostate cancer or have a family history of cancer; I would recommend seeing a urologist that is specifically trained in diagnosing prostate cancer.  I cannot put enough emphasis on the importance of taking early action with any prostate issue.  Some prostate problems have nothing to do with cancer but are a symptom of chronic inflammation which, over time, can lead to the formation of malignant tissue.


Digital Rectal Exam (DRE)

If you’re at least 30 years old and have had a physical then you have probably had a Digital Rectal Exam or DRE.  This test is performed by your doctor inserting his finger into the rectum to physically examine your prostate.  From this examination your physician can assess prostate volume (whether your prostate in enlarged or not) and if there is any palpable (able to be felt) disease.  In the days before the PSA blood test was developed, most prostate cancer was detected by this method.  Unfortunately, that meant that by the time prostate cancer was detected the patient already had a sizable tumor.  Today, with the increasing accuracy of blood tests, most prostate cancer is detected before there is any palpable disease.

This particular test is best performed by a urologist who diagnoses and treats prostate cancer everyday.  It takes some experience to be able to feel subtle changes in the prostate glad as well as accurately estimating it’s size.  The exam only takes a few seconds and can provide the well trained urologist with valuable information.  Even with modern blood testing, the DRE is still, and will continue to be, an important part of prostate cancer testing.


Prostate Specific Antigen (PSA)

Prostate Specific Antigen is a protein secreted by normal and cancerous prostate cells. If you are a male and have not had your prostate removed or treated with radiation, you will have some level of PSA circulating in your bloodstream.  The “normal” range for PSA is 0.0-4.0 (ng/ml).  An optimal PSA level for a healthy prostate would be 1.0 or less. If your PSA level goes above 1.0 it does not necessarily mean you have cancer but it is something you should keep an eye on. For levels of 2.5 or less dietary and other holistic interventions should be considered as well as having your physician monitor your prostate for changes.  For levels above 2.5 and below 4.0 you may want to consider additional testing as described below.  A level of 4.0 or higher is too high and further testing should be performed.  It is at this level when a physician will normally suggest a biopsy.

The PSA test can be confusing as it is not exclusively a test for cancer.  There are many things that can raise PSA levels that are not cancer.  Please see my article for more information about things that can raise your PSA.

A Dozen Things That Can Raise PSA Levels That Aren’t Cancer

Consequently, a reading above 4.0 does not mean you have cancer but a reading below 4.0 doesn’t rule it out either. Think of PSA as a marker of overall prostate health.  If it is starting to rise then you need to pay attention to what your body is telling you and take action to prevent a more serious health issue down the line.

Generally what your doctor is looking for is a high level or a level that is increasing rapidly.  The rate of PSA increase is measured in what is called PSA Doubling Time. Quite simply it is the amount of time it would take for your PSA to double if it were to continue rising in a linear fashion.  If you have been diagnosed with cancer this is something your doctor will monitor.  A short PSA doubling time means a more aggressive cancer and/or a faster rate of progression.  The rate of PSA rise is also referred to as PSA Velocity.  A negative PSA Velocity would mean your level is going down and vise versa.  For a PSA Doubling Time calculator click here.  If your PSA rise is over .75 ng/ml/year, there is an increased likelihood of malignancy.

Why should you pay attention to your PSA level if a higher level does not necessarily mean cancer?  Prostate Specific Antigen is a pro-enzyme, a protein that is converted to an enzyme within the prostate gland.  It’s purpose is to liquefy semen enabling sperm to swim more easily.  As levels rise above optimum the enzyme activity of PSA begins to break down the integrity of the prostate gland.  If the gland’s integrity is compromised enough and cancer is present, malignant cells could escape the prostate gland and enter the bloodstream.  This is how metastatic prostate cancer occurs.


Free PSA

Most of the Prostate Specific Antigen circulating in the bloodstream is bound to proteins but a small percentage is not.  This is called Free PSA.  When prostate cancer is present the ratio of Free PSA to Total PSA is decreased.  Free PSA is calculated as a percentage of Total PSA.  The lower the percentage of Free PSA the greater the likelihood cancer is present.  Like PSA, Free PSA will increase immediately after ejaculation.  A high Free PSA (over 20%) indicates a low risk of prostate cancer, while a low reading (less than 11%) indicates a high risk of cancer.


The following chart is an amalgam of several sources of data and indicates potential cancer risk based on Free PSA.


                                                            Potential Cancer Risk

Free PSA % Age 50-64 Years Age 65-70 Years
<= 10% 56% 55%
>10 – 15% 24% 35%
>15% – 20% 17% 23%
>20 – 25% 10% 20%
Over 25% 5% 9%


4K Score

The 4K Score is a newer test that moves slightly beyond just PSA.  Combining four specific prostate assays (Total PSA, Free PSA, Intact PSA*, hK2*) along with clinical data (age, DRE and prior biopsy status), to predict the chances of prostate cancer metastasis over the next 20 years.  Please note that Intact PSA and hK2 are bio-markers that are proprietary to OPKO Health.

Taken directly from the laboratories website:

“The 4Kscore Test has undergone extensive clinical research and laboratory test validation. The biomarkers utilized in the 4Kscore Test are based on over a decade of research conducted by scientists at the Memorial Sloan-Kettering Cancer Center and leading research centers in Europe, encompassing over 10,000 patients. The results have recently been replicated in a prospective blinded clinical study conducted at 26 urology centers across the United States on 1,012 patients. Based on the results of this clinical study, as many as 30-58% of biopsies are avoidable using the 4Kscore Test.”

For more information on this test, how it works and where to get it; please go to


Urine PCA3

PCA3 is a diagnostic test performed on urine that detects mRNA, a substance secreted by epithelial cells lining the prostatic ducts.  Prostate cancer cells produce far more PCA3 than normal cells.  This test is most useful for monitoring changes over a period of time.  A reading of 35 is generally considered the cutoff for PCA3.  A reading under 35 indicates a decreased likelihood of cancer while a reading over 35 indicates a increased probability of a positive biopsy.

This test must be performed in the urologists office as a digital rectal massage is required just before the blood draw.  For more information about how PCA3 helps in the diagnosis of prostate cancer click here.


Prostatic Acid Phosphatase (PAP)

Prostatic Acid Phosphatase is an enzyme that is produced by prostate epithelial cells and is found in abundance in seminal fluid.  Higher levels of this enzyme are associated with prostate cancer.  Doctors use PAP along with PSA to help determine prognosis or to monitor the course of treatment in those patients who have high PSA levels.  For a detailed explanation of PAP and it’s role in prostate cancer click here.


Circulating Tumor Cells Assay

This test detects and measures of cancer cells that have detached from a solid tumor and are circulating in the bloodstream.  This test is particularly useful in assessing the status of metastatic prostate cancer.  Doctors use this test to determine overall prognosis and survival.


What’s Next?

Your doctor has performed all the relevant blood work and feels that further investigation is necessary.  So what’s next?  At this point your physician will probably want to do a biopsy.  But before a biopsy is done, the experienced urologist will want to do some imaging of your prostate to determine exactly what areas are in question.  This helps him to determine the possible extent of your disease and aids in needle placement when performing the actual biopsy.  There are several imaging techniques that are used for diagnosing prostate cancer, all having their strengths and weaknesses.  A well informed urologist will most likely use a combination of several imaging methods to provide the most complete picture.


Magnetic Resonance Imaging (MRI)

For over 30 years Magnetic Resonance Imaging has been used in the diagnosis of prostate cancer.  Recent advancements in technology have only served to improve it’s accuracy.  For prostate cancer detection a technique called multi-parametric MRI is used.  This type of MRI utilizes four separate types of MRI sequences to create a highly accurate picture of the prostate’s structure.  MRI’s strength lies in it’s superior soft tissue resolution.  With the information gathered though multi-parametric MRI, your physician is able to identify target areas for biopsy and formulate a surgical plan if required.

Please note, all MRI machines are NOT created equal.  For the best possible images of your prostate make sure your doctor sends you to a facility that has a 3T MRI. Taken directly from “A procedure in which radio waves and a powerful magnet linked to a computer are used to make detailed pictures of areas inside the body. These pictures can show the difference between normal and abnormal tissue. 3T MRI has a stronger magnet and makes better images of organs and soft tissue than other types of MRI do. It is used to make images of the brain, the spine, the soft tissue of joints, and the inside of bones and blood vessels. Also called 3 Tesla magnetic resonance imaging and 3 Tesla MRI.”   Additionally, 3T MRIs do not require the use of an endorectal coil, a device placed inside the rectum to enhance images taken with lower resolution MRI machines.

If your prostate MRI is the first step toward a “fusion biopsy”, the MRI results should be no older than seven days if that image is to be merged with an ultrasound image.  The prostate can change in size and shape depending on various factors, thus, the newer the image the more accurate the fusion biopsy will be.

To read more about Magnetic Resonance Imaging, click here.


Transrectal Ultrasound

Ultrasound is an imaging technique that uses sound waves to create images of the prostate.  Much like RADAR, sound waves (not radio waves) are reflected back to the transmitting probe and interpreted by a computer that processes the received data into an image.  Ultrasound imaging is especially useful for measuring the size of the prostate, evaluating prostate nodules, distinguishing between benign prostate conditions and cancer, detecting increased vasculature (configuration of blood vessels in and around the prostate) and to guide needle placement during a biopsy.


Color Doppler Ultrasound

Color Doppler Ultrasound is a ultrasound technique specifically designed to map blood flow within the body.  Much like conventional ultrasound Color Doppler Ultrasound uses sound waves to create images with one distinct advantage.  Doppler ultrasound is able to detect the direction of blood flow within the body by reading the Doppler shifts of the returning sound waves and distinguishes them by assigning different colors for each value.  Whereas a conventional ultrasound would just show you variations in a grey scale image, Color Doppler utilizes color images to show the actual direction of blood flow.  This makes it an invaluable tool for mapping blood flow and velocity in and out of a tumor site.  With this information your physician can see exactly how far the tumor has spread, determine treatment options and devise surgical plans.  Like conventional ultrasound, Color Doppler Ultrasound can be done both externally and transrectally.


Typically, the above imaging techniques with be the only imaging required before your biopsy.  The following imaging methods are usually only used if you have already been diagnosed with prostate cancer to check for metastasis or progression.


Nuclear Bone Scan

If prostate cancer cells escape the prostate they can attach to bone and cause “hot spots” to appear on a bone scan.  During this test the patient is given a radioactive tracer that can be picked up by a special camera.  After injection of the tracer it takes about four hours for it to be completely absorbed by your bone.  After absorption, the patient lies on a table where images of your skeleton are captured.  A normal bone scan will show an even distribution of the tracer throughout your skeletal structure.  If prostate cancer has metastasized to the bones it will show up as either light or dark spots on the scan.  Radiation exposure for this test is low and the tracer used is considered to have a low toxicity.


Quantitative Computed Tomography (QCT)

Osteoporosis can not only be a symptom of prostate cancer but also a side effect of prostate cancer treatment.  Thus, if you have been diagnosed with prostate cancer, there may come a time when your physician will want to assess your bone density.  While similar to a regular CT scan, QCT has the added advantage of calculating volume, mass and density of bone based on the images obtained.  This type of bone density measurement has been shown to be far superior to the standard bone density tests such as DEXA.  Studies have shown that DEXA testing can read calcium in other parts of the body as bone density not suggesting bone loss when indeed there is osteoporosis present.  QCT can also distinguish between cortical and trabecular bone, the softer tissue that comprises the center of the bone.  These two types of bone are replaced at different rates and thus have different potentials for cancer growth.


Choline C-11 PET Scan

If you have been previously treated for prostate cancer and your doctor is concerned that it may have returned, he may prescribe a C-11 PET scan.  Choline is a vitamin-like essential nutrient present in many foods.  Prostate cancer cells love choline and absorb it quite rapidly.  A Choline C-11 PET scan uses choline bound to a radioactive tracer to highlight prostate cancer cells that may have spread to other parts of the body.  C-11 has a very short half life (about 20 minutes), thus it’s toxicity is low.  While there is no “perfect” imaging for prostate cancer, C-11 PET scans show great promise in detecting small tumors anywhere in the body.  For an overview of the various types of PET scans used for the detection of prostate cancer, please see the following from Prostate Cancer Research Institute.


After all your blood work has been completed and all imaging performed it is now time for your prostate biopsy.  There are a few different methods of performing a prostate biopsy, some better than others.


Fusion Biopsy

Now considered the Gold Standard for mapping of the prostate gland, the Fusion Biopsy “fuses” or merges two images (MRI & Ultrasound), for greater accuracy of needle placement during the biopsy.

During a fusion biopsy your physician places an ultrasound guided biopsy probe into the rectum.  The biopsy needle is inserted through the rectum into the prostate.  Because the biopsy needle is passing through the rectum antibiotics are required before and after the biopsy to prevent infection.

During the biopsy your physician is actively imaging your prostate via ultrasound.  This ultrasound image is “fused”, via computer, with the images from the 3T MRI you had previously.  This provides for greater accuracy and confidence of needle placement.  For your first prostate biopsy 12-16 “cores” or samples will be taken.  To accurately map the prostate gland, 12 cores are taken, four from each quadrant.  An additional four cores may be taken from suspicious areas as identified by Magnetic Resonance Imaging.  Generally, all areas of the prostate are accessible via this method.  The procedure takes 20-30 minutes and can be done in the doctors office or in the operating room under sedation.  For some this procedure can be quite painful, so if you have any concerns in this area speak with your physician regarding sedation for your procedure.


MRI Guided Biopsy

Depending on the results from your fusion biopsy it may be necessary to further investigate certain areas of your prostate.  For this your doctor may order an MRI Guided Biopsy.

For exact needle placement nothing beats the accuracy of an MRI Guided Biopsy.  This test is performed in the operating room under sedation, usually by an Interventional Radiologist.  Before the biopsy, a special tape that contains “grid lines” is placed on the abdomen directly above the prostate and on the perineum (the space between the rectum and scrotum).  These grid lines will be seen by the MRI and are used as coordinates for needle placement.  The patient is then sedated and placed inside the MRI tube.  The radiologist then uses the grid pattern superimposed over the prostate to direct the biopsy needle to the desired area.  Because the biopsy needles are inserted through the perineum, antibiotics are not required for this procedure, a distinct advantage over a transrectal biopsy.

During the biopsy the radiologist verifies, in real time, each needle placement with an MRI image.  Because of this, each sample takes longer to collect but usually only several cores are taken.  The advantage of this type of biopsy over the Fusion Biopsy is that an actual human being verifies the needle placement in real time before each sample is taken, as opposed to a computer making “it’s best guess” as to what angle and how far to insert the needle.  This is important as the prostate can change size and shape depending on various factors.  Thus, an old or poor MRI image prior to a fusion biopsy will yield less than perfect results.

The only disadvantages to an MRI Guided Biopsy are not all facilities are equipped to perform such a procedure.  If may take some investigation and/or travel on your part to find such a facility but it will be well worth the effort.  The other disadvantage to this procedure is that some parts of the prostate may be difficult to reach via this method.  The skill of your radiologist plays an important role here.


TRUS Biopsy

A Transrectal Ultrasound Biopsy or TRUS Biopsy is just like the Fusion Biopsy except there is no MRI imaging done beforehand.  Although many refer to this method as the gold standard, performing this procedure as a standalone is, in my opinion, less than optimal.  First, an ultrasound cannot detect what an MRI can detect so far as cancer is concerned.  If your physician is just mapping and has no concern for any particular areas, a TRUS Biopsy as a standalone procedure would be sufficient.  But how does one know if there are areas of concern prior to the biopsy with performing some type of imaging?  The answer is, you don’t.  Thus, should your doctor find something suspicious during the standalone TRUS biopsy, you are now headed for the MRI that you should have had in the first place and another biopsy.  Requesting a Fusion or MRI Guided Biopsy as your first biopsy could spare you the discomfort and inconvenience of a second.


The Results

After your biopsy your physician will send your “cores” or samples to pathology for analysis.  The pathologist examines the tissue and looks for certain cell patterns that are indicative of cancer and assigns what is called a Gleason Score.  Two values are combined to give the Gleason Score.  The first number pertains to the first most abundant cell formations and the second number pertains to the second most abundant cell formations.  So a Gleason Score looks something like 3+3=6 or 4+3=7.  Patients with a Gleason Score of 6 or less are ideal candidates for Active Surveillance.  Higher Gleason Scores usually require some type of treatment.

Please note that not all Gleason Scores are created equal.  For instance a patient can have a Gleason 7 cancer that could be 4+3 or 3+4.  A 4+3 Gleason 7 is worse than having a 3+4 Gleason 7 as the first number in the scoring carries more weight.  Knowing the details of your Gleason Score may provide you with additional treatment insights, so do your homework!

I highly recommend getting a second opinion on your pathology results should they be positive or negative.  Experience levels of pathologists varies greatly and the more eyes you have on your tissue slides the better.  I know several people who have had their Gleason Scores downgraded or upgraded based on the second opinion of an expert.  Good doctors will not take offense at your requesting a second opinion.  In fact, good doctors will encourage it.

There are two pathologists I recommend for second opinions on pathology.  The first is Jonathan Epstein at Johns Hopkins.  The second being Daniel Margolis at UCLA.


A Word About Genetic Testing

I always recommend to my clients that they send all biopsy samples out for genetic testing.  Genetic analysis can provide valuable insights into your particular cancer.  For instance, a patient diagnosed with Gleason 6 prostate cancer considering Active Surveillance may elect to be treated sooner rather than later if a genetically more aggressive cancer is detected.  There are currently two well known genetic tests being used in cases of prostate cancer.  They are Prolaris and Oncotype DX.  Talk to your doctor about these two very important tests.  Do so before any biopsy is done so that arrangements can be made to ship your samples in a timely manner.


What Else Can I Do?

When it comes to cancer, knowledge is power.  Finding out all you can about your cancer can only help you make a more educated decision. Geographically, I have noticed tremendous disparities in treatment recommendations.  When going for a second opinion you may want to consider going out of your home area.  Some areas/doctors/hospitals just see more cancer and thus have become more proficient in it’s treatment.

If you have been diagnosed with prostate cancer, have an enlarged prostate or have any prostate concerns whatsoever, consider holistic interventions.  You would be surprised at what can change when you change what you put in your body.  Heading off prostate cancer before it occurs is easier than dealing with the disease.  If your biopsy was negative, congratulations!  But something had to have happened to get you to that biopsy, so don’t ignore your body’s warning.

Should you desire information on effective holistic interventions for prostate cancer, feel free to contact me.  I am always happy to pass along my knowledge and insights to those who want to help themselves.


Best in Health,


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