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PSA and Prostate Cancer Testing

Prostate specific antigen (PSA) is a blood test which saves lives, if used properly.  Still, there are controversies surrounding this widely used test.  The following article is not intended to be a treatise on the controversies of PSA testing and prostate cancer screening.  Herein we share information that we sometimes use to introduce our patients to practical issues concerning the evaluation of men having been found to have abnormal PSA results.  This information may be provided to patients at their initial visit with us.  It is intended primarily for men who have not previously been diagnosed with prostate cancer.


Dear Sir:


It is our understanding that your visit with us today relates to the results of a blood test called prostate specific antigen (PSA).  If this is not the case, you should disregard this letter and notify the nurse immediately.  You have been asked to read this document to provide you with information that you may use today to help with decisions concerning prostate cancer screening and evaluation.  Please take a few moments now to carefully read all this information.  Doing so will prepare you to speak with the urologist in a few minutes.


The PSA blood test is often considered to be a test for prostate cancer.  However, an abnormally elevated PSA does not necessarily mean that you have prostate cancer.  Likewise, even when PSA is within normal range, prostate cancer is still possible.  Obviously, PSA is a less than perfect test. 


PSA is not a test for any cancer other than prostate cancer.  While PSA will detect no other cancer, it is likely the best all around cancer detection blood test in medicine today. 


Side note:  Patients commonly perceive that they are being tested for cancer each time their primary doctors draw blood.  This is NOT the case.


While PSA can detect prostate cancer, it also can detect other prostate problems. Possible causes for an abnormally elevated serum PSA include:

  • infection of the prostate

  • abnormal cellular changes within the prostate called prostate intraepithelial neoplasia (PIN), a condition which may be precancerous or may be found in association with cancer

  • benign noncancerous enlargement of the prostate

  • prostate cancer

  • essentially any form of inflammation of the prostate gland 


The PSA test only becomes elevated (high) when something is medically afoul involving the prostate gland.  In this way, the test is suitably named prostate specific antigen.  While PSA is indeed is specific for a prostate problem, it is NOT specific for prostate cancer.


Urology specialty evaluation is critical.  Depending on your history and other findings your urologist may offer one or more of several tests to evaluate an abnormal PSA:

  • digital rectal examination (DRE) of the prostate

  • molecular PCR or DNA testing of the urine after intense prostate massage (NextGen)

  • oral antibiotics followed by repeat PSA blood testing

  • genomic DNA testing of the urine after intense prostate massage (Select MDx)

  • prostate ultrasound

  • prostate magnetic resonance imaging (MRI)

  • prostate biopsy


Your board-certified urologist will discuss these matters with you and offer you a digital rectal examination (DRE) of the prostate.  A rectal examination is necessary for the doctor to evaluate for possible lumps or bumps on the prostate (indicating possible cancer or other abnormalities), possible prostate tenderness (possibly indicating inflammation or infection) or other abnormalities which might only be found by this physical examination. 


Yet, it must be appreciated that the DRE of the prostate alone (without other testing) may not tell the full story.  Even if the DRE is normal, prostate cancer can still be present.  Also, an abnormal DRE does not confirm prostate cancer.  Like PSA, DRE also is not a perfect test for cancer.  A good urologist is needed to sort out the possibilities.


Side note:  The purpose of the DRE of the prostate is strictly to assess problems of the prostate.  This examination has little or nothing to do with the colon or rectum.  Most men (and women) 45-years-of-age and older also need to see a gastroenterologist (GI specialist) to be screened for colon cancer.  Screening for colon cancer should be considered at an even younger age in individuals at higher risk for the disease, such as those with strong family histories of colon cancer.  The point here is that the examinations for colon cancer are vastly different than the simple DRE that is performed in screening men for prostate cancer.


Ultrasonography (ultrasound) is commonly performed with needle biopsies of the prostate when the PSA is elevated or when the DRE of the prostate is abnormal.  Prostate ultrasonography is done by placing an ultrasound probe about the size of a finger into the rectum and scanning the prostate using sound waves.  Unfortunately, the ultrasound scan alone cannot reliably exclude prostate cancer.  For this reason, prostate needle biopsies are often performed at the time of the ultrasound examination. 


To confirm a diagnosis of prostate cancer, a tissue diagnosis is necessary.  Prostate tissue can be obtained by needle biopsy (through the skin of the perineum or through the wall of the rectum) or by transurethral resection (through a scope placed through the penis into the bladder).  At the present time, nearly all prostate tissue for biopsy is obtained by means of transrectal (through the rectal wall) needle biopsy.


Transrectal needle biopsy means that a small needle is passed through the wall of the rectum into the prostate usually under ultrasound guidance.  Tiny needle-cores of prostate tissue are thus removed and sent to a pathology specialist.  After special chemical staining of the biopsy core, the pathologist examines the tissue under a microscope.  By this method, the pathologist may confirm the diagnosis of prostate cancer and even assign a Gleason score, depending on the microscopic architecture of the caner.  The pathologist’s Gleason score is one of the most important tools that urologists uses to estimate a cancer’s clinical significance (less aggressive vs. more aggressive).


Ultrasound guided prostate biopsy procedures are uncomfortable but usually not painful.  It is generally not necessary to use general anesthesia for this procedure.  Medications used by mouth for pain and anxiety are commonly used and sometimes a local anesthetic (prostate block) is administered. 


The risks of the ultrasound and needle biopsy include infection, severe infection, bleeding, pain, lightheadedness, fainting, difficulties urinating, inability to urinate, possible need for a bladder catheter, allergic reaction to medications and a few others.  Antibiotics are given to help prevent infection.  Bleeding is usually mild, if you have been off blood thinning type medications for an adequate period of time.  Blood thinning medications include aspirin, non-aspirin over-the-counter pain relievers (NSAIDs), prescription arthritis type medications (NSAIDs), Plavix (clopidogrel), Coumadin (warfarin), Effient (prasugrel), Xarelto (rivaroxaban) and many others.  This list is not a complete list of all blood thinners.  For safety reasons, you must provide a complete and accurate list of medications to your urologist prior to considering prostate ultrasound / biopsy. 


Understand that it is not unusual to see some blood in the stool, blood in the urine or even the blood in the ejaculate (semen) after a prostate biopsy.  These are expected findings.  However, you should report any significant fever, chills, difficulties urinating or any other concerning symptoms after a prostate ultrasound/biopsy procedure, as these may be signs of serious impending infection.


Having explained the prostate ultrasound procedure, you must remember that you may choose not to undergo such a procedure immediately.  Certainly, the final decision is yours, concerning this and all medical decisions. 


Instead of undergoing immediate prostate ultrasound/biopsy, some patients choose simply to wait and repeat the PSA at a later date.  Sometimes an elevated PSA may return to normal range without any intervention at all.  Results of future PSA testing are difficult to predict, so naturally patients must consider potential dangers in waiting.  Patients choosing any wait and see approach must agree to close and careful urology specific medical followup and they must remember that inaction might allow a prostate problem such as infection or cancer to progress.


As an alternative, some patients chose to use a course of empiric oral antibiotics and recheck of the PSA at a later date.  The word empiric in this case implies antibiotics selected based on what typically works for most prostate infections. 


Patients typically use antibiotics for about four weeks, then wait an additional 2-3 weeks before having the PSA blood test repeated.  About one week after repeating the PSA, patients return to see the urologist for review of the newest PSA results.  If the abnormal PSA is due to infection, antibiotics are intended to attack the infection and reduce the PSA.  While PSA normalization does not absolutely exclude cancer, PSA normalization may preclude the need for immediate prostate biopsy.  Possible side effects of antibiotics include tendinitis, tendon rupture, skin rash, GI upset, interactions with other medications and many others.


If you choose the antibiotic option, there are several important points to be considered:


  • keep all follow-up appointments with your urologist including repeated PSA testing

  • antibiotics may be effective or not effective (cancer may be present)

  • antibiotics may produce allergic reactions or other side effects

  • antibiotics alone cannot exclude the possibility of prostate infection

  • antibiotics may decease the PSA, but you may still have prostate cancer 


Molecular microbial urine analysis testing may also be considered when your urologist suspects prostate infection as the cause for the abnormal PSA.  Next-Gen is one of many tests used for this purpose.  A first void urine sample is obtained after the doctor performs DRE of the prostate.  The fluid thus collected is sent for laboratory examination by means of polymerase chain reaction (PCR) and deoxyribonucleic acid (DNA) sequencing in hopes of identifying bacteria possibly responsible for causing prostate inflammation and resulting PSA elevation.


Identification of microorganisms by this method may guide your urologist in selecting appropriate antibiotics to combat a prostate infection leading to lower PSA levels.  Like many of the other tests, this test may be imperfect.  The following points must be kept in mind as it pertains to Next-Gen and similar testing:


  • always keep your follow-up urology appointments including repeated PSA testing

  • the test requires a vigorous and briefly uncomfortable DRE

  • vigorous DRE could possibly exacerbate a potential prostate infection

  • the test may identify irrelevant bacteria (cancer may be present)

  • test results may recommend antibiotics leading to allergic reactions or other side effects

  • test results may recommend antibiotics that may decease the PSA, but you may still have prostate cancer 


Genomic urine analysis testing may also be considered at the time of your initial DRE.  Select MDx is one of many tests used to identify prostate DNA changes suggestive of prostate cancer.  Just as with the molecular microbial test (above), a first void urine sample is obtained after the doctor performs DRE of the prostate.  The fluid is sent for laboratory examination by means of DNA genomic analysis.  When combined with other clinical information (such as DRE results and PSA results) this test will estimate your likelihood of having a clinically significant prostate cancer if you should eventually decide to undergo prostate biopsy.


Should your Select MDx (or similar) urinary genomic prostate cancer test suggest a substantial chance of significant prostate cancer, prostate biopsy may be recommended.  On the other hand, if the test suggests a low risk of clinically significant prostate cancer, some patients opt against undergoing immediate prostate biopsy.  Obviously, any decision short of prostate biopsy implies the need for close urology followup for many years. 


As of the time of this writing, the precise role of urinary microbial and genomic testing remains under debate.  Obviously, these tests may be helpful to many patients; but the final positioning of these tests within the urologist’s prostate cancer testing armamentarium is undecided.  The following points must be kept in mind as it pertains to NextGen and similar testing:


  • regardless of test results, always keep your follow-up urology appointments including repeated PSA testing

  • the test requires a vigorous and briefly uncomfortable DRE

  • vigorous DRE could possibly exacerbate a potential prostate infection

  • test results may suggest a high chance of a significant prostate cancer, but cancer may not be identified on subsequent biopsy 

  • the test could possibly suggest a low chance of prostate cancer, but cancer may be present


Finally, prostate magnetic resonance imaging (MRI) has emerged as an important tool both for diagnosing and staging prostate cancer.  This is not the same a standard MRI performed for other reasons.  This is a highly specialized test that requires distinctive software to perform and interpret.  Many centers require two or more radiologists to confer and agree as to the final interpretation of results.


Like genomic testing, MRI may be able to identify clinically significant (serious) prostate cancer, while leaving less significant (less aggressive) prostate cancer undetected.  Neither MRI nor any other test is perfect in this regard.  Yet MRI is better than ultrasound and other imaging modalities for the accurate detection of prostate gland cancer.


A challenge arises when prostate MRI finds an area of suspicion (lesion) within the gland.  At present, it is difficult to perform a prostate needle biopsy using MRI guidance outside of research settings.  However, technology now allows importation of MRI data into new generation ultrasound machines with MRI-ultrasound image fusion.  The urologist may thus view archived MR images of the prostate simultaneously with live ultrasound prostate imaging, allowing the urologist to target any abnormal appearing area for biopsy. Advantages of this technology are obvious, at least for those men having been found to have an abnormal lesion by MRI before undergoing ultrasound guided needle biopsy.


Unfortunately, an inconsistency exists as it concerns using MRI to detect prostate cancer.  Many insurers will not cover the cost of prostate MRI unless the patient has previously undergone prostate biopsy.  Unless a patient pays out-of-pocket for the MRI (about $800-1000), MRI-ultrasound fusion biopsy is not possible in such cases.  This paradoxical reasoning defeats the purpose of prostate MRI as a diagnostic test for prostate cancer, eliminating MRI-ultrasound fusion needle biopsy as the first (and sometimes best) option for accurate and efficient prostate biopsy. 


Despite your abnormal PSA test results, you should understand that you are not required to have a prostate biopsy and you are not required to undergo other testing.  There are many reasons why you may choose not undergo additional tests and procedures.  Consider some basic information about prostate cancer described here.


Besides skin cancer, prostate cancer is the most common cancer of all!  In fact, there are more men diagnosed with prostate than there are men and women (combined) with colon cancer, lung cancer, breast cancer and others.  Even though prostate cancer is very common, it does not always cause symptoms, complications, or death.  For example, many more men are diagnosed with prostate cancer than are diagnosed with lung cancer.  However, more men die of lung cancer than prostate cancer.  This is to say that many men (but not all) with prostate cancer live out their lives and die of causes other than prostate cancer.  This is especially true of very elderly or extremely ill men (for example men of advanced age or men with severe heart or lung disease).


For younger and healthier men, prostate biopsy is more commonly indicated.  Younger men with significant prostate cancer are expected live long enough to potentially suffer the ill-effects of more aggressive prostate cancers.  Some prostate cancers are so destructive that the cancer cannot be cured, even when aggressively treated in younger men.  Still, there are many men who carry less aggressive forms of prostate cancer that might never cause them any problem, particularly if the patient is older or chronically ill. 


It is sometimes difficult to know who should and who should not undergo prostate ultrasound and biopsy.  It is also true that once cancer is diagnosed, it is sometimes difficult to choose which patients should be treated and which patients should not be treated.  Balancing age, health, patient desires, cancer characteristics and potential side effects of treatment can be a daunting task for this very prevalent but variably injurious disease.


Prostate cancer is a malignancy that does not generally cause symptoms in its early stages.  Many men who have prostate cancer have no symptoms whatsoever.  When patients wait until they have symptoms of the cancer, the cancer is usually advanced and often it has spread outside of the prostate.  Once the cancer is outside of the prostate, there is no certain cure.


Treatments for prostate cancer include observation (without treatment), medication, surgery, radiation therapy and cryotherapy (freezing of the prostate).  There are many ways to perform these various treatments.  Your urologist will answer your questions about treatment options, but this topic is so involved that we generally reserve detailed treatment counseling for men who are definitively diagnosed with prostate cancer.


Your urologist will help you work through these issues, however, the decision to have prostate biopsy must be your own.  Some men may decide that even though treatments are available for most every stage of prostate cancer, they will not consider undergoing treatment.  Within reason, we will offer essentially all men with an abnormal PSA a prostate biopsy.  Of course, you may refuse prostate biopsy, at your digression.  We are glad to take all the time necessary to provide you with all the information and resources needed to make an informed decision.  The decision is yours.


Thank you for reading this information about this somewhat confusing subject.  More information will be provided anytime you ask.  You do not have to decide about this matter today; however, do not delay your decision too long as this is a serious matter which could well affect your future health.  Now, it is time for you to speak with your urologist and to make essentially one of the following decisions.  You will be asked to decide if you want to ...

  • undergo digital rectal examination (DRE) of the prostate today

  • schedule a prostate biopsy, with follow-up here

  • repeat your PSA, with urology follow-up here

  • use a course of antibiotics and repeat the PSA, with follow-up here

  • undergo urine testing for infection and genomic testing today, with follow-up here

  • schedule a prostate MRI, with follow-up here

  • consider MRI-ultrasound fusion biopsy if your MRI is abnormal

  • combinations of the above

  • disregard the recent abnormal PSA test results and decline all future testing for reasons such as very advanced age or very severe health problems unrelated to prostate cancer


All but the last choice above involve mandatory follow-up with your urologist and additional PSA testing no matter the results of any future biopsy, no matter other test results and no matter future PSA results.  This is to say that once you have had an abnormal PSA, we recommend that you continue to undergo surveillance, specifically by a qualified urologist.  We also want you to know that it is your personal responsibility to make very certain that you make and keep future urology appointments.  Failure to do so could lead to permanent loss of your health. 


We hope that this information is helpful.  Your urologist will be in to see you shortly today and discuss any questions or concerns that you may have.

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