The PSA Controversy Part I

 

Life Extension® is on the front lines of assisting people afflicted with metastatic cancer finding therapies overlooked by their oncologist. In too many cases, advanced-stage cancers fail to respond to treatment, or a tumor that goes into remission recurs. If these metastatic cancers were detected earlier, the probability of cure would have been significantly greater.

The most common cancer striking men has a blood marker that can enable very early detection, thereby enabling curative therapies to be employed before metastasis strikes. The name of this blood marker is PSA (prostate-specific antigen) and it has spared tens of thousands of men agonizing deaths from metastatic prostate cancer.

The problem is that most urologists and oncologists are not properly interpreting PSA results, nor are they efficiently implementing further diagnostic and treatment protocols.

Instead of recommending that medical professionals upgrade their protocols to deliver state-of-the-art technology, a federal government supported group called the United States Preventive Services Task Force suggests that aging men not undergo PSA screening—at all!

In this first article, prostate oncologist Stephen B. Strum, MD, FACP, discusses the critical role PSA screening plays in preventing prostate cancer death, and why certain arms of the medical establishment have failed to recognize this simple truth.

Introduction

 

The issue of PSA screening is a current hot bed of discussion.

A recent decision by the United States Preventive Services Task Force (USPSTF) concluded that PSA should not be used as a diagnostic screening tool for any man, regardless of age, race or family history. This has resulted in a hailstorm of critical responses.1-4

The USPSTF bases their decision on the adverse effects of invasive prostate cancer (PC) treatment(s) in comparison to the indolent behavior most often seen as part of the natural history of untreated PC.2 Where does this leave the patient and the physician? Is prostate specific antigen (PSA) blood testing of critical importance in the detection of PC (prostate cancer) in healthy men? Has such testing resulted in detecting PC at an earlier stage where cure is more likely? Has the PSA increased cancer-specific survival and thus lessened PC associated mortality? "What should I do?" is the question asked by many confused men and their loved ones fearing the threat of the most common malignancy of males.

I would like to share with you my experience in 30 years of medical work that span the years of the pre-PSA era (prior to 1987 when the FDA approved the PSA test), and up to the present time. My focus on PC started in 1983, working with Fernand Labrie, MD, of Laval University in Quebec, Canada. I was one of a handful of American co-investigators with Dr. Labrie evaluating the anti-androgen drug Flutamide in combination with an agent (d-tryp-6, now called Triptorelin) that blocks pituitary stimulation of testosterone production by the testicles. Men with advanced PC were studied, and a large number of these men had been told they had six months or less to live. At that time, approximately 60% of these PC patients presented with advanced or bulky disease at the time of diagnosis. Survival in these patients was greatly enhanced by blocking endogenous testosterone production.

In response to this reversal of disease in these advanced stage cases, my medical oncology practice in Culver City, California, was overrun with men who traveled from the United States and abroad seeking a treatment that would extend their lives. Many of these men outlived the very physicians who had predicted their deaths, and the obvious "teaching lesson" was that "MD" does not stand for Medical Deity, but rather should stand for Medical Detective. Within a short time, my general oncology practice was totally focused on PC—an unheard of occurrence back in the 1980s. In the decades that followed, I became an intimate part in the lives of many thousands of men with PC along with their circle of family and friends. Indeed, this has been very fulfilling for me as a physician (Medical Detective) and a member of society.

So, is the PSA worth testing? In a nutshell, the PSA is the most valuable biologic marker (biomarker) involved with this common malignancy. The general issue of PSA testing, however, merits a full and frank discussion, and not an abridged or curbstone response. And please be aware that the concepts presented in the following discussion are of great consequence to anyone involved in a life-changing decision. What I will share with you will be presented in two parts. The first of which follows below and is a medical-philosophical discussion relating to PSA screening. Part II is the story of a 43-year-old man who through empowerment learned how PSA testing is rationally performed and how it has led to a superior patient outcome.

What You Need to Know

PSA: Pestilence or Promise?

 

• The most common cancer striking men has a blood marker known as prostate-specific antigen that can enable very early detection, thereby enabling curative therapies to be employed before metastasis strikes.
• Most urologists and oncologists are not properly interpreting PSA results, nor are they efficiently implementing further diagnostic and treatment protocols.
• Ejaculation and certain activities such as bike riding within 48-hours of testing may falsely elevate PSA values.
• Monitoring PSA values and rate of change over time and incorporating various PSA derivative tests such as the free PSA percentage and more recently the PCA-3 test can add important information to PSA testing particularly if the PSA is rising quickly or is elevated above 4 ng/mL.
• A federally-funded task force has concluded that PSA should not be used as a diagnostic screening tool for any man, regardless of age, race, or family history.

Foundational Principles Crucial to Understanding the PSA Test

Optimal decision making, or more properly stated, the formulation of strategy that optimizes outcome, is dependent upon employing—in real-time—what I term "foundational principles." For a man with PC, the three most important of these principles in a successful strategy are:

1. Selection of treatment(s) appropriate to the patient.
2. Preparation of the patient for the intended treatment(s).
3. Choice of highly talented and dedicated physicians (I refer to these as artists) throughout the course of the illness.5

The three-step approach above works. And, it is entirely appropriate to the entire time course of PC—from PSA testing for screening purposes, to using the PSA to diagnose men who are at a high risk for PC, and for PSA testing to monitor the success or failure of any therapy against PC. In fact, using this three-step approach, or modus operandi (method of operation), will enhance the outcomes of virtually all health-related challenges in our lives.

Many of you remember Paul Harvey and his famous radio broadcasts that began with a "story" and ended with, "And now you know—the rest of the story." So many of the issues that humankind has always faced, and will continue to face, are characterized by this need for more data in order to make an "informed" decision—to get as close as possible as we can to the truth.

Why I believe this is to be a fact of life is founded in the nature of "information" and also in the human element, i.e., our human frailties. When it comes to understanding a situation, most of us want the condensed version, the abridged account, the "fast-food" explanation, or the nitty-gritty. Likely, this is because we lead hurried lives and there is too much to learn.

This information overload leads us to a form of attention-deficit dysfunction. We are bees flitting from one flower to the next and sometimes one doctor to the next. We want the truth and we want it fast. Understandably, we lack the depth of knowledge about a particular subject because there is so much to know in today's world of thousands of journals and millions of published articles. Too often we add insult to injury when decisions about what is right or wrong, good or bad, are made without reference to the context of the problem.

My favorite example is, "They must have weapons of mass destruction, let's invade." The same failure to understand status unfortunately is a common occurrence in our medical care. Medical doctors fall short in evaluating our internal biology and our external environment. We just don't get the importance of "the rest of the story" i.e., status. I recognized in the general practice of medical oncology that there was no humanly possible way for any oncologist to consistently be up-to-date on 30 or more different kinds of cancers. I chose PC to focus on in my attempt to get as close to the truth as possible. Maybe it is no accident that my initials "SBS" is also an abbreviation for Status Begets Strategy.

Intimately coupled with an inappropriate evaluation of status are four additional issues:

All of life is a double-edged sword and virtually everything that can be of help to us can also work against us. Thus there is no black or white; there is no absolute right or wrong. All of biology strives towards balance and communication, and thrives when these are achieved. The Yin and Yang of Asian philosophy, and the Socratic plea to "know thyself" speaks to the crucial nature of these concepts.

There are many levels of understanding, just as there are many levels of human skill or artistry. What one person understands and puts to good use may well become a weapon in the hands of a less informed person. This is the nature of the bell-shaped curve as it relates to society, and physicians are not exempt. The medical student graduating first in his class is called "doctor," but so is the student graduating last in his class.

That we often confuse the message with the messenger. In medical care, the messenger is the person(s) that turns the message into action. If truly valuable messages exist, should society at large toss them out because they can be misused, or do we create and enforce guidelines for their proper use?

Coupled with the above, we often throw out the "baby with the bathwater." PC SPES is a combination of 8 different herbs that, although primarily used in cases of non-hormonal PC, proved effective against a range of prostate cancer cell types.6 PC SPES was an excellent treatment for many men with advanced PC, but when drugs not indicated on the label were identified in the product, it was banned and a major treatment for androgen-independent PC was lost.6

Thus, in the authentic world of medicine the gears of science and translational medicine have core components of philosophy, morality, and judgment. Some of us, cognizant as well as sensitive that we intimately affect the welfare of others, equate this evolved approach in human endeavors as "artistry." In medicine, I call such individuals "real physicians," those whose true joy is in seeing a human life benefited by their interventions.

In public talks and writings I have stated the role of the healthcare practitioner should be a focus on patient outcome, and not on physician income. And if the physician focuses on the former as the "prime directive," almost always the latter will naturally follow. All of the above, sadly, but truly, relate to the issue of PSA screening. No fast-food medical article is going to clarify this issue. Our due diligence coupled with an earnest caring to understand all issues is required. As Martin Luther King said, "Our lives begin to end the day that we become silent about things that matter." Perhaps King should also have added "and striving to be as close to the truth as possible."

What Is PSA Screening?

Screening, in general, sorts out apparently well persons who likely have a disease from those who probably do not.7 A screening test is not intended to be diagnostic.7 Persons with positive or suspicious findings are usually referred to other physicians for diagnosis and necessary treatment. For example, Dr. Jones, a general practitioner, in his yearly examination of patient John Doe includes a PSA test as a screening tool for PC. The result is 3.6 ng/mL and John is told his prostate is fine; or the PSA is 4.1 ng/mL and John is referred to a urologist for further testing. The PSA result provides information as to the status of prostate health. The PSA normal range is given as 0-4.0 ng/mL. A level above 4.0 ng/mL is theoretically a trigger for further investigation(s). But we have learned, hopefully, that a truly healthy prostate, one not affected by benign prostate enlargement (BPH), prostatitis, or prostate cancer is associated with a PSA result of 1.0 ng/mL or less.8 Therefore, the first-time result of PSA testing can inform us to the presence of a perfectly healthy prostate versus an unhealthy one. Since the very first PSA test a man has is his baseline, we do not have any comparison value to assess the rate of increase in PSA. But importantly, this initial PSA reading provides a foundation as to the status of the prostate gland for a particular patient.

Caveats to Proper PSA Testing

 

There are caveats to optimize the value of PSA testing. Understand, however, that these are my personal convictions that resulted from my first-hand experiences in using PSA in thousands of men and over a time period of three decades. Medicine is notorious for controversy and issues that relate to PSA are no exception.

First, men tested for PSA are virtually never informed that ejaculation due to sexual intercourse or masturbation has been associated with a greater amount of PSA in the blood, because the ejaculate contains PSA (an enzyme to liquefy the semen, and facilitate fertilization of the woman's ova). In fact, one of the early uses of PSA was in instances of alleged rape to prove that insemination had occurred by virtue of PSA being present in the vaginal fluid of women who were raped.9 The numerous articles on the effect of ejaculation on PSA, and free PSA are not in uniform agreement;10-31 and in light of this unresolved controversy I recommend that men going for PSA testing should be informed that no ejaculation should occur for 48 hours prior to PSA testing. In 30 years of work in this field, I have never had a single patient acknowledge that this has been discussed with him. In addition, any kind of manipulation of the prostate- be it a DRE (digital rectal exam) or bicycle riding should be avoided as well. Given the lack of consensus findings on all of these issues, there is no downside to following these recommendations.

The PSA level in the blood, like many lab tests, has a rhythm based on the time of the day i.e., a diurnal rhythm. Therefore, obtain your PSA blood tests in either the morning or the afternoon, but not both. And, the laboratory testing method (assay) and even the lab itself doing the PSA can lead to variability in results, so make sure the same methodology is used e.g. Hybritech, Tosoh, DPC, etc, and return to the same lab facility for all your PSA testing. Following these recommendations will decrease aberrant PSA test results. You may hear your local physician say that all of the above is controversial, but you have nothing to lose and possibly something to gain by avoiding these possibly confounding issues.

An additional, commonly forgotten issue is that there are various PSA derivative tests which can add important information; these are the Free PSA percentage, and more recently the PCA-3 test. With the former, the total PSA and the free PSA absolute values are given, and the free PSA percentage is calculated. Note that the total PSA obtained from this derivative test is NOT comparable to the total PSA obtained with the stand-alone PSA test that is most commonly performed. Being mindful of the above enhances the value of PSA testing, and it is part of "the rest of the story." The PCA-3 test is performed on urine rather than blood and detects genetic material that is excreted into the urethra via the epithelial cells that line the prostatic ducts.32 Prostate cancer cells tend to over-produce this genetic material far more than normal cells do.32 The PCA3 urine test has to be done in a urologist's or other doctor's office as it requires a digital rectal exam (three strokes per lobe) just prior to collection of the urine.

The Importance of PSA Values Over Time

 

Many healthcare practitioners consider benign prostatic hypertrophy (BPH) a normal part of human aging. I do not. For sure it is not nearly as much concern as PC, but it is still a form of pathology as is prostatitis (inflammation of the prostate).

In fact, inflammation and aging share so many characteristics that the term "inflammaging" has been coined.33-37 I consider inflammation, aging and cancer the three horsemen of the apocalypse of health. I started my own PSA testing in 1985, two years prior to FDA approval of this lab test. My initial result was 0.75 ng/mL. Now, over 25 years later my PSA is in the range of 0.90 ng/mL.

There is a peer-review article that indicates that a truly healthy prostate is associated with a change in PSA per year of no more than 0.1 ng/mL.38 In other words, this rate of PSA change per year, or PSA velocity (PSAV), is dramatically slower by comparison with the threshold value of 0.75 ng/mL/yr which is used as a red flag for possible PC.

My PSA has increased by 0.15 ng/mL/yr over 25 years which equates to a PSAV of 0.006 ng/mlL/yr. When I obtain multiple PSA tests on an individual patient, I am happy to find a PSAV of 0.1 ng/mL/yr and even up to 0.3 ng/mL/yr. At a PSAV of 0.3 ng/mL/yr or higher my medical concern is heightened that I may be dealing with a man with PC. Do not confuse the PSA velocity with the absolute or total PSA value. Note also, there are published papers on age-adjusted as well as race-adjusted PSA testing. However, I have not found these latter two PSA derivative tests helpful. Instead, I rely heavily on baseline PSA and change in PSA over time and I remember to include all of the constraints detailed so far to optimize valid testing.8

Remember that PSA screening involves using the PSA blood test to facilitate a diagnosis of PC in apparently healthy men. Note that "healthy men" excludes various categories such as men with a family history of PC or a family history of breast cancer or colorectal cancer, since all three diseases are associated with a higher risk of PC compared to men that do not have this history. Incorrectly, in my opinion, the USPSTF recommended excluding PSA testing in men with a family history of PC. Moreover, the USPSTF did not mention the co-relation between PC, breast cancer and colorectal cancer and the need for PSA testing in any man with such a family history. In this regard, the USPSTF confused the message not with the messenger, but with the context of the problem that many men face who have genetic factors that place them at greater risk for PC. This includes a family history of PC, as well as breast cancer and also colorectal cancer.39-43

It is also important to mention that the USPSTF did not include a physician focused on PC. No urologist, medical oncologist or radiation oncologist was part of the panel. This situation is tantamount to having generals whom have never been at the front lines of a war decide on battle strategy. Working with hundreds, if not thousands of patients with PC gives a physician an entirely different perspective on how to use the PSA test. It is said that "context is everything;" at the very least, understanding context clearly plays a huge part in rational decision making. Experience makes context more understandable and appreciated.

All of the issues discussed above should clarify the currently muddied waters about PSA testing. The PSA is an extremely valuable test that remains the deciding factor on whether a man with PC is stable, getting better or declining. The PSA has the same implications in the context of assessing the health of prostate tissue: is it healthy, getting healthier or is it sick? The pivotal issue in the use of PSA is whether physicians can be sufficiently educated to maximize the insights afforded by PSA testing or will their understanding of perhaps the most valuable biomarker affecting the most common malignancy of men remain stuck in the mediocrity of today's system of assembly line medicine.

In the second part of this report which begins on page 74, I will share detailed information on a particular patient who represents many thousands of men who have a father or brother with PC and who decide to undergo PSA testing despite the USPSTF's recommendations. I will point out how PSA testing can be used to not only make an early diagnosis of PC, but lead to a proper evaluation of various aspects of this man's health (his status), then correct many unrecognized findings of his ill health, while ensuring stability of the PC process without implementing any invasive procedure.

Summary

 

Prostate-Specific Antigen (PSA) is a blood marker that can enable very early detection of the most common cancer striking men, thereby enabling curative therapies to be employed before metastasis strikes. By allowing for this early detection, PSA testing has literally spared tens of thousands of men agonizing deaths from metastatic prostate cancer. However, a federally funded group, the United States Preventive Services Task Force (USPSTF) has concluded that PSA should not be used as a diagnostic screening tool for any man, regardless of age, race or family history and that it should not be performed at all! As a practicing prostate oncologist for nearly 30 years, the problem is not the PSA test itself, the problem is that most urologists and oncologists are not properly interpreting PSA results, nor are they efficiently implementing further diagnostic and treatment protocols. Factors such as the change in PSA values over time and the rate of change in PSA per year (known as PSA velocity or PSAV) must be considered as well as PSA derivative testing like Free PSA Percentage and the recent PCA3 test in order to garner a complete picture.

Members who have questions about their PSA results or proper PSA testing can call a Life Extension® Health Advisor at 1-866-864-3027.

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