PSA Discoverer Says Antigen Test Is Misused, Unreliable

In this edition of Medscape One-on-One, host and Medscape Editor-in-Chief Eric J. Topol, MD, interviews Richard J. Ablin, PhD, DSc (Hon), who first discovered prostate-specific antigen (PSA) in 1970. At the time, Dr. Ablin and colleagues were trying to identify an antigen that was specific to prostate cancer. What Dr. Ablin identified instead was that PSA was present not only in malignant prostates but also in benign prostates. He did agree, however, that elevated levels of PSA might be useful in predicting a recurrence of prostate cancer in men who were thought to be in remission.

It was much to Dr. Ablin's dismay that more than 2 decades later, in the mid-1990s, the US Food and Drug Administration (FDA) approved the use of PSA not only to test for recurrence of cancer, but also as a possible predictor of cancer. Since then, Dr. Ablin maintains, the United States spends billions each year administering a preventive prostate cancer screening test to men, using PSA, that produces false positives in the majority of cases. In his interview with Dr. Topol, Dr. Ablin explains why physicians and patients should proceed with caution when using PSA as a marker for preventive screening.

The Discovery of Prostate-Specific Antigen

Eric J. Topol, MD

Eric J. Topol, MD: This is Eric Topol here for Medscape One-on-One, with Richard Ablin at the University of Arizona. Dr. Ablin has recently coauthored a book titled The Great Prostate Hoax (Macmillan, 2014).^[1] This is a very interesting opportunity to speak with the discoverer of PSA. Welcome, Dr. Ablin.

Richard J. Ablin, PhD: Thanks very much. Having followed your work, this is a treat for me. I hope that in the course of our conversation, people and families will understand what they should know about prostate cancer moving forward, so thank you for this opportunity.

Richard J. Ablin, PhD, DSc (Hon)

Dr. Topol: Let's talk about your background. You were at Lake Forest College, and then at SUNY in Buffalo. You worked at the well-known cancer center at Roswell Park. You were in Chicago at Cook County for a while, and now you are at the University of Arizona.

Let's go back to 1970, around the time that you first came across what is now called PSA. What were your thoughts about it at that time?

Dr. Ablin: To be as brief as possible, in 1967 I had joined 2 urologists in Buffalo at a teaching hospital there (my background is immunology) who were working on an alternative treatment for prostate cancer called cryosurgery -- freezing instead of cutting. In the course of our studies, when we were freezing the prostates of experimental animals -- rabbits, dogs, baboons, rhesus monkeys -- we were observing an immune response similar to that seen following a vaccine. When we froze more than once, we saw a characteristic booster response.

When we were following up some of our clinical studies by looking at x-rays, we saw in a patient an initial remission of metastasis in his lungs. This patient had stage IV lung cancer and metastatic prostate cancer, but he still had his prostate. On the basis of our experimental studies, we wondered whether the remission of these metastases had something to do with an immune response, which I subsequently characterized as cryoimmunotherapy.

We subsequently treated more patients by multiple cryotherapy of their prostates, and observed that several of these patients underwent remission of their metastases at distant sites. There was a lot of press and questions from the medical and lay communities about what was happening. Why is there an immune response? Is there is a tumor-specific or cancer-specific antigen? To answer that question, I started to look at the immunologic complexity, or the antigenicity, of the normal benign and malignant prostate. I hoped to find a cancer-specific antigen.

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