CureTalk’s Interview With Dr. Richard J. Ablin, Discoverer Of The Prostate Specific Antigen (PSA) – Part 1
Cure Talk had the honor of interviewing Dr. Richard J. Ablin, Professor of Pathology, University of Arizona College of Medicine, The Arizona Cancer Center, BIO5 Institute and President, Robert Benjamin Ablin Foundation for Cancer Research.
Dr. Ablin discovered the prostate specific antigen (PSA) in 1970, on which the current PSA test for prostate cancer is based upon.
Me: Tell us the story of the discovery of PSA (prostate specific antigen).
Dr.Ablin: On completion of a postdoctoral fellowship at the State University of New York at Buffalo School of Medicine in June 1968, I joined two urologists at the Millard Fillmore Hospital in Buffalo, who developed cryosurgery (cryoablation) for the treatment of prostate cancer by freezing vs. surgically removing the prostate or using radiation. In the post-operative follow-up of patients whose primary prostatic cancer were frozen and had advanced disease with metastases, e.g., to the lungs, shoulder, at the time of treatment, their metastases regressed or disappeared. Concurrently, cryoablating the prostate (or biological equivalent) in several laboratory animal species, we observed the animals developed an immune response to antigens (proteins) of the frozen tissue. The immune response paralleled that which occurs following vaccination, and as with repeated vaccination, repeated freezing resulted in an anamnestic (“booster”) response, i.e., a higher level of the immune response. These observations, in accord with those of the regression of cryoablated experimentally induced tumors in laboratory animals and their development of an immune response and in concert with observations in prostate cancer patients treated cryosurgically undergoing remission of metastatic disease, provided presumptive evidence that freezing was producing an immune response that had a therapeutic effect. Therefore, I coined the term -“cryoimmunoimmunotherapy.”
The foregoing, rather startling observations, of a ‘double-edged sword’ effect of cryosurgery resulting in the destruction of the localized cancer and concomitantly the development of an immune response to destroy cancer at distant sites, i.e., metastases, raised many questions in the biomedical community and media. Specifically: Did cryoablation of the prostate result in the release of prostate cancer (tumor)-specific antigens resulting in the ensuing immune response?
At this juncture, I began to do some immunological studies on the human prostate. I studied the antigenic composition of the normal, benign and malignant prostate and found that they contained tissue-specific, i.e., prostate-specific antigens. One was characterized as prostatic acid phosphatase and the other prostate-specific (PSA). PSA was present only in the prostate and not present in other tissues, e.g., liver, kidney, and lung. However, as PSA was present in the normal, benign, and malignant prostate, and therefore prostate-specific, it was not disease-specific, and most importantly, not cancer-specific. However, what I did observe was that prostate cancer patients who had a suggested high PSA (determined at the time by electrophoresis) prior to treatment, e.g., by radical prostatectomy or radiation, showed a lower PSA following treatment. This was in the 1970’s, and at a time, we did not have access to the subsequent availability of monoclonal antibodies and other to come sophisticated methodology.
Therefore, from the foregoing it was clear I had not, as I initially was looking for, identified a cancer (tumor)-specific antigen, and PSA could not be used as a diagnostic tool, it could however, be used as a prognostic indicator for the successfulness of treatment. For example, if a patient with prostate cancer underwent treatment and his PSA increased post-operatively it would suggest that the cancer had recurred.
Nine years following my discovery of PSA in 1970, and related observations, PSA was subsequently purified and characterized, and a PSA test developed. The FDA approved the PSA test for prognosis in 1986, meaning, if a person had prostate cancer and his prostate was removed or treated by some other means, his post-treatment PSA levels could indicate whether cancer recurred, so that he could possibly receive further treatment.
Shortly after FDA approval for the use of the PSA test for prognosis many members of the medical community, even without FDA approval started to use the PSA test to screen patients for prostate cancer since it was a noninvasive test and could be easily done. In 1994, the FDA, in spite of the absence of the cancer-specificity of PSA and subsequent criteria (discussed in that which follows) made a very bad mistake and approved it for diagnosis in combination with a digital rectal examination (DRE). Thereafter, the incidence of prostate cancer and number of patients treated rapidly increased with many patients being over-diagnosed and over-treated.
Me: Recently, the United States Preventive Task Force (USPTF) has recommended against routine screening of PSA for men below the age of 75. Can you validate?
Dr. Ablin: As quoted in the paper, http://cebp.aacrjournals.org/content/21/3/391.full
Screening is one of the cornerstones of preventive medicine. The purpose of screening is to identify preclinical and asymptomatic cases of disease in a population of risk, as opposed to making a diagnosis based on a patient’s presentation with symptoms and disease.
In looking back, one may appreciate why the PSA test cannot be used the way it is as evidenced from the following four fundamental “cruxes,”
- PSA is not cancer-specific.
- There is no level of PSA diagnostic for prostate cancer.
- The PSA test cannot distinguish an indolent cancer from an aggressive cancer. Prostate cancer is akin to a “turtle” and a “rabbit” in an open box. The “turtle” is the indolent, non-aggressive cancer; it wanders around inside the box and goes nowhere. The “rabbit” is the aggressive cancer; it hops around and might even jump out of the box at anytime spreading, i.e., metastasizing.
- Prostate cancer is an age-related cancer. Hence, e.g., if there is a group of asymptomatic men between the ages of 60 to 70 years and they have a prostatic biopsy, over 65% of the men would have prostate cancer. However, the PSA test cannot predict among these which the “turtles” are and which are the “rabbits,” Possibly not needing and needing treatment, respectively.
PSA is a normal component of the prostate, whether it is normal, benign, or malignant prostate. Hence, PSA is not cancer-specific, but prostate-specific. Note that the PSA test does not detect cancer, but the prostate-specific antigen.
The above-mentioned “cruxes” explain the inability of PSA test to screen for prostate cancer. The USPTF, finally on October 7, 2011, recommended that use of PSA test for screening of asymptomatic men for prostate cancer causes more harm than good and is a liability to public health.