On March 22, National Public Radio ran a segment (“Prostate Test: Lifesaver or Big Mistake?) on its “Morning Edition” program on prostate-specific antigen (PSA) and the controversy regarding the PSA test as an effective screening tool for prostate cancer. Richard J. Ablin, PhD, a research professor of immunobiology and pathology at the University of Arizona College of Medicine, was interviewed for this segment.
On March 10, the New York Times ran an Op-Ed piece (“The Great Prostate Mistake”) written by Dr. Ablin.
The take-home messages from these highly reputable news sources are that Dr. Ablin “discovered P.S.A. in 1970” and by virtue of that discovery, would be the obvious reigning authority on the use (and purported overuse) of the PSA test.
Prostate-specific antigen (PSA), a protein produced by the secretory epithelial cells of the prostate gland, is present in small quantities in the blood of normal men, and is often elevated in the presence of prostate cancer and in other prostate disorders. One should not confuse the current PSA with the "prostate-tissue-specific antigens" or proteins (the human prostate contains hundreds of proteins) that were discovered in the early 1970s.
While Dr. Ablin did discover a "prostate-specific antigen" that is confined to the normal prostate, he neither developed the PSA test nor discovered the PSA that the current test is based on.
That credit goes to Roswell Park Cancer Institute researcher T. Ming Chu, PhD, DSc, who, with an extraordinary team of over 20 researchers, including urologists and pathologists, discovered what the American Association for Cancer Research would later call one of the "landmark scientific discoveries of the 20th century."
Working with human prostate tissue from cancer and benign prostatic hyperplasia, Dr. Chu and his colleagues identified and purified PSA and later developed the simple PSA blood test that is used today for the early detection and management of prostate cancer.
The team published their first major paper in 1979 in Investigative Urology, followed by a 1980 paper in Cancer Research that used the PSA test to demonstrate PSA in the blood of prostate cancer patients. Subsequent papers published by the Roswell Park researchers appeared in Cancer Research, Journal of the National Cancer Institute, Methods in Cancer Research, and Journal of Urology, among others. A patent was issued in 1984 to the state of New York and Roswell Park Cancer Institute, and the technology was transferred to the biomedical industry for preparing testing kits. The PSA test received FDA approval in 1986 as a monitor for treatment response and disease recurrence, and in 1994, as a screening tool for diagnosis. Since then, an estimated one billion PSA tests have been given.
In recognition of his many contributions to the field of urology, Dr. Chu received the Presidential Award from the American Urological Association in 1993 and was featured in the April 15, 1998 issue of Cancer Research for his seminal research on the use of tumor cell products in the diagnosis and treatment of cancer, and for his leadership role in the discovery of PSA and the development of the PSA test.
Is the effectiveness of the PSA test no better than a coin toss, as Dr. Ablin contends in his recent remarks to the media? Let’s look at the facts. PSA has revolutionized our ability to detect prostate cancer in its early stages and monitor its course of treatment. Prior to the development of PSA, only 4% of men diagnosed with prostate cancer could be cured. Most were diagnosed with prostate cancer when it had spread to their bones and caused pain. The standard treatment was androgen deprivation therapy and the mean survival was three years. The development of the PSA test has completely changed the demographics of newly-diagnosed prostate cancer patients. Less than 10% of American men are diagnosed with incurable prostate cancer today, and the five-year survival after treatment is essentially 100%. In addition, one British study has shown that the prostate cancer mortality rate in the USA for the period 1994-2004 had a rate of decline greater than four times that of the United Kingdom, where the PSA test was not widely used.
As the pioneer of the PSA test, Roswell Park Cancer Institute has been in the frontlines of the recent national discussion on the challenges and value of mass prostate screening using the PSA test. Two Roswell Park faculty members, including myself as chair, serve on the National Comprehensive Cancer Network (NCCN) Guidelines Panel for Prostate Cancer, the group that develops the national/international “best practice” guidelines. On March 4, I was invited to give expert testimony at an important hearing (“Prostate Cancer: New Questions About Screening and Treatment”) before the House Committee on Oversight and Government Reform. My testimony, I believe, provided some clarification as to why the PSA controversy continues to be waged.
For example, the incidence of prostate cancer if one autopsied the prostate is approximately the age of the man. In other words, 20% of 20 year olds already have cancer in their prostate and 80% of 80 year olds have prostate cancer. Prostate biopsies will find about 1⁄2 of these autopsy cancers. Thus, 40% of 80 year olds and 10% of 20 year olds will be found to have prostate cancer if their prostates are biopsied. Because PSA can be elevated for many reasons, many men who undergo prostate biopsy may have an autopsy-type prostate cancer diagnosed rather than one that poses a threat to their life expectancy.
There is legitimate concern that widespread use of the PSA test may over-diagnose prostate cancer and put men at risk for complications from unnecessary treatments such as surgery and radiation. But it’s not the use of the PSA test that’s at the root of the national debate – it’s deciding what to do with the information it yields.
Indiscriminate use of PSA and aggressive diagnosis and treatment of prostate cancer is unlikely to impact significantly the survival of American men and may adversely affect the quality of life of American men. The NCCN has responded by changing the 2010 Guidelines to focus on a more careful detection of aggressive prostate cancer in younger men while urging a more conservative approach to early detection of prostate cancer in older men; NCCN recommends that attempts to find prostate cancer cease when a man’s life expectancy falls to <10 years. The NCCN 2010 Guidelines also recommend active surveillance of men who were found to have low risk prostate cancer when life expectancy is <10 years. In addition, the NCCN has created a new prostate cancer risk category, very low risk prostate cancer; active surveillance is the only recommended treatment in this group of men when life expectancy is <20 years. These changes allow appropriate aggressive treatment of men who are at high risk of death from prostate cancer while avoiding overtreatment of men at low risk of prostate cancer death.
At Roswell Park, we continue to build on the milestone contributions of Dr. Chu and his colleagues. Our research is focused on developing a better PSA test, one that will distinguish aggressive, life-threatening prostate cancers from those that are slow-growing and not life-threatening so that appropriate treatment decisions can be made.
The need for a more precise early detection tool is both challenging and urgent. On this point, we are all in agreement.
James Mohler, MD
Senior Vice President for Translational Research
Chair, Urology Department
Roswell Park Cancer Institute