Letter to the Editor: More Thoughts on PSA


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An article that appeared in the August 15 issue of The ASCO Post (“Rethinking the Role of PSA Screening in Public Health”) contains false statements about the discovery of prostate-specific antigen (PSA) and its effectiveness as a test for early detection of prostate cancer.

Contrary to what’s reported in this article, Richard Ablin, PhD, did not discover the PSA that forms the basis for the PSA test. Dr. Ablin discovered a “prostate-specific antigen” that appears in normal prostate tissue, but Roswell Park Cancer Institute (RPCI) researcher T. Ming Chu, PhD, DSc, and an extraordinary team of more than 20 researchers identified and purified another protein, initially called “prostatic antigen” and later renamed “prostate-specific antigen,” from normal, benign, and malignant human prostate tissue. This PSA was developed into the PSA blood test that is used today for the early detection of, and monitoring of treatment for, prostate cancer.

A patent was issued in 1984 to the State of New York and RPCI, and the technology was transferred to the biomedical industry for preparing and marketing of testing kits. The PSA test received U.S. Food and Drug Administration approval in 1986 for monitoring treatment response, and in 1994 for early detection of prostate cancer.

Novel Discoveries

In the August 15 article, Dr. Ablin apparently refers to Dr. Chu and his RPCI colleagues when he suggests that “some other researchers rediscovered [his] work and subsequently developed what we know as the PSA test.” This statement is false. The findings made by Dr. Chu and his team were novel discoveries of a distinct molecule that has been fully characterized biochemically and biophysically, and bears no connection to the unknown antigen of the same name discovered by Dr. Ablin. The two antigens are different because Dr. Ablin’s antigen was found only in normal prostatic tissue, while Dr. Chu’s PSA is found not only in prostate tissue but in prostatic fluid and semen. This issue was resolved 27 years ago in a published interchange between Drs. Ablin and Chu.1,2

The Chu team’s efforts were documented in a series of articles published in major journals, such as Investigative Urology, Cancer Research, Journal of the National Cancer Institute, Methods in Cancer Research, and Journal of Urology, and some of these publications have been celebrated by the American Urological Association, Journal of Urology, and American Association for Cancer Research as “landmark,” practice-changing papers. This record contrasts with the paucity of material supporting Dr. Ablin’s claims.

Acknowledging Limits and Benefits

The PSA test has its limits, to be sure. Dr. Ablin notes correctly that PSA testing is not, of itself, an indicator of prostate cancer aggressiveness. However, PSA, when used in combination with prior PSA values, Gleason score, and tumor stage, is a very good tool for assessing prostate cancer aggressiveness.

An important fact left out of the recent article is that prostate cancer mortality in America has fallen by more than 40% since the introduction of the PSA test. PSA has revolutionized our ability to detect prostate cancer in its early stages and monitor the effectiveness of treatment. Before we had the PSA test, very few men diagnosed with prostate cancer could be cured and too many were diagnosed with prostate cancer when it had spread to their bones and caused pain.

We share Dr. Ablin’s apprehensions about improper use of PSA testing and overtreatment of prostate cancer. There is legitimate concern that indiscriminate use of the PSA test may overdiagnose prostate cancer and put men at risk for complications from unnecessary treatments. The value of PSA for early detection of prostate cancer has been diminished by its application to older men who are at low risk of death from prostate cancer; unfortunately, as many as one-fourth of American men over 85 have had a PSA measured in the past year.

But it’s not the use of the PSA test that’s at the root of the national debate—it’s how physicians and patients respond to the information it yields. In up to 40% of men in whom prostate cancer is detected by an elevated PSA, the cancer probably does not require treatment. But to cease all use of PSA testing in asymptomatic men, as Dr. Ablin and the U.S. Preventive Services Task Force would have us do, would almost certainly return us to the days when most men who were diagnosed with prostate cancer were likely to die a long, painful death from it.

Appropriate Use

There is a reasonable way to use PSA appropriately that is based on reliable medical evidence: Use PSA testing to detect prostate cancer in men who are at increased risk for developing aggressive prostate cancer and who will live long enough to suffer death from prostate cancer. Men should:

Know their risk for developing prostate cancer, which is considerably higher if they are African American or have a father or brother who developed the disease prior to age 65

Have their PSA levels tested according to the recommendations of any of the three main prostate cancer guidelines organizations—the National Comprehensive Cancer Network (NCCN), the American Urological Association, or the American Cancer Society

Make any decisions about whether and how to treat their prostate cancer after weighing their options—including deferring treatment in favor of active surveillance, observation, operation, and radiation—carefully and in consultation with their physician.

This is a straightforward, effective approach to using PSA—appropriately—for early detection of prostate cancer.

Challenging and Urgent Need

We agree that the need for a more precise early-detection tool is both challenging and urgent. Researchers at RPCI and other institutions are focused on developing a test that will distinguish aggressive cancers from those that are slow-growing and not life-threatening, so that appropriate treatment decisions can be made more easily.

While Dr. Ablin is entitled to share his views on the merits and limitations of PSA testing, your readers deserve to be accurately informed about his accomplishments. Dr. Ablin had no role in the discovery of the molecule now known as PSA or in development of the PSA test used worldwide, and has not been involved in the clinical diagnosis or treatment of prostate cancer. Publications that continue to misidentify Dr. Ablin as the discoverer of, and an authority on, PSA may seek to “add clarity to this ongoing debate,” but they do just the opposite. ■

James Mohler, MD
Chair, Department of Urology,
Roswell Park Cancer Institute
Chair, National Comprehensive
Cancer Network Prostate Cancer
Guidelines Panel

 

Donald L. Trump, MD
President & CEO, Roswell Park
Cancer Institute

References

1. Letter to the Editor and Reply Re: Carl S. Killian et al. Prognostic importance of prostate-specific antigen for monitoring patients with stage B2 to D1 prostate cancer. Cancer Res 45:5984-5985, 1985.

2. Wang MC, Valenzuela LA, Murphy GP, Chu TM: Which prostate antigen is which? Clin Chem 31:1405-1406, 1985


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