Prostate Cancer Screening: The Role of PSA Testing

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Prostate cancer screening has been making news.  One of the standard screening tools, the PSA (prostate-specific antigen) test, has come under scrutiny.  Some experts advise that the test should be dropped, others say it still has value.  Who’s right?  If we drop the test, does this mean that men will no longer be screened for prostate cancer?

PSA is an enzyme that is secreted by cells in the prostate gland.  It helps to liquefy the semen to make it easier for sperm to move, and may help facilitate the passage of sperm into the uterus by dissolving cervical mucus.  It is normally present in small quantities.  Prostate disorders, including prostate cancer, may result in higher levels of PSA.

Research on prostate antigens began in the 1960’s.  By 1987, work was underway to define the value of PSA as a clinical marker of prostate cancer (1).  From the beginning, this was considered controversial because while PSA rises with development of cancerous tumors, it also increases for other reasons, such as the presence of benign prostatic hypertrophy, and in response to procedures such as prostate massage, needle biopsy and resective surgery.

A 1986 study conducted by a company researching PSA testing concluded that a “normal” test result would be below 0.4 ng/ml based on observations of over 400 apparently healthy men (2).  Experts at the time the test came into clinical use acknowledged that the cut-off was arbitrary, and that it tended to detect changes unrelated to the presence of cancer (3).

To further complicate matters, it seems the term “prostate-specific antigen” is inaccurate, because the antigen is not, in fact, specific to the prostate and its secretions.  It is also detectable in amniotic fluid, breast milk, and the urine and serum of women (4).

So, the good news is we have a test.  The bad news is the test results may be misleading.

In 1987, before the PSA test was in widespread use as a screening device, the approximate number of new prostate cases in Canada was 8,200 and the number of prostate cancer deaths was 2,800.  The numbers for 2013: 23,600 new cases, and 3,900 deaths (5), (6), (7). Survival rates improved from about 86% in the 1992-94 period to about 95% in the 2006-2008 period (7).

It’s clear that more cases of prostate cancer are being detected and successfully treated.  What about harms from over-treatment?

The PSA test is known to have a high rate of false positives; this can lead to invasive investigations of healthy men.  It’s sensitivity can also result in the detection of small, slow-growing cancers that would never require treatment – the problem here is the idea of living with a cancerous tumor, even one that is not a health-threat, may frighten people into demanding care they do not actually need. These limitations make reliance on the PSA test as a major screening tool a problem.

Stepping back from routine use of the PSA test does not mean we are abandoning screening.  

On the contrary, it means we should rely more on physical examinations, supported by additional testing (such as the PSA test) when the person’s medical risks and exam results indicate these are warranted, in accordance with the new Canadian Task Force on Preventive Health Care guidelines.

References
(1)  Stamey, Thomas A., et al. “Prostate-specific antigen as a serum marker for adenocarcinoma of the prostate.” New England Journal of Medicine 317.15 (1987): 909-916.
(2) Myrtle JF, Klimley PG, Ivor L, Bruni JF (1986). “Clinical utility of prostate specific antigen (PSA) in the management of prostate cancer”. Advances in Cancer Diagnostics. San Diego: Hybritech Inc.
(3) Kolota, Gina (May 30, 2004). “It Was Medical Gospel, but It Wasn’t True”The New York Times.
(4) Laux, Dale L., and Sarah E. Custis. “Forensic detection of semen III. Detection of PSA using membrane based tests: sensitivity issues with regards to the presence of PSA in other body fluids.” Midwestern Association of Forensic Sciences (2004).
(5) Canadian Cancer Society: Canadian Cancer Statistics 1987, Toronto 1987 via http://bit.ly/1wuBg3T
(6) National Cancer Institute of Canada. Canadian cancer statistics 2000. Toronto, Ont: National Cancer Institute of Canada; 2000. via http://bit.ly/1rZccvs
(7) Canadian Cancer Society’s Advisory Committee on Cancer Statistics. Canadian Cancer Statistics 2013. Toronto, ON: Canadian Cancer Society; 2013 via http://bit.ly/1rZoeF0