PSA:

PSA Use for Prostate Cancer Sharply Questioned

By Dr. Ralph Moss
from CancerDecisions.com Newsletter (8/10/03)

Another pillar of the cancer establishment is tottering. The widely used Prostate Specific Antigen (PSA) blood test, designed to detect prostate cancer while it is still in its early stages, has been found to miss 82 percent of tumors in men under 60, and 65 percent of cancers in older men, according to a recent study published in the New England Journal of Medicine.

At the present time a reading under 4.0 is considered the sign of a healthy prostate. But scientists at Harvard Medical School and elsewhere have responded to these findings by suggesting that the cut-off point for a "healthy" PSA score should be lowered to 2.6. Indeed, the Prostate Cancer Coalition already advocates checking men with lower PSA levels. If this new yardstick were generally adopted, it would mean that thousands more men every year would be told to have surgical biopsies to see if they really have prostate cancer. Many more men who do not have prostate cancer would undergo these biopsies just to make sure.

The PSA test was approved by the FDA in 1986 and was purported to have an 80 percent rate of accuracy in detecting prostate cancer in its early phase. However, studies have repeatedly shown that the PSA test is decidedly unreliable. In up to 82 percent of cases of men under 60 years of age who actually do have prostate cancer, the PSA test gives a normal reading (4.0 or below).  Conversely, in 12 percent of men who do not actually have prostate cancer, the PSA test will give a suspicious reading of 4.1 or above. Other conditions, such as prostatitis (inflammation of the prostate gland) can lead to false positive readings.

If the "healthy" score were lowered to 2.6, scientists say, then the percentage of men without cancer who would be subjected to an unnecessary biopsy would rise from 2 percent to 6 percent.

The widespread use of PSA screening has created a boom in biopsies, according to the January 2002 issue of the journal Urology. Lowering the normal score by several points will generate even more office traffic for urologists. But will it really save the lives of those who submit to it? In an editorial in the same issue of the New England Journal of Medicine, Drs. Fritz Schroder and Ries Kranse of the Erasmus Medical Center in Rotterdam, Netherlands, say no. They point out that there is no conclusive evidence showing that the PSA screening test actually reduces the risk of death from prostate cancer, without reducing many men's quality of life.

There is no doubt that we need a way to detect aggressive prostate cancer. Prostate cancer kills about 29,000 American men each year and is the second most common cancer killer of US men, after lung cancer. However, there are so many problems with the PSA that it can really no longer be considered a reliable means of finding early but life-threatening cancer. To complicate matters even further, many experts point out that prostate cancer is usually a slow-growing disease and in fact, in older men, often does not require any treatment at all, except "watchful waiting."  

The very name "Prostate Specific Antigen" implies that this marker is found only in prostate tissue. However, in 1995 scientists at Fox Chase Cancer Center, Philadelphia, showed that genetic material (RNA) contained in PSA was also present in several non-prostate cell lines, including ovarian cancer, lung cancer, myeloid leukemia, as well as occasionally in normal blood. Oddly, Canadian scientists have also found this "prostate-specific" marker expressed by female breast cancers (Zarghami 1996). So the idea that PSA is specific to prostate cancer is inaccurate, to say the least.

I am not saying that PSA tests are worthless. In fact, they are still very important in diagnosing the progress of the disease, once established. But PSA is what scientists call a "dynamic measure." What is really important is how it changes over time. A rising PSA, for example, is a valuable indicator that the cancer is progressing. And a PSA above zero in a man whose prostate has been removed is usually an indication of recurrent disease. But as an absolute measure it is of doubtful value, and may now lead to a tremendous extension of surgical biopsies. This is a questionable development.

In a prostate biopsy, a visualizing device, called a transrectal ultrasound (TRUS), is inserted into the rectum, and a tiny needle is threaded through the rectal wall and into the prostate. Most doctors take six samples, but others take as many as 45 samples of the prostate in a needle-in-the-haystack search for cancer. The more elaborate biopsy requires anesthesia. Everyone agrees that the procedure hurts, although many urologists downplay the pain, claiming that the prostate isn't especially sensitive to pain. (This will come as a surprise to any man who has suffered through a bout of prostatitis.) Researchers at Emory University have suggested that the common pain reliever lidocaine gel can significantly improve a patient's comfort. After the biopsy, there may be blood in the urine, stools, or semen for days.

According to the University of Pittsburgh Cancer Institute, fewer than 1 percent of all patients develop severe bleeding or an infection of the prostate or urinary tract following biopsy. However, the key word here is "severe." Another study done at the Mayo Clinic showed that of 2,258 prostate biopsies, 17 percent were associated with at least one complication.

The total number of complications per biopsy remained relatively constant between 1980 and 1997. But the age-adjusted complication rate (per 100,000 men) during this period more than doubled, from 26 to 60. This is because the use of prostate biopsies also more than doubled in the same period, from 138 per 100,000 to 374 per 100,000.

"The prevalence of post-biopsy complications in the community has increased tremendously because of the increased use of prostate biopsies," the Mayo authors reported. One can predict that if the normal PSA score is reduced from 4.0 to 2.6, as proposed, this will contribute even more to the rising number of biopsies, as well as increasing the incidence of complications needing further treatment.

I don't have any simple solution to the PSA dilemma.   However, I hope that medical practitioners will take another look at the old-fashioned but nonetheless useful method of digital rectal examination (DRE), which, for all its limitations, at least does not poke holes in a sensitive organ, nor frequently cause complications, as does needle biopsy.

What will doctors do about patients (and they number in the thousands) who have had a relatively stable PSA score between 2.6 and 4.0? Are they really going to send all of those men for painful and potentially dangerous biopsies? And will men willingly submit to such invasive procedures? I hope not.

Once again, I lift my eyes to Heaven and exclaim, "There's got to be a better way!" 

References:

Djavan B, et al. Safety and morbidity of first and repeat transrectal ultrasound guided prostate needle biopsies. The Journal of Urology. September 2001. 166: 856-860.

Emery, Gene. Prostate Test Misses Tumors, Study Finds. Reuters.  Wed July 23, 2003.

Issa, MM, et al. A randomized prospective trial of intrarectal lidocaine for pain control during transrectal prostate biopsy: the Emory University experience. Journal of Urology 2000: August; 164 (2):405.

Roberts RO, Bergstralh EJ, Besse JA, Lieber MM, Jacobsen SJ. Trends and risk factors for prostate biopsy complications in the pre-PSA and PSA eras, 1980 to 1997.  Urology. 2002 Jan;59(1):79-84.

Smith MR, Biggar S, Hussain M.  Prostate-specific antigen messenger RNA is expressed in non-prostate cells:  implications for detection of micrometastases.  Cancer Res.  1995 Jun 15;55(12):2640-4.  

Zarghami N, Diamandis EP. Detection of prostate-specific  antigen mRNA and protein in breast tumors. Clin Chem. 1996  Mar;42(3):361-6.