At a news conference on February 11, 2003, Senator John F. Kerry, 59 years old, disclosed that he had prostate cancer and would have his prostate removed. Mr. Kerry is one of the Democratic presidential candidates seeking nomination for the presidency in 2004. His cancer was first noticed when he had a routine screening blood test, the PSA, which detects a protein that leaks from the prostate. This screening seeks to identify a group of men with early stage prostate cancer in whom prompt radical treatment will alter outcome.

As we have written previously, there is some controversy about PSA screening. Evidently, many prostate cancers do not become clinically significant and do not need to be aggressively treated. The main forms of radical treatment are radical prostatectomy or radiotherapy (external beam or brachytherapy). Both forms carry a significant side-effect profile, particularly with regard to sexual function and incontinence rates, quite apart from the pain and hospitalization required for the procedure. It still remains unclear which tumors merit such drastic treatment. In Mr. Kerry’s case, his doctor, Patrick C. Welsh of Johns Hopkins Hospital, who has had experience with 2000 patients who were followed for a decade after surgery, indicated that the chances of Mr. Kerry having incontinence as a side effect were 3 to 4 percent. He further indicated that Mr. Kerry had a 90% chance of recovering his sexual function and that there is a 95% chance that Mr. Kerry’s cancer will be undetectable when the test is done 10 years after the operation.

Prostate tumors are graded on a scale called the Gleason score. Mr. Kerry’s score was 6, with the most aggressive tumors at the high end of the scale. Mr. Kerry has another risk factor. His father died of prostate cancer at the age of 85, 10 years after his prostate was removed. For men with prostate cancer, 13% have an affected first-degree relative, compared with 5% for a controlled population. The relative risk conferred by having an affected first-degree relative is between 2.2 and 2.7 times the population mean, The research literature suggests that men over 75 are not considered candidates for either prostatic radiotherapy or radical prostatectomy, because their actuarial life expectancy is less than 10 years. (3). In fact, some researchers suggest an upper limit of 70 for testing (4).

As far as testing is concerned, only one study has shown a decrease in the prostate cancer death rate from screening. This was the Quebec Screening Trial (8) of 46,198 men, which showed a significant fall in prostate-specific deaths, from 49/100000 to 15/100000. It would appear that much of the early benefit of screening comes from prompt initiation of hormonal treatment of men with metastatic prostate cancer (14).

Crawford et al (2) suggest that the chances of detecting prostate cancers are higher if both PSA and digital rectal examination are used. In their study, 116,073 individuals were screened with a PSA test and digital rectal examination. They found the predictive value of PSA alone, with a cut off level of 4.0 ng/ml, was 28%, for a digital rectal examination alone the predictive value was 18%, but when both were abnormal, 56% of the men had a cancer. They further determined that when they used an age-specific reference PSA level, the positive predictive value rises to 64% if both are abnormal.

It is well known that PSA values rise with age. It is why some physicians suggest that it is more advisable to use age-referenced values of PSA. Gustafsson (4), in his study of 1782 men, came up with the following age-related mean values for the PSA test: 55-59 years—5.2; 60-64 years—5.8; 65-70 years—6,7. Another research group, Oesterling et al (12), used the following criteria: 45-49 years—2.5; 50-59 years—3.5; 60-69 years—4.5; 70-79 years—6.5. The higher reference ranges in older men did not dramatically reduce the chances of discovering a potentially curable cancer.

Keep in mind that PSA test results may show intraindividual variation (7). The same person may have a different PSA result on different days. Difference in diet is thought to explain some of the heterogeneity in clinical prostate cancer incidence observed worldwide. Epidemiological data have also revealed a significant inverse relationship between ultraviolet radiation and prostate cancer mortality, suggesting that increased ultraviolet radiation and subsequent vitamin D synthesis may be associated with a reduced risk of prostate morbidity (13.) Berndt et al (1) studied this hypothesis and found "No significant association or trends…between calcium, phosphorous, vitamin D, fructose and animal protein and the risk of prostate cancer…Dairy products were not significantly associated with prostate cancer…No significant trend was found between higher milk intake and risk of prostate cancer. No difference in prostate cancer risk was observed among different types of milk (whole, low fat, and skim)". These researchers concluded that their study suggest calcium intake within moderate limits is not associated with a notably increased risk of prostate cancer. This study appeared to contradict the study by Hayes and his group that showed a high intake of dairy products to be associated with an increased risk of prostate cancer. They may not be contradictory because of the words they use in their conclusion: "moderate" and "high" intake. Too much is potentially bad, with moderate not harmful.

Research has further indicated that when the cut-off score of 4.0 ng/ml or higher is used, and clinical diagnosis of prostatitis, benign hypertrophy (BNH) are excluded, then 17-27% of the cases biopsied will be positive for carcinoma (10). Hugosson et al (6) showed that when frozen blood samples were tested for PSA in a group of 658 men, aged 67 years, sixteen years later, the risk of developing prostate cancer within 15 years of a PSA score of 3-10 was 22 percent, rising to 45%, if the PSA was >10ng/ml.

What is alarming in all this research is that prostate cancer can subsequently be detected in patients whose PSA is below 4.0ng/ml. Ito et al (7) has shown that the risk, as determined from a cohort of 8595 men over 50, who tested between 2.0 and 4.0ng/ml, was 1.2% after 3 years. This group recommended that screening in this PSA range should take place annually, and for lower values every three years. The Gustafsson study (4) estimated that chances of a 67 year old man developing cancer with an initial PSA of 3 ng/ml or less, was 3.6% during the next 15 years.

This review of the research literature is suggestive of the caution one should take in evaluating the results of PSA testing (11). Could it be that the PSA testing is including many individuals who will not develop prostate cancer in their lifetime and are subjecting themselves to a painful experience with aggressive treatment? It suggests careful collaboration with the treating physician about steps to be taken. There is a strong need for risk-cost benefit analysis.

We would recommend the following web sites for further information about PSA:

1. www.nelc.org.uk/docs/psa This site has three versions of patient information leaflets describing pros and cons of PSA screening
2. www.prostate.com This site advises "Men over the age of 50, and those men over the age of 40 who are in high risk groups such as African-American men and/or men with a family history of prostate cancer, should have a PSA blood test and digital rectal examination once every year.
3. www.cancereducation.com This site is aimed at both physicians and patients.
4. www.psa-rising.com A pro-testing patient-centered website..

1. Berndt SJ, Carter HB, Landis P, Tucker KZ. et al. Calcium intake and prostate cancer risk in long-term aging study: The Baltimore Longitudinal Study of Aging. Urology 2002; 60: 1118-1123.
2. Crawford ED, Leewansangtong S, Goktas S. et al. Efficiency of prostate-specific antigen and digital rectal examination in screening, using 4.0 ng/ml and age-specific reference range as a cut-off for abnormal values. Prostate 1999; 38(4): 296-302.
3. Dearnaley DP, Kirby RS, Kirk D, et al. Diagnosis and management of early prostate cancer, report of a British Association of Urological Surgeons working party. Br J Urol Int 1999; 83(1): 18-33.
4. Gustafsson D, Mansour E, Norming U. et al. Prostate-specific antigen (PSA), PSA density and age-adjusted PSA reference values in screening for prostate testing: a study of randomly selected population of 2400 men. Scand J Urol Nephrol 1998; 32(6): 373-377.
5. Hayes RB, Ziegler RG, Gridley G et al. Dietary factors and risk for prostate cancer among blacks and whites in the US. Cancer Epidemiol Biomarkers 1999; 80: 1107-1113.
6. Hugosson J, Aus G, Becker C. et al Would prostate cancer detected by screening with prostate-specific antigen develop into clinical cancer if left undiagnosed? A comparison of two population-based studies in Sweden. Br J Urol Int 2000; 85(9): 1078-1084.
7. Ito K, Kubota Y, Yamamoto T. et al. Long term follow-up of mass screening for prostate carcinoma in men with initial prostate specific antigen levels of 4ng/ml or less. Cancer 2001: 91(4): 744-751.
8. Labrie F, Candas B, Dupont A et al. Screening decreases prostate cancer death: first analysis of the 1988 Quebec prospective randomized controlled trial. Prostate 1999; 38(2): 83-91.
9. Lamm DL. Long-term results of intravesical therapy for superficial bladder cancer. Uro Clin North Am 1992; 19:373-580.
10. Luboldt HJ, Bex A, Swoboda A et al. The Early Detection Project Group of the German Urological Association. Early detection of prostate cancer in Germany: a study using digital rectal examination and 4.0ng/ml prostate-specific antigen as cut-off. Eur Urol 2001; 39(2): 131-137.
11. Neal DE, Leung HY, Powell PH et al. Unanswered questions in screening for prostate cancer. Eur J Cancer 2000; 26: 1316-1321.
12. Oesterling JE, Jacobson SJ, Sooner WH. The use of age specific reference ranges for serum prostate specific antigen in men 60 years old or older. J Urol 1995; 153: 1160-1163.
13. Schwartz GG, Hulka BS. Is vitamin D deficiency a risk factor for prostate cancer (hypothesis)? Anticancer Res 1990; 10: 1307-1311.
14. Whitmore WF. Localized prostate cancer: management detection issues. Lancet 1994; 343: 1263-1267.
15. Yan Y. Intraindividual variation of prostate-specific antigen measurement and implication for early detection of prostate cancer. Cancer 2001; 94(4): 776-780

Please see:
Basic Information on Prostate Cancer-Part I
Predicting Survival After Prostate Surgery-Part II
Justice Ruth Bader Ginsburg and Colon Cancer

FOR AN INFORMATIVE AND PERSONAL ARTICLE ON PRACTICAL SUGGESTIONS WHEN SELECTING A NURSING HOME SEE OUR ARTICLE "How to Select a Nursing Home"

Harold Rubin, MS, ABD, CRC, Guest Lecturer
February 14, 2003

http://www.therubins.com

To email: rehabstrat1@aol.com or rubin@brainlink.com

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