Screening For Prostate Cancer
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Read the pamphlet text below or click here to download a PDF of this 3-fold pamphlet.

 

Most elderly men have prostate cancer— they just don’t know it.
And generally, they are better off that way. Men who are newly‐diagnosed with prostate cancer are thrust into a medical minefield—an efficient, well‐lubricated eight‐billion dollar business totally disposed to separating them from their prostate glands. A recent New England Journal of Medicine study estimates that our present system is so slanted toward treatment that 48 men receive unnecessary surgery or radiation for each individual that truly benefits.1

PSA Screening is Defensible and Correct
Some propose that the only way to end this flood of unnecessary treatment is by stopping PSA testing altogether. However, most experts believe that failing to diagnose High‐Grade disease in a timely manner shortens survival2 and degrades quality‐of‐life. Quality‐of‐life suffers because when the disease advances, hormone blockade and chemotherapy are necessary. Early diagnosis and cure can spare men from these toxic treatments.

Too Many Biopsies and Too Much Treatment
Ideally, PSA screening would detect High‐Grade disease and miss Low‐Grade disease. Unfortunately, the present system offers no selectivity. Primary care physicians generally refer to urologists at the first sign of a PSA elevation. Accordingly, 1.5 million men in the United States are biopsied annually. A positive biopsy usually leads to immediate surgery or radiation.

Primary Care Doctors to the Rescue – Providing Balanced Information
Primary care physicians can alter this landscape two ways: 1) Being more sophisticated with their method for selecting men for biopsy (see below). 2) Staying involved with their patients and counseling them about the various treatment options if the biopsy is positive (to no one’s surprise, studies show that urologists and radiation therapists are biased toward their own specialty). Up‐to‐date information about selecting treatment is concisely summarized in another brochure available from the PCRI titled, “How to Pick the Best Treatment for Prostate Cancer.

Biopsies are not Totally Benign
Over‐diagnosing Low‐Grade prostate cancer is not the only risk of doing a biopsy. Studies show that men can literally be frightened to death by the discovery of prostate cancer: During the first week after diagnosis, the risk of suicide goes up twenty‐two fold.3 Heart attacks are ten‐times more likely.4 Less dramatic risks include bleeding that is severe enough to require blood transfusion in 1‐2% of men and infections requiring hospitalization in another 1‐2%.5 Biopsies have also been reported to cause impotence.6

Estimating Cancer Risk
This brochure explains how to calculate a man’s likelihood of harboring High‐Grade prostate cancer prior to a biopsy. Once tabulated, this risk can be presented to the patient and compared and contrasted with the risk of being diagnosed with Low‐Grade prostate cancer (a condition that all too often leads to unnecessary surgery or radiation). A dialogue about the generally low malignant potential of prostate cancer, a discourse that may take place over several doctor visits, is best carried out prior to a biopsy, before the diagnosis of prostate cancer explodes into a man’s life.

Once the patient has been educated about his risks— both the risk of over‐diagnosis of Low‐Grade disease and the risk of under‐diagnosis of High‐Grade disease— the physician is partially liberated from ethical and legal concerns related to a delayed diagnosis of prostate cancer. In reality, the patient, rather than the doctor, is in a better position to weigh the pros and cons of an immediate biopsy because the diagnosis and treatment of prostate cancer is much more likely to affect quality-of‐life than survival.

PSA and Prostate Size = PSA Density

Since most PSA comes from the prostate gland, not from prostate cancer, PSA can only be termed normal or abnormal in the context of prostate size. A normal man’s PSA averages one‐tenth of the prostate volume. For example, the expected PSA for a 30cc prostate is 3, for a 50cc prostate, 5 and for a 100cc prostate is 10. Prostate volume in cubic centimeters is measured with ultrasound or MRI. Huge numbers of men with large prostates undergo unnecessary and repeated biopsy simply because their big prostates generate more PSA. A PSA is only “abnormal” when it is 50% above expected. For example: an abnormal PSA for a 30cc prostate is 4.5, a 50cc prostate, 7.5 and a 100cc prostate, 15.7

PSA is Not Perfect—Benign PSA Elevations

Infections, lab errors and recent sexual activity can all elevate PSA. Many of these vagaries can be circumvented by simply getting a second or third PSA test. With prostate cancer there is never a rush! Several tests over time, perhaps after a course of antibiotics, helps determine the “real” PSA level.

PSA Velocity

An even longer view of PSA testing is also useful. The rate of change of PSA from year to year adds additional information (ideally, using the same laboratory). A rise in PSA of more than two points within one year (confirmed by repeat testing) suggests the possibility of High‐Grade prostate cancer.8 On the other hand, a PSA rise of less than 0.4/year may simply be the slow expansion of the prostate from progressive benign prostatic hypertrophy (BPH).

Free PSA
Free PSA percentage rises as BPH worsens. Men with a PSA levels between 4 and 10, and a Free PSA over 25%, are likely to have some BPH. Unfortunately, the degree of prostate enlargement cannot be determined by Free‐PSA. The only conclusion that can be drawn is that men with a Free PSA < 10% are unlikely to have BPH. Results between 10% and 25% provide no useful information about prostate size. Be aware that Free‐PSA percentages are artificially suppressed when prostatitis is present.

Another Modifying Factor—PCA-3

PCA‐3 measures ribonucleic acid (RNA) secreted by the cancer cells into the urine following manual massage of the prostate. The amount of PCA‐3 in the urine increases in proportion to the size and grade of prostate cancer. Unlike PSA, PCA‐3 is unaffected by the size of the gland. Low amounts of PCA‐3, say less than 40, send a strong signal that significant amounts of aggressive cancer are unlikely. Levels between 40 and 80 are more consistent with Low‐Risk cancer. Levels of 80 and above may suggest aggressive cancer.9 PCA‐3 levels can vary from test to test. An average of two or three tests may be more accurate.

Cancer Risk Calculation

Additional factors such as age, race and family history also impact the risk of prostate cancer. A simple program that incorporates all these factors, including PCA‐3, can calculate the risk that a biopsy will diagnose Low‐Grade or High‐Grade disease. The calculator is accessible via a Google search: “risk of biopsy-detectable prostate cancer.”10

Imaging
After all these factors have been considered, men that are still undecided about proceeding with a biopsy can consider imaging with endorectal MRI. In the hands of an experienced radiologist using state-of‐ the‐art 3 Tesla MRI, High‐Grade cancer can be diagnosed with decent accuracy.11

Conclusion
Screening is an ongoing diagnostic and educational process. Patients desperately need better information about this unique entity called “prostate cancer” before getting a biopsy. With more accurate information, they can begin to participate and assume some of the inherent risks associated with the screening process—the larger chance of diagnosing Low‐Grade cancer and getting swept up into unnecessary and damaging treatment, and the smaller chance, that of delaying the diagnosis of a High‐Grade cancer.

 

References
1. Schröder FH, Hugosson J, et al Screening and prostate-cancer mortality in a randomized European study. N Engl J Med 360:1320, Mar 2009
2. Albertsen PC. Efficacy vs effectiveness in prostate-specific antigen screening. J Natl Cancer Inst 102:288, Mar 2010
3. Valdimarsdottir U. Completed suicides among newly diagnosed prostate cancer patients GU Can Symp Abst 104, Feb 2008
4. Fang F. Cardiovascular events among newly diagnosed prostate cancer patients GU Can Symp Abst 12, Feb 2008
5. Rodriguez LV, Terris MK. Risks and complications of transrectal ultrasound guided prostate needle biopsy: a prospective study and review of the literature J of Urol 160:2115, Dec 1998
6. Zisman A, Leibovici D, et al. The impact of prostate biopsy on patient well-being: : a prospective study of pain, anxiety and erectile dysfunction J of Urol 165:445, Feb 2001
7. Allan RW, Sanderson H, Epstein JI. Correlation Of Minute (0.5 MM or Less) Focus of Prostate Adenocarcinoma On Needle Biopsy With Radical Prostatectomy Specimen: Role of Prostate Specific Antigen Density J of Urol 170:370, Aug 2003
8. Loeb S, Kettermann A, et al. PSA doubling time versus PSA velocity to predict high-risk prostate cancer: data from the Baltimore Longitudinal Study of Aging. Eur Urol 54:1073, July 2008
9. Nakanishi H, Groskopf J, et al. PCA3 Molecular Urine Assay Correlates With Prostate Cancer Tumor Volume: Implication in Selecting Candidates for Active Surveillance, J of Urol 179:1804, May 2008
10. Nguyen CT, Yu C, et al. Performance of Prostate Cancer Prevention Trial Risk Calculator in a Contemporary Cohort Screened for Prostate Cancer and Diagnosed by Extended Prostate Biopsy, J of Urol 183:529, Feb 2010
11. Joseph T, McKenna DA, et al. Pretreatment Endorectal Magnetic Resonance Imaging and Magnetic Resonance Spectroscopic Imaging Features of Prostate Cancer as Predictors of Response to External Beam Radiotherapy, Int J Rad Onc 77:665, Mar 2009