The prostate produces PSA for several beneficial purposes, not simply as a response to cancer. This is why your doctor might not consider a PSA of 4 ng/ml to be particularly serious, depending on your age, race, and other factors. And, according to the NCCN, about 25 percent of men who have prostate cancer have a low PSA.

LEVELS

Numbers and Assays There is no single set of numbers for PSA. Different assays give different numbers and ranges. For example, Hybritech, the most commonly used assay,has a "normal" range of 0 to 4, while the Yang range is 0 to 2.5. Find out what test you are given, and sure to use the same test every time you have your PSA checked. Changing assays makes it difficult to tell if your PSA is stable.

PSA and Age   Because PSA rises with age (and with BPH), a level that would be alarming in a twenty-year-old could be normal for a sixty-year-old.

PSA and Race  PSA ranges differ by race. The normal, or safe, range for European-American men from 50 to 80 is 0 to 3.5 ng/ml. The range for African-American men is 0 to 2.0 ng/ml for men in their 40s, rising to 4.0 when they are in their 50s, 4.5 in their 60s, and 5.5 in their 70s. New England Journal of Medicine,1996; 335:304-310

TESTS

The PSA Test   The PSA blood test only screens for complex-serum PSA. That includes not just the PSA that might be produced in response to a cancer but also that which the prostate naturally produces and any that is the result of BPH. The value of routine PSA testing has been questioned, partly because of the number of false-positive results. However, a community-based survey found PSA levels to be highly accurate in predicting cancers. Journal of Urology, 1995;151:1283-1290 .

The Free-PSA (PSA II) Test   This test was developed to compare the amount of complex PSA with the amount of another form of PSA that is known to be produced by prostate cancers. (That form is called PSA or unbound PSA.) The free-PSA test may be given if a man's PSA level is elevated (that is, between 4 and 10) but his digital rectal exam shows nothing abnormal. A low level of free PSA indicates cancer, and the less free PSA there is in relation to total PSA, the more aggressive the tumor is likely to be. Urology 1997;49:379-384

The principal benefit of the test is that it can eliminate many unnecessary biopsies. The Hybritech Free-PSA test is reported to have detected 95% of prostate cancers. And those that it missed were mostly small and not life-threatening. Journal of the American Medical Association, May 20, 1998

Although it would seem to make sense to use the Free-PSA test instead of the usual one, its results can be misleading. (For example, prostatitis causes a reduction in Free-PSA.) In the end, a steady rise in PSA is still a better indicator of cancer.

• Hybritech Free-PSA test
• Free-PSA test, FAQ

THINGS THAT MAY CAUSE YOUR PSA TO RISE

Be sure to review these before you take a PSA test. An elevated reading caused by something other than cancer could cause needless anxiety.

Lab error isn't likely, but it is possible. If you have an unusually big rise in PSA, you should retest.

Infections, including prostatitis. If you have a burning feeling when urinating, and your PSA reading seems abnormally elevated, suggest to your doctor that you take antibiotics for a couple of weeks before re-testing. Be sure to stop long enough before the test to avoid having it be affected by the antibiotics (which would cause your PSA to fall).

• About prostatitis

Benign Prostatic Hyperplasia (BPH), a noncancerous growth in the prostate that may put pressure on the urethra and lead to more frequent urination.

• About BPH

Anything that might massage the prostate, such as long bike rides.

Ejaculation within the previous 48 hours. (Studies seem to be evenly split on whether or not this has an effect, so abstinence is the safest course.)

Any procedure that may stimulate the prostate, such as a TURP (transurethral resection of the prostate, a surgical treatment of benign prostatic tumors), a biopsy, a digital-rectal exam, or a cystoscopy (an examination of the urethra, prostate, bladder, and/or kidneys that involves a catheter-like instrument).

• biopsy    
• digital rectal exam    
• cystoscopy    
• TURP

Brachytherapy Men who have been seeded should not expect to have a stable PSA for the first two years and should be aware of the phenomenon called the "one-year bump." This seems to apply to both Palladium (Pd-103) and Iodine (I-125) seed treatments. This comment by Dr. Dattoli was reported on SeedPods:

PSAs are often noted to unexpectedly rise within 12-24 months and then fall back to nadir levels (typically with the aid of medications used to treat prostatitis, such as antibiotics, Ibuprofen, Hytrin, Cardura, or Flomax. Even though there is no precise explanation, reasons postulated include radiation-related tissue changes. The important thing is that patients be aware of this phenomenon and not panic if it occurs.

THINGS THAT MAY CAUSE YOUR PSA TO FALL

More things to remember when you have your PSA tested. A misleadingly low reading caused by one of these might lead to a delay in treatment. If you must take one of these medications for an extended period, you should have your PSA tested before you begin and again in six months to get an idea of how much the drug (or rest) has affected it.

Proscar (finasteride), which is used to treat BPH, and Propecia, which is the same drug but marketed for hair restoration.

• About Proscar

Drugs used for hormone blockade, notably Zoladex (goserlin), Lupron (leuprolide), Eulexin (flutamide), and Casodex (bicalutamide).

• About hormone blockade

Saw palmetto, an herb sold in drugstores and health-food shops, which some men use in hopes of treating BPH.

• About saw palmetto and BPH

PC-SPES, a mixture of herbs currently being tested as a possible treatment for prostate cancer.

• About PC-SPES

Medications used to treat prostatitis, such as antibiotics, Ibuprofen, Hytrin, Cardura, and Flomax (from the one-year bump comment, above)

PSA AFTER TREATMENT

"Safe" levels following treatment vary according to the procedure. If the PSA level rises above a certain number, the cancer is probably active again. However, lower numbers do not necessarily mean freedom from disease.

• Information about assays

After External-Beam Radiation Therapy 0.2 ng/ml or less is excellent. DeKalb Medical Center suggests that a PSA higher than 0.5 means the cancer will recur. In Prostate & Cancer, Dr. Sheldon Marks says it should be under 1.0.

After External Beam Radiation Therapy plus Brachytherapy According to Critz et al., "the definition of disease freedom for radiotherapy should be men who achieve and maintain a PSA nadir of 0.2 ng/mL or less." New England Journal of Medicine, January 2000 Others place it higher.

After Brachytherapy under 1.0, according to Brachytherapy Made Complicated, the textbook by Drs. Wallner, Blasko, and Dattoli (but see one-year bump)

After a Radical Prostatectomy theoretically 0.0, but 0.1 ng/ml is okay. According to Daniel W. Chan, Director of Clinical Chemistry at Johns Hopkins, 0.2 is the point of biological recurrence. DeKalb puts the crucial point at 0.5.

After Cryotherapy The Crittenton website seems to say that less than 0.5 ng/ml is safe. NEMC.org puts it at no higher than 0.3.

These figures may not be accurate for everyone. For example, one brachytherapist has several patients who have had a steady PSA of 2.0 for many years. Technically, they have suffered biochemical failure, yet they are alive and well more than a decade later.

PSA Velocity

A single elevated reading is not significant, but a steady rise over a series of readings is. The rate of change in PSA level, the velocity, is the key factor. A rise of more than 0.75 ng/ml over one year is cause for concern.

PSA Anxiety

Many men worry excessively about PSA levels following treatment. A slight shift upwards is likely to panic them, and the fear may end up doing more harm than the rise in PSA.

According to Dr. Susan Slovin of Memorial Sloan Kettering Cancer Center, a rising PSA does not always indicate cancer or a recurrence. Moreover, even a steady rise and a very high PSA do not necessarily mean that a man will die of prostate cancer. A recent study suggests that a rising PSA "may indicate that the body is attempting to fight cancer by producing its own antiangiogenic proteins." The authors suggest that it may even be feasible to introduce PSA into the body as part of a treatment for cancer. Journal of the National Cancer Institute 1999;91:1635-1640

One problem, according to pathologist Dr. Chan of Johns Hopkins, is that PSA tests today are ultrasensitive. "From day to day, the results could vary—it could be 0.03, or maybe even 0.05." He, too, emphasizes that biochemical recurrence does not indicate an immediate problem, adding "People need to understand that it might take months or even years before there is any clinical physical evidence." Prostate Cancer Update newsletter, Vol. V, No. 1

Salvage

If a rising PSA suggests a recurrence at some point following treatment, you should discuss possible salvage procedures with your doctors.

• Salvage (section in this guide)