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Dr. Catalona and Dr. Stacy Loeb at an American Urological Association (AUA) meeting.

Unlike many other malignancies, symptoms are uncommon early in the course of prostate cancer.

Instead, symptoms such as bone pain or obstructive or irritating urinary symptoms typically do not occur until the disease is advanced and/or incurable.

Accordingly, efforts are focused on detection of prostate cancer during the early, asymptomatic phase when the possibility of cure is more likely.

Currently, the primary methods used for early prostate cancer screening are the prostate-specific antigen blood test and digital rectal examination. This article explains PSA Testing.

Variations on PSA Testing

PSA testing is not just a number.

That first PSA value, hopefully a baseline test at age 40, is just the beginning of a diagnostic process.

For example, whereas prostate cancer can cause a rise in PSA, benign prostatic enlargement can also cause a PSA elevation. Thus, a given PSA level may be of more concern for possible prostate cancer if the prostate gland is small than if it is large.

To adjust for this variation, the PSA level is divided by the sonographically measured prostate volume in a calculation called PSA density.

Alternatively, the rate of change in PSA (called PSA velocity) may be used to help guide the clinical suspicion for prostate cancer.

Sanjina Shrestha, Dr. Catalona’s nurse, with a patient.

Prostate cancer is more likely to cause a rapid rise in PSA than benign prostatic hyperplasia; thus, keeping track of PSA rises can be used to suggest the condition of BPH or of prostate cancer.

A persistent increase of PSA of more than 0.35 ng/ml/year is associated with an increased risk of prostate cancer and later prostate cancer mortality; while an increase of 0.15 ng/ml/year is more characteristic of BPH).

In addition, a PSA velocity greater than 2 ng/ml/year is associated with the risk of death from prostate cancer after treatment among men who are diagnosed with the disease. However, prostatitis can also cause sudden PSA elevations so if prostatitis is suspected, a repeat PSA measurement after a course of antibiotics or after a short interval of observation may be reasonable alternatives.

Finally, PSA circulates in both free and bound forms, and a lower relative proportion of “free” PSA is associated with a greater risk of prostate cancer and more adverse tumor features.

For example, in a study of men with total PSA levels of 4 to 10 ng/ml, a cutoff of 25 percent for free PSA detected 95 percent of biopsydetectable prostate cancers while avoiding 20 percent of unnecessary prostate biopsies.

Free PSA may also be useful in men with total PSA levels less than 4ng/ml.

PSA and Recommendation for Biopsy

The Food and Drug Administration initially approved PSA for prostate cancer screening in 1994, using a threshold value of 4 ng/ml for recommending a biopsy.

More recent findings showed biopsy-detectable prostate cancer in at least 15 percent of men with normal DRE findings and a PSA less than 4 ng/ml.

Studies showed the use of lower PSA thresholds (such as 2.5 to 3 ng/ml) improved the sensitivity and reduced the likelihood of missing prostate cancers.

In addition, prostate cancers found at lower total PSA levels had more favorable pathology features and were more likely to be cured with definitive therapy.

Many urologists currently use a threshold of 2.5 ng/ml to recommend a biopsy, although the criteria for recommending prostate biopsy remains controversial because of a concern that a greater proportion of “insignificant” tumors that may not have led to clinical consequences may be detected at lower PSA levels.

Also, because the risk of prostate cancer correlates directly with the total PSA level, there is a risk of performing unnecessary prostate biopsies at lower PSA levels.

The authors strongly support a 2.5 ng/ml threshold for a prostate biopsy, along with using other diagnostic guidelines. (See article in this issue: Dr. Catalona's Position On the Life-Saving Benefits of PSA Screening)

Baseline PSA Is Good Predictor

The age to start screening is controversial because prostate cancer is much less common among men under 50 years old, but baseline PSA measurements at a young age are highly predictive of later prostate cancer development and also enable the diagnosis of prostate cancer in some patients with early aggressive disease.

Prostate cancer screening has been demonstrated to reduce the incidence of metastatic disease in the European Randomized Study of Screening for Prostate Cancer. (see article in this issue: Two Studies: ERSPC and PLCO)

Also, in the United States, during the PSA era, there has been more than a 85 percent reduction in the rate of metastatic disease at diagnosis and a 40 percent decrease in the age-adjusted prostate cancer-specific mortality rate.

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