3 - Abnormal Prostate-Specific Antigen or Digital Rectal Examination | Smiths General Urology, Seventeenth Edition (LANGE Clinical Medicine)

Authors: Macfarlane, Michael T.

Title: Urology, 4th Edition

> Table of Contents > Part One - Chief Presentations > Chapter 3 - Abnormal Prostate-Specific Antigen or Digital Rectal Examination

Chapter 3

Abnormal Prostate-Specific Antigen or Digital Rectal Examination

An abnormal or elevated level of prostate-specific antigen (PSA) is one of the most frequent reasons for urologic referral. PSA screening is used to detect early prostate cancer. Men between age 50 and 70 years should have a serum PSA and digital rectal examination (DRE) yearly. Men with a family history of prostate cancer should begin screening at age 40 years or younger. The normal range for PSA is up to 4.0 ng/mL (using the Tandem R assay).

Patients are often referred for urologic consultation because of some abnormality noted on routine DRE. The DRE is an important part of every physical examination and deserves special attention. Twenty-five percent of men with prostate cancer have normal PSA levels of less than 4.0 ng/mL. The combination of a DRE and serum PSA is the best screening method for early detection of prostate cancer. The primary function of the DRE in men is to detect prostate cancer. The size of the prostate noted on DRE correlates poorly with obstructive voiding symptoms and thus should not be used to screen for or rule out benign prostatic hyperplasia.

Prostate-Specific Antigen

The prostate is an exocrine gland and PSA is produced by both normal and malignant prostate cells. PSA is normally disposed of through the prostatic ducts and urethra in the semen. Normally, only small amounts of PSA diffuse back into the circulation. PSA elevations occur as a result of disruption of the normal glandular structure of the prostate that allows PSA to diffuse back into the prostatic circulation, as occurs with cancer. An elevated PSA level above 4.0 ng/mL suggests the presence of prostate cancer. However, PSA elevations are not specific for cancer. PSA can be elevated in the presence of prostatitis; with an enlarged prostate;

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or after lower urinary tract instrumentation, prostate biopsy, or surgery. Bicycling has also been shown to elevate PSA. A routine DRE, however, does not cause falsely elevated PSA values. An abnormal PSA level, in the absence of any of the preceding circumstances, warrants transrectal ultrasound-guided prostate biopsy. PSA measurement should be avoided if urinary tract infection is suspected.

Measurement of PSA has the highest positive predictive value of any test for prostate cancer. The positive predictive value for PSA of greater than 10 ng/mL is approximately 60%, and for PSA between 4.0 and 10 ng/mL it is approximately 20%. PSA sensitivity can be enhanced with age-specific normal values and PSA velocity to improve early detection. PSA specificity can be enhanced by PSA density and percent free PSA measurements. PSA specificity enhancements are generally used only after the first negative prostate biopsy to help determine the need for further prostate biopsies.

Age-Specific Prostate-Specific Antigen

The normal PSA level changes with age. Age-specific ranges for PSA follow: men up to age 50 years, 0 to 2.5 ng/mL; men aged 50 to 60 years, 0 to 3.5 ng/mL; and men older than 60 years, 0 to 4.0 ng/mL.

Prostate-Specific Antigen Velocity

The rate of increase of PSA over time is greater for men with prostate cancer than for men without. It has been observed that a PSA velocity of 0.75 ng/mL per year or higher is predictive of clinical prostate cancer. Obtaining at least three repeated PSA measurements over a minimum follow-up of 18 months has been suggested for PSA velocity determinations to be useful.

Prostate-Specific Antigen Density

PSA density (PSAD) is a measure of the serum PSA divided by the prostate volume. PSAD is an attempt to normalize the PSA value to the volume of the prostate because PSA level is roughly proportional to the volume of benign prostatic hyperplasia. Prostate volume must be measured by transrectal ultrasound. A PSAD of greater than 0.15 suggests cancer.

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Percent Free Prostate-Specific Antigen

Most serum PSA is bound to ₁-antichymotrypsin and ₂-macroglobulin, whereas the smallest portion is in the free form. Levels of free PSA are higher in men without prostate cancer, and the level of complexed PSA bound to serum proteins is greater in men with malignancy. The ratio of free PSA to total PSA is higher in men with benign histology and lower in men with prostate cancer. The cut-off point for the ratio of free PSA to total PSA (approximately 18%) may differ between assays; therefore, check the specific assay for the correct values. Percent free PSA measurement is currently only recommended in men with at least one negative biopsy and a total PSA between 4.0 and 10.0 ng/mL.

Complexed Prostate-Specific Antigen

The complexed PSA assay (Immuno-1 Bayer) measures PSA bound to ₁-antichymotrypsin, which has been demonstrated to be higher in men with malignancy. In early studies, the complexed PSA assay has shown enhanced specificity over total PSA, without loss of sensitivity.

Digital Rectal Examination

The DRE should be gently performed with a well-lubricated, gloved index finger. The patient can be in a knee-chest position on his side (lateral decubitus position) or knees, or he can bend over while standing. The finger is slowly inserted into the anus until the prostate can be palpated. The prostate gland should be palpated in a systematic manner, paying careful attention to its size, shape, and consistency. Any irregularities should be noted, particularly firm or hard areas. The normal prostate gland is the size and shape of a chestnut with a rubbery consistency similar to the cartilage at the end of the nose. It can take hundreds of prostate examinations before enough experience is gained to confidently differentiate a normal from an abnormal gland. Findings and what they suggest include the following:

Nodules nontender firm or hard nodules are highly suggestive of prostate cancer and must be biopsied.
Irregularities markedly irregular areas, especially if firm or hard, suggest prostate cancer and should be biopsied.

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Indistinct borders loss of the normal border contours, or the impression that the gland is adherent to the pelvic sidewall, suggests prostate cancer.
Tenderness marked tenderness to palpation with swelling suggests prostatitis.
Fluctuant fluctuant areas associated with tenderness should suggest acute prostatitis complicated by prostatic abscess.
Crepitus a crunchy sensation during palpation occurs in chronic prostatitis when large prostatic stones are present.

Workup

A PSA level above 4.0 ng/mL (or above age-specific levels) in the absence of infection, or an abnormal DRE suggestive of prostate cancer, warrants prostate needle biopsy. The continued importance of DRE is based on the fact that 25% of men with prostate cancer have a normal PSA level (<4.0 ng/mL). Transrectal ultrasound is only performed to enhance needle placement accuracy and has no inherent ability to distinguish between benign and malignant prostate tissue. If prostatitis is suspected as the cause of an abnormal PSA, then antibiotic therapy should be instituted for 4 to 6 weeks and the PSA retested.

A negative prostate biopsy does not rule out prostate cancer. A repeat PSA measurement should be made in 3 months and at regular intervals thereafter. If subsequent PSA levels remain high or are rising, careful consideration should be given to repeat the biopsy. The percent free PSA and PSA density can be helpful in this setting to enhance PSA specificity. Repeat biopsy should be considered when high-grade prostatic intraepithelial neoplasia is found on needle biopsy. There is a 30% to 50% risk of finding carcinoma on subsequent biopsies in the setting of high-grade prostatic intraepithelial neoplasia.