Clinical Correlates with Biopsy: Serum Prostate-Specific Antigen, Digital Rectal Examination, and Imaging Techniques

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Needle biopsies of the prostate are typically performed either because of an abnormal rectal exam or elevated serum prostate-specific antigen (PSA) level; some men are screened because of a strong family history of prostate cancer.


Asymmetry, induration, and discrete hard nodules are findings on digital rectal examination (DRE) that are suspicious for cancer. The positive predictive value of core needle biopsy of the prostate varies depending on the degree of the palpable abnormality of the prostate, with marked induration or a nodule more likely representing carcinoma than mild firmness.

The positive predictive value of an abnormal DRE is only 22% to 36%.1 A more serious limitation of DRE is its low sensitivity (i.e., missing cancer). Currently, the majority of cancers clinically detected by needle biopsy are nonpalpable (stage T1c). Although some of these tumors are small, 51% are more than 0.5 cc and located in the peripheral zone, so that one would have expected them to be palpable. Another 15% to 25% of stage T1c prostate cancers are located in the transition zone (anteriorly) where they are not palpable due to their location.2,3

There is poor interobserver reproducibility even among urologists as to what is an abnormal DRE.4


The most commonly used imaging modality for prostate cancer remains transrectal ultrasound (TRUS). The majority of prostate cancers appear on TRUS as hypoechoic relative to the normal peripheral zone, although tumors may also be hyperechoic or isoechoic. Despite initial studies claiming a great value of this test for the detection of prostate cancer, subsequent reports have noted poor sensitivity and specificity limiting its usefulness.5,6

Cancer is as likely to be found in areas that are normal by TRUS as they are to be detected in radiographically abnormal areas. Currently, the major role of TRUS is to direct the needle biopsies of the prostate in either a sextant or alternative (see Chapter 2) distribution. Another function of TRUS is to estimate the size of the prostate that can be used to calculate PSA density (see the following text). Even this role of TRUS is limited because there is not a great correlation between prostate volume estimated by TRUS and actual prostate volume.7

In part, limitations of TRUS relate to differences in the equipment used and that the exam is heavily operator dependent. Enhanced TRUS modalities include the use of ultrasound contrast agents and color and power Doppler ultrasound, which have only demonstrated incremental improvements over standard gray-scale ultrasonography.

Over the last decade, endorectal magnetic resonance imaging (MRI) and, more recently, multiparametric MRI (mpMRI) have increasingly been used in clinical staging of localized prostate cancer patients. mpMRI adds other modalities beyond the morphology provided by standard T2-weighted images. Some of the more common techniques in mpMRI include diffusion-weighted images (DWI) where the denser packing of prostate cancer relative to benign tissue restricts water diffusion. Another often performed function is dynamic contrast-enhanced (DCE) images where following injection of intravenous contrast, neoangiogenesis can be seen. Less commonly used, mpMRI spectroscopy can quantify the ratio of choline/citrate. Although mpMRI has shown the potential to improve the accuracy of clinical staging and the positive yield (sensitivity) of prostate biopsy,810 its use has yet to become a standard of care given its relatively modest sensitivity and specificity (76% and 82%, respectively) and the need for larger prospective trials. mpMRI role in prostate cancer patients eligible for active surveillance is under intense investigation.1113

Several positron emission tomography (PET) tracers are active in early-stage and late-stage prostate cancer. F18-fluorodeoxyglucose (FDG), C11/F18-choline, and sodium F18-fluoride have been studied most extensively. There is growing evidence supporting the use of choline in early-stage prostate cancer. FDG and sodium F18-fluoride are more valuable in advanced disease, especially for assessing bone metastases. Prostate-specific membrane antigen (PSMA) PET tracers are in the early stages of clinical development. Prospective clinical imaging trials are needed to establish the optimal role of PET in prostate cancer.14


PSA is synthesized in the ductal epithelium and prostatic acini. It is found in normal, hyperplastic, and malignant prostate tissue.15

PSA is secreted into the lumina of the prostatic ducts to become a component of the seminal plasma. It reaches the serum by diffusion from the luminal cells through the epithelial basement membrane and stroma where it can pass through the capillary basement membranes. PSA is a serine protease of the human glandular kallikrein family. In the seminal fluid are gel-forming proteins that function to trap spermatozoa at ejaculation. PSA functions to liquefy the coagulum and break down the seminal clot through proteolysis of the gel-forming proteins into smaller, more soluble fragments, thus releasing the spermatozoa.

Total Serum Prostate-Specific Antigen

Numerous studies have shown that patients with prostate cancer have, in general, elevated serum PSA levels relative to men without prostate cancer. The most commonly used cutoff for PSA is 4 ng/mL. When serum PSA concentrations are 4 to 10 ng/mL, the incidence of cancer detection on prostate biopsy in men with a normal DRE is approximately 25%. With serum PSA levels over 10 ng/mL, the incidence of prostate cancer on a biopsy increases to approximately 67%. However, the risk of cancer is proportional to the serum PSA level even at values below 4 ng/mL. With a serum PSA of less than 2 ng/mL, the probability of cancer is less than 2%, rising to about 18% for PSA values of 2.5 to 4.0 ng/mL. As large screening trials have demonstrated clinically significant cancers in men with serum PSA levels of 2.5 to 4.0 ng/mL, some experts have proposed lowering the PSA cutoff to 2.5 ng/mL to improve the early detection of cancer in younger men.15

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Nov 27, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Clinical Correlates with Biopsy: Serum Prostate-Specific Antigen, Digital Rectal Examination, and Imaging Techniques
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