Savvas Tandeles, MD

Transrectal ultrasound provides clear images of the prostatic anatomy and accurate guidance for prostate biopsy.1 The technique has become useful for the evaluation of patients with prostatic disease, but its success depends greatly on individual operators. It is important for radiology staff to understand the correct approach to prostate scanning and biopsy procedures, as well as the indications and limitations.

The prostate is an exocrine gland composed of glandular and nonglandular tissue. The anterior fibromuscular stroma and prostatic urethra are both nonglandular elements. The inner glandular prostate consists mainly of the transition zone, which lies centrally around the urethra. The transition zone makes up around 5% of the prostate in young men but becomes progressively larger due to benign prostatic hyperplasia. The outer glandular prostate comprises the peripheral and central zones. The central zone lies posterosuperiorly, enclosing the transition zone in young adults. The peripheral zone lies posteriorly, occupying 70% of the prostate in young men.

Enlargement of the transition zone in benign prostatic hyperplasia causes the central zone to become compressed. This may not be apparent on imaging. The prostate's surgical capsule consists of compressed tissue between the hyperplastic transition zone and the surrounding peripheral zone.2

The middle lobe is part of the hyperplastic transition zone that protrudes into the urinary bladder. The prostate is surrounded by vessels, connective tissue, and fat. The seminal vesicles lie posterosuperiorly to the prostate, and the neurovascular bundles (consisting of venous plexuses with arteries and nerves) pass posterolaterally to the prostate.

Radiological assessments of the prostate subdivide this anatomy into two parts: the peripheral zone, and the central gland, which includes both the transition zone and the central zone. Transrectal ultrasound cannot distinguish between different prostate zones in young men (Figure 1).

Progressive enlargement of the transition zone causes the central gland to become hypoechoic and heterogeneous, with nodules, cysts, and calcifications. The peripheral zone appears uniformly echogenic and thin. The anterior fibromuscular stroma is hypoechoic at the anterior part of the prostate. The seminal vesicles, depending on the contained fluid, appear cyst-like or as hypoechoic formations, and they are surrounded by hyperechoic fat.1

Prostatitis predominantly affects the peripheral zone. Around 70% of adenocarcinomas also arise in this zone. Another 20% develop in the transition zone, and 10% in the central zone. Benign prostatic hyperplasia primarily affects the transition zone.

Digital rectal examination (DRE) refers to a subjective method of prostate assessment.3 The prostate gland is evaluated for asymmetry, presence of palpable nodules, and induration. DRE has a tendency to understage advanced disease, and it is not particularly useful when staging nonpalpable prostate cancer.4

Prostate tumors are graded according to their invasiveness and metastatic potential,5 most commonly with the Gleason grading system. Pathologists assign a primary grade ranging from 1 to 5 to the predominant cancer pattern in a biopsy specimen, and a secondary grade (again from 1 to 5) to the second most prevalent cancer pattern. The Gleason score equals the sum of the primary and secondary grades.

The primary Gleason grade is decisive in the differentiation of patients with the same overall Gleason score. Grade 1 shows a well-differentiated tumor, and grade 5 a poorly differentiated one. Two patients with the same Gleason score may have a different prognosis because the first patient's score of, for example, 7, was the sum of 5+2, while the second patient's was the sum of 2+5. Thus, the first patient has more poorly differentiated cells than the second patient. Well- and moderately differentiated tumors will have a Gleason score of 2 to 6, while poorly differentiated tumors score 8 to 10. Tumors with a Gleason score of 7 lie between those two groups.4 Grading errors can occur due to tissue sampling variation, tumor heterogeneity, and tumor volume.5 Large tumors tend to have increased heterogeneity.

The tumor, nodes, metastasis system (TNM) is used for tumor staging. This complex system gives a grade describing the volume of prostate cancer and whether it is organ-confined or extended beyond prostatic borders, a grade describing the presence (or not) of metastatic nodes, and a grade for the presence (or not) of metastatic disease. Transrectal ultrasound has poor accuracy for T-stage assessment (especially T4 tumors) and tumor localization.6 Local staging is designed to differentiate disease confined to the prostate (stages T1 and T2) from locally invasive disease (T3) and tumors invading adjacent tissue (T4).6

Extracapsular extension of cancer describes tumor extension beyond the prostatic capsule and into periprostatic fat, lymphatics, vessels, and seminal vesicles. It is difficult to diagnose early extracapsular extension with transrectal ultrasound. Perineural invasion is mostly a pathologic finding, and its absence does not exclude extracapsular extension.5

Prostatic intraepithelial neoplasia (PIN) describes a pathologic entity at the precancerous borderline of cellular proliferation toward cancer. Identification of high-grade PIN on biopsy indicates the need for repeat biopsy at six to 12-month intervals to detect concurrent adenocarcinoma.5 Repeat biopsy should be scheduled if an atypical small acinar proliferation is seen. Biopsy follow-up is not needed for observations of low-grade PIN.

Transrectal ultrasound has become a widespread, standard method of prostate imaging. Handheld 5 to 7-MHz transducers with biopsy needle guides provide high-resolution prostate images and enable precise localization of biopsy sites.1

Indications for transrectal ultrasound evaluation are an abnormal DRE and/or elevated prostate-specific antigen (PSA) test. The presence of obstructive and irritating urinary symptoms in aging men is another indication. The patient is placed in a right lateral decubitus position for a DRE. The patient then assumes left lateral decubitus position with bent legs. The examiner inserts the transducer in the rectum and examines the prostate carefully.

Prostate volume is determined initially by measuring width (W), length (L), and height (H) (volume = 0.52 x W x L x H). Operators perform gray-scale axial scanning from apex to base followed by gray-scale sagittal scanning from left to right. Any abnormality should be visualized in both projections.7

Color Doppler interrogation in both axial and sagittal planes completes the examination. The color window should include the entire prostate. Every suspicious gray-scale or color Doppler area should be reexamined at the image center to avoid lateral resolution loss.

Benign prostatic hyperplasia affects 8% of men by the time they reach their 40th birthday. Nearly 80% of men will eventually develop the condition. As mentioned above, the transition zone enlarges progressively with aging and compresses the peripheral and central zones. The transition zone is hypoechoic compared with the peripheral zone and demonstrates inhomogeneity, sometimes with a pattern of single or multiple nodules. Areas of calcification and small cyst formations are common (Figure 2).1

Chronic prostatitis is difficult to differentiate from benign hyperplasia or even prostate cancer on transrectal ultrasound, and it may sometimes coexist with either disease or both. Scans of patients with chronic prostatitis alone may show inhomogeneities or multiple calcifications with no acoustic shadowing. Periprostatic fat is clear, prostate margins are distinct, and color Doppler signals are unremarkable.6,7 Active phases during chronic prostatitis may show increased vascularity nonetheless.

Prostate cancer is the most commonly diagnosed malignancy in the U.S. and Western Europe, and it is the second leading cause of cancer-related death among men.7 Prostatic adenocarcinomas account for 95% of all malignant prostatic neoplasms. The remaining 5% are rare tumors.8,9

Transrectal ultrasound alone cannot detect early PIN, atypical small acinar proliferations, or early cancers. Greater diagnostic capabilities may emerge from research with ultrasound contrast agents and ultrasensitive color flow hardware for tumor microneovascularity detection.6,10

Only cancers located in the peripheral zone are visible on transrectal ultrasound examinations. Between 60% and 70% of prostate cancers appear hypoechoic (Figure 3). The differential diagnosis for a hypoechoic lesion in the peripheral zone includes atrophy, focal acute prostatitis, granulomatous prostatitis, and lymphoma.8 Up to 40% of cancers are isoechoic. Hyperechoic prostate cancers are rare. Approximately 30% of prostate cancers present as nodules, 50% as nodules with infiltrative components, and 20% merely as infiltrative.

Cancerous areas may demonstrate hypervascularity on color Doppler scanning (Figure 4). Focal hypervascularity is not specific for cancer, and not all cancers demonstrate this characteristic. Color Doppler cannot detect tumor microvasculature.

Transition zone cancers have no specific ultrasound characteristics and are found only by systematic biopsy.11 Any abnormality to prostate contours, such as a bulge or asymmetry, observed on gray-scale imaging deserves further evaluation. Periprostatic fat should always be evaluated for the presence of hypoechoic strands, which may indicate extracapsular extension, especially around neurovascular bundles (Figure 5). Seminal vesicles should be evaluated for asymmetry, soft-tissue echogenicity, and loss of normal "beak" in sagittal images.

Most prostate cancers are detected by ultrasound-guided biopsy. The superiority of transrectal ultrasound over digitally guided biopsy is well demonstrated.12 Indications for prostate biopsy are an abnormal DRE and/or serum PSA over 4 ng/mL for men older than 50, or over 2.5 ng/mL for men aged 40 to 49.7,13 Suspicious transrectal ultrasound findings should also be followed up on biopsy.

Black men and patients with a family history of prostate cancer are at higher risk of contracting the disease.1,3,7 Certain PSA characteristics can also indicate an increased likelihood of prostate cancer:

- free PSA/total PSA ratio lower than 25%;

- PSA increased by more than 0.75 to 1 ng/mL in one year; and

- PSA density higher than 0.15 ng/mL/mL. PSA density is defined as the total serum PSA level (ng/mL) divided by the volume of the prostate (in mL).

Men with some of these risk factors should have an initial biopsy, even if they are younger than 50. Older patients with few or no risk factors may choose a more conservative follow-up approach, with repeated PSA measurements and transrectal ultrasound rather than immediate biopsy.

Biopsy preparation includes discontinuation of any anticoagulative medication and an international normalized ratio count. Patients receive a second-generation oral quinolone antibiotic twice daily for three days, starting the morning before the procedure day. A low bowel enema is used to clean the rectum. Modern spring-loaded biopsy guns used for the prostate make this procedure well tolerated without local anesthesia (Figure 6).13 Because younger patients report greater discomfort, we use transrectal-guided infiltration of 2 mL of 2% lidocaine around neurovascular bundles to eliminate pain. We regularly use local anesthesia in patients younger than 55 years but only in selected patients above this age.

Biopsy protocols undergo regular reappraisal and revision. Sextant biopsy with six cores (three from each lobe at the level of apex, middle, and base) and target-only biopsy have proven insufficiently sensitive for detecting small cancers and transition zone carcinoma.14 Several extended field protocols in clinical use recommend as many as 30 core biopsies per patient.15

We use an extended field protocol with three biopsy levels: apex, middle, and base. Each level has two laterally directed peripheral zone biopsies and two biopsies in the parasagittal plane, including both peripheral and transition zones (Figure 7). The alternative would be to obtain peripheral and transition zone biopsies separately. An additional transverse level with four more biopsies is added if prostate gland volume exceeds 60 cm3. Suspicious focal peripheral zone or seminal vesicle findings are checked on additional targeted biopsies.

We do not biopsy seminal vesicles routinely. We perform transition zone biopsies regularly, though opinions on this practice differ.3,4,8,13-15 Primary transition zone cancers are rare, but advanced peripheral zone cancers often infiltrate the transition zone.

Negative results can prompt repeat tests if the initial biopsy found a high-grade PIN lesion, the patient has one or more risk factors for contracting prostatic cancer, prostate volume is greater than 50 to 60 cm3, and/ or the PSA is higher than 4 ng/mL.16,17

Transrectal ultrasound-guided biopsy is considered safe and is performed in an outpatient setting. As many as 70% of patients will experience at least one minor complication, including local pain, mild hematuria, hematospermia, and rectal bleeding.13 These complications are self-limiting and require no further treatment.

Patients are advised to stay home for two days following biopsy, to increase fluid uptake, and to abstain from alcohol for a week. Fewer than 1% of biopsies lead to severe complications. Patients suffering postbiopsy urinary retention will require Foley catheterization. Massive rectal bleeding may necessitate emergency endoscopy and coaptive coagulation, epinephrine injection, or Foley balloon tamponade.18 Any patient developing sepsis should be hospitalized and given intravenous antibiotics.

Dr. Papatheodorou is an attending radiologist, and Dr. Tandeles and Dr. Ellinas are residents, all at the Hellenic Red Cross Hospital in Athens, Greece. Assisting in the preparation of this manuscript were Fotios Takis, Irene Nikolaou, and Nikolaos Batakis.

Articles

Transrectal sonography clearly visualizes prostate anatomy

Transrectal ultrasound provides clear images of the prostatic anatomy and accurate guidance for prostate biopsy.

 The technique has become useful for the evaluation of patients with prostatic disease, but its success depends greatly on individual operators. It is important for radiology staff to understand the correct approach to prostate scanning and biopsy procedures, as well as the indications and limitations.

Enlargement of the transition zone in benign prostatic hyperplasia causes the central zone to become compressed. This may not be apparent on imaging. The prostate's surgical capsule consists of compressed tissue between the hyperplastic transition zone and the surrounding peripheral zone.

 The middle lobe is part of the hyperplastic transition zone that protrudes into the urinary bladder. The prostate is surrounded by vessels, connective tissue, and fat. The seminal vesicles lie posterosuperiorly to the prostate, and the neurovascular bundles (consisting of venous plexuses with arteries and nerves) pass posterolaterally to the prostate.

Digital rectal examination (DRE) refers to a subjective method of prostate assessment.

 The prostate gland is evaluated for asymmetry, presence of palpable nodules, and induration. DRE has a tendency to understage advanced disease, and it is not particularly useful when staging nonpalpable prostate cancer.

Prostate tumors, like all other carcinomas, are graded according to their invasiveness and metastatic potential,

 most commonly with the Gleason grading system. Pathologists assign a primary grade ranging from 1 to 5 to the predominant cancer pattern in a biopsy specimen, and a secondary grade (again from 1 to 5) to the second most prevalent cancer pattern. The Gleason score equals the sum of the primary and secondary grades.

The primary Gleason grade is decisive in the differentiation of patients with the same overall Gleason score. Grade 1 shows a well-differentiated tumor, and grade 5 a poorly differentiated one. Two patients with the same Gleason score may have a different prognosis because the first patient's score of, for example, 7, was the sum of 5+2, while the second patient's was the sum of 2+5. Thus, the first patient has more poorly differentiated cells than the second patient. Well- and moderately differentiated tumors will have a Gleason score of 2 to 6, while poorly differentiated tumors score 8 to 10. Tumors with a Gleason score of 7 lie between those two groups.4 Grading errors can occur due to tissue sampling variation, tumor heterogeneity, and tumor volume.

 Large tumors tend to have increased heterogeneity.

The tumor, nodes, metastasis system (TNM) is used for tumor staging. This complex system gives a grade describing the volume of prostate cancer and whether it is organ-confined or extended beyond prostatic borders, a grade describing the presence (or not) of metastatic nodes, and a grade for the presence (or not) of metastatic disease. Transrectal ultrasound has poor accuracy for T-stage assessment (especially T4 tumors) and tumor localization.6 Local staging is designed to differentiate disease confined to the prostate (stages T1 and T2) from locally invasive disease (T3) and tumors invading adjacent tissue (T4).

Extracapsular extension of cancer describes tumor extension beyond the prostatic capsule and into periprostatic fat, lymphatics, vessels, and seminal vesicles. It is difficult to diagnose early extracapsular extension with transrectal ultrasound. Perineural invasion is mostly a pathologic finding, and its absence does not exclude extracapsular extension.

Prostatic intraepithelial neoplasia (PIN) describes a pathologic entity at the precancerous borderline of cellular proliferation toward cancer. Identification of high-grade PIN on biopsy indicates the need for repeat biopsy at six to 12-month intervals to detect concurrent adenocarcinoma.

 Repeat biopsy should also be scheduled if an atypical small acinar proliferation is seen. Biopsy follow-up is not needed for observations of low-grade PIN.

Prostate volume is determined initially by measuring width (W), length (L), and height (H) (volume = 0.52 x W x L x H). Operators perform gray-scale axial scanning from apex to base followed by gray-scale sagittal scanning from left to right. Any abnormality should be visualized in both projections.

Benign prostatic hyperplasia affects 8% of men by the time they reach their 40th birthday. Nearly 80% of men will eventually develop benign prostatic hyperplasia. As mentioned above, the transition zone enlarges progressively with aging and compresses the peripheral and central zones. The transition zone is hypoechoic compared with the peripheral zone and demonstrates inhomogeneity, sometimes with a pattern of single or multiple nodules. Areas of calcification and small cyst formations are common (Figure 2).

Chronic prostatitis is difficult to differentiate from benign hyperplasia or even prostate cancer on transrectal ultrasound, and it may sometimes coexist with either disease or both. Scans of patients with chronic prostatitis alone may show inhomogeneities or multiple calcifications with no acoustic shadowing. Periprostatic fat is clear, prostate margins are distinct, and color Doppler signals are unremarkable.

 Active phases during chronic prostatitis may show increased vascularity nonetheless.

Prostate cancer is the most commonly diagnosed malignancy in the U.S. and Western Europe, and it is the second leading cause of cancer-related death among men.7 Prostatic adenocarcinomas account for 95% of all malignant prostatic neoplasms. The remaining 5% are rare tumors.

Transrectal ultrasound alone cannot detect early PIN, atypical small acinar proliferations, or early cancers. Greater diagnostic capabilities may emerge from intensive research with ultrasound contrast agents and ultrasensitive color flow hardware for tumor microneovascularity detection.

Only cancers located in the peripheral zone are visible on transrectal ultrasound examinations. Between 60% and 70% of prostate cancers appear hypoechoic (Figure 3). The differential diagnosis for a hypoechoic lesion in the peripheral zone includes atrophy, focal acute prostatitis, granulomatous prostatitis, and lymphoma.

 Up to 40% of cancers are isoechoic. Hyperechoic prostate cancers are rare but not unknown. Approximately 30% of prostate cancers present as nodules, 50% as nodules with infiltrative components, and 20% merely as infiltrative.

Cancerous areas may demonstrate hypervascularity on color Doppler scanning (Figure 4). Focal hypervascularity is not specific for cancer, and not all cancers demonstrate this characteristic. Color Doppler cannot, unfortunately, detect tumor microvasculature.

Transition zone cancers have no specific ultrasound characteristics and are found only by systematic biopsy.

 Any abnormality to prostate contours, such as a bulge or asymmetry, observed on gray-scale imaging deserves further evaluation. Periprostatic fat should always be evaluated for the presence of hypoechoic strands, which may indicate extracapsular extension, especially around neurovascular bundles (Figure 5). Seminal vesicles should be evaluated for asymmetry, soft-tissue echogenicity, and loss of normal "beak" in sagittal images, another possible marker of extracapsular extension.

Most prostate cancers are detected by ultrasound-guided biopsy. The superiority of transrectal ultrasound over digitally guided biopsy is well demonstrated.12 Indications for prostate biopsy are an abnormal DRE and/or serum PSA over 4 ng/mL for men older than 50, or over 2.5 ng/mL for men aged 40 to 49.

Suspicious transrectal ultrasound findings should also be followed up on biopsy.

Black men and patients with a family history of prostate cancer are at higher risk of contracting the disease.

 Certain PSA characteristics can also indicate an increased likelihood of prostate cancer:

- free PSA/total PSA ratio lower than 25%

- PSA increased by more than 0.75 to 1 ng/mL in one year

Biopsy preparation includes discontinuation of any anticoagulative medication and an international normalized ratio count. Patients receive a second-generation oral quinolone antibiotic twice daily for three days, starting the morning before the procedure day. A low bowel enema is used to clean the rectum. Modern spring-loaded biopsy guns used for the prostate make this procedure well tolerated without local anesthesia (Figure 6).

 Because younger patients report greater discomfort, we use transrectal-guided infiltration of 2 mL of 2% lidocaine around neurovascular bundles to eliminate pain. We regularly use local anesthesia in patients younger than 55 years but only in selected patients above this age.

Biopsy protocols undergo regular reappraisal and revision. Sextant biopsy with six cores (three from each lobe at the level of apex, middle, and base) and target-only biopsy have proven insufficiently sensitive for detecting small cancers and transition zone carcinoma.

 Several extended field protocols in clinical use recommend as many as 30 core biopsies per patient.

We do not biopsy seminal vesicles routinely. We perform transition zone biopsies regularly, though opinions on this practice differ.

 Primary transition zone cancers are rare, but advanced peripheral zone cancers often infiltrate the transition zone.

Negative results can prompt repeat tests if the initial biopsy found a high-grade PIN lesion, the patient has one or more risk factors for contracting prostatic cancer (as outlined above), prostate volume is greater than 50 to 60 cm3, and/or PSA is higher than 4 ng/mL.

Transrectal ultrasound-guided biopsi is considered safe, and it is performed in an outpatient setting. As many as 70% of patients will experience at least one minor complication, including local pain, mild hematuria, hematospermia, and rectal bleeding.

 These complications are self-limiting, however, and require no further treatment.

Patients are advised to stay home for two days following biopsy, to increase fluid uptake, and to abstain from alcohol for a week. Fewer than 1% of biopsies lead to severe complications. Patients suffering postbiopsy urinary retention will require Foley catheterization. Massive rectal bleeding may necessitate emergency endoscopy and coaptive coagulation, epinephrine injection, or Foley balloon tamponade.

 Any patient developing sepsis should be hospitalized and given intravenous antibiotics.

DR. PAPATHEODOROU is an attending radiologist, and DR. TANDELES and DR. ELLINAS are residents, all at the Hellenic Red Cross Hospital in Athens. Assisting in the preparation of this manuscript were FOTIOS TAKIS, IRENE NIKOLAOU, AND NIKOLAOS BATAKIS.

1. Grossfeld GD, Coakley FV. Benign prostatic hyperplasia: clinical overview and value of diagnostic imaging. Radiol Clin N Am 2000;38(1):31-47.

2. Coakley FV, Hricak H. Radiologic anatomy of the prostate gland: a clinical approach. Radiol Clin N Am 2000;38(1):15-30.

3. Partin AW, Stutzman RE. Elevated prostate-specific antigen, abnormal prostate evaluation on digital rectal examination and transrectal ultrasound and prostate biopsy. Urol Clin North Am 1998;25(4):581-589.

4. Presti CJ Jr. Prostate cancer: assessment of risk using digital rectal examination, tumor grade, prostate-specific antigen and systematic biopsy. Radiol Clin N Am 2000;38(1):49-58.

5. Iczkowski KA, Bostwick DG. Prostate biopsy interpretation. Current concepts, 1999. Urol Clin N Am 1999;26(3):435-452.

6. Yu KK, Hricak H. Imaging prostate cancer. Radiol Clin N Am 2000;38(1):59-85.

7. Littrup PJ, Bailey SE. Prostate cancer: the role of transrectal ultrasound and its impact on cancer detection and management. Radiol Clin N Am 2000;38(1):87-113.

8. Clements R. Ultrasonography of prostate cancer. Europ Radiol 2001;11(11):2119-2125.

9. Varghese SL, Grossfeld GD. The prostatic gland: malignancies other than adenocarcinomas. Radiol Clin N Am 2000;38(1):179-202.

Savvas Tandeles, MD

Articles

Transrectal sonography clearly visualizes prostate anatomy

Transrectal scans give clear view of prostate