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Author: Richard Clements, MBBCh, Consultant, Department of Clinical Radiology, Royal Gwent Hospital, South Wales

Richard Clements is a member of the following medical societies: British Medical Association, Royal College of Radiologists, and Royal College of Surgeons of England

Editors: John L Haddad, MD, Clinical Associate Professor, Department of Radiology, Weill Medical College of Cornell University; Director of Body MRI, Department of Radiology, Methodist Hospital in Houston; Bernard D Coombs, MB, ChB, PhD, Consulting Staff, Department of Specialist Rehabilitation Services, Hutt Valley District Health Board, New Zealand; Bruno D Fornage, MD, Professor of Radiology and Surgical Oncology, Department of Diagnostic Radiology, Division of Diagnostic Imaging and Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center; Robert M Krasny, MD, Consulting Staff, Department of Radiology, The Angeles Clinic and Research Institute; Eugene C Lin, MD, Consulting Staff, Department of Radiology, Virginia Mason Medical Center

Author and Editor Disclosure

Synonyms and related keywords: prostate carcinoma, prostatic cancer, prostatic carcinoma, prostatic adenocarcinoma, prostatic intraepithelial neoplasia, PIN, prostate-specific antigen, PSA, digital rectal examination, DRE, comedocarcinoma

Background

Prostate cancer is an important growing health problem, presenting a challenge to urologists, radiologists, and oncologists. Prostate cancer is the most common nondermatologic cancer, yet despite this frequent occurrence, the clinical course is often unpredictable. Most prostate cancers are slow growing and do not manifest themselves during the man's lifetime; in fact, many men are found to have had incidental microscopic foci of prostate cancer at postmortem examination. Thus, many men die with prostate cancer rather than from prostate cancer; however, some prostate cancers are aggressive, with a rapidly worsening course.

At present, many men are identified as having early prostate cancer through the use of prostate-specific antigen (PSA) screening, but few indicators currently distinguish progressive prostate tumors from those that are more indolent.

The treatment of prostate cancer is controversial; different options range from early aggressive treatments, such as radical prostatectomy and radical radiotherapy, to deferred treatments (ie, treating men if and when the disease progresses and becomes symptomatic).

Pathophysiology

Approximately 95% of prostate cancers are adenocarcinomas that develop in the acini of the prostatic ducts. Other rare histopathologic types of prostate cancer occur in approximately 5% of patients; these include small cell carcinoma, mucinous carcinoma, endometrioid carcinoma (prostatic ductal carcinoma), transitional cell carcinoma, squamous cell carcinoma, basal cell carcinoma, adenoid cystic carcinoma (basaloid), signet-ring cell carcinoma, and neuroendocrine carcinoma.

Prostate cancer is frequently multifocal within the prostate; 70% of prostate cancers occur in the peripheral zone (PZ), and approximately 20% are found in the transition zone (TZ). Some authors have claimed that TZ prostate cancers are relatively nonaggressive, whereas PZ cancers are more aggressive and tend to invade the periprostatic tissues.

Contemporary biopsy strategies concentrate on the PZ and largely ignore cancer in the TZ. A study of 148 patients with TZ cancers based on radical prostatectomy specimens revealed that 80% of TZ tumors were organ confined.1 A secondary tumor was found in the PZ in 52% of cases. About 15% of the cases had capsular penetration; 2.7%, seminal vesicle invasion; and 3.4%, lymph node metastases.

Histopathologic diagnosis of prostate cancer

Disturbances of architecture, invasion, and anaplasia are the important histopathologic criteria for the diagnosis of prostate cancer. Dysplastic lesions of the prostate occur and are characterized by loss of cellular polarity, increase in nuclear size with hyperchromicity, and pleomorphism. Such dysplastic lesions are termed prostatic intraepithelial neoplasia (PIN). PIN is a histologic appearance that many pathologists consider to be a preinvasive stage of some prostate cancers and may be classified as low grade or high grade. In its most severe form, PIN is regarded as carcinoma in situ.

Grading

Various grading systems have been proposed, but the Gleason system is one of the most widely used internationally. It recognizes a primary and a secondary pattern, as well as 5 subpatterns in each. The sum of the 2 patterns is the Gleason score, which has prognostic significance. Patients with a Gleason score of 4 or less do well clinically, whereas patients with a score of 8-9 do poorly.

Staging

The prostate does not have a true capsule, but it does have an outer fibromuscular band called the capsule. Tumor spread outside the prostate may occur by means of capsular penetration, invasion of the seminal vesicles, or local extension along the neurovascular bundles. The usual sites of metastases from prostate cancer are the lymph nodes, bones, and lungs. Skeletal metastases are common in advanced prostate cancer, but hepatic metastases are uncommon.

The spread of prostate cancer to the lymph nodes involves the obturator nodes, then the common iliac and para-aortic lymph nodes. Pelvic lymph nodes are involved initially; the inguinal nodes are not involved. Metastatic spread to bone is common in patients with advanced prostate cancer; this typically occurs as osteoblastic sclerotic metastases. Occasionally, lytic metastases are seen.

The TNM (tumor, node, metastasis) staging system was revised in 1997 and is considered the international standard for prostate cancer staging and categorizes the prostate as follows2:

  • Primary tumor (T)

    • TX - Primary tumor is not assessable

    • T0 - No evidence of primary tumor

    • T1 - Clinically inapparent tumor, not palpable or visible by imaging

      • T1a - Incidental histologic finding in 5% or less of the tumor resected (tissue is obtained during transurethral resection for symptoms of outflow tract obstruction)

      • T1b - Incidental histologic finding in more than 5% of the tissue resected (tissue is obtained during transurethral resection for symptoms of outflow tract obstruction)

      • T1c - Tumor identified by needle biopsy (performed because of elevated PSA levels)

    • T2 - Tumor confined within the prostate

      • T2a - Tumor involving 1 lobe

      • T2b - Tumor involving both lobes

    • T3 - Tumor extending through the prostatic capsule

      • T3a - Extracapsular extension (unilateral or bilateral)

      • T3b - Tumor invading the seminal vesicles

    • T4 - Tumor fixed or invading adjacent structures other than the seminal vesicles, bladder neck, external sphincter, rectum, levator muscles, and/or pelvic wall

  • Regional lymph nodes (N)

    • NX - Regional lymph nodes not assessable

    • N0 - No regional lymph node metastasis

    • N1 - Regional lymph node metastasis

  • Distant metastasis (M)

    • MX - Distant metastasis is not assessable

    • M0 - No distant metastasis

    • M1 - Distant metastasis

      • M1a - Nonregional lymph node metastasis

      • M1b - Bone metastasis

      • M1c - Metastasis at other sites

The most recent version of the TNM classification system is from 2002.2

Frequency

United States

Prostate cancer is the most common nondermatologic cancer and the second most common cause of cancer-related deaths in American men. The number of prostate cancers recorded in cancer registries in the United States and the United Kingdom has increased markedly in the past 15 years. This change predominantly represents an increase in the number of cancers diagnosed rather than a real increase in the number of cancers in the population. In 2006, 234,460 new cases and 27,350 deaths were estimated to occur. It was determined that approximately 91% of these new cases would be diagnosed at local or regional stages.3

International

Incidence and mortality rates vary widely throughout the world, with the highest reported incidence in black American men. South American countries, such as Brazil, and Scandinavian countries, such as Sweden and Norway, also have high reported incidences, whereas Asian countries, such as Japan and China, report low incidences. (See also the US data above.)

Mortality/Morbidity

In a man aged 50 years, risk analysis shows that the lifetime risk of microscopic prostate cancer is approximately 42%, the risk of clinical prostate cancer is 10%, and the risk of fatal prostate cancer is 3%.

  • Mortality for prostate cancer has decreased in the United States since 1992, and it has decreased in the United Kingdom since 1995. The decrease in the United States is greater than that in the United Kingdom.
  • Maximum mortality (ie, the greatest rate of mortality) is in those aged 85 years and older.

Race

  • The incidence of prostate cancer is higher in blacks (100 cases per 100,000) than in whites (70 cases per 100,000).
  • African Caribbean and African American men are at higher risk than men in other ethnic groups.
  • The incidence is low in Hispanics and Asians.

Age

The incidence of prostate cancer increases markedly with age. In fact, the incidence is exponentially related to age.

  • With advances in the treatment of heart disease, stroke, and other malignancies, men are living longer; this change in life expectancy increases the risk of having and dying from prostate cancer.
  • Prostate cancer is rare in men younger than 50 years.
  • One half of all cases occur in men older than 75 years. Maximum mortality rate is in those aged 85 years and older.

Anatomy

McNeal et al first proposed the histologic division of the prostate into an outer PZ, a central zone (CZ), and an inner TZ.4 In the young adult prostate, approximately 5% of prostatic glandular tissue is in the TZ located on both sides of the prostatic urethra. This is the area where benign hyperplasia develops in older patients.

The TZ is separated from the PZ and CZ by the surgical capsule, in which calcified corpora amylacea may be found. The CZ is situated at the base of the prostate, and the ejaculatory ducts reach the verumontanum by passing through CZ tissue. The CZ is relatively resistant to disease processes and constitutes approximately 25% of the glandular tissue of the prostate in the young adult. The PZ constitutes 70% of the prostate and lies on the posterior and lateral aspects of the gland surrounding the TZ. Its ducts drain into the urethra distal to the verumontanum. Approximately 75% of prostate cancers occur in the ultrasonic PZ, and 25% occur in the TZ.4

Clinical Details

Clinical presentation

Patients with prostate cancer may be asymptomatic. The diagnosis is usually made when abnormal digital rectal examination (DRE) results or elevated PSA levels are further investigated. Alternatively, cancer may be detected in tissue obtained during transurethral resection to treat a urinary outflow tract obstruction. Patients may present with symptoms of advanced disease, including weight loss, lethargy, bladder outflow obstruction, and bone pain. (Men with newly diagnosed prostate cancer and PSA levels of less than 20 ng/mL are unlikely to have skeletal metastases resulting from prostate cancer.)

Rhabdomyosarcomas of the prostate and pelvis represent a childhood malignant tumor. These appear as soft-tissue masses infiltrating the bladder and prostate. As such, they have a presentation and radiologic features completely different from those of prostatic adenocarcinomas.

PSA screening

PSA is a single-chain glycoprotein with a molecular weight of 34,000 daltons. Physiologically, PSA is produced in the prostatic ductal epithelium by both abnormal and normal prostate tissue, secreted into the prostatic ducts, then concentrated in the seminal plasma. This glycoprotein acts to liquefy the seminal coagulum formed with ejaculation. In serum, PSA reaches the circulation by diffusing through the prostatic stroma.

PSA screening is currently the single best test for prostate cancer and is widely used in the diagnosis of prostate cancer, but it does not help in determining whether the detected cancer will cause clinically significant disease. Whereas PSA is an excellent marker for the follow-up of patients with established prostate cancer, some men with prostate cancer may have normal PSA levels, a moderate elevation of the PSA level (4-10 ng/mL) has a low specificity for prostate cancer, and an elevated PSA level is not specific for prostate cancer. Elevated serum PSA levels may also be associated with prostatitis, prostate infarction, PIN, prostate biopsy, transurethral resection of the prostate, and urethral catheterization.

Because of the limitations of PSA screening, there have been efforts to improve its diagnostic specificity through the use of derivative indices such as PSA density, age-related PSA levels, TZ–PSA density, PSA velocity, free PSA levels, complexed PSA (cPSA) measurements, and free-to-total PSA ratios. The free-to-total PSA ratio measures both bound and free PSA as a percentage of total PSA and is a useful additional discriminator between cancer and benign pathology, especially in patients with moderately elevated serum PSA levels (4-10 ng/mL). This ratio is also useful in determining whether a repeat biopsy is appropriate in a patient with a moderately elevated PSA level whose initial systematic biopsy results are negative. The lower the percentage of free PSA, the higher the likelihood of cancer.

An assay for cPSA is now available and primarily measures alpha1-antichymotrypsin cPSA. Some studies have shown an increased specificity with the cPSA assay for the diagnosis of prostate cancer compared with the specificity of total PSA and free-total PSA. In the future, cPSA could conceivably replace total PSA measurements.

Serum PSA levels increase with age. The traditional upper limit of reference range levels of PSA is 4 ng/mL, but age-specific PSA reference range levels devised by Oesterling et al can be used.5 Age-related PSA reference range levels are as follows:

  • Patients aged 40-49 years, 0-2.5 ng/mL

  • Patients aged 50-59 years, 0-3.5 ng/mL

  • Patients aged 60-69 years, 0-4.5 ng/mL

  • Patients aged 70-79 years, 0-6.5 ng/mL

Serum PSA levels are lowered with finasteride treatment for benign prostatic hyperplasia (BPH), and this treatment must be considered when PSA levels are assessed and before the decision to perform prostatic biopsy is made.

Risk factors for prostate cancer

Possible risk factors for prostate cancer include dietary, genetic, occupational, racial, and other factors.

High fat consumption is a possible risk factor, and diets low in animal fat and protein decrease the risk. Substances that may offer some protection include vitamin E, selenium, and lycopene from tomato-based foods. Some authors have postulated that high soya consumption may be protective because of the ingestion of plant phytoestrogens.6, 7

A family history of prostate or breast cancer is a risk factor, as is farming or exposure to radiation and cadmium. Blacks are at increased risk for prostate cancer. Neither alcohol consumption nor cigarette smoking is associated with a risk of prostate cancer.

Preferred Examination

Histopathologic evaluation is needed to diagnose prostate cancer after abnormal DRE results or elevated PSA levels are found. This evaluation is best performed with a sample obtained during biopsy guided with transrectal ultrasonography (TRUS), because the precise anatomic placement of the needle with TRUS is more accurate than digitally guided biopsy. Samples should include cores obtained during systematic biopsy, as well as those from focal ultrasonic PZ abnormalities.

Color or power Doppler ultrasonography may also be used to identify areas for biopsy under TRUS guidance. In the future, interventional magnetic resonance imaging (MRI) equipment may be used to guide needle biopsy of the prostate.

For the staging of prostate cancer, MRI is preferred to computed tomography (CT) scanning because it permits more accurate T staging. Both techniques can be used in N staging, and they have equivalent accuracy. Bone scintigraphy is used in M staging.

Limitations of Techniques

No optimal imaging technique has been developed for the demonstration of cancer within the prostate.

Currently, TRUS offers the best opportunity to demonstrate prostate cancer. It is widely available, has a relatively low cost, and provides the opportunity for precise and accurate needle biopsy of the gland. However, because many prostatic tumors are both isoechoic and multifocal, TRUS has major limitations in fully demonstrating prostate cancers. Furthermore, TRUS has low echotexture specificity because many pathologic conditions may demonstrate similar appearances as hypoechoic areas in the PZ of the prostate. For this reason, diagnostic assessment of cancer in the prostate must be made by means of the histopathologic interpretation of biopsy samples.

Current CT scanning techniques cannot demonstrate intraprostatic pathology, and signal-intensity changes in the PZ on MRI have a low specificity, as with TRUS.



Paget Disease

Other Problems to Be Considered

Hypoechoic area in prostate PZ on TRUS:

Cancer
Prostatitis
Prostatic infarct
PIN
Muscle around ejaculatory duct

Multiple sclerotic lesions within bone:

  • Developmental: Bone islands, osteopoikilosis, Voorhoeve disease (osteopathia striata), and tuberose sclerosis (or tuberous sclerosis)
  • Neoplastic: Metastases, lymphoma, osteomata, and myeloma (sclerosis may occur in as many as 3% of patients)
  • Paget disease
  • Vascular: Bone infarcts



Findings

A chest radiograph may be used in the evaluation of a patient with known prostate cancer to assess chest symptoms, weight loss, localized bone pain, or constitutional symptoms. Skeletal radiographs may show sclerotic metastases or lytic lesions with bone destruction.

Degree of Confidence

Plain radiographs of the pelvis cannot be used to demonstrate localized disease in the prostate. A radionuclide bone scan is more sensitive than a radiograph for depicting skeletal metastases: bone scans may demonstrate an area of abnormal tracer activity even if the plain radiographic findings are normal.



Findings

Arterial-phase multisection CT scanning can help differentiate between prostate PZ and prostate TZ regions, but it cannot demonstrate intraprostatic pathology; however, it may be helpful in detecting nodal involvement.

CT scan and MRI depict lymph node enlargement and have similar accuracy for the evaluation of lymph node metastases. CT scan can be used to search for lymph node metastases and to stage the primary tumor by depicting extracapsular spread in patients in whom advanced disease is suspected, particularly when radiation therapy is planned.

CT scan studies cannot depict T1 or T2 tumors accurately, but invasion of periprostatic fat or seminal vesicles by T3 tumors may be demonstrated. Evidence-based guidelines for the use of CT scanning in prostate cancer staging have been produced. CT scanning may also be used to depict soft-tissue metastases elsewhere in the body.

Degree of Confidence

Previous studies have shown that both DRE and imaging techniques cause the understaging of cancer localized within the prostate. The most accurate imaging technique for staging prostate cancer appears to be endorectal MRI, but even this may cause significant understaging in approximately 30% of prostate cancers.

Nodal staging relies on assessment of lymph node size, and neither CT scan nor MRI can demonstrate cancer within lymph nodes that are not enlarged. For the evaluation of lymph node metastases, CT scan and MRI have similar accuracy. CT cannot depict T1 or T2 tumors accurately.

Currently, the clinical prognosis of prostate cancer may be predicted by means of artificial neural networks or nomograms (eg, Partin tables), which take into account details such as the patient's age, the grade of the tumor, and the serum PSA level.

False Positives/Negatives

Because staging with CT scanning is performed by assessing the outline of the prostate, there should be little diagnostic confusion if an overt capsular breach is apparent. However, cancer is understaged by using CT scanning because the scans may fail to demonstrate microscopic spread through the prostatic capsule. This spread may be particularly difficult to assess at the apex and base of the prostate.



Findings

MRI can demonstrate the internal anatomy of the prostate and help clinicians to identify areas of altered signal intensity, which represent focal pathology in the gland. This technique provides the most complete evaluation of patients with prostate cancer because it can be used to assess primary disease in the prostate, as well as any involvement of the local lymph nodes. Although MRI is used primarily for staging, the availability of interventional MRI units means that MRI is likely to have a future role in the diagnosis of prostate cancer.

On T1-weighted images, the prostate appears homogeneous with medium signal intensity; neither the zonal anatomy nor intraprostatic pathology is displayed. However, zonal anatomy and intraprostatic pathology are depicted on T2-weighted images, in which the cancer appears as an area of low signal intensity in the hyperintense PZ. The specificity of this appearance is low.

As with TRUS, MRI cannot accurately depict cancer in the TZ. In addition, cancer assessment with MRI may be complicated by postbiopsy hemorrhage; therefore, MRI should not be performed until at least 3 weeks after biopsy.

The current role of MRI is the assessment of local extracapsular extension and invasion of the seminal vesicle. Signs of extracapsular spread include the following: irregular bulging of the prostatic outline, breach of the capsule with extracapsular spread, asymmetry of the neurovascular bundles, and loss of the rectoprostatic angle.

Contiguous areas of low signal intensity extending into the seminal vesicles from the base of the prostate are evidence of invasion of the seminal vesicle. On T2-weighted images, reduced signal intensity in the seminal vesicles may be seen after radiation therapy or prostatic biopsy.

The optimal MRI technique for the staging of prostate cancer has not been established. Endorectal MRI appears more accurate than body-coil MRI in the local staging of the primary tumor. Dynamic endorectal MRI with gadolinium enhancement may provide optimal visualization of cancer in the prostate. Magnetic resonance spectroscopy performed with citrate and choline can provide specific information regarding prostatic metabolism; these data may be useful in assessing the biologic potential of the primary tumor and the extracapsular extension of the tumor. New approaches with 3T MRI (or 3 Tesla MRI) scanners and diffusion-weighted sequences are currently under evaluation in research centers.

Gadolinium-based contrast agents (gadopentetate dimeglumine [Magnevist], gadobenate dimeglumine [MultiHance], gadodiamide [Omniscan], gadoversetamide [OptiMARK], gadoteridol [ProHance]) have recently been linked to the development of nephrogenic systemic fibrosis (NSF) or nephrogenic fibrosing dermopathy (NFD). For more information, see the eMedicine topic Nephrogenic Fibrosing Dermopathy. The disease has occurred in patients with moderate to end-stage renal disease after being given a gadolinium-based contrast agent to enhance MRI or MRA scans. As of late December 2006, the FDA had received reports of 90 such cases. Worldwide, over 200 cases have been reported, according to the FDA. NSF/NFD is a debilitating and sometimes fatal disease. Characteristics include red or dark patches on the skin; burning, itching, swelling, hardening, and tightening of the skin; yellow spots on the whites of the eyes; joint stiffness with trouble movingorstraightening the arms, hands, legs, or feet; pain deep in the hip bones or ribs; and muscle weakness. For more information, see the FDA Public Health Advisory or Medscape.

A technique to detect clinically occult lymph node metastases using "MR lymphography" with a highly lymphotropic MR contrast agent was reported in 2003.8 Intravenous lymphotropic paramagnetic nanoparticles of iron oxide, ferumoxtran-10 (Combidex; Advanced Magnetics, Cambridge, MA), were administered, and patients were examined by MRI 24 hours after contrast administration. Small lymph node metastases were identified with higher sensitivity than with conventional MRI; this potentially valuable test needs further evaluation, but the contrast agent is not widely available pending approval and licensing, respectively, in the US and Europe.

Degree of Confidence

Previous studies have shown that both DRE and imaging techniques cause the understaging of cancer localized within the prostate. The most accurate imaging technique for staging prostate cancer appears to be endorectal MRI, but even this may cause significant understaging in approximately 30% of prostate cancers.

Currently, the clinical prognosis of prostate cancer may be predicted by means of artificial neural networks or nomograms (eg, Partin tables), which take into account details such as the patient's age, the grade of the tumor, and the serum PSA level.

Nodal staging relies on assessment of lymph node size, and neither CT scan nor MRI can demonstrate cancer within lymph nodes that are not enlarged. The new technique of MR lymphography appears to be able to detect metastases in nonenlarged pelvic lymph nodes.

False Positives/Negatives

Extracapsular extension of a prostatic cancer is usually diagnosed with some certainty. A more difficult assessment is the interpretation of subtle bulges of the capsular outline. A significant number of prostatic cancers may be understaged, even when endorectal MRI is used.



Findings

TRUS plays a central role in the contemporary diagnosis of prostate cancer because it enables accurate image-guided biopsy of the gland. Patients are usually referred for TRUS because an abnormality is found during DRE or because the serum PSA level is elevated.

Imaging findings

With TRUS, the prostate is shown to be divided into an outer gland (PZ and CZ) and an inner gland (TZ). Calcification in the corpora amylacea in the surgical capsule between the outer and inner parts of the prostate is common. Particular attention should be paid to the PZ in prostate cancer diagnosis. The most frequently noted abnormality caused by prostate cancer is a hypoechoic area in the PZ. Rarely, cancer may appear as a hyperechoic area.

Both prostate cancer and prostatitis may have increased vascularity, as shown on color and power Doppler sonograms. This focal alteration in the prostatic vasculature is most commonly found in hypoechoic areas in the PZ, as depicted on gray-scale images. No cancer-specific flow pattern has been identified, and some cancers that are demonstrated clearly on gray-scale Doppler imaging show no focal hypervascularity.

Lymphoma of the prostate tends to present in younger men, and large hypoechoic masses in both the TZ and PZ have been reported.

Prostate cancers frequently demonstrate isoechoic findings. This observation is the basis for the systematic biopsy approach in which multiple cores are taken from both lobes in a standardized manner. Color and power Doppler study results have been disappointing, and they have not been significantly helpful in detecting cancers that are isoechoic on gray-scale examination.

Few reports in the published literature describe the detailed sonographic appearances of the rarer histologic variants of prostate cancer. In comedocarcinoma—the most malignant form of prostate cancer—stippled, multiple, small, hyperechoic foci within the hypoechoic area of the cancer have been reported. In one study (Terris, 1999), multiple small cysts in the prostate were identified in 2 patients with adenoid cystic carcinoma of the prostate.

Staging

TRUS may be used for local staging of prostate cancer because it can demonstrate bulges of the prostate capsular outline or overt extracapsular extension. TRUS findings have been found to be inaccurate in the staging of localized prostate cancer, but PZ tumors longer than 2.3 cm that contact the fibromuscular rim surrounding the prostate may be associated with extracapsular invasion.

TRUS-guided biopsy

The original systematic approach for biopsy included the acquisition of 6 cores: 1 core taken bilaterally from each of the prostate lobes at the base, mid-gland, and apex in a parasagittal plane (ie, a "sextant" biopsy). Current practice is to obtain an increased number of cores (ie, lateral PZ cores, mid-gland cores, or TZ cores) in addition to the standard 6 cores. A 10-core biopsy that incorporates the traditional 6 parasagittal samples plus 2 lateral samples from the right and left prostatic lobes is now a standard technique for systematic biopsy.

Systematic biopsy may be supplemented with cores obtained through hypoechoic PZ lesions. Focal areas of hypervascularity in the PZ of the isoechoic prostate, as shown on color Doppler examination, may also be targeted.

Opinions differ regarding whether TZ cores should be routinely obtained during an initial biopsy procedure or whether the samples may be obtained during repeat biopsy in a patient with an elevated PSA level after the initial systematic biopsy results are negative for malignancy.

Most TZ cancers are found by analyzing systematic biopsy cores specifically obtained from the TZ. Little attention has been paid to assessing hypoechoic areas in the TZ because of the lower frequency of cancer in the TZ and the perceived lower potential for metastatic spread of primarily TZ cancer. No specific studies in the literature report the biopsy results in focal TZ hypoechoic areas or in areas of specific focal alterations of TZ vascularity, as identified by use of color or power Doppler imaging.

Some authors describe a saturation biopsy approach in which as many as 40 cores are obtained under general anesthesia or sedation. The precise biopsy approach must be individually tailored on the basis of the patient's clinical features (eg, DRE and PSA levels).

Future perspectives

Currently, research studies are under way to investigate whether ultrasonographic contrast agents have a role in the identification of cancer in the prostate and whether by demonstrating tumor vascularity they have a role in establishing prognosis of a patient with biopsy-detected prostate cancer. The use of ultrasonographic contrast agents increases the time and cost of ultrasonography-guided prostate biopsy procedures. No marked improvement has been found in the accuracy of prostate cancer diagnosis with contrast agents. These agents remain experimental, and they have not been adopted into standard uroradiologic practice.

The impact of ultrasonographic contrast agents on radiologic practice could be considerable if future research proves that they enable the quantitative preoperative assessment of microvascular density or that they provide prognostic information in an individual patient.

Research studies are also being conducted to assess the value of elastography in the diagnosis of prostate cancer; however, the role of this technique is still unclear.

Degree of Confidence

TRUS is widely available, well tolerated by patients, and relatively inexpensive. It currently offers the best opportunity to demonstrate a prostate cancer, but because many prostatic tumors are both isoechoic and multifocal, TRUS has major limitations in fully demonstrating prostate cancers. Furthermore, TRUS has a low specificity because many pathologic conditions may appear as similarly hypoechoic areas in the PZ of the prostate. For this reason, diagnostic assessment of cancer in the prostate must be made by means of histologic interpretation of biopsy samples. TRUS provides the opportunity for accurate and comprehensive biopsy of the prostate gland while providing an imaging examination.

False Positives/Negatives

Many pathologic processes can appear as a hypoechoic area in the PZ of the prostate or as a hypervascular area on color or power Doppler sonograms. The differential diagnoses of a hypoechoic area in the PZ include prostatitis, tuberculous prostatitis, granulomatous prostatitis, PIN, and prostatic atrophy and infarction. These are accurately differentiated only by using biopsy of the focal ultrasonographic abnormality. Furthermore, because many prostate cancers are isoechoic, these can be identified only by using systematic biopsy techniques.



Findings

Radionuclide bone scanning after the injection of a technetium-99m (99mTc) tracer is the standard method for assessing potential bone metastases from prostate cancer. With diffuse bone metastases, a "superscan" may be seen; this superscan demonstrates high uptake throughout the skeleton, with poor or absent renal excretion of the tracer. Evidence-based guidelines for the use of radionuclide bone scans in patients with serum PSA levels greater than 10 ng/mL have been devised.

Positron emission tomography (PET) with fluorodeoxyglucose (FDG) may have a role in the detection of lymph node metastases from prostate cancer, particularly in patients with relapsed disease after primary treatment. Localized disease within the prostate and pelvic lymph nodes can be difficult to image because of the proximity of bladder activity. Currently, the sensitivity of FDG-PET for detection of recurrence after radical prostatectomy is less than 50%. Carbon 11 (C11)–acetate and C11-choline have shown promise as alternatives to FDG in prostate cancer, but they are still under assessment and are less readily available than FDG. Retrospective image fusion of C11-acetate PET with CT scan and MRI is technically feasible and appears to be a promising technique.

The use of immunoscintigraphy to assess prostate cancer is under investigation. This method uses radiotracer-labeled antibodies both to acid phosphatase and to PSA. Initial studies used iodine-131–labeled antiprostatic acid phosphatase antibody, and subsequent studies have used indium-111 (111In )–labeled antibody. The use of labeled anticarcinoembryonic antigen (anti-CEA) antibodies is being investigated.

The most commonly used monoclonal antibody (mAb) is capromab pendetide (ProstaScint; Cytogen, Princeton, NJ), which is 111In-labeled mAb 7E11-C5.3 (CYT-356, which recognizes an intracellular epitope of prostate-specific membrane antigen [PSMA]). This immunoscintigraphic technique is approved for the imaging of soft-tissue metastases from prostate cancer but not bone metastases. In a large review of 631 scans,9 the sensitivity and specificity of this method for lymph node metastases were 62% and 72%, respectively. The sensitivity and specificity for prostatic fossa recurrence were 49% and 71%, respectively. Two potential roles of capromab pendetide imaging may be advocated: evaluation of newly diagnosed high-grade prostate cancer before definitive treatment, and the assessment of men with rising PSA levels after definitive treatment (radiotherapy or radical surgery). Image fusion of capromab pendetide images with CT scan or MRI can provide details of prostate cancer localization andimprove the low spatial resolution of the capromab pendetide images.

Degree of Confidence

Bone scans have a high sensitivity but low specificity for metastatic prostate cancer.

FDG-PET has a reported sensitivity of approximately 50% for the detection of skeletal prostatic metastases. In general, FDG-PET has an excellent detection rate for lytic skeletal metastases, but it has a poor detection rate for sclerotic metastases. Disease that localizes within the prostate and pelvic lymph nodes can be difficult to image because of the proximity of bladder activity. The sensitivity of FDG-PET for detecting disease recurrence after radical prostatectomy is currently less than 50%. C11-acetate and C11-choline imaging have shown promise as alternatives to FDG-PET imaging in prostate cancer, but these are less readily available than FDG-PET techniques.

False Positives/Negatives

False-positive bone scan findings may be the result of increased uptake on bone scans not caused by a skeletal abnormality. Artifacts may result from the presence of tracer at the injection site, scars from recent operations, and sweat in the axillae. Physiologic variants that cause false-positive findings may include calcification of cartilage, an inferior angle of the scapula, and bladder diverticulum. Increased tracer uptake on bone scan may be demonstrated as a result of metastatic disease, joint disease, fracture, Paget disease, osteomyelitis, or surgery.



Patient education

For excellent patient education resources, visit eMedicine's Prostate Health Center and Cancer and Tumors Center. Also, see eMedicine's patient education article, Prostate Cancer.

Medical/Legal Pitfalls

  • Biopsy must be performed with prophylactic antibiotic coverage because deaths have been reported when such antibiotic coverage has not been used. Many antibiotic regimens are in use. It is the author's current practice to use both a quinolone antibiotic and specific prophylaxis against anaerobic bacteria.



Media file 1:  Axial transrectal ultrasonographic (TRUS) scan shows extensive hypoechoic area (arrows) in the right peripheral zone. Biopsy revealed prostatic adenocarcinoma.
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Media file 2:  Axial transrectal ultrasonographic (TRUS) scan shows a hypoechoic area in left peripheral zone and a small hypoechoic area in right peripheral zone (arrows). Biopsy revealed an adenocarcinoma (Gleason grade 6).
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Media file 3:  Axial transrectal sonogram in a patient with normal results during digital rectal examination and a prostate-specific antigen (PSA) level of 9 ng/mL. Image shows extensive bilateral but predominantly left-sided hypoechoic areas in the peripheral zone (arrows). Biopsy confirmed a Gleason grade 8 prostate cancer. Minor capsular irregularity is present on the left; this is consistent with a T3 tumor.
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Media file 4:  Axial transrectal ultrasonographic (TRUS) power Doppler scan in the same patient as in Image 3. The patient had normal results with digital rectal examination and a prostate-specific antigen (PSA) level of 9 ng/mL. A generalized increase in vascularity was noted in the posterior aspect of the prostate (arrows). However, this finding is not specific to the hypoechoic area in the left peripheral zone, illustrating the difficulty of using Doppler techniques in the assessment of prostate cancer.
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Media file 5:  Axial transrectal ultrasonographic (TRUS) scan in a patient with clinical benign prostatic hyperplasia (BPH) and a serum prostate-specific antigen (PSA) level of 11 ng/mL. Enlargement of the transition zone is present, but no focal abnormality is observed in the peripheral zone. Systematic 6-core biopsy revealed adenocarcinoma from both lobes of the prostate (ie, this is an isoechoic tumor in the peripheral zone of both prostatic lobes).
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Media file 6:  Sonogram shows an extensive, hypoechoic T3 tumor (arrowheads). Capsular irregularity is present, particularly on the right and posteriorly, with a suggestion of infiltration into the rectal wall (arrow).
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Media file 7:  Coronal T2-weighted magnetic resonance image (MRI) study of the prostate gland obtained by using an external coil. Low signal intensity (arrow) is seen on the left side of the prostate at the site of a biopsy-proven prostate cancer.
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Media file 8:  Endorectal magnetic resonance imaging in a patient with extensive prostate carcinoma. Image shows a bulge in the capsular outline on the right side (arrow). This is a stage T3 tumor.
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Media file 9:  Endorectal axial T2-weighted magnetic resonance imaging in a patient with a prostate-specific antigen level of 8 ng/mL and right-sided prostate cancer. Low signal intensity is demonstrated in the right peripheral zone (arrow).
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Media file 10:  Patient with biopsy-proven prostate cancer. Axial T1-weighted magnetic resonance imaging of the pelvis shows an enlarged left obturator node (arrow).
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Media file 11:  Isotope bone scans show multiple areas of increased tracer activity from metastatic prostate cancer.
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Media file 12:  Isotopic bone scans. Diffuse metastases demonstrate a superscan appearance. Note that no renal excretion of radioactive tracer is demonstrated.
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Media file 13:  Pelvic radiograph shows widespread osteoblastic sclerotic metastases from prostate cancer.
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Media file 14:  Axial computed tomography (CT) scan at the level of the kidneys shows extensive para-aortic lymphadenopathy (arrows), which result from advanced prostate cancer
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Media file 15:  Metastatic prostate cancer (arrows) involves the soft tissues at the right side of the skull base. The patient presented with right-sided cranial nerve XII palsy.
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Prostate Carcinoma excerpt

Article Last Updated: Apr 18, 2007