Radiography
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.
Computed Tomography
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.
Magnetic Resonance Imaging
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.
Ultrasonography
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.
Nuclear Imaging
Findings
Radionuclide bone scanning after the injection of a technetium-99m (99m Tc) 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 (111 In )–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 is111 In-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.
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Further Reading
Keywords
prostate carcinoma, prostatic cancer, prostatic carcinoma, prostatic adenocarcinoma, prostatic intraepithelial neoplasia, PIN, prostate-specific antigen, PSA, digital rectal examination, DRE, comedocarcinoma
