Imaging in Prostate Carcinoma 

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. The image below depicts prostate cancer metastases on radiography.

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.

Arterial-phase, multisection CT scanning can help to differentiate between prostate PZ and prostate TZ regions, but it cannot demonstrate intraprostatic pathology. However, it may be helpful in detecting lymph node involvement.^[6]

CT and MRI scans depict lymph node enlargement and have similar accuracy for the evaluation of lymph node metastases. However, 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.

CT scanning can also be used 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. The CT scans below depict metastatic prostate cancer.

Degree of confidence

Previous studies have shown that digital rectal examination (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.

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.

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 modality can be used to provide 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.^{[7, 8, 9, 10]} Images of prostate cancer on MRI are provided below.

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 (see the image below), 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, and 3Tesla (3T) MR scanners give improved image quality on T2-weighted sequences compared with 1.5T systems.

Diffusion-weighted and contrast-enhanced imaging

Dynamic endorectal MRI with gadolinium enhancement may provide optimal visualization of cancer in the prostate. MR 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 diffusion-weighted imaging (DWI) sequences and dynamic contrast-enhanced (DCE) MRI sequences are currently under evaluation on 3T and 1.5T scanners in research centers.^[11]

DWI and DCE MRI are technically feasible in the prostate. Investigators have studied the potential of DWI with endorectal or phased array coils for the identification and staging of cancer within the prostate. Prostate cancer tissue has a higher cellular density than normal prostate PZ tissue, and this decreases the value of the apparent diffusion coefficient (ADC) on diffusion sequences when compared with normal prostate tissue.

DWI in the prostate suffers from poor spatial resolution compared with T2-weighted images but may be useful as a supplementary technique in drawing attention to areas of suspicion at 1.5T and 3T.

Contrast-enhanced MRI may be used as a complementary technique to T2 imaging; some studies have suggested that it is superior to T2-weighted MR for prostate cancer localization. Technical issues related to the use of contrast-enhanced MRI remain to be clarified and standardized.^[12]

Gadolinium-based contrast agents have been linked to the development of nephrogenic systemic fibrosis (NSF), also known as nephrogenic fibrosing dermopathy (NFD). The disease has occurred in patients with moderate to end-stage renal disease after they were given a gadolinium-based contrast agent to enhance MRI or MR angiography (MRA) scans. 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 moving or straightening the arms, hands, legs, or feet; pain deep in the hip bones or ribs; and muscle weakness.

Nodal staging

Nodal staging relies on assessment of lymph node size, and neither CT scanning nor MRI can demonstrate cancer within lymph nodes that are not enlarged. However, a technique to detect clinically occult lymph node metastases using MR lymphography with a highly lymphotropic MR contrast agent was reported.^[13] Intravenous lymphotropic paramagnetic nanoparticles of iron oxide, ferumoxtran-10 (Combidex; Advanced Magnetics, Cambridge, MA), were administered, and patients were examined using MRI 24 hours after contrast administration. Small lymph node metastases were identified with higher sensitivity than with conventional MRI.

3-D versus 2-D imaging

Rosenkrantz et al compared 3-dimensional (3-D), T2-weighted imaging sequences with conventional multiplanar, 2-D, turbo spin-echo, T2-weighted sequences for prostate cancer detection, staging, and image quality in 38 men with prostate cancer and found that 3-D, T2-weighted SPACE (sampling perfection with application optimized contrasts sequence with different flip angle evolutions) MRI provided a time saving of about 8 minutes, had similar image quality and accuracy in diagnosing tumors and extracapsular extension, and had better tumor conspicuity.

Images that were obtained with 2-D, turbo spin-echo sequences had a higher signal-to-noise ratio (SNR) for normal peripheral zones, but the SPACE images had greater tumor-to-peripheral zone contrast.^[14]

Degree of confidence

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.

Previous studies have shown that 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.

Transrectal ultrasonography (TRUS), shown in the images below, 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.^[15]

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.

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.

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.

Prostate cancer and prostatitis each 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 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, multiple small cysts in the prostate were identified in 2 patients with adenoid cystic carcinoma of the prostate.^[16]

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 2.3cm that contact the fibromuscular rim surrounding the prostate may be associated with extracapsular invasion.

TRUS-guided biopsy

The original systematic approach to biopsy included the acquisition of 6 cores, with 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, midgland 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.^{[17, 18, 19, 14]}

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.

However, 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.

Nonetheless, 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.^[20]

In other research, Onik et al found that 3-D prostate mapping biopsy (3-D–PMB; carried out transperineally using a brachytherapy grid under TRUS guidance) can safely and accurately stage prostate cancer patients. The investigators compared 3-D–PMB with traditional TRUS biopsy in 180 patients with unilateral prostate cancer on TRUS biopsy. A median of 50 cores were obtained with 3-D–PMB. In 110 patients (61.1%), biopsies were positive bilaterally, and in 41 patients (22.7%), Gleason scores were increased to 7 or higher.^[18]

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 10ng/mL have been devised.^{[21, 22, 23, 24, 25, 26, 27]}

Bone scans have a high sensitivity but low specificity for metastatic prostate cancer. Isotopic bone scans revealing metastatic prostate cancer are shown below.

Positron emission tomography (PET) scanning 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 (¹¹ C) acetate and ¹¹ C 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 of¹¹ C-acetate PET scanning with CT scanning 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 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 is indium-111 (¹¹¹ 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 imaging soft-tissue metastases from prostate cancer but not for bone metastases.

Degree of confidence

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%.¹¹ C-acetate and¹¹ C-choline imaging have shown promise as alternatives to FDG-PET imaging in prostate cancer, but these are less readily available than FDG-PET techniques.

In a review of 631 scans,^[28] the sensitivity and specificity of capromab pendetide for lymph node metastases were 62% and 72%, respectively; for prostatic fossa recurrence, they were 49% and 71%, respectively. Two roles of capromab pendetide imaging may be advocated: evaluation of newly diagnosed high-grade prostate cancer before definitive treatment and assessment of men with rising PSA levels after definitive treatment (radiotherapy or radical surgery). The fusion of capromab pendetide images with CT or MRI scans can provide details of prostate cancer localization and improve the low spatial resolution of the capromab pendetide images.

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.