In many ways, cancer of the prostate (CaP) is an oncologic anomaly. For most cancers, a patient in reasonably good health will almost certainly receive treatment. With CaP, however, this is not true, as many of these lesions are not clinically significant. Approximately 20% of US men will have clinical CaP during their lives, yet as many as 46% of men older than 50 years have at least microscopic cancer in their prostate glands.1 Also, the morbidity of treatment may outweigh its benefits. In Europe, it is common not to treat asymptomatic men for CaP if they are older than 70 years.

The anomalies of CaP go further. In contrast to cancer of the breast, the present consensus is that imaging has no role in screening for CaP. However, there are important applications of ultrasonography and, increasingly, MRI in the prostate. This article looks at the role of imaging in answering critical questions about CaP.

Is Cancer Present?

The chief tool for CaP screening is the serum concentration of prostate specific antigen (PSA), with a lesser role being played by digital rectal examination. However, PSA is not specific for cancer: as many as 80% of the men with an elevated serum PSA concentration do not have CaP.2 The only accepted diagnostic method is histologic examination. If a palpable abnormality is found by digital rectal examination, it is an obvious target for biopsy, but if not, where does the urologist direct the needle?

With the introduction of 5- to 7.5-MHz transducers, transrectal ultrasonography (TRUS) has attained a prominent place in the evaluation of men with possible CaP. The gland is examined in axial and sagittal views, and its volume is estimated.

Unfortunately, TRUS has several deficiencies. Only tumors in the peripheral zone can be detected reliably3 (for a summary of prostate anatomy, see related story on page 00). Also, although 60% to 70% of CaP lesions are hypoechoic, most of the remainder are isoechoic and thus invisible by TRUS.4 Moreover, hypoechogenicity is not specific for cancer. Color Doppler sonography may improve the positive predictive value, although perhaps at a cost of lower sensitivity.5 Two presentations at the American Institute of Ultrasound in Medicine (AIUM) meeting held in Orlando, Fla, in March of this year suggested that use of contrast medium improves the sensitivity and specificity of TRUS.

Another approach is under development at the Riverside Research Institute in New York, namely three-dimensional ultrasonography with spectral analysis. In retrospective studies, neural network analysis of these data for determining whether a given area of the prostate contained cancer was more accurate than conventional ultrasonography.6

The chief role of TRUS at present is in guiding biopsies. Visibly abnormal areas are sampled, and sextant biopsies are carried out. Approximately 20% of men with CaP require more than two sets of biopsies to confirm the lesion.7 This may change with the introduction of contrast agents. At the AIUM meeting, Ferdinand Frauscher, MD, of University Hospital in Innsbruck, Austria, reported a 50% reduction in the number of biopsy specimens required for diagnosis if contrast was used, producing a significant cost savings that compensated for the expense of the agent.

How Large and How Aggressive?

Once a CaP has been identified, the urologist needs to know the extent of the tumor and its degree of aggressiveness. If the tumor is not palpable (stage T1), watchful waiting may be appropriate if the tumor is well differentiated. On the other hand, in the United States, definitive local treatment (radical prostatectomy, brachytherapy, or external-beam radiation) is often indicated if the same tumor is poorly differentiated. Either radical prostatectomy or radiation is considered appropriate for a palpable tumor that appears to be confined to the prostate (stage T2), but if the tumor has penetrated the capsule (T3) or invaded adjacent organs (T4), external-beam radiation usually is the treatment of choice. Because of its morbidity, cost, and lack of benefit, local treatment for other than palliative purposes is contraindicated if metastases are documented. (The complexities of risk assessment in CaP were reviewed recently by Littrup and Bailey.8)

Nonsurgical staging of the primary tumor is unsatisfactory at present. Digital rectal examination, the traditional method, is unreliable: as many as 60% of men with stage T2 tumors by physical examination are found to have extracapsular tumor after prostatectomy. The serum PSA concentration is suggestive but not sufficient. The value of TRUS in staging CaP is controversial, as published data on the identification of extracapsular extension show an accuracy as low as 58%.

Growing Interest in MRI

Anatomy, Function, and Pathology of the Prostate

The prostate produces much of the seminal fluid. A particularly notable feature is its special metabolic machinery for the synthesis and release of citrate.
The prostate has three zones. The crescent-shaped peripheral zone contains three quarters of the secretory glands and has a high citrate concentration. It is the site of 75% of prostate cancers, almost half (40%) of which arise in the region anterior to the midline, ie, out of reach of the urologist’s finger. Neoplastic transformation leads to changes in cellular function and tissue organization, causing a decline in citrate and an increase in choline. The extent of these changes roughly parallels the degree of anaplasia of the cancer.
The transitional zone is insignificant in young men. With age, however, benign hyperplasia develops. About 20% of prostate cancers arise in the transitional zone. Finally, there is the central zone, which is the location of only 10% of prostate cancers.
There is a clear correlation between the degree of differentiation of a prostate cancer and the patient’s prognosis, so histologic grading of a tumor is critical. The standard method is that formulated by Gleason, which is based on the glandular pattern seen at low magnification. The most and second most prevalent patterns are assigned grades from 1 (well differentiated) to 5 (anaplastic). The two grades are added to produce the Gleason score, which therefore can range from 2 to 10.

There is increasing interest in MRI to stage primary CaP. The best results are obtained with a combination of endorectal and pelvic phased-array coils at high field strength (1.5T).3 Fast spin echo sequences improve the signal-to-noise ratio and reduce motion artifacts. Thin slices (3-4 mm) and small fields of view (eg, 14 cm) increase the resolution. Also recommended are analytic image correction and strict application of standardized interpretation criteria.3

A wide range of accuracy figures can be found in the literature, from 54% to 90%. With the use of appropriate parameters, however, MRI can be expected to be superior to digital rectal examination in detecting extracapsular extension.3 A study at Harvard University suggested that endorectal MRI significantly improves the detection of extracapsular extension and local invasion.9

Although gadolinium is not necessary for routine imaging of the prostate, CaP enhances more rapidly and to a greater degree than normal tissue during the first pass on fast dynamic imaging. Importantly, poorly differentiated tumors show the fastest enhancement.10 Further exploration of this technique is needed before it can be applied routinely.

MR spectroscopy may be helpful both for local staging and for noninvasive determination of the aggressiveness of a CaP. Typically, stimulated echo acquisition mode (STEAM) or point-resolved spatial selection (PRESS) is used with three-dimensional phase encoding (chemical shift imaging). The data can be fused with anatomic images. Because of their higher rate of cell proliferation and their greater cellular density, CaPs have higher than normal concentrations of choline. Also, the amount of citrate is lower than in normal tissue. There is little overlap in the range of choline:citrate ratios in cancers and the normal peripheral zone.11

The latest approach to local staging is fusion of images from MRI, SPECT, and CT into a three-dimensional image that can be rotated to view the prostate from all angles. This investigational technique is based on software written by Zhenghong Lee, PhD, assistant professor of radiology at Case Western Reserve University, Cleveland.

Are There Lymph Node Metastases?

Computed tomography is helpful in looking for metastases to the pelvic lymph nodes. Typically, a dynamic scan with a bolus injection of contrast medium is used, and nodes 1 cm or larger are considered suspect. Under these conditions, the accuracy of CT is between 70% and 94%. Some authors recommend CT-guided biopsy of all suspect nodes to confirm the diagnosis.

Routine use of CT in the patient with a newly discovered CaP is not cost-effective, however. If the tumor is stage T1 or T2 with a low Gleason score and the serum PSA concentration is <20 ng/mL, the probability of metastases is less than 1%. M. Huncharek and J. Muscat of Massachusetts General Hospital have calculated that avoiding use of CT in low-risk patients would reduce the cost of CaP management by $20 million to $50 million a year.12

A new approach to the work-up for metastases is immunoscintigraphy using indium 111-labeled monoclonal antibodies against a prostate tissue antigen. With planar imaging and SPECT, this antibody appears to identify lesions 5 mm or larger and may be helpful in high-risk patients with newly diagnosed CaP or a rising serum PSA concentration after definitive local therapy and as a means of determining whether a patient is likely to respond to salvage radiotherapy. Its role in clinical practice is still being defined.13

Are There Distant Metastases?

An almost universal site of CaP spread in advanced disease is the pelvis and lumbar spine. Before PSA, many men with CaP had bone metastases at presentation, and radiologic examination of the skeleton was routine. Today, when most CaPs present in lower stages, selective bone studies are appropriate. A common rule is to perform a skeletal survey in a patient with a serum PSA concentration >20 ng/mL and in any patient with a stage T3 or T4 primary tumor or a tumor with a Gleason score of 8 to 10.

Radionuclide scintigraphy with 99mTc diphosphonate is the method of choice. Whole-body planar imaging is used initially. Because of the low specificity, SPECT or MRI may be needed to characterize lesions, for example, to distinguish degenerative joint disease from cancer.

Imaging for Treatment Planning

A new approach to guidance for external-beam radiation therapy was described by James Wong, MD, chairman of the Department of Radiation Oncology at Morristown Memorial Hospital in Morristown, NJ, and associate clinical professor of radiology at Columbia University College of Physicians and Surgeons in New York.

“In Europe, where older patients do not receive treatment for asymptomatic prostate cancer, 85% of them are alive at 5 years,” Wong points out. “This makes it particularly important for us to minimize the toxicity of any treatment we give. The prostate is not in the same position every day: it moves depending on the amount of urine in the bladder and the amount of feces in the rectum. If you use narrow margins around a tumor, you have to give more radiation to compensate for missing the tumor some days. The alternative is to use wider margins, which means that more normal tissue in the bladder and rectum is irradiated. The result is a reduction in the patient’s quality of life.”

At Morristown Memorial Hospital, a CT scanner and linear accelerator share a treatment table in the radiation oncology suite.

“We do a CT scan before every treatment, and if there has been any change in the position of the prostate from the previous session, we adjust the radiation field to accommodate that movement,” he says.

Wong has treated approximately 30 patients in this way. Although no long-term results are available, he points out that they treat patients to a dose of 7,000 rads, which has produced excellent results with conventional radiotherapy techniques.

Growth in Brachytherapy

There is growing enthusiasm for prostate brachytherapy, use of which has grown 20% to 40% annually for the last 5 years. At Texas Prostate Brachytherapy Services in San Antonio, 1,500 patients have been treated with permanent implants of the radioisotope seeds. The medical director, Bradley Prestidge, MD, says that a two-step image-guided placement protocol is used.

“We map how many needles and seeds will be needed using axial and longitudinal ultrasound images that are reconstructed by computer into a three-dimensional image of the prostate,” he explains. “The needles and seeds are placed in a second session using the same ultrasound equipment. After seed implantation, we acquire CT scans at 3-mm intervals and fuse these images with plain radiographs of the prostate. The latter show the exact position of the seeds, whereas CT depicts the soft-tissue boundaries of the prostate, rectum, and bladder. We then generate dose-volume histograms that show us the dose being received by the prostate and the normal tissues.”


Although imaging offers much that can assist urologists in managing men with suspected or known prostate cancer, much more is needed. Thornbury and associates2 pointed out the need for functional and molecular imaging of the prostate to obtain the best results in this common disease. “Ultimately,” they noted, “new methods will need to reflect genetic aspects of prostate cancer.”

Judith Gunn Bronson, MS, is a contributing writer for Decisions in Axis Imaging News.


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