Материал: Advanced Imaging of the Abdomen - Jovitas Skucas

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between gray-scale and Doppler US findings and biopsy results were minimally superior to chance, and the authors concluded that sextant biopsies are still necessary (29). A number of controlled studies suggest that gray-scale US detects about half or less of prostatic cancers. One study found that endorectal gray-scale US detected less than half of 190 subsequently found cancers (30); targeted biopsies detected 57% of these cancers, with the rest detected by sextant biopsies, and the authors concluded that targeted biopsies should be accompanied by sextant biopsies. Although sensitivity and specificity obtained with US is disappointing, US has an established role in biopsy guidance and a potential future role in evaluating tumor blood supply and possibly assessing temperature distribution during some therapeutic heat applications.

Preliminary studies suggest that contrastenhanced US aids cancer detection. Using biopsy sites showing prostate cancers as a gold standard, gray-scale and Doppler US sensitivity of cancer detection increased from 38% precontrast to 65% postcontrast, but the specificity was unchanged (31). Endorectal US and color Doppler US achieved a 78% sensitivity in detecting proven prostate carcinomas (32); use of a contrast agent (Levovist) improved the sensitivity significantly to 93%. Of interest is that post-Levovist, most of the cancers appeared avascular within a strongly enhancing peripheral gland.

Most malignant tumors are associated with angiogenesis and increased blood velocity through these vessels. Although color Doppler US detects such increased velocity, small neoplasms are missed. Also, some infiltrating cancers are isovascular and isoechoic. Some studies suggest a positive correlation between tumor blood supply and Gleason score. One should keep in mind that some benign lesions also have increased flow.

Magnetic Resonance Imaging: Of all imaging modalities, MRI shows the greatest potential in detecting prostatic carcinomas. It is performed with either a body coil or, preferably, an endorectal coil. Compared to histopathological results in consecutive patients with prostate cancer, endorectal coil MRI cancer detection rate for tumors <5mm was only 5% but increased to 89% for tumors >10mm (33). MRI

using endorectal and pelvic phased-array coils detects more prostate cancers than digital rectal examination or endorectal US; predicted tumor volume obtained from MRI correlates with resected tumor volume.

On T2-weighted images a prostatic carcinoma typically is hypointense relative to the higher intensity normal peripheral zone. Nevertheless, a hypointense peripheral zone is not pathognomonic for a prostatic cancer; prostatitis, benign prostatic hyperplasia, or an infarct can have a similar appearance. A wedge shape and diffuse extension without mass in a hypointense peripheral zone suggest benignity, while a large size is associated with malignancy (34). Cancers in the central and transitional zones are difficult to identify with MRI; when large, they tend to disrupt the normal gland architecture. On gadolinium enhanced images the normal prostate enhances more in the central zone than peripheral zone; a carcinoma, on the other hand, ranges from enhancing more than the normal peripheral zone, to about the same enhancement and occasionally even less than peripheral zone and gadolinium-enhanced images do not appear reliable in MR imaging of prostatic carcinoma. Overlap also exists with hyperplasia. Dynamic contrast enhanced images may, however, provide better tumor definition by outlining tumor margins more clearly than with unenhanced images. Currently gadolinium is not routinely employed in evaluating prostatic carcinomas.

Dynamic contrast-enhanced images, on the other hand, may provide better tumor definition by outlining tumor margins more clearly than with unenhanced images. Currently gadolinium is not routinely employed in evaluating prostatic carcinomas.

1H–MR spectroscopy reveals a correlation between water T2-relaxation time and tissue citrate concentration. Endorectal 1H–MR spectroscopy detects metabolic differences between normal prostatic tissue, benign disease, and cancer, and thus potentially can differentiate benign from malignant disease. Significantly higher choline levels and significantly lower citrate levels are found in cancer tissue compared with BPH and normal tissue. Men with cancer have a significantly lower citrate-to- choline ratio than those with BPH. A present limitation in differentiating tumors is MR

spatial resolution. MR spectroscopy appears to be useful in a setting of negative biopsy and a rising PSA level. Also, with extensive postbiopsy distortion, such as hemorrhage, adding MR spectroscopic imaging to MR imaging improves prostate cancer detection rates; cancer is identified at MR spectroscopic imaging by an elevated metabolite ratio above normal.

Adding 3D proton MR spectroscopic imaging to MRI improves prostate cancer detection and localization compared to the use of MRI alone (35).

Scintigraphy: Attempts have been made to differentiate BPH and prostate cancer with 2- [18F]-fluoro-deoxy-D-glucose positron emission tomography (FDG-PET), but results are unreliable. Regions of high tumor uptake blend with radioactivity in urine and measures should be taken to eliminate the latter. Likewise, PET is not as sensitive as bone scintigraphy in detecting bone metastases. On the other hand, prostate cancers have an increased uptake of choline, which is needed for phosphatidylcholine synthesis, a cell membrane phospholipid. Positron emission tomography after IV carbon-11-choline in men with prostate cancer reveals marked tumor uptake and negligible urine radioactivity. Occasionally a positive choline scan detects a tumor in the face of a negative PET-FDG scan (36).

Radioimmunoscintigraphy using Tc-99m- labeled monoclonal antibody (CYT-351) against a membrane antigen in men with suspected prostatic malignancy shows potential in imaging both the primary site and metastatic foci.

Biopsy: Six sextant core needle biopsies represent the current standard in detecting stage T1c and T2 prostate cancer. Ultrasonography guidance using an endorectal approach and an automated biopsy gun are some of the refinements available. More extensive biopsies are obtained from sonographically detected hypoechoic regions. Combining the two techniques yields a higher positive rate than with either one alone. Using a sextant biopsy pattern, cancer detection rates appear higher if the prostate is small; a greater sampling error is probably introduced with a large prostate, and thus more samples are needed with a large gland. The positive yield of systematic sixsector biopsy decreases when the prostate gland volume is enlarged. In men with a clinical sus-

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picion of prostate cancer, a correlation exists between serum PSA level and a likelihood of obtaining a positive biopsy.

Aspiration cytology rather than core biopsy is also feasible, although aspiration cytology detects somewhat fewer cancers than a needle biopsy and appears to be an inadequate screening modality for occult carcinomas in a setting of a normal digital rectal examination and normal acid phosphatase level. An advantage of a core needle biopsy is that with sufficient carcinoma tissue in the biopsy, grading is similar to that obtained from prostatectomy tissue, because most prostatic cancers tend to be highly malignant.

Prostatic cancer detection is improved if instead of six biopsies, additional US-guided transrectal prostatic biopsies are obtained. Thus 10 instead of six biopsies increases cancer detection several percentages, with a greatest improvement found in those with a small cancer. An increased number of biopsies should be balanced, however, against an increased risk for complications.

Although some studies suggest that USguided transrectal biopsy results are similar to those obtained with finger-guided transperineal biopsy (37), most authors consider the transperineal approach to be less reliable and use it when a transrectal approach is contraindicated. Biopsy sensitivity is superior when using US guidance versus digital rectal guidance, and, in fact, often a primary use of endorectal US is in directing a biopsy needle into suspicious regions.

Instead of endorectal US, endourethral US guidance is an alternative for transperineal prostate biopsies; this approach provides biopsy guidance for those men who had a previous rectal resection.

Endorectal MR is potentially useful both to identify tumor sites and as a guide for prostatic biopsy, replacing US.

Few major but frequent minor complications are encountered after transrectal prostatic biopsy. The most common complication is persistent hematuria; infectious complications are rare. Postbiopsy hemorrhage affects MR spectroscopy by hiding metabolic peaks and this test should be performed prior to biopsy or at least a month later.

What should be suggested in a setting of an elevated PSA level or an abnormal digital rectal

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examination but negative transrectal US-guided biopsies? Several studies suggest that among this subset of men a repeat biopsy within 6 weeks to 6 months will be positive in 10% to 50%. The chance of a second biopsy being positive increases if the serum PSA level is >10 ng/mL or if premalignant changes are detected on the initial biopsy. A negative sextant biopsy thus does not exclude a tumor and is of limited prognostic value. Also, prior hormone therapy influences biopsy results; some men who undergo hormone therapy have sparse tumor cells.

Staging

Whether a cancer is confined to the prostate or extends beyond the prostatic capsule is of obvious importance because it influences whether a prostatectomy or nonsurgical therapy is considered. A cancer growing beyond the prostate most often is in the posterolateral portion of the gland. At times a sharp beak extending from the prostate at this location is identified, representing tumor penetration through the capsule. The capsule itself is not identified. A bulging prostate capsule is suggestive but not diagnostic of extension beyond the capsule.

Table 13.2 outlines the tumor, node, metastasis (TNM) clinical staging system. Although a biopsy specimen Gleason score and digital rectal examination are relatively reliable in predicting tumor stage, the initial serum PSA level has evolved to be of greatest prognostic significance. It not only correlates directly with the probability of extracapsular tumor spread, but also is a predictor of treatment failure.

Prostate-Specific Antigen Level: In some institutions prostate cancer staging consists of a digital rectal examination, measurement of serum tumor markers, and a radionuclide bone scan,with CT or MRI performed only as needed. Others do not obtain bone scans and skeletal radiography in the routine staging of prostatic carcinoma, believing that these studies are useful primarily with clinical suspicion of bone involvement or if the PSA level is elevated (bone metastases are discussed later; see Distal Spread).

Prostate volume can be calculated from US data and density of serum PSA relative to total

Table 13.2. Tumor, node, metastasis (TNM) staging (clinical) of prostate tumors

G: Gleason score

Gx Grade cannot be assessed

G1 Well-differentiated tumor (Gleason 2–4)

G2 Moderately differentiated (Gleason 5–6)

G3–4 Poorly differentiated/undifferentiated (Gleason 7–10)

Source: From the AJCC Cancer Staging Manual, 6th edition (2002), published by Springer-Verlag, New York, NY, used with permission of the American Joint Committee on Cancer (AJCC), Chicago, IL.

prostate volume or transition zone volume then obtained. The PSA density appears useful in men with prostate cancer and PSA levels of 4 to 10ng/mL. In suggesting extracapsular invasion, PSA density values calculated using the transitional zone volume appear superior to PSA den-

sities obtained from total prostate volume. The results depend on the ability to obtain accurate sonographic total prostate and transitional zone volumes.

Local Extension: Differentiation of intraprostatic tumor (pT2) from extraprostatic spread (pT3) has both prognostic and therapeutic implications, yet this differentiation is often made mostly on indirect evidence. Thus a Gleason score >7, perineural invasion, and most biopsies being positive argue for extraprostatic spread, while a low Gleason score or only one out of six positive biopsies suggest an intraprostatic tumor. A rough estimate of cancer spread can be based on the serum PSA level. In one study of men with prostate-confined tumors (pT2N0), mean total PSA was 7ng/ml, while in those with extracapsular spread (pT3pN0/N+) it was 10ng/ml (38)]; the free/total PSA ratios were not significant. A PSA level >20ng/ml has a specificity of almost 100%

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in predicting extracapsular spread. Similarly, significant differences are evident in serum PSA levels between all T stages and metastases.

Study comparisons of tumor extension should be viewed critically; some authors use microscopic capsular penetration as detected by histology as their gold standard, while others rely on macroscopic criteria. Imaging detects gross morphological changes, thus its accuracy is limited in evaluating a disease notorious for microscopic tumor spread.

Computed tomography has a relatively low accuracy in staging local tumor extension; capsule penetration is difficult to detect (Fig. 13.4). Even invasion of seminal vesicles or lymph nodes correlates poorly with subsequent postoperative staging. In general, with a newly diagnosed, untreated prostate cancer and a serum PSA level of <20ng/mL, the likelihood of an abnormal CT finding is extremely low. Most published studies were done prior to the intro-