Should ultrasound criteria of the prostate be redefined to better evaluate when and where to biopsy.

During the past 10 years, it has been suggested, and accepted by some, that transrectal ultrasound (TRUS) of the prostate should be used to identify a hypoechoic lesion or, if needed, guide biopsy into nonspecific areas. Retrospectively, the authors attempted to evaluate the need to identify areas that were on pathologic analysis, prostate cancer, but were not hypoechoic, but would require random/systematic biopsy to exclude prostate cancer. Six-hundred fifteen consecutive men were referred to the authors because of a concern found on digital rectal examination or because of increase in prostate-specific antigen. All patients underwent TRUS-guided biopsy of the prostate using either the four-quadrant or sextant biopsy technique. Each area undergoing biopsy was characterized as: 1) normal-appearing; 2) hypoechoic; 3) mixed echogenic (containing both hypoechoic and hyperechoic elements); 4) subtly hyperechoic (containing no calculi); or 5) isoechoic (lesion was seen because of distortion of the normal architecture). A diagnosis of carcinoma was made in 197 patients (32%). Of these, 99 (50.2%) patients had a hypoechoic lesion as the primary site, corresponding to their highest Gleason grade. Twenty-five (12.7%) had mixed echogenicity, nine (4.6%) had hyperechoic foci, and 23 (11.7%) had isoechoic biopsy-proven foci of prostate cancer. Forty-one (20.8%) patients with adenocarcinoma had normal ultrasound findings. The median Gleason grade for cancer in visible mixed echogenic and hyperechoic areas were generally higher than that for cancer in hypoechoic sites. Hypoechoic cancer sites had a Gleason grade range of 2 to 10 (median 5); mixed echogenic foci had a Gleason range of 2 to 10 (median 6); hyperechogenic cancers had a Gleason range of 2 to 8 (median 6); isoechoic cancers had a Gleason range of 2 to 7 (median 5); normal foci had a Gleason range of 2 to 8 (median 5). Results of this study suggest that 50% of clinically significant prostate cancers are not purely hypoechoic, and 37% of all diagnosed cancers contain no hypoechoic elements.

Should prostate-specific antigen or prostate-specific antigen density be used as the determining factor when deciding which prostates should undergo biopsy during prostate ultrasound.

Prostate ultrasound has been accepted as the appropriate tool for prostate biopsy guidance to determine the presence of prostate cancer if the prostate-specific antigen (PSA) level is not normal. Prostate-specific antigen density (PSAD) has been used to determine if an increased PSA level may be because of benign enlargement of the gland or possible presence of cancer. The specific "cutoff" for PSA and PSAD to delineate which patients are at highest risk has been controversial. We attempted to assess which PSA level or PSAD level should be used. A retrospective analysis of 600 consecutive men, referred for prostate ultrasound and possible biopsy because of an abnormal DRE result or increased PSA level was undertaken. All had prostate volume determined by biplanar endorectal ultrasound. One hundred sixty-six men had cancer confirmed by biopsy. This latter group was further analyzed and was divided into PSA <4.0, PSA 4 to 10, or PSA >10.0 ng/ml. Groups were divided according to those with PSAD <0.10, <0.12, and <0.15 ng/ml. Correlation with Gleason grade of the tumor was made. Of the 166 men with cancer, 15 had PSA levels <4 ng/ml (all palpable), and 81 had PSA levels between 4.0 and 10.0 ng/ml (48 were not palpable by digital rectal examination [DRE]). There were 38 (22.8%) of 166 men with cancer who had a PSAD <0.15. Using the Gleason scoring system, 30 of 38 men had mid-grade or high-grade cancers. Twenty-one (12.6%) of 166 men with cancer had a PSAD <0.12. Of these, 17 of 21 men had mid-grade or high-grade cancers. Fifteen (9.0%) of 166 men with cancer had a PSAD <0.10. Of these, 13 of 15 had mid-grade or high-grade cancer. If the PSA level is more than 4.0 ng/ml, even if no palpable lesion is discerned by DRE, suspicion for the presence of cancer should be raised. The use of PSAD threshold of 0.15 is not inclusive enough to identify clinically important cancer, and it should not be used. Our data demonstrate that 7.9% of men with cancer had a PSAD <0.15 and mid-grade or high-grade, i.e., clinically important, cancer. Although more negative biopsy results will be obtained, we recommend the use of a lower PSAD "cutoff" than the literature has suggested. We recommend that those men with PSA levels more than 4 ng/ml and a PSAD higher than 0.10 should undergo a prostate biopsy to detect clinically important cancer.

Efficacy of including the transition zone in routine biopsies of the prostate in men at high risk.

Prostate cancer originates in the outer gland in 80% of patients and in the transition zone (TZ) in 20%. Transition zone lesions have historically been the most difficult to identify. There have been discrepancies regarding the importance of routinely performing biopsies of the inner gland when performing biopsies of the outer gland. To determine how often TZ tumors were diagnosed as the sole area of cancer, and to determine how frequently TZ tumors contained higher-grade cancer than the outer gland, we attempted to assess the value of including the TZ in routine biopsies of the prostate when no lesions are seen by gray-scale ultrasound (US). A retrospective review of 619 consecutive ultrasound-guided biopsies divided the subjects into: 1) directed biopsies of specific US-identified lesions (N = 140); 2) directed biopsies of specific US-identified lesions and quadrants (N = 165) or sextants (N = 174), including the TZ; and 3) quadrant (N = 46) or sextant (N = 93) biopsies without a focal US-identified lesion. Overall, 185 patients (29.9%) with cancer were identified. Of these, 21.4% (N = 30) of men with US-identified, focal lesion biopsies alone had cancer. Of those men with cancer, 35.8% (N = 59) with US-identified lesions and quadrant biopsies had cancer; 37.4% (N = 65) of those with focal lesions and sextant biopsies had cancer; 23.9% (N = 11) of men without focal lesions but quadrant biopsies had cancer; 21.5% (N = 20) of men without focal lesions but with sextant biopsies had cancer. A total of 267 sextant biopsies were performed: 3.0% (N = 8) of these patients were found to have cancer in the TZ alone without involvement of the outer gland; 12.4% (N = 33) had TZ and outer gland cancers, of which 18.2% (N = 6) had a higher Gleason grade cancer in the TZ than in the outer gland. Routine sextant biopsies in lieu of quadrant biopsies, including the TZ, for men with or without focal lesions will yield a small increase in the number of prostate cancers diagnosed or may identify a higher grade of cancer than would be expected from using quadrant biopsies alone.

Color Doppler imaging of the prostate: important adjunct to endorectal ultrasound of the prostate in the diagnosis of prostate cancer.

The purpose of this article is to evaluate color Doppler imaging (CDI) as an adjunctive tool to gray-scale ultrasound (US) in the diagnosis of prostate cancer and to correlate CDI-positive lesions to cancer grade. We retrospectively analyzed 619 consecutive patients who underwent prostate US, CDI, and biopsy because of abnormal digital rectal examination results or prostate-specific antigen levels. All had directed (into a specific lesion) biopsies or directed biopsies along with systematic four-quadrant or sextant biopsies, or systematic biopsy alone. Color Doppler imaging was compared with gray-scale findings and histologic results. There were 222 (35.9%) biopsy-proven cancers (n = 197) or prostatic intraepithelial neoplasia (n = 25). Of these, 106 (47.7%) had color-flow abnormalities. Of these 106 patients, 26 (24.5%), or 11.7% of all cancer patients, had relatively normal gray-scale US findings but had focal CDI abnormalities as the method of identification. Overall, 76.9% of these were moderate to high Gleason grades and were considered clinically significant lesions. Color Doppler imaging can identify a large number (11.7%) of clinically significant prostate cancers that are poorly seen by gray-scale US. Positive lesions on CDI are of clinical importance because 76.9% are histologically, moderately, or poorly differentiated. We recommend that CDI be used in all diagnostic and biopsy-guided US examinations of the prostate.

Visual inspection of the prostate biopsy specimen: aid to diagnosis and management.

The purpose of this article is to assess if the visual inspection of the prostate biopsy specimen can be used as a guide when deciding whether to attempt to sample another core of tissue from the same area if a less than adequate specimen was obtained during the first attempt. Five hundred thirty-seven specimens from 84 patients, referred because of an increased prostate-specific antigen (PSA) level and/or a suspicious result on digital rectal examination (DRE), were sampled and prospectively graded based on the lack of formation and amount of liquid in the specimen (grade I) compared to a highly rigid, solid core (grade V). Specimens were then fixed in formalin and retrospectively compared, and the pathologic diagnosis was compared with the subjective visual grade assigned to the specimen. Receiver-operator curve techniques were used to quantify the results and to test for statistical significance. Rigid biopsy specimens were cancer, and liquid, formless specimens were benign. Most biopsy specimens were solid, with moderate consistency, and could not be diagnosed accurately by visual inspection. Diagnosis of prostate cancer, despite the use of PSA, DRE, or diagnostic endorectal ultrasound, requires biopsy for definitive confirmation. Although the use of spring-loaded biopsy needles routinely yields good-quality cores of tissue for pathologic analysis, there are many occasions when a less than optimal specimen is obtained. The question of whether a repeat biopsy in that region is indicated always arises. These data suggest that if the initial specimen is grade I or II, repeat biopsy is probably not indicated. If the initial specimen is grade IV or V, repeat biopsy is recommended.

The prognostic significance of proliferation-associated nucleolar protein p120 expression in prostate adenocarcinoma: a comparison with cyclins A and B1, Ki-67, proliferating cell nuclear antigen, and p34cdc2.

BACKGROUND: In this study, the authors evaluated the prognostic significance of the expression of nucleolar antigen p120, along with other cell proliferation-associated proteins, in prostate adenocarcinomas (PACs) and compared the results with previously reported data on p34cdc2 cyclin-dependent kinase (p34 cdk). METHODS: Archival sections from 132 PACs were immunostained with monoclonal antibodies against p120, cyclin A, cyclin B1, Ki-67, and proliferating cell nuclear antigen (PCNA). The DNA content of each tumor was determined by the Feulgen method using image analysis. The immunohistochemistry (IHC) results were correlated with tumor grade, stage, margin positivity, metastasis, ploidy, and postsurgical disease recurrence. RESULTS: The overall positivity for the various proteins follows: p120, 36%; cyclin A, 35%; cyclin B1, 43%; Ki-67, 46%; and PCNA, 32%. p120 correlated with grade (P = 0.004), stage (P = 0.01), ploidy (P = 0.02), margin positivity (P = 0.03), and metastasis (P = 0.004). Cyclin B1 correlated with ploidy (P = 0.04) and grade (P = 0.05), Ki-67 with grade (P = 0.02) and margins (P = 0.03), and PCNA with grade (P = 0.01). Significant coexpression among these proteins was noted, as was a significant association between the expression of these markers and that previously reported for p34 cdk. In univariate analysis, p120 (P = 0.01), cyclin A (P = 0.01) and p34 cdk (P = 0.002) correlated with disease recurrence. In multivariate analysis of all these proteins, only p34 cdk independently predicted postsurgical recurrence (P = 0.05). CONCLUSIONS: Nucleolar antigen p120 expression appears to be an additional marker of aggressiveness in PACs. The significant coexpression of the various cell cycle regulatory proteins support their collective role in tumor cell proliferation, with p34 cdk positivity being an independent predictor of postsurgical recurrence.

Needle biopsy DNA ploidy status predicts grade shifting in prostate cancer.

DNA ploidy analysis of prostate needle biopsy specimens was performed to determine whether ploidy status could predict tumor grade shifting at radical prostatectomy. The paired needle biopsy and radical prostatectomy specimens from 111 randomly selected men with prostate cancer were obtained from the surgical pathology files of the Albany Medical Center Hospital. The original tumor grades were assigned by a staff of 12 surgical pathologists according to the Gleason system. Tumors with original Gleason scores < or = 6 were classified as low grade, and tumors with scores of > or = 7 were considered high grade. DNA ploidy analysis was performed on the needle biopsy specimens using the CAS 200 image analyzer (Becton Dickinson Immunocytometry Systems, Mountain View, CA, USA) on Feulgen stained 5-microm tissue sections. There were 88 diploid and 23 nondiploid cases. Thirty-eight of 111 (34%) of cases had grade shifting from needle biopsy to radical prostatectomy specimens. Of 89 low-grade needle biopsy cases, 28 (31%) were upgraded at radical prostatectomy. Of 22 high-grade needle biopsy cases, 10 (45%) were downgraded to low grade at radical prostatectomy. Of the 28 low-grade needle biopsy specimens that were upgraded at radical prostatectomy, 19 (68%) featured an aneuploid histogram and 9 (32%) were diploid. Nineteen of 28 (68%) of aneuploid low-grade tumors on needle biopsy became high-grade at radical prostatectomy. Nine of 10 (90%) diploid high-grade tumors at needle biopsy became low-grade at radical prostatectomy. Of the 38 cases in which ploidy and grade were incongruous, 28 (74%) had grade shifting. In a multivariate regression analysis, a high-grade Gleason score on radical prostatectomy specimens correlated significantly with needle biopsy ploidy (p = 0.0001) but not with needle biopsy grade (p = 0.15). The sensitivity of the needle biopsy grade in the detection of high-grade tumors on radical prostatectomy was 30%, and the specificity was 86%. The sensitivity of ploidy status in the prediction of high grade at radical prostatectomy was 78%, and the specificity was 96%. With a prostate-specific antigen (PSA) level of >0.4 ng/ml as the indicator of post-radical prostatectomy disease recurrence on a subset of 106 patients, on univariate analysis, disease recurrence was predicted by needle biopsy ploidy (p = 0.001) and radical prostatectomy grade (p = 0.04) but not by needle biopsy grade (p = 0.39). On multivariate analysis, needle biopsy DNA ploidy status independently predicted disease recurrence (p = 0.002), whereas needle biopsy and prostatectomy grade did not. These results indicate that DNA ploidy analysis of needle biopsy specimens of prostate cancer predicts grade shifting, that it is a more sensitive and specific indicator of final tumor grade at radical prostatectomy than is the original needle biopsy grade, and that ploidy status independently predicts postoperative disease recurrence.

Prognostic significance of HER-2/neu gene amplification status by fluorescence in situ hybridization of prostate carcinoma.

BACKGROUND: HER-2/neu gene amplification, established as a prognostic factor in breast carcinoma and other cancers, has not been correlated with outcome in prostate carcinomas (PCs). METHODS: HER-2/neu gene amplification was determined by automated fluorescence in situ hybridization (FISH) using a unique sequence cosmid probe on 113 formalin fixed, paraffin embedded 4-microns tissue sections and the results compared with tumor grade, DNA ploidy, HER-2/neu protein expression by immunohistochemistry (IHC), serum prostate specific antigen, pathologic stage, and postoperative disease recurrence (mean follow-up of 44 months). RESULTS: HER-2/neu gene amplification by FISH (41% of PCs) correlated with tumor grade (P = 0.001) and DNA ploidy status (P = 0.0003). HER-2/neu protein overexpression by IHC (29% of PCs) correlated with grade (P = 0.03), but not with DNA ploidy. A trend for similar HER-2/neu status in each PC by IHC and FISH did not reach statistical significance (P = 0.25). On univariate analysis, HER-2/neu amplification by FISH (P = 0.029), tumor grade (P = 0.013), and DNA ploidy (P = 0.016) correlated with postoperative disease recurrence. HER-2/neu expression by IHC did not correlate with outcome. On multivariate analysis, grade (P = 0.0001) and ploidy (P = 0.001) were independent outcome predictors; HER-2/neu amplification by FISH reached near-independent significance (P = 0.125). CONCLUSIONS: HER-2/neu gene amplification by FISH on archival PCs significantly correlates with grade and DNA ploidy status, is more sensitive than IHC in detecting HER-2/neu gene abnormalities, predicts postoperative disease recurrence, and may prove important in planning therapy for patients with prostate carcinoma.

MR imaging of pelvic lymph nodes in primary pelvic carcinoma with ultrasmall superparamagnetic iron oxide (Combidex): preliminary observations.

The potential of ultrasmall superparamagnetic iron oxide (Combidex)-enhanced MRI of pelvic lymph nodes in patients with primary pelvic carcinoma is evaluated. Fifteen histologically classified lymph nodes in six patients with known primary pelvic cancer (four prostate; one rectum; one uterus) were evaluated with T2-weighted fast spin-echo (FSE) and T2*-weighted gradient-echo (GRE) MRI at 1.5T 12 to 48 hours after intravenous administration of Combidex at a dose of 1.7 mg Fe/kg. Quantitative image evaluation was performed by comparing signal intensity of individual nodes on pre- and postcontrast images. All patients proceeded to pelvic lymph-node biopsy or surgical dissection, where six were found to be benign and nine were malignant. Of the 15 lymph nodes, four nodes showed a decrease in signal intensity. Of these, three, in which signal loss was homogenous were benign, and one, in which the signal-intensity decrease was heterogeneous, was malignant (micrometastases). No signal change was noted in 11 of 15 lymph nodes of which three were benign (inflammatory) and eight were malignant. Combidex is a promising MR contrast agent for evaluating pelvic lymph nodes. Our preliminary observations suggest that the agent is most useful for classifying normal lymph nodes.

Ultrasound assessment of testicular and paratesticular masses.

This article discusses the role of ultrasound in the workup of patients with suspected or palpable scrotal masses. By characterizing masses as intra- or extratesticular, the differential diagnosis can be narrowed considerably. Neoplasm is the primary concern with intratesticular masses, although non-neoplastic conditions, such as hematoma and focal orchitis, may have a similar appearance. Correlation with the patient's history is essential. The sonographic presentation of extratesticular pathology, including varicocele and masses of epididymal origin, is also described.

Endo-rectal coil magnetic resonance imaging in clinically localized prostate cancer: is it accurate?

PURPOSE: We assessed the staging accuracy of endo-rectal coil magnetic resonance imaging (MRI) in patients with clinically localized prostate cancer. MATERIALS AND METHODS: In a prospective study 56 consecutive patients underwent endo-rectal coil MRI before scheduled surgery. The ability of MRI to identify tumor involvement of the periprostatic soft tissue, seminal vesicles and pelvic lymph nodes was assessed by comparison with final pathological stage. RESULTS: Specificity of MRI was relatively high (84% for periprostatic soft tissue, 93% for seminal vesicles and 91% for pelvic lymph nodes) and sensitivity was low (22, 23 and 0%, respectively). Accuracy was 64% for identification of periprostatic soft tissue invasion, 77% for seminal vesicle invasion and 86% for pelvic lymph node metastases. Had we excluded from surgery patients with MRI evidence of extraprostatic disease our organ confined disease rate would have improved by 16.6%. However, this improvement would have been obtained at the expense of incorrectly excluding from surgery 21% of our patients with pathologically organ confined disease because of false-positive MRI predictions. CONCLUSIONS: Endo-rectal coil MRI is not sufficiently accurate to influence the treatment of patients with clinically localized prostate cancer. Therefore, we advise against routine use of this imaging modality in staging such cases.

Transient arteriovenous fistulae after transrectal prostate biopsy: diagnosis with color Doppler ultrasonography.

To assess the prevalence and significance of arteriovenous fistulae after prostate biopsy, we performed color Doppler ultrasonography immediately after 136 consecutive transrectal prostate needle biopsies. Pathologic results were correlated with color Doppler ultrasonographic findings. Arteriovenous fistulae developed after 17 biopsies (13%), all closed spontaneously within 18 minutes, and none were associated with unusual bleeding. Carcinoma was noted in 25 biopsy specimens (18%), 10 (40%) of which were followed by arteriovenous fistula. The correlation between malignancy and postbiopsy arteriovenous fistula was statistically significant (P < 0.0004), consistent with hypervascularity known to be present in many prostate cancers.