Prostate Needle Core Biopsies Research Articles

The percentage of prostate needle biopsy cores with carcinoma from the more involved side of the biopsy as a predictor of prostate specific antigen recurrence after radical prostatectomy: results from the Shared Equal Access Regional Cancer Hospital (SEARCH) database.

The authors previously found that, although the total percentage of prostate needle biopsy cores with carcinoma was a significant predictor of prostate specific antigen (PSA) failure among men undergoing radical prostatectomy (RP), there was a trend toward a lower risk of recurrence in patients with positive bilateral biopsies, suggesting that high-volume, unilateral disease was a worse predictor of outcome than an equivalent number of positive cores distributed over two lobes. In the current study, the authors sought to compare the total percentage of cores with carcinoma directly with the percentage of cores from the more involved or dominant side of the prostate with carcinoma for their ability to predict outcome among men who underwent RP. A retrospective survey of 535 patients from the Shared Equal Access Regional Cancer Hospital database who underwent RP at 4 different equal-access medical centers between 1988 and 2002 was undertaken. The total percentage of cores positive was compared with the percentage of cores positive from the dominant and nondominant sides for their ability to predict biochemical recurrence after RP. The best predictor then was compared with the standard clinical variables PSA, biopsy Gleason score, and clinical stage in terms of ability to predict time to PSA recurrence after RP using multivariate analysis. The adverse pathologic features of positive surgical margins and extracapsular extension were significantly more likely to be ipsilateral to the dominant side on the prostate biopsy. The percentage of cores positive from the dominant side provided slightly better prediction (concordance index [C] = 0.636) for PSA failure than the total percentage of cores positive (C = 0.596) and markedly better than the percentage of cores from the nondominant side (C = 0.509). Cutoff points for percentage of cores positive from the dominant side were identified (< 34%, 34-67%, and > 67%) that provided significant risk stratification for PSA failure (P < 0.001). On multivariate analysis, the percentage of cores positive from the dominant side was the strongest independent predictor of PSA recurrence (P < 0.001). Biopsy Gleason score (P = 0.017) also was a significant, independent predictor of recurrence. There was a trend, which did not reach statistical significance, toward an association between greater PSA values and biochemical failure (P = 0.052). Combining the PSA level, biopsy Gleason score, and percentage of cores positive from the dominant side of the prostate resulted in a model that provided a high degree of prediction for PSA failure (C = 0.671). The percentage of cores positive from the dominant side of the prostate was a slightly better predictor of PSA recurrence than was the total percentage of cores positive. Using the percentage of cores from the dominant side along with the PSA level and the biopsy Gleason score provided significant risk stratification for PSA failure.

Correlation Of Minute (0.5 MM or Less) Focus of Prostate Adenocarcinoma On Needle Biopsy With Radical Prostatectomy Specimen: Role of Prostate Specific Antigen Density

Few studies have examined the radical prostatectomy followup of a minute focus of adenocarcinoma on prostate needle core biopsy. We searched the surgical pathology data base (1999 to 2000) for patients with a minute focus of Gleason score 6 adenocarcinoma (defined as a single focus less than or equal to a 40 x microscopic field) who subsequently underwent radical retropubic prostatectomy at our institution. Potentially insignificant tumors were defined as those with a radical prostatectomy tumor volume of less than 0.5 cc, Gleason score 6 or less and organ confined disease. A total of 54 patients (mean age 58 years, range 45 to 70) were evaluated. The average number of prostate cores per biopsy was 6.3. All had Gleason score 6 by study design. Mean prostate specific antigen (PSA) was 6.0 (range 0.8 to 15). Average tumor volume at radical prostatectomy was 0.39 cc. Of the 54 tumors 24 (44%) were 0.1 cc or less. Two-thirds of the tumors were clinically potentially insignificant. Using a PSA density (PSAD) cutoff of 0.15 we identified 30 of 36 patients (83%) with potentially insignificant tumors. Of those with a PSAD of 0.15 or less with clinically significant tumors, 5 of 6 still had relatively small, organ confined tumors with Gleason score less than 7. In the era of PSA screening most patients with a minute focus of Gleason score 6 or less adenocarcinoma on needle biopsy had potentially insignificant tumors. However, one-third of patients had clinically significant tumors warranting definitive therapy. The smallest focus of cancer on needle biopsy is not a guarantee of a clinically insignificant tumor. PSAD may have some value within this group in guiding clinicians and patients as to the likelihood of having clinically insignificant tumors.

Percent of Prostate Needle Biopsy Cores With Cancer is Significant Independent Predictor of Prostate Specific Antigen Recurrence Following Radical Prostatectomy: Results From SEARCH Database

Recent studies have suggested that the percent of positive cores in the prostate needle biopsy is a significant predictor of outcome among men undergoing radical prostatectomy or radiation therapy for prostate cancer. We evaluate whether either percent of cores with cancer or percent of cores positive from the most and least involved side of the prostate needle biopsy was associated with a worse outcome among men treated with radical prostatectomy. A retrospective survey of 1,094 patients from the SEARCH Database treated with radical prostatectomy at 4 different equal access medical centers in California between 1988 and 2002 was undertaken. We used multivariate analysis to examine whether total percent of prostate needle biopsy cores with cancer, percent of cores positive from each side of the prostate and other clinical variables were significant predictors of adverse pathology and time to prostate specific antigen (PSA) recurrence following radical prostatectomy. On multivariate analysis serum PSA and percent of positive cores were significant predictors of positive surgical margins, nonorgan confined disease and seminal vesicle invasion. Percent of positive cores (p <0.001), serum PSA (p = 0.008) and biopsy Gleason score (p = 0.014) were significant independent predictors of time to biochemical recurrence. On a separate multivariate analysis that included the variables of total percent of positive cores, percent of positive cores from the most involved side of the biopsy, percent of positive cores from the least involved side of the biopsy and whether the biopsy was positive unilaterally or bilaterally, only the percent of positive cores from the most involved side of the biopsy was a significant independent predictor of PSA failure following radical prostatectomy. Percent of positive cores was used to separate patients into a low risk (less than 34%), intermediate risk (34% to 50%) and high risk (greater than 50%) groups, which provided significant preoperative risk stratification for PSA recurrence following radical prostatectomy (p <0.001). Percent of positive cores cut points were able to further risk stratify men who were at low (p = 0.001) or intermediate (p = 0.036) but not high (p = 0.674) risk for biochemical failure based on serum PSA and biopsy Gleason score. Percent of positive cores in the prostate needle biopsy was a significant predictor of adverse pathology and biochemical failure following radical prostatectomy, and the cut points of less than 34%, 34% to 50% and greater than 50% can be used to risk stratify patients preoperatively. The finding that percent of positive cores from the most involved side of the biopsy was a stronger predictor of PSA failure than the total percent of cores involved suggests that multiple positive biopsies from a single side might be a better predictor of a larger total cancer volume and thus correlate with clinical outcome.

P504S immunohistochemical detection in 405 prostatic specimens including 376 18-gauge needle biopsies.

P504S is a recently described, prostate cancer-specific gene that encodes a protein involved in the beta-oxidation of branched chain fatty acids. A recent study has shown that immunohistochemical detection of P504S gene product is a sensitive and specific marker of prostatic carcinoma in formalin-fixed, paraffin-embedded tissues. We performed a detailed analysis of P504S protein expression in a large series of prostate and bladder specimens with special emphasis on staining in specific morphologic patterns of prostatic adenocarcinoma, posthormonal and radiation therapy cases, and invasive urothelial carcinoma. A total of 366 prostate needle core biopsies from 124 patients with prostate cancer, 10 biopsies from 2 patients without prostate cancer, 28 prostatectomy specimens (16 with specific morphologic patterns, 7 posthormonal therapy and 5 postradiation therapy specimens), 5 bladder specimens with invasive urothelial carcinoma, and a single transurethral resection specimen from a patient with hormonally treated prostate cancer and invasive urothelial carcinoma were stained with P504S monoclonal antibody at a 1:250 dilution using standard heat-induced epitope retrieval and avidin-biotin technique. Extent (0, no staining; 1+, 1-10% staining; 2+, 11-50% staining; 3+, > or =51% staining) and location (luminal, subluminal, and diffuse cytoplasmic) of immunoreactivity in carcinoma and benign tissues were recorded. A total of 153 of 186 biopsies (82%) with prostatic adenocarcinoma stained for P504S. Pseudohyperplastic, atrophic, ductal, and mucinous prostatic carcinomas stained similarly, as did cases treated with hormone or radiotherapy. In 81 of 377 (21%) foci of benign prostatic tissue there was staining that was almost always focal, faint, and noncircumferential. Seminal vesicles did not stain for P504S. Five of six (83%) specimens with invasive urothelial carcinoma had 2+ staining and one case had focal staining. We conclude that immunohistochemistry for P504S has potential utility in the diagnosis of prostate cancer, including those treated by hormones and radiation. Circumferential luminal to subluminal and diffuse cytoplasmic staining is the most specific staining pattern for prostatic carcinoma and is almost never associated with benign prostatic tissue. However, a negative P504S immunostain does not automatically rule out prostate cancer, as 18% of cases were negative. Additionally, occasional benign glands, high-grade prostatic intraepithelial neoplasia, atypical adenomatous hyperplasia, and urothelial carcinoma may express P504S. Therefore, we think that P504S is best used only in conjunction with strict light microscopic correlation and preferably with high molecular weight cytokeratin immunostaining.

Identification of numerical chromosomal changes detected by interphase fluorescence in situ hybridization in high-grade prostate intraepithelial neoplasia as a predictor of carcinoma.

High-grade prostate intraepithelial neoplasia (HPIN) is the most likely precursor of prostate cancer. The condition of many patients with a diagnosis of HPIN in prostate needle core biopsy could, if left untreated, progress to invasive cancer. Currently there is no available clinical, immunohistochemical, or morphologic criteria that are predictive of this progression. To determine whether chromosomal instability in these precursor lesions could increase their predictive value for cancer detection. Dual-color interphase fluorescence in situ hybridization analysis was performed on archived prostate needle core biopsies from 54 patients with initial diagnosis of isolated HPIN and follow-up of 3 years or more. We used commercially available centromere probes for chromosomes 4, 7, 8, and 10. We had interpretable results in 44 patients as follows: (1) group A: 24 HPIN patients with persistent HPIN and/or benign lesions in the follow-up biopsies, and (2) group B: 20 HPIN patients with progression to prostate carcinoma. Twenty-five percent of the patients in group B displayed numeric chromosomal aberrations. Only 8.3% of the patients from group A had chromosomal abnormalities (P =.1). The observed overall chromosomal changes in HPIN were higher than those in normal or hyperplastic epithelium, with a statistically significant difference (P <.05). All aberrations were detected in the form of chromosomal gain. Overall, the commonest aberration was gain of chromosome 8, followed by gains of chromosomes 7 and 10. These results indicated that although no single numeric chromosomal abnormality could be assigned as a predictor of HPIN progression to carcinoma, the overall level of numeric chromosomal abnormalities shows a trend of elevation in HPIN patients whose condition subsequently progressed to carcinoma.

Prediction of tumour volume and pathological stage in radical prostatectomy specimens is not improved by taking more prostate needle‐biopsy cores

To determine what, if any, additional prognostic information is available from the prostate needle biopsy by comparing the number of biopsy cores obtained with the pathology assessed from the radical retropubic prostatectomy (RRP) specimen. The results from 135 consecutive patients who underwent RRP at a single institution were reviewed. Needle biopsy information (number of cores, percentage of positive cores, laterality of the positive cores, and Gleason sum) were compared with the pathological data of the RRP specimen, including stage, Gleason sum and tumour volume. Patients were further stratified into those with six or fewer cores (96 men) or more than six cores (39 men). Clinical data, including biopsy information and pathological findings, were compared using univariate and multivariate models. Overall, univariate analysis showed that the total prostate-specific antigen (PSA) level, number of positive cores, bilateral positive cores and percentage of positive cores were directly correlated with tumour volume (P=0.01). Also, PSA and percentage of positive cores were directly correlated with extracapsular extension (P=0.008 and P=0.01, respectively). In the multivariate model, the most important independent predictors of RRP tumour volume and pathological stage were the preoperative PSA level and percentage of cancer in the biopsy (P<0.01). There was no significant relationship between the number of cores obtained and the predicted pathology of the RRP specimen. There were no differences in the number of positive cores, bilateral positive cores or percentage tumour in the cores between men with more or less than six biopsies. In men with more than six core biopsies, there was no significant increase in prognostic information for tumour volume and extracapsular extension, or a correlation between the Gleason sum on biopsy and the RRP specimen. Taking more than six biopsies did not result in a significantly greater detection of potentially indolent tumours (defined as a tumour volume of <0.5 mL). While taking more prostate needle biopsy cores seems to improve the detection of prostate cancer, there appears to be no major improvement in prognostic information over that gained from traditional sextant biopsies. Furthermore, the results suggest that the percentage of positive cores is the best predictor of both pathological stage and tumour volume, from among the information readily available from prostate needle biopsy. Given the variability in the number of cores obtained for diagnosis in clinical practice, these results add credence to the use of the percentage of positive cores in the biopsy set, with known predictors such as PSA and Gleason score, into future models that attempt to predict tumour biology.

Prostate biopsy protocols: 3D visualization-based evaluation and clinical correlation.

Systematic needle core biopsy is commonly used for the diagnosis of prostate cancer by urologists worldwide. As accurate and early diagnosis will result in more and better options for treatment, it is critical that the best possible protocols for biopsy be used clinically. In this study, we develop three-dimensional (3D) modeling and simulation technologies to evaluate most of the biopsy protocols in current clinical use, and correlate the results with those from clinical cases. Using deformable modeling techniques, 3D computerized prostate surface models were reconstructed from step-sectioned, whole-mounted radical prostatectomy specimens with localized prostate cancer. A 3D computer simulation system was developed to accurately depict the anatomy of the prostate and all individual tumor foci. A user-friendly interface was developed in the system so that a physician can easily and interactively use it for prostate needle core biopsy. A total of 281 prostate models were reconstructed, and 18 biopsies were performed by a urologist on each model to determine the detection rates of seven different biopsy protocols. Clinical biopsies from 35 patient cases were also reviewed and correlated with the simulation results. The most commonly used sextant biopsy had only a 71.5% detection rate, while rates for the 10-pattern and 12-pattern protocols were much higher (96.4% and 97.2%, respectively). Even the lateral 4-pattern protocol performed better than the sextant protocol, with a detection rate of 89.3%. The lateral sextant biopsy protocol (using sites similar to, but more lateral than, those in the sextant protocol) achieved a rate of 92.5%. Although the rate of the 14-pattern biopsy was a little higher (97.5%), it used four more biopsies to achieve this increase, which, according to McNemar's test, is not statistically significant when compared to results with the 10-pattern protocol. The 5-region protocol, which uses 12 biopsies, had a detection rate of 89.7%. Transition zone and seminal vesicle biopsies did not result in a significantly increased detection rate when added to the patterns above. The clinical correlation also confirmed that the 10-pattern protocol was significantly superior to the traditional sextant biopsy pattern. The 10-pattern biopsy protocol was the most optimized among all the protocols evaluated. This protocol supplemented the sextant biopsy protocol with four more lateral biopsies in the mid and apical sites on both sides.

Prostate Biopsy Protocols: 3D Visualization-Based Evaluation and Clinical Correlation

Objectives: Systematic needle core biopsy is commonly used for the diagnosis of prostate cancer by urologists worldwide. As accurate and early diagnosis will result in more and better options for treatment, it is critical that the best possible protocols for biopsy be used clinically. In this study, we develop three-dimensional (3D) modeling and simulation technologies to evaluate most of the biopsy protocols in current clinical use, and correlate the results with those from clinical cases.Materials and Methods: Using deformable modeling techniques, 3D computerized prostate surface models were reconstructed from step-sectioned, whole-mounted radical prostatectomy specimens with localized prostate cancer. A 3D computer simulation system was developed to accurately depict the anatomy of the prostate and all individual tumor foci. A user-friendly interface was developed in the system so that a physician can easily and interactively use it for prostate needle core biopsy. A total of 281 prostate models were reconstructed, and 18 biopsies were performed by a urologist on each model to determine the detection rates of seven different biopsy protocols. Clinical biopsies from 35 patient cases were also reviewed and correlated with the simulation results.Results: The most commonly used sextant biopsy had only a 71.5% detection rate, while rates for the 10-pattern and 12-pattern protocols were much higher (96.4% and 97.2%, respectively). Even the lateral 4-pattern protocol performed better than the sextant protocol, with a detection rate of 89.3%. The lateral sextant biopsy protocol (using sites similar to, but more lateral than, those in the sextant protocol) achieved a rate of 92.5%. Although the rate of the 14-pattern biopsy was a little higher (97.5%), it used four more biopsies to achieve this increase, which, according to McNemar's test, is not statistically significant when compared to results with the 10-pattern protocol. The 5-region protocol, which uses 12 biopsies, had a detection rate of 89.7%. Transition zone and seminal vesicle biopsies did not result in a significantly increased detection rate when added to the patterns above. The clinical correlation also confirmed that the 10-pattern protocol was significantly superior to the traditional sextant biopsy pattern.Conclusions: The 10-pattern biopsy protocol was the most optimized among all the protocols evaluated. This protocol supplemented the sextant biopsy protocol with four more lateral biopsies in the mid and apical sites on both sides.

Diagnostic effect of an improved preembedding method of prostate needle biopsy specimens

The authors compared the influence of a conventional and an optimized submitting method of prostate core needle biopsy specimens on the frequency of cancer detected and the pathologic characteristics of the adenocarcinoma bearing biopsy specimens. The patients included were part of the prostate-specific antigen (PSA) screening program of Tyrol/Austria. Of the systematic core needle biopsy specimens from 500 unselected men obtained within 1 year from the Urological Department, University of Innsbruck, the core biopsy specimens of 250 cases were submitted conventionally, floating free in formalin-filled containers, whereas the biopsy specimens of the other 250 cases were stretched and orientated between 2 meshes in tissue cassettes at the time of biopsy before formalin fixation. On 136 cases diagnosed as adenocarcinoma the number and the length of cores as well as number of the cores involved by cancer and the tumor size were morphometrically determined. The diagnosis of benign prostatic hyperplasia, isolated high-grade prostatic intraepithelial neoplasia (PIN), atypical foci suspicious for cancer, and carcinoma was made in 66%, 5.6%, 4.8%, and 23.6% after conventional submission and in 61.6%, 6.4%, 1.2%, and 30.8% of the cases after optimized preembedding respectively. In the adenocarcinoma cases the optimizedly preembedded material showed higher mean total core length (126.5 mm versus 93.9 mm; P < .0001), a higher mean total tumor length (14.1 mm versus 8.6 mm; P = .01), and more cores involved by cancer (2.9 versus 2.4; P = .01) compared with the conventionally worked-up biopsy specimens. Optimized preembedding of core needle biopsy specimens in tissue cassettes could be quickly and routinely done by the assistance of the urologists at the time of biopsy. The significant improvement of the histologic yield of optimizedly preembedded prostatic needle biopsy specimens led to a higher frequency of cancer diagnosis, a reduction of cases with atypical foci suspicious for cancer and a significantly lower number of cases with only 1 core biopsy involved by cancer. H UM P ATHOL 31:1102-1107.

Diagnostic frozen prostate sextant biopsies: an approach for preserving protein and RNA for additional studies.

Primary prostate cancer represents 29% of newly diagnosed visceral cancers in men. Despite this common occurrence, relatively little is known about the pathogenesis of this malignancy. High-grade prostatic intraepithelial neoplasia (HGPIN) is generally accepted as a precursor to invasive prostate carcinoma. There is a lack of adequate animal models, and the available cell culture lines are limited. Tissue from prostate needle core biopsies that have been frozen can provide adequate material for both diagnosis and research. Transrectal sextant needle biopsies were snap-frozen, serially sectioned and alternately stained with hematoxylin-eosin or reacted with a basal cell-specific antibody. Two pathologists examined all of the sections, which were scored for the presence or absence of carcinoma and HGPIN. Portions of the remaining tissue were used for studies of protein expression and gene expression. The incidence of carcinoma was 39%, comparable to the mean percent positive cases reported using conventional fixation and paraffin embedding. The incidence of HGPIN was 33%, higher than previously reported. Prostate carcinoma can be accurately diagnosed using frozen material. The observed high frequency of HGPIN is attributed to the instability of nuclear structure in the frozen material of the atypical nuclei, resulting in inflated grading of PIN lesions. Sufficient material remained in the frozen blocks for additional studies of protein and gene expression.

Adenosquamous carcinoma of the prostate: case report with DNA analysis, immunohistochemistry, and literature review

We diagnosed prostatic adenosquamous carcinoma by prostate core needle biopsy in a 55-year-old man with no history of prostate cancer. The prognosis, DNA analysis, and histogenesis of this extremely rare tumor are controversial. To our knowledge, this is the first case of adenosquamous carcinoma diagnosed by core needle biopsy in a patient with no history of prostate cancer or hormonal therapy. We performed immunohistologic and DNA analysis to further characterize this cancer. The clinical presentation and abnormal DNA analysis portend an aggressive course.

Adequate tissue sampling of prostate core needle biopsies.

Prostatic carcinoma is increasingly diagnosed on small foci of core needle biopsy specimens. What constitutes adequate sampling of this tissue has not been investigated. Two hundred twenty-nine cases were reviewed, which included 47 cores with atypical foci, 22 with high-grade prostatic intraepithelial neoplasia (PIN), and 533 diagnostic of carcinoma. Six core specimens were obtained for each case, and two blocks were prepared containing three cores each. At least three slides containing multiple serial sections were prepared from each block. Ninety-seven percent of atypical foci, 0% of high-grade PIN foci, and 25% of carcinomatous foci comprised less than 5% of the tissue in the core and measured less than 1 mm in greatest dimension. Thirteen percent of atypical foci, 0% of high-grade PIN foci, and 3% of carcinomatous foci were not present on the first slide. In every case, the tissue containing the focus was not present on the first slide. Thirteen percent of atypical foci and 3% of carcinomatous foci are not present on the first slide of prostate core needle biopsy specimens because the tissue containing these foci simply is not cut. As proposed in this report, at least three slides are necessary to detect all lesions.

Interpretation of Bilateral Positive Biopsies in Prostate Cancer

Purpose When 6 systematic prostate needle core biopsies are positive for cancer bilaterally, prediction of clinical cancer volume is limited by the unpredictable presence of contralateral incidental tumors. Criteria were sought to improve prediction. Materials and Methods Core cancer lengths were summed unilaterally (3 biopsies) and bilaterally (6) in 65 patients with bilateral positive cores. Of the patients 31 had true bilateral cancer spread and 34 had unilateral disease with contralateral incidental tumors. Results For both groups correlation with prostatectomy cancer volume (r = 0.65, p less than 0.001) was the same for the sum of 3 ipsilateral cores as for all 6 cores. Conclusions Core cancer length sum of 3 ipsilateral biopsies predicts the largest prostatectomy cancer volume as well as the bilateral sum. Contralateral biopsies do not contribute to prediction nor distinguish bilateral spread from contralateral incidental cancers.