Consecutive Radical Prostatectomy Specimens Research Articles

Dynamic Contrast-enhanced–magnetic Resonance Imaging Evaluation of Intraprostatic Prostate Cancer: Correlation with Radical Prostatectomy Specimens

To determine the diagnostic performance of dynamic contrast-enhanced-magnetic resonance imaging (DCE-MRI) in the identification of intraprostatic cancer foci related to cancer volume at histopathology, in patients with clinically localized cancer treated by radical prostatectomy, with whole-mount histopathologic sections as the reference standard. Eighty-three consecutive radical prostatectomy specimens from patients referred for a prostate-specific antigen elevation were correlated with prebiopsy MRI. MRI results ranked on a 5-point scale were correlated with the findings of histopathology maps in 8 prostate sectors, including volume, largest surface area, and percentage of Gleason grade 4/5. The area under the receiver operating characteristic curve was used. Median prostate-specific antigen was 8.15 ng/mL. DCE-MRI was suspicious in 55 (66%) out of 83 patients. A separate cancer foci (mean 2.55 per patient) was present in 212 (34%) of 664 octants and DCE-MRI was suspicious in 68 of 212. Sensitivity and specificity of DCE-MRI at score 3.4 or 5 for identification of cancer foci at any volume was 32% and 95%, respectively. For identification of cancer foci > 0.5 mL, the sensitivity and specificity were 86% and 94%, respectively, with the under the receiver operating characteristic curve of 0.874. Mean volume of DCE-MRI detected and missed cancers were 2.44 mL (0.02-14.5) and 0.16 mL (0.005-2.4), respectively. Sensitivity and specificity of DCE-MRI for identification of > 10% of Gleason grade 4/5 were 81% and 82%, respectively. DCE-MRI can accurately identify intraprostatic cancer foci. Possible applications are guidance for biopsies, selection of patients for watchful waiting, and focal treatment planning.

TMPRSS2-ERG Fusion Heterogeneity in Multifocal Prostate Cancer: Clinical and Biologic Implications

To characterize the clonality of TMPRSS2-ERG fusion in multifocal prostate cancer. From 80 consecutive radical prostatectomy specimens, we identified 32 cases with multiple spatially separate tumors. In each case, we assessed two to three tumor foci for TMPRSS2-ERG fusion using an ERG break-apart interphase fluorescence in situ hybridization assay. Individual tumor foci showed homogeneity for fusion status (intrafocal clonal homogeneity). In 19 (59%) of the 32 cases, all foci within a case had the same fusion status (interfocal homogeneity). In 15 (80%) of the 19 cases, no foci had fusion, and in 4 (20%), all foci had fusion. Of the 32 cases, 13 (41%) demonstrated heterogeneity for fusion status within a case (interfocal clonal heterogeneity). In this study, we have demonstrated interfocal heterogeneity and intrafocal homogeneity for TMPRSS2-ERG fusion in prostate cancer with multiple tumors. These findings support the multiclonal nature of prostate cancer with clinical implications for needle biopsy strategies and the development of urine-based screening tests.

The 3-dimensional Structure of Isolated and Small Foci of Prostatic Adenocarcinoma

Transitional histopathologic changes from high-grade prostatic intraepithelial neoplasia (HGPIN) into early prostatic adenocarcinoma (PAC) have not been well studied to date. To investigate the histogenesis of PAC, we examined isolated and small foci of PAC (ISPAC) found in prostatectomy specimens and the 3-dimensional structure of these foci. Twelve consecutive radical prostatectomy specimens having ISPAC, performed for peripheral zone PAC (10 cases) and for transitional zone PAC (2 cases), of Gleason score were studied. One to 2 tissue blocks with representative sections were used. Eight ISPAC, with Gleason score 3 + 3 had complete serial sections of the entire lesion. PAC consisted of continuous, tortuous and branching tubules and acini arising from benign ducts displaying: (a) HGPIN in 5 ISPAC and (b) no HGPIN in 3 ISAPC. At the junctions between benign epithelia with or without HGPIN and malignant epithelia, there were transitional lesions with HGPIN involving small ducts and acini. PAC develops as a result of multiple outpouchings of the epithelium with formation of small ducts and acini showing cytologic atypia and gradual or abrupt loss of basal cells. Grade 3 ISPAC consists of a system of continuous duct pushing into the stroma. There is also evidence suggestive of HGPIN as being both a precursor lesion and an accompanying lesion of PAC.

Predictive value of prostatic adenocarcinoma after a negative prostate biopsy

To investigate the predictive value (PV) for all prostate cancers and for clinically significant cancer undiagnosed after a 10-core biopsy protocol, as the 10-core transrectal ultrasonography-guided biopsy is considered the standard technique of prostatic biopsy due to its high rate of detection of prostatic adenocarcinoma. In all, 132 consecutive radical prostatectomy (RP) specimens, with their corresponding 10-core biopsies, were reviewed. Cases with unilateral core involvement by prostate cancer were retained for study. Morphometric analysis was conducted on the biopsy-negative hemi-prostates to determine the PV of the biopsy protocol with respect to the size, position and clinical significance of the lesion. In all, 70 resected prostates (RP) had unilateral core involvement by prostate cancer. In 38 cases, there was cancer in the biopsy-negative hemi-prostates (group 1); in the remaining 32 the hemi-prostates were free of cancer (group 2). Group 1 was categorized by morphometric criteria. Specifically, 23 cases had one to eight foci of prostate cancer in the posterior nontransitional zone (NTZ) (group 1a), while 15 had two to six foci of prostate cancer in the transitional zone (TZ), or the anterior horn (AH) of the peripheral zone or the TZ and AH (group 1b). There were two cases with clinically significant prostate cancer in group 1a, and six in group 1b. The PV of a negative five-core biopsy protocol on a hemi-prostate is 54% for prostate cancer and 11% for clinically significant prostate cancer. Most clinically significant prostate cancers were in the AH/TZ of the prostate.

Immunohistochemical Stains for p63 and α-Methylacyl-CoA Racemase, Versus a Cocktail Comprising Both, in the Diagnosis of Prostatic Carcinoma

The diagnosis of prostatic carcinoma and especially minimal prostatic carcinoma can sometimes be challenging on needle core biopsy and occasionally immunohistochemistry is an aid in the diagnosis. Immunostains, such as those directed against the basal cell marker p63 and, more recently, employing antibodies reactive with alpha-methylacyl-CoA racemase (AMACR), can be useful in this situation. The aim of this investigation was to assess the diagnostic utility of a p63/AMACR antibody cocktail and compare the staining pattern it produces with that using the individual antibodies alone. A retrospective review of 31 consecutive radical prostatectomy specimens and 150 prostate needle biopsy samples was performed to select histologic sections showing foci of prostatic carcinoma and/or minimal prostatic carcinoma, high-grade prostatic intraepithelial neoplasia (HGPIN), as well as common benign mimickers of prostatic carcinoma, to include atrophy and basal cell hyperplasia, especially with prominent nucleoli. Serial histologic sections from the corresponding paraffin blocks were stained with hematoxylin and eosin and by immunostains for p63, AMACR, and a prediluted antibody cocktail comprising both. The diagnostic utility of the cocktail was assessed, and the staining characteristics it produced were compared with those using the individual immunostains. In 430 foci, the cocktail produced a p63 staining profile identical to that using the single p63 antibody. Distinction of the nuclear p63 signal from the cytoplasmic AMACR localization was readily accomplished. There was an excellent agreement (kappa=0.91; P<0.0001) between the AMACR staining profile using the cocktail and the single AMACR antibody alone. The cocktail was very useful in highlighting prostatic carcinoma associated with HGPIN, flat and cribriform HGPIN, and distorted foci of minimal prostatic carcinoma. These data indicate that use of a p63/AMACR cocktail is essentially equivalent to use of each antibody separately for immunohistochemical confirmation of a diagnosis of prostatic carcinoma in needle biopsy. This cocktail would be of diagnostic utility when only limited tissue is available for immunohistochemical evaluation of small, diagnostically difficult foci in prostate needle biopsy tissue.

IS TUMOR VOLUME AN INDEPENDENT PROGNOSTIC FACTOR IN CLINICALLY LOCALIZED PROSTATE CANCER?

There continues to be debate regarding the prognostic significance of tumor volume (TV) in radical prostatectomy (RP) specimens. We assessed the prognostic significance of TV in a large series of patients followed for a long time to discover whether the effect of TV has changed with earlier detection of smaller tumors. TV was measured planimetrically in 1,302 consecutive RP specimens with clinical stage T1-3 prostate cancer from 1983 to 2000. We correlated TV with standard clinical and pathological features, and determined the prostate specific antigen nonprogression rate. Median followup was 46 months (range 1 to 202). TV was weakly associated with other clinical and pathological features. Median TV decreased significantly over time (2.16 cm3 before 1995 vs 1.25 cm3 after 1995, p <0.001) and this decrease was also found within each clinical stage. In univariate analysis TV correlated strongly with the probability of progression. However, in multivariate analysis TV was not a significant independent predictor of prognosis, either in the whole cohort of patients or in those with peripheral zone cancer only. Even in univariate analysis TV had no effect on prognosis for patients in whom cancer was either confined to the prostate or was Gleason score 2 through 6. TV provides no independent prognostic information when considered in multivariate analysis with Gleason score and pathological stage. Measurement of TV before treatment is less likely to characterize prostate cancer accurately than assessment of tumor grade and extent. There seems to be little reason to measure TV routinely in RP specimens.

Heterogeneity of Gleason grade in multifocal adenocarcinoma of the prostate.

The Gleason grading system uniquely combines data from different areas of carcinoma in the same prostate specimen. Prostatic adenocarcinoma often is multifocal, and different Gleason grades may be present in different foci. The current study was undertaken to compare the Gleason grades of individual adenocarcinoma foci in a given specimen with the overall Gleason grades (primary and secondary) of that specimen. Data were obtained from 115 consecutive radical prostatectomy specimens via whole-mount processing and complete sectioning. Diagrams were constructed by tracing the outline of each whole-mount section, and tumor maps subsequently were generated. The largest focus was considered the index tumor. Each prostatectomy specimen was assigned primary and secondary Gleason grades, and each tumor focus was assigned its own primary and secondary Gleason grades. Tumor volume was measured using the grid method. Two or more adenocarcinoma foci were present in 87% of all specimens (2 foci, n = 20; 3 foci, n = 33; 4 foci, n = 17; 5 foci, n = 13; > 5 foci, n = 17). Specimens (n = 15) containing a single tumor were excluded from further analysis. Among the remaining specimens (n = 100), all tumor foci had Gleason grades that were the same as the corresponding overall Gleason grades in only 9 cases (9%). The Gleason score (i.e., the sum of the primary and secondary grades) of the index tumor was correlated with the overall Gleason score in 68% of specimens. The primary grade of the index tumor was the same as the overall primary grade in 97 specimens, whereas the secondary grade of the index tumor was the same as the overall secondary grade in only 68 specimens. The primary and secondary grades of the index tumor, compared with the overall Gleason primary and secondary grades, were reversed in 17 specimens. The findings of the current study demonstrated the histologic heterogeneity of multifocal prostate malignancies. Although the Gleason grading system was used to determine an overall score for prostate carcinoma within a specimen, the scores of individual tumors, including index tumors, often did not agree with this overall score. These findings may have implications with respect to future biomarker and tissue array studies.

Prognostic significance of tumor volume after radical prostatectomy: a multivariate analysis of pathological prognostic factors.

To analyze the association between Gleason score, stage and status of surgical margins with tumor volume in prostate cancer progression after radical prostatectomy. 200 consecutive radical prostatectomy specimens were analyzed. Preoperative clinical stage, PSA, results of prostate biopsies as well as pathological results were noted. A biochemical recurrence was defined as a single, postoperative detectable PSA level (>0.2 ng/ml). Tumor volume was compared to postoperative staging, Gleason score, and surgical margin status to predict tumor progression. Univariate and multivariate analysis using stepwise logistic regression were used to identify parameters with additional prognostic value. Pathological results of the prostatectomy specimens showed 149 (74.5%) pT2a-b, 29 (14.5%) pT3a and 22 (11%) pT3b tumors. Tumor volume was 0.57 cc for pT2a, 1.2cc for pT2b, 1.7cc for pT3a and 2.9cc for pT3b, respectively (p<0.05). Taken together, mean volume for pT2 and pT3 were 1.06 and 2.2 cc, respectively (p<0.0001). Five-year progression-free actuarial survival was 69.7%. Using univariate analysis, tumor progression correlated with final Gleason score (p<0.0007), positive surgical margins (p=0.02), tumor volume (p=0.009) and stage (p<0.0001). In a multivariate analysis, tumor progression correlated only with the final Gleason score (p=0.04) and stage (p=0.0002). Gleason score and pathological stage are independent factors to predict prostate cancer progression after radical prostatectomy. When these parameters are known, tumor volume does not provide additional information.

Central zone histology of the prostate: A mimicker of high-grade prostatic intraepithelial neoplasia

The central zone (CZ) is located at the base of the prostate adjacent to the seminal vesicles. Its histology as a potential mimicker of high-grade prostatic intraepithelial neoplasia (PIN) has not been formally studied. Three groups were evaluated. Group 1 comprised 30 consecutive radical prostatectomy specimens assessed for the extent of CZ and of Roman arch and/or cribriform formation in the CZ. Group 2 comprised 100 consecutive cases of nonconsult prostate needle biopsies, screened in a random blinded fashion to identify CZ histology and the specificity of its identification on biopsy. Group 3 comprised 34 consult cases (1984 to the present) with CZ histology on needle biopsy. For group 1, the average maximum diameter of CZ histology was 5 mm. Two cases (6.7%) did not contain the classic features of CZ histology. The average amount of cribriform and/or Roman arch formation in the areas with CZ histology was 16.5%. In group 2, 10% of prostate needle biopsy cases had CZ histology. Of these, 80% were located on biopsy specimens designated as the base of the prostate, 10% were located in the base and midportion of the prostate, and 10% were located in the midportion of the prostate. For group 3, CZ histology occupied on average 32% of the involved core. The 2 most common histologic features were eosinophilic cytoplasm (97%) and location at the end of a core (97%). Other features were Roman arch formation (59%), a prominent basal cell layer (32%), cribriform formation (26%), and associated thick muscle bundles typical of bladder neck (24%). On average, cribriform and/or Roman arch formation occupied 22% of the CZ area seen on biopsy. Twenty-six of the consult cases were sent in with preliminary outside diagnoses. Of these, 21 (81%) were either PIN or atypical: 11 (42%) high-grade PIN, 7 (27%) PIN, and 3 (12%) atypical glands. Our findings show that CZ histology is distinctive, as seen in radical prostatectomy specimens. Less frequently it is found on needle biopsy, where the presence of Roman arch and/or cribriform formation mimics PIN. Recognition of the distinctive features of CZ histology (i.e., tall columnar cells with eosinophilic cytoplasm, prominent basal cell layer, and lack of cytologic atypia) can help avoid a misdiagnosis of PIN or “atypia” on needle biopsy. HUM PATHOL 33:518-523. Copyright 2002, Elsevier Science (USA). All rights reserved.

PREDICTORS OF GLEASON PATTERN 4/5 PROSTATE CANCER ON PROSTATECTOMY SPECIMENS: CAN HIGH GRADE TUMOR BE PREDICTED PREOPERATIVELY?

Radical prostatectomy provides excellent cancer control in men with clinically localized prostate carcinoma. However, to our knowledge preoperative parameters for distinguishing indolent from clinically significant cancer are not well characterized. In fact, recent evidence suggests that the percent of Gleason pattern 4/5 carcinoma in the complete radical prostatectomy specimen is one of the strongest predictors of prostate cancer progression and a valid measure of cancer severity. However, it is unclear whether preoperative parameters, including biopsy Gleason pattern 4/5 carcinoma, may predict radical prostatectomy Gleason pattern 4/5 disease and, thereby, distinguish indolent from clinically significant cancer. We prospectively obtained 101 consecutive radical prostatectomy specimens and processed them in whole mount fashion. In addition to total tumor volume, we determined tumor volume for each Gleason pattern. Biopsy tumor area was measured in a similar fashion. Univariate and multivariate analyses were performed to identify preoperative clinical and pathology parameters for predicting Gleason pattern 4/5 carcinoma on prostatectomy specimens. Biopsy Gleason score 7 or greater, Gleason pattern 4/5 carcinoma, perineural invasion and biopsy tumor area had statistically significant associations for identifying Gleason pattern 4/5 carcinoma on prostatectomy specimens. Logistic regression models for predicting any or greater than 10% Gleason pattern 4/5 carcinoma on prostatectomy specimens revealed that an area of pattern 4/5 disease of greater than 0.01 cm.2 on biopsy was the best single predictor with odds ratios of 15.0 (95% confidence interval 3.3 to 69.0, p = 0.0005) and 3.9 (95% confidence interval 1. 4 to 10.9, p = 0.009), respectively. For predicting any pattern 4/5 carcinoma on prostatectomy specimens a biopsy area of pattern 4/5 disease of greater than 0.01 cm.2 had only 38% sensitivity but 96% specificity. Similarly for predicting significant pattern 4/5 disease on prostatectomy specimens, defined as 10% or greater pattern 4/5, sensitivity and specificity for a biopsy area of greater than 0.01 cm.2 were 34% and 88%, respectively. Therefore, due to high false-negative rates these models had limited predictive value on an individual basis. Biopsy parameters such as Gleason pattern 4/5 carcinoma may provide adequate specificity for predicting clinically significant cancer, as defined by high grade Gleason patterns in the corresponding radical prostatectomy specimen. However, the accuracy of these parameters for predicting indolent cancer is limited by a prohibitive rate of false-negative findings.

WHOLE MOUNTED RADICAL PROSTATECTOMY SPECIMENS DO NOT INCREASE DETECTION OF ADVERSE PATHOLOGICAL FEATURES

The optimal method to process radical prostatectomy specimens to maximize the detection of adverse pathological features is unclear and accurate staging is critical. We compare the ability of whole mounted sections to detect these features compared to partially submitted radical prostatectomy specimens. A total of 93 consecutive radical prostatectomy specimens were processed as whole mounts. Tissue sections were analyzed and the pathological outcomes measured included Gleason score, surgical margin status, and presence or absence of extraprostatic tumor extension and/or seminal vesicle invasion. The pathological outcomes of the preceding cohort were compared to those of a similar cohort consisting of 554 men whose radical prostatectomy specimens were processed as partially submitted glands. A multivariate logistic regression analysis was performed to determine the effect of the method of tissue processing on the pathological outcomes. When considered alone or adjusted for various preoperative patient characteristics (prostate specific antigen, biopsy Gleason score and clinical stage), there were no significant differences in the ability of whole mounted specimens to detect the various outcomes compared to partially submitted specimens (all p >0.4). Whole mounted sampling of the radical prostatectomy specimen does not improve detection of adverse pathological features.

Recursive partitioning for prognostic grouping of patients with clinically localized prostate carcinoma

Patients treated with radical prostatectomy for clinically localized prostate carcinoma present considerable heterogeneity in terms of disease free survival outcome. Multiple studies have attempted to create prognostic groupings of these patients in the perioperative phase, using information available regarding several clinicopathologic variables. Such groupings allow physicians to make early yet prudent decisions regarding adjuvant combination therapies. The current study presents results from a statistical analysis that enables the natural identification of such prognostic groups. Examination of consecutive radical prostatectomy specimens was performed between January 1991 and December 1995 at Wayne State University, Harper Hospital, Detroit, Michigan. Disease free survival in a cohort of 485 of these men was analyzed using recursive partitioning and amalgamation technique. Clinicopathologic parameters evaluated included age, race, preoperative prostate specific antigen (PSA) level, clinical and pathologic stage, and Gleason grade of the fine-needle biopsy as well as the radical prostatectomy specimen. A binary decision tree representation was generated for classifying patients based on the clinicopathologic variables mentioned earlier. The worst prognosis was for patients with either advanced stage and a PSA level > 24.1 ng/mL or advanced stage, a PSA level </= 24.1 ng/mL, and age </= 65 years. This group had an estimated median disease free survival of only 10.3 months. Patients with lower pathologic stage, prostatectomy Gleason scores of </= 7, and a preoperative PSA level </= 22.7 ng/mL had the best prognosis. The recursive partitioning analyses allows easy characterization of a patient for prognosis shortly after radical prostatectomy. This will enable a physician to make more prudent decisions regarding whether to employ watchful waiting, proceed with accepted adjuvant therapy (radiotherapy or hormonal therapy), or refer patients to a research center that is able to administer experimental adjuvant therapy. [See editorial counterpoint on pages 232-3 and reply to counterpoint on pages 234-5, this issue.]

Recursive partitioning for prognostic grouping of patients with clinically localized prostate carcinoma

BACKGROUND Patients treated with radical prostatectomy for clinically localized prostate carcinoma present considerable heterogeneity in terms of disease free survival outcome. Multiple studies have attempted to create prognostic groupings of these patients in the perioperative phase, using information available regarding several clinicopathologic variables. Such groupings allow physicians to make early yet prudent decisions regarding adjuvant combination therapies. The current study presents results from a statistical analysis that enables the natural identification of such prognostic groups. METHODS Examination of consecutive radical prostatectomy specimens was performed between January 1991 and December 1995 at Wayne State University, Harper Hospital, Detroit, Michigan. Disease free survival in a cohort of 485 of these men was analyzed using recursive partitioning and amalgamation technique. Clinicopathologic parameters evaluated included age, race, preoperative prostate specific antigen (PSA) level, clinical and pathologic stage, and Gleason grade of the fine-needle biopsy as well as the radical prostatectomy specimen. RESULTS A binary decision tree representation was generated for classifying patients based on the clinicopathologic variables mentioned earlier. The worst prognosis was for patients with either advanced stage and a PSA level > 24.1 ng/mL or advanced stage, a PSA level ≤ 24.1 ng/mL, and age ≤ 65 years. This group had an estimated median disease free survival of only 10.3 months. Patients with lower pathologic stage, prostatectomy Gleason scores of ≤ 7, and a preoperative PSA level ≤ 22.7 ng/mL had the best prognosis. CONCLUSIONS The recursive partitioning analyses allows easy characterization of a patient for prognosis shortly after radical prostatectomy. This will enable a physician to make more prudent decisions regarding whether to employ watchful waiting, proceed with accepted adjuvant therapy (radiotherapy or hormonal therapy), or refer patients to a research center that is able to administer experimental adjuvant therapy. [See editorial counterpoint on pages 232-3 and reply to counterpoint on pages 234-5, this issue.] Cancer 2000;89:404–11. © 2000 American Cancer Society.

Modified Extrafascial Radical Retropubic Prostatectomy Technique Decreases Frequency of Positive Surgical Margins in T2 Cancers

Objectives: In an effort to decrease the frequency of postoperative positive surgical margins (+SM), a modified extrafascial radical prostatectomy technique was developed and evaluated.Methods: 402 consecutive radical prostatectomy specimens removed for clinical stage T2 cancers from 1987 to 1994 were histologically examined prospectively for tumor volume, extraprostatic extension and +SM. Surgical technique modification was introduced in 1990. We compared the histologic status and biological outcome of the prostatectomy cases in 1987–1989 (n = 166) to those treated from 1990 to 1994 (n = 236).Results: The two series were comparable in (1) clinical stage and preoperative (PSA, (2) tumor volume, grade and location, and (3) capsular penetration, seminal vesicle and lymph node status. +SM fell from 32 to 25% overall, but for 146 (36%) prostates with a tumor volume <2 cm³, +SM fell from 21 to 6% which was statistically significant. Outcome measured by biological progression showed a decrease from 33% for +SM to 13% for –SM for cases with a tumor volume <2 cm³. For cancer volumes >2 cm³, the incidence of +SM did not vary significantly. We describe the anatomic details necessary for exposure of periprostatic fascias and extrafascial dissection at (1) the prostatourethral junction which ensures wide excision of the anterior and apical aspect of the prostate, (2) the posterior and apical area (development of the prerectal space), lateral and posterior areas at the base of the prostate which ensures wide excision of the rectoprostatic fascia (Denonvilliers’s fascia) and lateral prostatic fascia.Conclusions: Differences in surgical technique probably accounted for the significant decrease in +SM for those T2 cancers with volumes ≤2 cm³ which represents 36% of the T2 cancers in our series. Recent screening with PSA (T1c cancers) increases the incidence of these cancers ≤2cm³. This modified uni– or bilateral anatomic extrafascial prostatectomy with improved +SM and biological progression rates for T2 cases should be evaluated for T1c cases.

Extent of extracapsular extension in localized prostate cancer

Objectives. To measure the radial extent of extracapsular penetration by tumor cells, thereby providing estimates of the margins needed around target volumes. New radiotherapeutic techniques, like brachytherapy and conformal radiotherapy, irradiate small volumes and reduce the dose to periprostatic tissues. Even in the early stages of localized prostate cancer, extracapsular extension (ECE) is commonly seen. Methods. Two hundred sixty-five consecutive radical prostatectomy specimens were analyzed for the presence of ECE. ECE was found in 92 of all cases (35%); measurements were performed in 79 of the 92 cases. A total of 98 ECE sites were evaluated in the 79 cases. The distance of tumor outside the capsule was measured in millimeters. Extension less than 0.1 mm was considered as “focal.” Results. The site of ECE was posterolateral in 53% of cases, lateral in 24%, posterior in 13%, and at the base in 10%. The median amount of ECE at all sites was 1.1 mm (mean 1.7). However, the range was wide; the minimum measurable extent was 0.1 mm and the maximum 10.0 mm. The extent was within 3.8 mm for 90% of all cases. By stratifying cases with favorable and unfavorable tumors, the 90th percentiles of ECE were as follows: 3.3 mm for favorable tumors (clinical Stage T1-2, initial prostate-specific antigen 10 ng/mL or less, and biopsy Gleason score 6 or less) and 3.9 mm for unfavorable tumors (clinical Stage T3, initial prostate-specific antigen greater than 10 ng/mL, or biopsy Gleason score 7 or greater). Conclusions. Most of the ECE was at posterolateral sites. The extent of disease outside the prostate was within 4 mm in 90% of cases. Since ECE was observed in 30% to 60% of all patients with clinical Stage T1-2 prostate cancer, only 3% to 7% of all such cases would have disease extent exceeding 4 mm. The present study provides useful estimates of the amount of ECE. These estimates could be potentially used in planning the target volumes for treatment of prostate cancer with either conformal radiotherapy or brachytherapy.

Relationship of p21(WAF1) expression with disease-free survival and biochemical recurrence in prostate adenocarcinomas (PCa).

The p21(WAF1) gene is considered to be one of the major regulators of the cell cycle. Its level of expression has been shown to correlate with pathologic stage and Gleason score in prostatic cancer. However, its relationship to clinical outcome is not yet well-characterized. Immunohistochemical staining for p21(WAF1) protein expression was performed in 62 consecutive radical prostatectomy specimens from our institution. The results were correlated with the disease-free survival and biochemical recurrence of the patients. Thirty-four of the 62 patients were Caucasian and 28 were African American. There was a significant correlation between p21(WAF1) expression and biochemical recurrence after radical prostatectomy (P < 0.0095). However, while p21(WAF1) staining in prostate cancer was a prognostic indicator of disease-free survival in Caucasians (P < 0.0001), it appeared not to be a factor in African-American men (P = 0.908). This study suggests that p21(WAF1) may have a role in the pathogenesis and progression of prostate carcinoma, and may serve as a predictor of biochemical recurrence of this tumor. The differences in the values of p21(WAF1) as a prognostic marker of disease-free survival in Caucasians vs. African Americans suggest that progression of prostate cancer may have different mechanisms in different ethnic groups.

Relationship of p21WAF1 expression with disease‐free survival and biochemical recurrence in prostate adenocarcinomas (PCa)

BACKGROUND The p21WAF1 gene is considered to be one of the major regulators of the cell cycle. Its level of expression has been shown to correlate with pathologic stage and Gleason score in prostatic cancer. However, its relationship to clinical outcome is not yet well-characterized. METHODS Immunohistochemical staining for p21WAF1 protein expression was performed in 62 consecutive radical prostatectomy specimens from our institution. The results were correlated with the disease-free survival and biochemical recurrence of the patients. RESULTS Thirty-four of the 62 patients were Caucasian and 28 were African American. There was a significant correlation between p21WAF1 expression and biochemical recurrence after radical prostatectomy (P < 0.0095). However, while p21WAF1 staining in prostate cancer was a prognostic indicator of disease-free survival in Caucasians (P < 0.0001), it appeared not to be a factor in African-American men (P = 0.908). CONCLUSIONS This study suggests that p21WAF1 may have a role in the pathogenesis and progression of prostate carcinoma, and may serve as a predictor of biochemical recurrence of this tumor. The differences in the values of p21WAF1 as a prognostic marker of disease-free survival in Caucasians vs. African Americans suggest that progression of prostate cancer may have different mechanisms in different ethnic groups. Prostate 40:256–260, 1999. © 1999 Wiley-Liss, Inc.

Should African‐American men be tested for prostate carcinoma at an earlier age than white men?

BACKGROUND. There have recently been challenges to testing high risk populations, i.e., African-American men younger than 50 years, for prostate carcinoma (PCa). The mortality rate of patients with PCa between ages 40 and 60 years is nearly 3 times greater among African-American men (AAM) compared with white men (WM). The literature in support of testing AAM at an earlier age than WM is sparse. Therefore, the authors present clinical and histologic data that support the testing of AAM at a younger age, utilizing data on patients with clinically localized PCa. METHODS. Examination of consecutive radical prostatectomy specimens from AAM and WM was performed from January 1991 to June 1996 among AAM and WM at Wayne State University, Harper Hospital, Detroit, Michigan. International, salvage prostatectomy, and neoadjuvant hormonal therapy patients were excluded, as were patients with lymph node metastasis. The authors examined biochemical recurrences of PCa in this cohort of men treated from January 1991 through December 1995. Univariate analysis of contingency tables was performed, using chi-squared-tests to assess the correlation between stage and race after stratification of patients by age group. Biochemical recurrence was analyzed using the Kaplan-Meier method and the log rank test. RESULTS. The authors examined radical prostatectomy specimens from 759 patients and biochemical recurrence outcome of 655 patients. AAM patients ages 50-69 years had higher prostate specific antigen levels, worse Gleason scores, more advanced stages of disease, and a higher recurrence rate. However, among men ages70-79 years, there was no difference in these parameters between AAM and WM. Among men ages 40-49 years, a larger sample size is necessary to make meaningful comparisons. CONCLUSIONS. Data on the outcomes of men treated for clinically localized PCa demonstrated more advanced disease and more frequent recurrence among young AAM than among WM, young and of advanced age. These differences in disease severity and recurrence, in addition to the disproportionate mortality among young AAM, are strong evidence that AAM should be tested for PCa at an earlier age than WM.

Should African-American men be tested for prostate carcinoma at an earlier age than white men?

There have recently been challenges to testing high risk populations, i.e., African-American men younger than 50 years, for prostate carcinoma (PCa). The mortality rate of patients with PCa between ages 40 and 60 years is nearly 3 times greater among African-American men (AAM) compared with white men (WM). The literature in support of testing AAM at an earlier age than WM is sparse. Therefore, the authors present clinical and histologic data that support the testing of AAM at a younger age, utilizing data on patients with clinically localized PCa. Examination of consecutive radical prostatectomy specimens from AAM and WM was performed from January 1991 to June 1996 among AAM and WM at Wayne State University, Harper Hospital, Detroit, Michigan. International, salvage prostatectomy, and neoadjuvant hormonal therapy patients were excluded, as were patients with lymph node metastasis. The authors examined biochemical recurrences of PCa in this cohort of men treated from January 1991 through December 1995. Univariate analysis of contingency tables was performed, using chi-squared-tests to assess the correlation between stage and race after stratification of patients by age group. Biochemical recurrence was analyzed using the Kaplan-Meier method and the log rank test. The authors examined radical prostatectomy specimens from 759 patients and biochemical recurrence outcome of 655 patients. AAM patients ages 50-69 years had higher prostate specific antigen levels, worse Gleason scores, more advanced stages of disease, and a higher recurrence rate. However, among men ages 70-79 years, there was no difference in these parameters between AAM and WM. Among men ages 40-49 years, a larger sample size is necessary to make meaningful comparisons. Data on the outcomes of men treated for clinically localized PCa demonstrated more advanced disease and more frequent recurrence among young AAM than among WM, young and of advanced age. These differences in disease severity and recurrence, in addition to the disproportionate mortality among young AAM, are strong evidence that AAM should be tested for PCa at an earlier age than WM.

Bcl-2 Oncoprotein Positivity and High MIB-1 (Ki-67) Proliferative Rate Are Independent Predictive Markers for Recurrence in Prostate Carcinoma

Predicting the clinical behavior of prostate carcinoma can be difficult; one approach is to identify molecular prognostic markers. We evaluated proliferative rate (MIB-1 antibody) and expression of bcl-2, p53, and retinoblastoma (pRB) proteins, which have cell cycle-related functions, in 208 consecutive radical prostatectomy specimens. Values were correlated with histopathologic parameters (Gleason tumor score, tumor amount, capsule invasion, and involvement of surgical margins, seminal vesicles, or lymph nodes) and with recurrence-free survival (4-year median follow-up). A high MIB-1 proliferative rate was associated with all of the measured histopathologic parameters, p53 overexpression with tumor amount, and pRB expression with positive lymph nodes. pRB and p53 expression levels were not associated with differences in recurrence-free survival. A high MIB-1 proliferative rate and bcl-2 positivity were associated with increased recurrence, both considered individually, and also independently and additively when examined together and with the most predictive histopathologic factors (Gleason tumor score and seminal vesicle involvement). MIB-1 proliferative rate and bcl-2 positivity may prove to be useful markers for poor prognosis in prostate carcinoma.