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BACKGROUND:Selecting appropriate candidates for postprostatectomy radiotherapy is challenging, because adverse pathological features cannot accurately predict clinical recurrence. Biomarkers that identify residual disease activity may assist clinicians when counseling patients on the risks, benefits and costs of secondary treatment. NADiA ProsVue PSA slope results ⩽2.0 pg ml−1 month−1 are predictive of a reduced risk of clinical recurrence; however, its clinical utility has not yet been studied.METHODS:We prospectively enrolled men treated by radical prostatectomy in a multicenter, institutional review board-approved clinical trial. At postsurgical follow-up, investigators (N=17) stratified men into low-, intermediate- or high-risk groups for prostate cancer recurrence based on clinicopathological findings and other factors. Investigators documented their initial treatment plan for each subject and serially collected three serum samples for ProsVue testing. After the ProsVue result was reported, investigators recorded whether or not the initial treatment plan was changed. The proportion of cases referred for secondary treatment before and after ProsVue was reported, and the significance of the difference determined.RESULTS:Complete assessments were reported for 225 men, 128 (56.9%) of whom were stratified into intermediate- and high-risk groups. Investigators reported that they would have referred 41/128 (32.0%) at-risk men for secondary treatment. However, after results were known, they referred only 15/128 (11.7%) men. The difference in proportions (−20.3%, 95% confidence interval (CI) −29.9 to −10.3%) is significant (P<0.0001). Odds of a referral was significantly reduced after results were reported (odds ratio 0.28, 95% CI 0.15-0.54, P<0.0001).CONCLUSIONS:Knowledge of a ProsVue result had significant impact on the final treatment plan. A ProsVue result ⩽2.0 pg ml−1 month−1 significantly reduced the proportion of men at risk of recurrence who otherwise would have been referred for secondary treatment. [ABSTRACT FROM AUTHOR]

Background:Standard treatment options are limited for the management of non-metastatic castration-resistant prostate cancer (CRPC). This study, part of the ENTHUSE (EndoTHelin A USE) phase III programme, evaluated the efficacy and safety of the oral specific endothelin (ET)A receptor antagonist zibotentan vs placebo in patients with non-metastatic CRPC (non-mCRPC).Methods:This was a multicentre, randomized, double-blind, phase III study. Patients (n=1421) with non-mCRPC and biochemical progression (determined by rising serum PSA levels) were randomized to receive zibotentan 10 mg or placebo once daily. Based on the lack of efficacy signal in another ENTHUSE phase III study, an interim analysis was performed to determine whether the study was likely to achieve the co-primary objectives of improved overall survival (OS) and progression-free survival (PFS).Results:Criteria for continuation of this study were not met. A total of 79 deaths and 293 progression events were recorded at final data cutoff. Zibotentan-treated patients did not significantly differ from placebo-treated patients for OS (hazard ratio (HR): 1.13; 95% confidence interval (CI): 0.73-1.76, P=0.589) or PFS (HR: 0.89; 95% CI: 0.71-1.12, P=0.330). The most commonly reported adverse events in zibotentan-treated patients were peripheral oedema (37.7%), headache (26.2%) and nasal congestion (24.9%); each occurred with >15% higher incidence than in the placebo group.Conclusions:This trial was terminated early because of failure at interim analysis of the efficacy data to meet the defined criteria for continuation. Owing to the absence of demonstrable survival benefits in the ENTHUSE clinical studies, zibotentan is no longer under investigation as a potential treatment for prostate cancer. [ABSTRACT FROM AUTHOR]

Background:To investigate racial differences in tumor burden (cancer volume, cancer percentage and cancer to PSA ratios) in a large cohort of men undergoing radical prostatectomy (RP).Methods:Demographic, clinical and pathological data of patients undergoing RP between 1993-2010 were reviewed and compared between African-American (AA) and non African-American (nAA) men. Further assessments of pathological tumor burden (estimated tumor volume, percent of cancer involvement, and estimated tumor volume/PSA ratios) were performed across Gleason score categories.Results:Of 4157 patients in the analysis, 604 (14.5%) were AA. Overall, AA patients were younger, had higher Gleason scores, PSA levels and incidence of palpable disease (all P<0.001). Despite comparable prostate weights (39.4 vs. 39.6 g), AA men had higher percent cancer involvement and estimated tumor volume (all P<0.001) but similar estimated tumor volume/PSA ratios (P>0.05). When stratified by Gleason scores, prostate weights were comparable; however, estimated tumor volume, percent cancer involvement and estimated tumor volume/PSA ratios were higher in AA men with low grade (6) prostate cancer (PCa), similar in intermediate grade (7-8) and lower in high grade (9-10) PCa compared to nAA men.Conclusions:In this large series, AA patients had higher disease burden (estimated tumor volume, percent cancer involvement, estimated tumor volume/PSA ratios) compared to nAA but this association was especially pronounced in low grade (Gleason 6) cancers. These data depict a complex picture of relations between race and tumor burden across the spectrum of PCa aggressiveness. Further investigation is warranted to understand the mechanisms of racial disparities in PCa. [ABSTRACT FROM AUTHOR]

Background:Active surveillance (AS) is increasingly utilized in low-risk prostate cancer (PC) patients. Although black race has traditionally been associated with adverse PC characteristics, its prognostic value for patients managed with AS is unclear.Methods:A retrospective review identified 145 patients managed with AS at the Duke Prostate Center from January 2005 to September 2011. Race was patient-reported and categorized as black, white or other. Inclusion criteria included PSA <10 ng ml−1, Gleason sum 6, and 33% of cores with cancer on diagnostic biopsy. The primary outcome was discontinuation of AS for treatment due to PC progression. In men who proceeded to treatment after AS, the trigger for treatment, follow-up PSA and biopsy characteristics were analyzed. Time to treatment was analyzed with univariable and multivariable Cox proportional hazards models and also stratified by race.Results:In our AS cohort, 105 (72%) were white, 32 (22%) black and 8 (6%) another race. Median follow-up was 23.0 months, during which 23% percent of men proceeded to treatment. The demographic, clinical and follow-up characteristics did not differ by race. There was a trend toward more uninsured black men (15.6% black, 3.8% white, 0% other, P=0.06). Black race was associated with treatment (hazard ratio (HR) 2.93, P=0.01) as compared with white. When the analysis was adjusted for socioeconomic and clinical parameters at the time of PC diagnosis, black race remained the sole predictor of treatment (HR 3.08, P=0.01). Among men undergoing treatment, the trigger was less often patient driven in black men (8 black, 33 white, 67% other, P=0.05).Conclusions:Black race was associated with discontinuation of AS for treatment. This relationship persisted when adjusted for socioeconomic and clinical parameters. [ABSTRACT FROM AUTHOR]

Background:Incremental cost-effectiveness ratios (ICERs) of finasteride for prostate cancer prevention are consistent with estimates beyond $100 000 per quality-adjusted life-year (QALY). The majority of these analyses are based on chemoprevention starting in men aged 50-55 years. We sought to evaluate the impact of varying both age at commencement of therapy and length of therapy on the cost-effectiveness of finasteride.Methods:A probabilistic Markov model was designed to estimate lifetime prostate health-related costs and quality-adjusted survival for men receiving or not receiving chemoprevention with finasteride. ICERs across scenarios varying age at start of therapy and duration of chemoprevention were compared.Results:The ICER for men starting chemoprevention at age 50 and continuing to age 75 was $88 800 per QALY when assuming finasteride causes a constant risk reduction across all tumor grades (base case 1) and $142 300 per QALY when assuming a differential treatment effect according to Gleason score (base case 2). When starting age is increased, the ICERs trend downward and nadir at 65 years to $64 700 per QALY (base case 1) and $118 600 per QALY (base case 2). Altering duration of therapy had minimal impact. Patient-level experiences with finasteride and BPH significantly influenced the cost-effectiveness of chemoprevention.Conclusions:Initiating chemoprevention at ages when prostate cancer incidence is higher improves its cost-effectiveness profile. Only when assuming a constant risk reduction for all tumor grades, did finasteride fall below $100 000 per QALY, but this finding was not upheld when accounting for side effects associated with the drug. [ABSTRACT FROM AUTHOR]

The American Cancer Society's updated screening guidelines for prostate cancer (CaP) render digital rectal examination (DRE) optional. We investigated the impact of DRE on CaP detection among obese men. Data from 2794 men undergoing initial prostate biopsy at three centers were analyzed to assess CaP risk attributed to abnormal DRE across body mass index (BMI) categories. Predictive accuracies of a combination of PSA, age, race, center and biopsy year including or excluding DRE findings were compared by areas under the receiver-operating characteristics curves. In all cohorts, obese men were less likely to have abnormal DREs diagnosed than non-obese men. As BMI category increased, abnormal DREs became stronger predictors for overall CaP in individual (P-trends0.05) and combined (P-trend<0.001) cohorts, and for high-grade CaP in the Italian (P-trend=0.03) and combined (P-trend=0.03) cohorts. DRE inclusion improved the predictive accuracy for overall and high-grade CaP detection among all obese men (P0.032) but not normal-weight men (P0.198). DRE inclusion also near-significantly improved overall CaP detection in obese men with PSA<4 ng ml-1 (P=0.081). In conclusion, the predictive value of DRE is dependent on obesity and is significantly higher among obese men than normal-weight men. [ABSTRACT FROM AUTHOR]

The objective of this study was to preoperatively predict non-organ-confined disease in patients considering radical prostatectomy. To account for the stage migration seen in prostate cancer, we included only those patients who underwent prostatectomy after the year 2000. Information on a cohort of 1895 patients who underwent radical prostatectomy from 2000 to 2008 was retrieved from the Duke Prostate Center database. Race (African American, non-African American), body mass index, age at surgery, PSA, biopsy Gleason sum (<7, 7 and >7) and clinical tumor stage (cT1, cT2/3) were analyzed by univariate analysis followed by logistic regression analysis. The Duke Interactive Clinical Equation for staging (DICE-S score) was calculated from the logistic regression model. The model was then internally validated using a bootstrapping technique. Biopsy Gleason sums 7 and >7 were more likely to have non-organ-confined disease compared with <7 (OR=2.97, Gleason sum=7; OR=3.25, Gleason sum>7). Clinical tumor stage, cT2/3, predicted non-organ-confined disease (OR=1.58). Older age was associated with non-organ-confined disease (OR=1.02), as was greater PSA (OR=1.12). DICE-S equation x=ln (p/1−p)=−3.627+0.019 (age)+0.109 (PSA)+1.087 (bGleason=7)+1.180 (bGleason >7)+0.459 (clinical T stage >T1), where p=(ex)/(1+ex). A concordance index (prediction accuracy) of 0.73 was reached on internal validation. Using the DICE-S score, age, PSA, biopsy Gleason sum and clinical tumor stage, we can predict non-organ-confined disease in radical prostatectomy at an acceptable accuracy. Preoperative information on disease stage may aid in treatment decisions and surgical approach. [ABSTRACT FROM AUTHOR]

To evaluate whether race modifies the accuracy of nomograms to predict biochemical recurrence (BCR) after radical prostatectomy among subjects from the Shared Equal Access Regional Cancer Hospital (SEARCH) and Duke Prostate Center (DPC) databases. Retrospective analysis of 1721 and 4511 subjects from the SEARCH and DPC cohorts, respectively. The discrimination accuracy for BCR of seven previously published predictive models was assessed using concordance index and compared between African-American men (AAM) and Caucasian men (CM). AAM represented 44% of SEARCH and 14% of DPC. In both cohorts, AAM were more likely to experience BCR than CM (P<0.01). In SEARCH, the mean concordance index across all seven models was lower in AAM (0.678) than CM (0.715), though the mean difference between CM and AAM was modest (0.037; range 0.015–0.062). In DPC the overall mean concordance index for BCR across all seven nomograms was 0.686. In contrast to SEARCH, the mean concordance index in DPC was higher in AAM (0.717) than CM (0.681), though the mean differences between CM and AAM was modest (−0.036; range −0.078 to −0.004). Across all seven models for predicting BCR, the discriminatory accuracy was better among CM in SEARCH and better among AAM in DPC. The mean difference in discriminatory accuracy of all seven nomograms between AAM and CM was approximately 3–4%. This indicates that currently used predictive models have similar performances among CM and AAM. Therefore, nomograms represent a valid and accurate method to predict BCR regardless of race. [ABSTRACT FROM AUTHOR]

Obesity is associated with increased risk of positive surgical margins and prostate specific antigen (PSA) recurrence among men undergoing radical prostatectomy. To what degree positive margins contribute to poorer outcome is unclear. Thus, we sought to examine the association between body mass index (BMI) and more objective measures of tumor aggressiveness, tumor grade and size. We carried out a retrospective analysis of 2302 patients treated with radical prostatectomy at the Duke Prostate Center from 1988–2007. Tumor volume was calculated by multiplying prostate weight by percent of specimen involved with cancer. Associations between BMI and tumor volume and high-grade disease (Gleason4+3) independent of pre-operative clinical characteristics of age, race, PSA, clinical stage, biopsy Gleason sum, and year of surgery were assessed using linear and logistic regression, respectively. Mean and median BMI among all subjects was 28.1 and 27.6 kg m–2, respectively. Increased BMI was significantly associated with younger age (P<0.001), black race (P<0.001), more recent year of surgery (P<0.001), and positive surgical margins (P<0.001). After adjusting for multiple clinical pre-operative characteristics, higher BMI was associated with a greater percent of the prostate involved with cancer (P=0.003), increased tumor volume (P<0.001), and high-grade disease (P=0.007). Men with a BMI 35 kg m2 had nearly 40% larger mean tumor volumes than normal weight men (5.1 versus 3.7 cc), after adjustment for multiple clinical characteristics. In this study, obese men undergoing radical prostatectomy had higher-grade and larger tumors, providing further evidence that obese men undergoing radical prostatectomy have more aggressive prostate cancers. [ABSTRACT FROM AUTHOR]

We hypothesized that factors beyond pathological stage, grade, PSA and margin status would be important predictors of biochemical recurrence (BCR) after radical prostatectomy (RP). A cohort of 3194 patients who underwent RP between 1988 and 2007 and who had neither neoadjuvant therapy nor postoperative adjuvant hormonal therapy was retrieved from the Duke Prostate Center database. Age, prostate-specific antigen (PSA), pathological Gleason score (pG), lymph node status, seminal vesicle invasion (SVI), extracapsular extension (ECE), positive surgical margin (PSM) status, year of surgery, race, adjuvant radiation therapy (XRT), percent tumor involvement in the RP specimen and prostate weight were evaluated as possible predictors of BCR in multivariate Cox regression analysis. BCR was defined as a PSA of 0.2 ng ml−1 or higher at least 30 days after surgery. A nomogram was developed from the Cox model. Predictive accuracy was obtained by calculating bias-corrected Harrell's c and by bootstrap calibration. In multivariate analysis, PSA (hazard ratio 1.39 (95% confidence interval 1.29–1.51)), ECE (1.22 (1.04–1.44)), pG score (1.38 (1.14–1.68), 2.23 (1.76–2.84), 2.69 (2.12–3.40) for pG 3+4, 4+3, >7, respectively), SVI (1.72 (1.40–2.12)), PSM (2.05 (1.73–2.42)), year of surgery (0.65 (0.54–0.77)), African-American race (1.37 (1.13–1.66)), adjuvant XRT (0.19 (0.11–0.34)) and prostate weight (0.83 (0.76–0.92)) were identified as independent predictors of BCR (P0.018 for all factors). Predictive accuracy of the nomogram was 0.75. Race and prostate weight were independent predictors for BCR after RP. By incorporating these variables, we developed a nomogram, which provides a highly accurate means for estimating risk of BCR after RP.Prostate Cancer and Prostatic Diseases (2008) 11, 371–376; doi:10.1038/pcan.2008.18; published online 22 April 2008 [ABSTRACT FROM AUTHOR]

To determine the timing and patterns of late recurrence after radical prostatectomy (RP) alone or RP plus adjuvant radiotherapy (RT). Between 1970 and 1983, 159 patients underwent RP for newly diagnosed adenocarcinoma of the prostate and were found to have positive surgical margins, extracapsular extension and/or seminal vesicle invasion. Of these, 46 received adjuvant RT and 113 did not. The RT group generally received 45–50 Gy to the whole pelvis, then a boost to the prostate bed (total dose of 55–65 Gy). In the RP group, 62% received neoadjuvant/adjuvant androgen deprivation vs 17% in the RT group. Patients were analyzed with respect to timing and patterns of failure. Only one patient was lost to follow-up. The median follow-up for surviving patients was nearly 20 years. The median time to failure in the surgery group was 7.5 vs 14.7 years in the RT group (P=0.1). Late recurrences were less common in the surgery group than the RT group (9 and 1% at 10 and 15 years, respectively vs 17 and 9%). In contrast to recurrences, nearly half of deaths from prostate cancer occurred more than 10 years after treatment. Deaths from prostate cancer represented 55% of all deaths in these patients. Recurrences beyond 10 years after RP in this group of patients were relatively uncommon. Despite its long natural history, death from prostate cancer was the most common cause of mortality in this population with locally advanced tumors, reflecting the need for more effective therapy.Prostate Cancer and Prostatic Diseases (2006) 9, 254–260. doi:10.1038/sj.pcan.4500903; published online 1 August 2006 [ABSTRACT FROM AUTHOR]

PSGR is a novel member of the G-protein-coupled olfactory receptor family. Our initial report showed predominant expression of the PSGR in human prostate gland and significant alterations of PSGR expression in primary prostate cancer (CaP) specimens. The aim of this study was to provide in-depth evaluations of the expression profile of PSGR in prostatic epithelial cells of CaP patients and to evaluate the association of PSGR expression characteristics with clinico-pathologic features. In total, 220 RNA specimens, from laser capture microdissected paired benign and malignant prostatic epithelial cells of 110 CaP patients, were analyzed for PSGR expression by quantitative real-time PCR. The differential expression of PSGR between the prostatic epithelial cells of malignant and benign glands was statistically significant (P<0.0001). Comparison of PSGR expression between paired benign and tumor cells revealed prostate tumor cell-specific overexpression in 67.2% of tumor specimens (74 of 110), decreased expression in 20.9% of tumor specimens (23 of 110) and no difference of PSGR expression between tumor and normal cells in 11.8% of specimens (13 of 110). In representative cases, PSGR expression patterns were independently confirmed by in situ RNA hybridization. The PSGR overexpression associated with higher percentage of pathologic stage, pT3, and a higher level of preoperative serum PSA. CaP cells of African-American CaP patients exhibited about two-fold increase of PSGR expression in comparison to the Caucasian American CaP patients. Strikingly high-percentage CaP cells overexpress PSGR warrants further studies of PSGR expression alterations to define subsets of CaPs.Prostate Cancer and Prostatic Diseases (2006) 9, 56–61. doi:10.1038/sj.pcan.4500836; published online 18 October 2005 [ABSTRACT FROM AUTHOR]

Introduction and Objectives: The efficacy of adjuvant and salvage external beam radiation (AXRT+SXRT) for prostate cancer after radical prostatectomy (RP) has been debated because of the inability to rule out systemic occult metastasis, uncertainty that radiation eradicates residual local disease and the potential of exacerbating impotency and incontinence. To characterize the effectiveness and treatment morbidity a retrospective review was performed.Methods: In all, 38 patients received AXRT and 91 received SXRT. The SXRT group was stratified by PSA level, age, race, pathologic stage, margin status, worst Gleason sum, radiation dose and pelvic field. Complications evaluated were impotence and incontinence. Median follow-up was 60.2 months.Results: The 5-y disease-free survival (DFS) rate was 61.3% for AXRT and 36.3% for SXRT. Multivariate analysis of the SXRT cohort showed Gleason score, pathologic stage and pre-XRT PSA to be predictors of disease recurrence. After XRT 26% had worsened continence.Conclusions: Patients who recur after RP whose pathologic stage is pT2 or pT3c, Gleason score of 8 or higher or pre-XRT PSA is >2.0?ng/dl may have microscopic metastatic disease and a decreased chance of cure with SXRT alone. Continence was further impaired after XRT.Prostate Cancer and Prostatic Diseases (2004) 7, 170-177. doi:10.1038/sj.pcan.4500718 Published online 11 May 2004 [ABSTRACT FROM AUTHOR]

Objectives: A wide range of p53 mutations (5-65%), detected by various methods, has been reported in primary prostate cancers (CaP). IHC staining of radical prostatectomy specimens shows marked heterogeneity of focally distributed p53-positive cells. However, a significant relationship between the focal staining of p53 and cancer recurrence after radical prostatectomy has been noted. Increased frequency of p53 mutations has been generally observed in advanced stage CaP and metastatic prostate cancer cell lines. The significance of focal p53 immunostaining in primary CaP remains uncertain with respect to the p53 gene mutation or tumor progression. The goal of this study was to evaluate p53 gene mutations in focal regions of primary prostate cancers positive by p53 immunostaining.Methods: Whole-mount prostates from men with clinically organ-confined prostate cancer were immunostained for p53 protein. Laser capture microdissection (LCM) was used to harvest p53 positive cells from areas of tumor and prostatic intraepithelial neoplasia and benign gland. DNA from microdissected cells were amplified for p53 exons 5-8 by polymerase chain reaction (PCR) and analyzed for mutations by single strand conformation polymorphism and DNA sequencing. Mutation analysis of the p53 gene exons 5-8 was performed in the p53 immunostaining positive focal regions (1+ to 4+) of whole-mount prostate sections from 16 patients.Results: Of 16 patients with p53 IHC positive tumors, 11 (69%) had p53 gene mutations as determined by DNA sequence analysis. However, randomly microdissected tumor cells from 4 of 18 patients (22%) negative for p53 IHC also demonstrated mutations in the p53 gene. A significant fraction of prostate tumors with focally positive immunostaining for p53 have been confirmed to contain mutations in the p53 gene.Conclusions: p53 immunostaining guided LCM combined with DNA-based analyses emphasizes the presence of focal p53 mutations in primary prostate cancers and underscores the significance of previous observations showing a correlation between focal p53 immunostaining in primary CaP and cancer recurrence after radical prostatectomy.Prostate Cancer and Prostatic Diseases (2003) 6, 281-285. doi:10.1038/sj.pcan.4500665 [ABSTRACT FROM AUTHOR]

Benign prostatic hyperplasia (BPH) involves proliferation of smooth muscle cells and increased deposition of extracellular matrix (ECM). We recently found that pentosan polysulfate (PPS) has marked effects on growth and ECM of smooth muscle cells derived from vascular tissues. We examined smooth muscle cells cultured from human prostates and the effects of PPS on their growth and ECM production. Fragments of surgical prostatectomy specimens were diced, digested with collagenase (0.01%), and placed in culture medium supplemented with 20% fetal bovine serum. Outgrowths of elongated cells were characterized by light microscopic examination and immunohistochemical techniques by the presence of F-actin, a-smooth muscle actin, and myosin, which is a characteristic of smooth muscle cells. Two independent isolates were propagated, and growth curves and ECM production were assessed in the presence and absence of PPS (10 or 100?ug/ml). PPS decreased cell number beginning at day 1 and throughout the incubation period, up to 4 days. The amount of the ECM degradative enzymes, metallo-proteinases MMP-9 and MMP-2, was examined by zymography. PPS did not alter the amount of MMP-2 in the supernatants but MMP-9 was increased 234.4±17.23-fold over control cells. Tissue inhibitor of MMP (TIMPS), examined by reverse zymography, increased 200% over control. The amount of aI type (IV) and aI type (I) collagen released in the supernatant, measured by ELISA, significantly decreased in PPS-treated cultures. In conclusion, we found that the administration of PPS decreased proliferation as well as ECM production in prostate smooth muscle. Since smooth muscle proliferation and ECM are involved in the pathophysiology of BPH, PPS may have therapeutic potential.Prostate Cancer and Prostatic Diseases (2003) 6, 138-142. doi:10.1038/sj.pcan.4500632 [ABSTRACT FROM AUTHOR]

Presents a study which investigated the distribution of prostate cancer using three-dimensional computer simulation. Assessment of the distribution rate of prostate cancer; Development of an algorithm for tumor detection; Patient characteristics of the three-dimensional computer prostate models.

Presents a study which evaluated the efficacy of controlled close step-sectioned and whole-mounted radical prostatectomy specimen processing in the prediction of clinical outcome as compared to the traditional processing techniques. Pathological assessment of specimens; Evaluation of the effectiveness of radical prostatectomy; Use of the multi-variate logistic regression method.

African-American men and black men throughout the world have a higher rate of prostate cancer than other ethnic groups. They also are most likely to present at a younger age with more advanced disease and have historically had a poorer prognosis. Whether this observed difference is due to behavior, lack of access, environmental factors or genetics is hotly debated. Whatever the cause or causes, there is growing concensus that targeting screening to this high-risk group is justified. Focused education about risk and screening in black men can be effective and demonstration screening programs in African-American community settings have been successful. There is much debate about the proper normal values of PSA to be used in screening high risk black men. Some have argued for a very low normal range such as ≤2.0 ng/ml to improve sensitivity for detection of curable disease. Others, recognizing the balance between sensitivity (cancer detection) and specificity (avoiding unnecessary prostate biopsies), have proposed age-adjusted PSA ranges. Until randomized or prospective screening trials are completed, it seems reasonable to encourage black men to start screening at age 40 using a PSA threshold of ≤2.0 to 2.5 ng/ml to prompt further evaluation. Prostate Cancer and Prostatic Diseases (2000) 3, 248–255 [ABSTRACT FROM AUTHOR]

Serum albumin level has been implicated as a prognostic factor in various cancers, however it has not been studied in early stage prostate cancer. We examine the clinical prognostic value of the readily available pretreatment albumin level as a marker for determining staging and prognosis for men undergoing radical prostatectomy. A retrospective review was performed on 354 patients who underwent a radical prostatectomy at a tertiary facility from 15 April, 1990 until 3 December, 1996 who had a pretreatment serum albumin within 6 months prior to surgery. Albumin levels were analyzed and compared to the values of standard prognostic factors to assess the ability of albumin to predict pathological stage and serological recurrence by PSA level after radical prostatectomy. Albumin level was not of value in predicting serological disease recurrence, but interestingly was an independent prognostic factor in predicting risk of nonorgan-confined disease (T3 or T4). Our data also showed that, as expected, grade and pretreatment PSA levels were independent predictors of pathological stage. Albumin appears to be of clinical utility to augment assessment of pretreatment pathological stage. However, it is not of value in predicting serological disease recurrence following radical prostatectomy. Further study in other cohorts and in using additional analysis such as neural networks is indicated. Prostate Cancer and Prostatic Diseases (2000) 3, 186–190 [ABSTRACT FROM AUTHOR]

Urologists routinely use the systematic sextant needle biopsy technique to detect prostate cancer. However, recent evidence suggests that this technique has a significant sampling error and data based upon whole-mounted step-sectioned radical prostatectomy specimens using a three-dimensional computer-assisted prostate biopsy simulator suggests that an increased detection rate is possible using laterally placed biopsies. The simulated 10-core biopsy pattern (traditional sextant biopsy cores and four laterally placed biopsies in the right and left apex and mid portion of the prostate gland) was shown to be superior to the traditional sextant biopsy. The objective of this pilot study was to confirm the higher prostate cancer detection rate obtained using the 10-core biopsy pattern in patients. We reviewed data on 35 consecutive patients with a pathologic diagnosis of prostate cancer biopsied by a single urologist using the 10-core biopsy pattern. The frequency of positive biopsy was determined for each core. Additionally, the sextant and 10-core prostate biopsy patterns were compared with respect to prostate cancer detection rate. Of the 35 patients diagnosed with prostate cancer, 54.3%(19/35) were diagnosed by the sextant biopsy only. The 10-core pattern resulted in an additional 45.7%(16/35) of patients being diagnosed solely with the laterally placed biopsies. The laterally placed biopsies had the highest frequency of positive biopsies when compared to the sextant cores. In conclusion, biopsy protocols that use laterally placed biopsies based upon a five region anatomical model are superior to the routinely used sextant prostate biopsy pattern. Prostate Cancer and Prostatic Diseases (2000) 3, 43–46 [ABSTRACT FROM AUTHOR]

This session included five presentations in the areas of pathology of precursor lesions and carcinoma of the prostate, the value of determining neovascularity in the diagnosis and staging of prostate cancer, new ‘molecular’ markers, correlation between pre- and postoperative Gleason scores and a study dealing with transition zone PSA density. The abstracts and talks are summarized in the next few pages. [ABSTRACT FROM AUTHOR]

Purpose of our study was to develop a reliable model to define clinical stage I nonseminomatous germ cell tumors (NSGCT) being at low risk and at high risk for occult retroperitoneal metastases based on pathohistological and immunohistochemical parameters in order to stratify the therapeutic approach. 3-5 paraffin-embedded formalin fixed tissue blocks of 149 clinical stage I NSGCT were available from all patients and were analyzed for histopathological features associated with pathological stage: presence/absence of vascular invasion, presence/absence of tunical invasion, percentage of each histological cell type present in the primary tumor. Immunohistochemical expression of MIB-1, p53, bcl-2, cathepsin D and e-cadherin was evaluated using a semiquantitative scoring ystem. Statistical analysis was performed by univariate and multivariate logistic regression models. Percentage of embryonal carcinoma [%EC (p < 0.001)] and presence of vascular invasion [VI (p < 0.0001)] were the most significant independent risk factors associated with pathological stage II disease. Combination of %EC and VI allowed correct prediction of final pathological stage in 88% of patients. Cut-off values including both variables identified correct pathological stage in 131/149 patients (88%). Less than 45% EC and absence of VI correctly identified pathological stage I disease in 91.5%; more than 80% EC and presence of VI correctly predicted pathological stage II in 88% of the patients. %EC and presence/absence of VI appear to be reliable prognosticators to identify both patients at high risk and at low risk for occult retroperitoneal disease. P53, bcl-2, MIB-1, cathepsin D and e-cadherin did not appear to be of prognostic value in clinical stage I NSGCT. [ABSTRACT FROM AUTHOR]

Copyright of Der Urologe A is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The purpose of this study was to determine the incidence of patient-self reported post prostatectomy incontinence, impotence, bladder neck contracture or stricture, better, same or worse quality of life and willingness for same treatment again in a large group of radical prostatectomy (RP) patients and to determine if these morbidities are predictable with demographic, surgical or prostate cancer (PC) factors. Methods: A patient self-reporting questionnaire was completed and returned by 374 out of 458 eligible (81.7%) RP patients from one center, 267 (72.2%) have been operated since 1990 and all of whom were a minimum six month postoperative (75%>1 y). Questionnaire results were independently analyzed by a third party and correlated to demographic, operative, and tumor factors in an ongoing comprehensive PC database. Results: The patient self-reported incidence of post prostatectomy incontinence (any degree), impotence, and bladder neck contracture or stricture was 72.2, 87.4, and 25.9%, respectively. The reported rate of incontinence requiring protection was 39.0% and only 2.4% had persistent bladder neck contracture/stricture. Pathologic stage (continuous variable) was the only factor to significantly predict incontinence and no factor could predict impotence or bladder neck contracture/stricture in univariate analysis. No factor was predictive of morbidity by multivariate analysis. Despite incontinence and impotence significantly affecting QOL self-reporting (P=0.001, 0.001, respectively) and willingness to undergo RP again (P=0.001, 0.067, respectively), the majority of patients would choose surgery again. Conclusions: Although radical prostatectomy morbidity is common and affects patient-reported overall QOL, most patients would choose the same treatment again. Demographic, preoperative, operative, and tumor factors did not reliably predict patient-reported morbidity in this series. [ABSTRACT FROM AUTHOR]

Traces the causes of prostate cancer in African American males. Concept of race and prostate cancer; Screening for prostate cancer in African American men; Advantages and disavantages of population-based screening; Proper use of prostate specific antigen in African American men.

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Infection of Renca cells in vitro with a recombinant adenovirus expressing a marker gene β-galactosidase resulted in high level of the transgene expression. Renca tumors grown in Balb/C mice were also infectable with this recombinant adenovirus. The transgene expression in the tumors lasted for about 7 days, however, administration of another dose of Ad-βgal, on day 7 produced β-galactosidase expression. To investigate the effect of antibodies to adenovirus, animals were injected with multiple doses of adenovirus to produce neutralizing antibodies. To these animals Renca cells were injected and tumors formed. Interestingly, when Adβ-gal was administered into these tumors, a high level of transgene expression was still observed. We next explored the utility of a recombinant adenovirus expressing p53 (AdWTp53) in the Renca tumor model. Renca cells when exposed to an adenovirus expressing p53 (AdWTp53) produced a high level of p53 protein, a p53-inducible gene p21/WAF1/Cip1 and underwent apoptosis. A single injection of AdWTp53 (109 plaque forming units) resulted in significant inhibition of tumor growth. However, multiple administrations (four doses of 2.5 × 108 plaque forming units) of AdWTp53 were needed for tumor cures. Mixing uninfected and AdWTp53-infected cells showed a bystander effect of AdWTp53-infected Renca cells. Based on these results we believe that an appropriate dose scheduling of AdWTp53 can be efficacious for cancer gene therapy in immune-competent tumor-bearing animals. [ABSTRACT FROM AUTHOR]

A 65-year-old man with a history of combined pelvic external beam radiation therapy (EBRT) and brachytherapy for prostatic adenocarcinoma 15 years prior underwent total pelvic exenteration for presumed rectal sarcoma with prostatic invasion. Pathology revealed carcinosarcoma of prostatic origin. This patient exhibited the longest reported interval between initial presentation with prostatic adenocarcinoma and development of carcinosarcoma. This case is also the first reported case of prostatic carcinosarcoma occurring after combined EBRT and brachytherapy. The increasing use of such combination high-dose radiation therapy may potentially lead to an increased incidence of secondary malignancies such as prostatic carcinosarcoma in the future.Prostate Cancer and Prostatic Diseases (2006) 9, 195–197. doi:10.1038/sj.pcan.4500870; published online 28 March 2006 [ABSTRACT FROM AUTHOR]

The article discusses various reports published within the issue, including one on isoflavone supplementation in Japanese men experiencing effects on sex steroid production, and another on the effect of hormones and external radiotherapy on long-term quality of life.

Deals with issues concerning the clinical utility of serum prostate-specific antigen (PSA) testing for the early detection of prostate cancer. Concern on the inappropriateness of reassuring men whose PSA is below 4.0 ml that they are unlikely to acquire prostate cancer; Problem of those who advocate the early detection of prostate cancer; Several things to advice in men who may be suffering from localized prostate cancer and who wish to avoid developing advanced disease.

Focuses on a patient awareness campaign that was launched in April 2004, with support from the Prostate Research Campaign in Great Britain. Aim of the campaign; Prevalence of prostate cancer in Great Britain; Medical therapy that reduce disease progression and the incidence of acute urinary retention.

The article discusses various papers published within the issue including one about bone health and prostate cancer, a literature review on the impact of diabetes on prostate cancer and a study on prostate biopsy.

The article discusses various reports published within the issue, including one on the use of biomarkers for prostate cancer screening, and another on genetic polymorphisms.

A correction to the article "Frequent overexpression of ETS-related gene-1 (ERG1) in prostate cancer transcriptome" that was previously published in "Oncogene" is presented.

This article discusses various reports within the issue that pertain to prostate cancer research and treatment, including one about the awareness of prostate cancer among African American men, and one about the use of intensity-modulated radiotherapy to treat cancer.

The article discusses various reports published within the issue on prostate cancer and prostatic diseases.

Introduces several articles on prostate cancer research. Development of a risk progression model for benign prostatic hyperplasia (BPH); Application of complementary and alternative medicines for BPH; Medical screening technique for prostate cancer patients.

Combination hormonal therapy, comprising a luteinising hormone-releasing hormone analogue (LHRHa) with an antiandrogen, is widely used in the treatment of advanced prostate cancer. There is ongoing debate regarding the use of combination hormonal therapy as opposed to LHRHa monotherapy. The pivotal consideration is whether there are adequate benefits with combination hormonal therapy in terms of increased survival and decreased disease progression to outweigh the increased risk of adverse events and additional cost. The most recent meta-analysis by the Prostate Cancer Trialists'Collaborative Group indicates a small but statistically significant survival benefit with combination hormonal therapy using nonsteroidal antiandrogens. It is, however, noteworthy that combined conclusions derived from such meta-analyses may not apply across each of the individual antiandrogens. Individual studies have reported differences between antiandrogens in terms of both tolerability and efficacy-for example, bicalutamide has been shown to be better tolerated than flutamide, and may be associated with improved survival. In addition, it is essential that treatment decisions are taken in consultation with the patient. Owing to an increasing proportion of cases presenting with early-stage disease, combination hormonal therapy is increasingly used in the neoadjuvant or adjuvant setting with radiotherapy and, in cases of prostate-specific antigen recurrence after prior localised therapy. Further data are awaited to optimise the use of combination hormonal therapy in these new settings.Prostate Cancer and Prostatic Diseases (2004) 7, S2-S7. doi:10.1038/sj.pcan.4500741 [ABSTRACT FROM AUTHOR]

Introduces a series of articles about prostate cancer and prostatic diseases.

Editorial. Introduces a series of articles on prostate diseases published in the 2003 issue of "Prostate Cancer and Prostatic Diseases."

Presents information on the development of a complementary DNA microarray for prostate-androgen signaling associated proteins chip. Biologic effects of androgens on prostatic epithelial cells; Evaluation of expression profile in LNCaP cells.

Focuses on the U.S. Department of Defense Center for Prostate Disease Research which began operations in 1992. Use of nomograms; New gene which is only expressed in prostate tissue.