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Management guidelines encourage self-care in patients with symptomatic osteoarthritis (OA). We undertook this study to investigate the relationship between health literacy (HL) and appropriateness of selection of self-care strategies in people with self-reported symptoms of OA.We conducted an online national observational, demographically representative, cross-sectional survey of adults (ages 45-74 years). The eligibility criterion of "self-reported OA symptoms" was screened for using guideline-endorsed clinical criteria. Participants completed a custom-built questionnaire that included validated scales for HL, pain intensity, sleep quality, and OA function/disability. Management strategies were grouped into self-care activities, analgesics, and complementary medicines, and analyses of appropriateness were based on predefined, evidence-based quality indicators.Of 6,800 participants, 628 met the inclusion criteria and completed the survey. HL was categorized as follows: low (100 of 628, 15.9%), moderate (317 of 628, 50.5%), and excellent (211 of 628, 33.6%). In the past 7 days, mean pain intensity (0-10 scale) was 3.11 (95% confidence interval [95% CI] 3.06-3.16), and 71.7% of participants (450 of 628) had not achieved adequate pain relief. In the past month, 54.1% (340 of 628) reported disrupted sleep. Participants managed their pain with multiple self-care activities (mean 1.44; 95% CI 1.32-1.57), analgesics (mean 1.74; 95% CI 1.60-1.88), and complementary medicines (mean 1.01; 95% CI 0.90-1.12). There was a statistically significant (P 0.001) interaction between HL and appropriateness of current management strategies (HL low, guideline-recommended management strategies less likely). Higher HL did not always translate into making appropriate pain management choices.Appropriate selection and use of evidence-based management options is critical for patients with OA to obtain the full benefits from their treatment. Knowledge about suitable choices for OA self-care is suboptimal, and future education should be tailored to different levels of HL.

BACKGROUND For biopsies with Gleason 3 + 3 = 6 or 3 + 4 = 7 prostate cancer, the Genomic Prostate Score (GPS; OncotypeDx) is designed to predict severe pathology at prostatectomy, and, in some cases, recommends reclassification of the National Comprehensive Cancer Network (NCCN) risk category. We hypothesized that certain histopathologic features that were not considered in the original design of the assay actually would be associated with the NCCN risk category change indicated by GPS testing. METHODS For patients with recommended NCCN risk category change, the biopsy cores used for GPS were re-reviewed for stromal reaction, chronic inflammation, and tumor nuclear polarization. RESULTS Of 520 patients from May 2011 to December 2018, GPS testing suggested NCCN risk reclassification in 131 (25%); 127 of these slides were available. Of these, the NCCN risk category increased from intermediate to high in 8, low to intermediate in 15, very low to low in 1, and decreased from intermediate to low in 32, and low to very low in 71. Biopsies with NCCN risk increase were associated with moderate or severe stromal reaction (p

Background Molecular testing of prostate cancer biopsies with Gleason pattern 4 suggests the expansile cribriform pattern is more aggressive than the glomerulation pattern. These two extreme patterns have not been compared at prostatectomy. We hypothesized that at prostatectomy the expansile cribriform pattern would be associated with histopathologic and molecular features of aggressiveness and with greater risk of biochemical recurrence (BCR) than the glomerulation pattern. Methods In a retrospective cohort study, radical prostatectomy reports with expansile cribriform pattern or glomerulation pattern were analyzed for percentage of total pattern 4, extraprostatic extension (EPE), positive lymph nodes, seminal vesicle invasion (SVI), and intraductal carcinoma (IDC). Cases with pattern 5 or with both expansile cribriform and glomerulations patterns present were excluded. The electronic medical record was reviewed for BCR-free survival and for Decipher test results. Results Of 1020 radical prostatectomies from July 2015 to July 2018, 110 (11%) had either expansile cribriform or glomerulation pattern present. The expansile cribriform group was associated with more histopathologic features of aggressiveness, with higher average total percentage pattern 4 (43.7 vs 27.0, P = .002), a trend of greater extensive EPE (32.7% vs 17.2%, P = .06), a trend toward statistical significance of higher rate of SVI (11.5% vs 3.4%, P = .1), greater positive lymph nodes (9.6% vs 0%, P = .02), and a higher percentage of cases with or suspicious for IDC (23.1% vs 8.6%, P = .04). The risk of BCR was 4.4 (1.3-15.4) fold greater for the expansile cribriform group vs the glomerulations group (P = .02). For the 38 patients who underwent Decipher testing, the expansile cribriform group had a high-risk assay category mean score whereas the glomerulations group had an average risk assay category mean score (0.61 vs 0.47, P = .02). Conclusions In a comparison of prostatectomy cases with expansile cribriform pattern to those with glomerulation pattern, the expansile cribriform pattern was associated with more histopathologic features of aggressiveness, greater risk of biochemical failure, and higher scores with a molecular classifier (Decipher) test. These findings underscore the importance of reporting the types of pattern 4 and supports the argument that men with expansile cribriform likely require more aggressive management.

BACKGROUND Risk stratification of patients with urothelial carcinoma of the bladder (UCB) after cystectomy has important clinical and research implications. The authors assessed the relative effect of tumor stage and lymph node status on cancer-specific survival (CSS) after cystectomy and developed a simplified risk-assessment tool. METHODS In total, 14,828 patients who underwent cystectomy with lymph node dissection for UCB were identified from the Surveillance, Epidemiology, and End Results database (1988-2011). The relative importance of tumor stage and lymph node status with regard to CSS was assessed using stratified Kaplan-Meier and Cox proportional-hazards analyses. The patients were split randomly into development and validation cohorts. Additional validation using overall survival was performed on 19,362 patients from the National Cancer Data Base. The Cancer of Bladder Risk Assessment (COBRA) tool was created using a Cox model incorporating age, tumor stage, and lymph node density. Performance was validated using observed versus expected survival plots and the Harrell concordance index. RESULTS Patients with muscle invasive (T2), lymph node-positive disease had a survival curve similar to that in patients with extravesical (T3 and T4), lymph node-negative disease (2-year CSS, 67% and 70%, respectively). Each point increase in the COBRA score (range, 0-7) was associated with a 1.61-fold increase (95% confidence interval, 1.56-fold to 1.65-fold increase) in the risk of bladder cancer death in the development cohort. The model accurately stratified patients across risk levels in the development cohort and the 2 validation cohorts (C-index, 0.712, 0.705, and 0.68, respectively). CONCLUSIONS The COBRA score offers a straightforward, validated risk-stratification tool that incorporates the relative contribution of tumor stage and lymph node involvement to patient prognosis after cystectomy for UCB. Cancer 2017;123:4574-4582. © 2017 American Cancer Society.

Aims Effective transfer of information is vital for rational drug therapy. This is particularly important for older patients, who have a high prevalence of polypharmacy and are managed by multidisciplinary teams. We aimed to assess medicine information exchange (MIE) networks in geriatric medicine wards and whether they are associated with prescribing patterns. Methods We conducted network analysis in acute geriatric medicine wards from four hospitals to characterize MIE networks among multidisciplinary team members. Corresponding patient data were collected to analyze high-risk prescribing in conjunction with network characteristics. Results We found that junior doctors, senior nurses and pharmacists were central to MIE across all four hospitals. Doctors were more likely than other professions to receive medicines information in three hospitals. Reciprocity and the tendency to communicate within one's own profession also influenced network formation. No difference was observed in prescribing practice between hospitals. Conclusions Understanding MIE networks can identify gaps in multidisciplinary communication that can be addressed. Networks may identify targets for dissemination of interventions to improve prescribing.

BACKGROUND Benign tissue from a tumor-containing organ is commonly the only available source for obtaining a patient's unmutated genome for use in cancer research. While it is critical to identify histologically normal tissue that is independent of the tumor lineage, few additional considerations are applied to the choice of this material for such measurements. METHODS Normal formalin-fixed, paraffin-embedded seminal vesicle, and urethral tissues, in addition to whole blood, were collected from 31 prostate cancer patients having undergone radical prostatectomy. Genotype concordance was evaluated for DNA from each tissue source in relation to whole blood. RESULTS Overall, there was a greater genotype call rate for DNA derived from urethral tissue (97.0%) in comparison with patient-matched seminal vesicle tissues (95.9%, P = 0.0015). Furthermore, with reference to patient-matched whole blood, urethral samples exhibited higher genotype concordance (94.1%) than that of seminal vesicle samples (92.5%, P = 0.035). CONCLUSIONS These findings highlight the heterogeneity between diverse sources of DNA in genotype measurement and motivate the consideration of normal tissue biases in tumor-normal analyses. Prostate © 2016 Wiley Periodicals, Inc.

BACKGROUND Given the uncertainties inherent in clinical measures of prostate cancer aggressiveness, clinically validated tissue biomarkers are needed. We tested whether Alpha-2-Glycoprotein 1, Zinc-Binding (AZGP1) protein levels, measured by immunohistochemistry, and RNA expression, by RNA in situ hybridization (RISH), predict recurrence after radical prostatectomy independent of clinical and pathological parameters. METHODS AZGP1 IHC and RISH were performed on a large multi-institutional tissue microarray resource including 1,275 men with 5 year median follow-up. The relationship between IHC and RISH expression levels was assessed using the Kappa analysis. Associations with clinical and pathological parameters were tested by the Chi-square test and the Wilcoxon rank sum test. Relationships with outcome were assessed with univariable and multivariable Cox proportional hazards models and the Log-rank test. RESULTS Absent or weak expression of AZGP1 protein was associated with worse recurrence free survival (RFS), disease specific survival, and overall survival after radical prostatectomy in univariable analysis. AZGP1 protein expression, along with pre-operative serum PSA levels, surgical margin status, seminal vesicle invasion, extracapsular extension, and Gleason score predicted RFS on multivariable analysis. Similarly, absent or low AZGP1 RNA expression by RISH predicted worse RFS after prostatectomy in univariable and multivariable analysis. CONCLUSIONS In our large, rigorously designed validation cohort, loss of AZGP1 expression predicts RFS after radical prostatectomy independent of clinical and pathological variables. Prostate © 2016 Wiley Periodicals, Inc.

BACKGROUND Carotenoids are a class of nutrients with antioxidant properties that have been purported to protect against cancer. However, the reported associations between carotenoids and prostate cancer have been heterogeneous and lacking data on interactions with nucleotide sequence variations and genomic biomarkers. OBJECTIVE To examine the associations between carotenoid levels and the risk of high-grade prostate cancer, also considering antioxidant-related genes and tumor instability. METHODS We measured plasma levels of carotenoids and genotyped 20 single nucleotide polymorphisms (SNP) in SOD1, SOD2, SOD3, XRCC1, and OGG1 among 559 men with non-metastatic prostate cancer undergoing radical prostatectomy. We performed copy number analysis in a subset of these men (n = 67) to study tumor instability assessed as Fraction of the Genome Altered (FGA). We examined associations between carotenoids, genotypes, tumor instability and risk of high-grade prostate cancer (Gleason grade ≥ 4 + 3) using logistic and linear regression. RESULTS Circulating carotenoid levels were inversely associated with the risk of high-grade prostate cancer; odds ratios (OR) and 95% confidence intervals (CI) comparing highest versus lowest quartiles were: 0.34 (95% CI: 0.18–0.66) for α-carotene, 0.31 (95% CI: 0.15–0.63) for β-carotene, 0.55 (0.28–1.08) for lycopene and 0.37 (0.18–0.75) for total carotenoids. SNPs rs25489 in XRCC1, rs699473 in SOD3 and rs1052133 in OGG1 modified these associations for α-carotene, β-carotene and lycopene, respectively (P ≤ 0.05). The proportion of men with a high degree of FGA increased with Gleason Score (P

© 2014 The Authors BJU International © 2014 BJU International Published by John Wiley & Sons Ltd. Objectives To compare directly survival outcomes of primary androgen-deprivation therapy (PADT) in Japan, where this treatment is endorsed by guidelines, with outcomes in the USA, where it is not. Patients and Methods Data were compared between men receiving PADT in the USA Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry and the Japanese Cancer of the Prostate (J-CaP) registry database. Competing risks regression was used to assess prostate cancer-specific mortality (CSM), adjusting for age, Japan Cancer of the Prostate Risk Assessment (J-CAPRA) score, diagnosis year, and treatment type [combined androgen blockade (CAB) vs castration monotherapy], comorbidity, and practice type. Results Men on PADT in J-CaP (13 880 men) were older than those in CaPSURE (1633 men), and had higher-risk disease (mean J-CAPRA score 3.8 vs 2.1, P < 0.001). They more often received CAB: 66.9% vs 46.4% (P < 0.001). Despite different risk profiles between the cohorts, CSM was similar on univariate analysis (log-rank P = 0.88). On multivariable regression, the subhazard ratio for CSM was 0.52 for J-CaP vs CaPSURE (95% confidence interval 0.40-0.68). Conclusions Men on PADT in Japan have less than half the adjusted CSM than those in the USA. These findings support both existing guidelines endorsing PADT in Asia and discouraging its use in the West. Elucidating the reasons behind these substantial differences, which probably include both genetic and dietary/environmental factors, may help explain the varying epidemiology of prostate cancer on either side of the Pacific.

BACKGROUND Observational studies suggest an inverse association between selenium and risk of prostate cancer. However, randomized controlled trials of selenium supplementation have reported conflicting results. Thus, we examined plasma selenium and selenium-related genes in relation to risk of high-grade prostate cancer and prostate cancer recurrence among men initially diagnosed with non-metastatic disease. METHODS We measured plasma selenium and genotyped 73 single nucleotide polymorphisms in TXNRD1, TXNRD2, GPX1, GPX3, GPX4, SEP15, SEPP1, SELENBP1, OGG1, and CAT among 568 men with non-metastatic prostate cancer who underwent radical prostatectomy. We examined associations between plasma selenium, genotypes, and risk of high-grade prostate cancer (Gleason grade ≥8 or 7 with primary score ≥4; n = 111) using logistic regression, and risk of prostate cancer recurrence (61 events; 3.8 y median follow-up) using Cox proportional hazards regression. RESULTS Plasma selenium was not associated with risk of high-grade prostate cancer or prostate cancer recurrence. Less common alleles of rs11913319 in TXNRD2 and rs125701 in OGG1 were associated with an increased risk of high-grade prostate cancer. We observed associations between the risk of prostate cancer recurrence and multiple SNPs in TXNRD1, TXNRD2, GPX3, and SEP15. These associations were no longer statistically significant after adjustment for multiple comparisons. CONCLUSIONS Among men with non-metastatic prostate cancer, there is suggestive evidence that genetic variation in selenoproteins and related antioxidant enzymes may be associated with risk of high-grade disease at diagnosis and prostate cancer recurrence. Prostate 75:60–69, 2015. © 2014 Wiley Periodicals, Inc.

Objective To assess the ability of current nomograms to predict disease progression at repeat biopsy or at delayed radical prostatectomy (RP) in a prospectively accrued cohort of patients managed by active surveillance (AS). Materials and Methods A total of 273 patients meeting low-risk criteria who were managed by AS and who underwent multiple biopsies and/or delayed RP were included in the study. The Kattan (base, medium and full), Steyerberg, Nakanishi and Chun nomograms were used to calculate the likelihood of indolent disease (‘nomogram probability’) as well as to predict ‘biopsy progression’ by grade or volume, ‘surgical progression’ by grade or stage, or ‘any progression’ on repeat biopsy or surgery. We evaluated the associations between each nomogram probability and each progression outcome using logistic regression with (area under the receiver-operating characteristic curve (AUC) values and decision curve analysis. Results The nomogram probabilities of indolent disease were lower in patients with biopsy progression (P < 0.01) and any progression on repeat biopsy or surgical pathology (P < 0.05). In regression analyses, nomograms showed a modest ability to predict biopsy progression, adjusted for total number of biopsies (AUC range 0.52–0.67) and any progression (AUC range 0.52–0.70). Decision curve analyses showed that all the nomograms, except for the Kattan base model, have similar value in predicting biopsy progression and any progression. Nomogram probabilities were not associated with surgical progression in a subgroup of 58 men who underwent delayed RP. Conclusions Existing nomograms have only modest accuracy in predicting the outcomes of patients undergoing AS. Improvements to existing nomograms should be made before they are implemented in clinical practice and used to select patients for AS.

Purpose To investigate the potential clinical utility of endorectal MRI-guided biopsy in patients with known or suspected prostate cancer.

BACKGROUND Prostate cancer treatment after failure of primary therapy by either radical prostatectomy or radiation therapy can vary greatly. This study sought to determine trends and predictors of salvage treatment after failure of primary treatment in a community cohort over the past 10 years. METHODS From the community-based Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) database, 6275 patients were identified who initiated a form of primary treatment for prostate cancer; 839 of these were identified as failing treatment by biochemical recurrence or initiation of secondary treatment between 2000 and 2010. Salvage therapy was categorized as either systemic, local, or none. Patient characteristics were tested for association with salvage therapy using analysis of variance, Pearson chi-square tests, and multinomial logistic regression analysis. RESULTS Of the 839 patients identified as failing therapy, 390 (47%), 146 (17%), and 303 (36%) received systemic, local, or no salvage therapy, respectively. Type of primary treatment received was associated with type of salvage therapy (P

Purpose To evaluate a semiautomatic software-based method of registering in vivo prostate MR images to digital histopathology images using two approaches: (i) in which the prostates were molded to simulate distortion due to the endorectal imaging coil before fixation, and (ii) in which the prostates were not molded. Materials and Methods T2-weighted MR images and digitized whole-mount histopathology images were acquired for 26 patients with biopsy-confirmed prostate cancer who underwent radical prostatectomy. Ten excised prostates were molded before fixation. A semiautomatic method was used to align MR images to histopathology. Percent overlap between MR and histopathology images, as well as distances between corresponding anatomical landmarks were calculated and used to evaluate the registration technique for molded and unmolded cases. Results The software successfully morphed histology-based prostate images into corresponding MR images. Percent overlap improved from 80.4 ± 5.8% before morphing to 99.7 ± 0.62% post morphing. Molded prostates had a smaller distance between landmarks (1.91 ± 0.75 mm) versus unmolded (2.34 ± 0.68 mm), P

BACKGROUND Observational studies suggest an inverse association between vitamin E and risk of prostate cancer, particularly aggressive tumors. However, three large randomized controlled trials have reported conflicting results. Thus, we examined circulating vitamin E and vitamin E-related genes in relation to risk of high-grade prostate cancer and prostate cancer recurrence among men initially diagnosed with clinically organ-confined disease. METHODS We measured circulating α- and γ-tocopherol and genotyped 30 SNPs in SOD1, SOD2, SOD3, TTPA, and SEC14L2 among 573 men with organ-confined prostate cancer who underwent radical prostatectomy. We examined associations between circulating vitamin E, genotypes, and risk of high-grade prostate cancer (Gleason grade ≥ 8 or 7 with primary score ≥ 4; n = 117) using logistic regression, and risk of recurrence (56 events; 3.7 years median follow-up) using Cox proportional hazards regression. RESULTS Circulating γ-tocopherol was associated with an increased risk of high-grade prostate cancer (Q4 v. Q1 odds ratio [OR] = 1.87; 95% confidence intervals [CI]: 0.97–3.58; Ptrend = 0.02). The less common allele in SOD3 rs699473 was associated with an increased risk of high-grade disease (T > C: OR = 1.40, 95% CI: 1.04–1.89). Two independent SNPs in SOD1 were inversely associated with prostate cancer recurrence in additive models (rs17884057 hazard ratio [HR] = 0.49, 95%CI: 0.25–0.96; rs9967983 HR = 0.62, 95% CI: 0.40–0.95). CONCLUSIONS Among men with clinically organ-confined prostate cancer, genetic variation in SOD may be associated with risk of high-grade disease at diagnosis and disease recurrence. Circulating γ-tocopherol levels may also be associated with an increased risk of high-grade disease at diagnosis. Prostate 73:1786–1795, 2013. © 2013 Wiley Periodicals, Inc.

Author(s): Punnen, Sanoj; Cowan, Janet E; Dunn, Laura B; Shumay, Dianne M; Carroll, Peter R; Cooperberg, Matthew R | Abstract: ObjectiveTo evaluate the prevalence of depression, anxiety and distress among active surveillance (AS) and radical prostatectomy (RP) patients. To evaluate the impact of these symptoms at baseline on urinary and sexual quality of life at follow-up.Patients and methodsPatients managed with AS or RP who completed validated questionnaires assessing levels of depression, anxiety, distress and urinary (UF) and sexual function (SF) and bother comprised the final analytic cohort. These measures were completed at baseline, within 1 year, and between 1 and 3 years from baseline. Mixed model repeated measures analysis was used to examine associations between mental health at baseline and sexual and urinary outcomes in a subset of RP patients with complete follow-up.ResultsAmong 679 men who comprised the study cohort, baseline prevalence of moderate or higher levels of depression or anxiety were low (l5%), while levels of mild depression or anxiety ranged from 3-16% over time. Baseline levels of elevated distress ranged from 8-20%. Among men who provided data at baseline and follow-up, there were no significant differences between AS and RP patients in the proportion of men with elevated levels of depression, anxiety, or distress. Among 177 men who underwent RP and had complete follow-up moderate or higher levels of depression or anxiety appeared to be associated with post-treatment SF and bother, while elevated levels of distress were associated with post-treatment UF.ConclusionModerate or higher levels of depression or anxiety were low in men with localised prostate cancer but were associated with sexual outcomes, while elevated distress was associated with urinary outcomes. Greater attention should be paid to mental health symptoms among men with prostate cancer, as these symptoms may be associated with quality of life outcomes.

Purpose To investigate criteria that can identify dominant treatable prostate cancer foci with high certainty at endorectal magnetic resonance imaging (MRI) and MR spectroscopic (MRS) imaging, and thus facilitate selection of patients who are radiological candidates for MR-guided focal therapy. Materials and Methods We retrospectively identified 88 patients with biopsy-proven prostate cancer who underwent endorectal MRI and MRS imaging prior to radical prostatectomy with creation of histopathological tumor maps. Two independent readers noted the largest tumor foci at MRI, if visible, and the volume of concordant abnormal tissue at MRS imaging, if present. A logistic random intercept model was used to determine the association between clinical and MR findings and correct identification of treatable (over 0.5 cm3) dominant intraprostatic tumor foci. Results Readers 1 and 2 identified dominant tumor foci in 50 (57%) and 58 (65%) of 88 patients; 42 (84%) and 48 (83%) of these were dominant treatable lesions at histopathology, respectively. Within the statistical model, the volume of concordant spectroscopic abnormality was the only factor that predicted correct identification of a dominant treatable lesion on T2-weighted images (odds ratio = 1.75; 95% confidence interval = 1.08 to 2.82; P value = 0.02). In particular, all visible lesions on T2-weighted imaging associated with at least 0.54 cm3 of concordant spectroscopic abnormality were correctly identified dominant treatable tumor foci. Conclusion Patients with dominant intraprostatic tumor foci seen on T2-weighted MRI and associated with at least 0.54 cm3 of concordant MRS imaging abnormality may be radiological candidates for MR-guided focal therapy. J. Magn. Reson. Imaging 2014;39:519–525. © 2013 Wiley Periodicals, Inc.

What's known on the subject? and What does the study add? Previous studies have shown that robot-assisted radical prostatectomy (RARP) can be performed in men with high-risk prostate cancer with similar outcomes to that of open surgery. However, most of the literature consists of small case series and compares RARP outcomes to open outcomes from the literature. This study compared a cohort of high-risk patients undergoing open RP and RARP at a single institution with good follow up. We found no difference in positive margin rates or likelihood of prostate cancer recurrence. This adds to the growing evidence that RARP is a safe option for men with high-risk disease. Objective To compare oncological outcomes in high-risk patients who underwent open retropubic radical prostatectomy (RRP) and robot-assisted RP (RARP) at a single institution. Despite equivalent oncological outcomes between open RRP and RARP, the use of RARP in men with high-risk tumours has been debated. Patients and Methods A retrospective analysis of high-risk patients treated with open RRP or RARP at UCSF from 2002 to 2011 was conducted. The relationship between surgical approach and positive margin rate was assessed by multivariate logistic regression Cox proportional hazards regression assessed the effect of surgical approach on time to tumour recurrence. Results In all, 177 open RRP and 233 RARP patients made up the final cohort for analyses. The mean (SD) age was 61.6 (6.6) years and the median (range) follow-up was 27 (2–112) months. RARP patients had less blood loss (median 200 vs 400 mL, P < 0.01) and underwent complete bilateral nerve sparing more often (54% vs 34%, P < 0.01) than those undergoing open RRP. There were no differences by approach in pathological grade, stage, or positive margin rates. However, there was a trend towards higher positive margin rates with RARP early on. Recurrence-free survival was similar at 2 years (84% and 79%) and 4 years (68% and 66%) after open RRP and RARP, respectively (log-rank P = 0.53). Conclusions This study is novel in that it assesses outcomes of open RRP vs RARP in a cohort of high-risk men at a single institution. RARP appears to be a feasible option for men with high-risk prostate cancer and displayed equivalent oncological outcomes compared with open RRP.

What's known on the subject? and What does the study add? Satisfaction with care is a comprehensive measure that incorporates structure, process, and outcome elements of individual patient's interaction with the healthcare system. Despite the worldwide public health burden of prostate cancer, little is known about predictors of satisfaction with prostate cancer care. Available data has evaluated differences in post-treatment satisfaction by treatment and demographic factors; however, few data exist regarding the contribution of both baseline and post-treatment patient-reported measures on satisfaction with care. We evaluated the relationship of various demographic, clinical, treatment, and patient-reported measures on satisfaction with care. Interestingly, while none of the evaluable demographic, clinical, or treatment parameters were associated with satisfaction, numerous patient-reported parameters were associated with satisfaction with prostate cancer care. Specifically, baseline general health-related quality of life (HRQOL) and change in prostate cancer-specific HRQOL after treatment were associated with satisfaction. Additionally, fear of cancer recurrence was also found to be associated with satisfaction. Taken together, these data may be used, in part, to identify a cohort of patients at-risk for dissatisfaction with prostate cancer care. Identification of such a group may allow for incorporation of these data into treatment counseling and/or implementing intervention strategies to improve post-treatment satisfaction. Objective To evaluate the impact of demographic, clinical, treatment and patient-reported parameters on satisfaction with prostate cancer care. Despite the significant worldwide impact of prostate cancer, few data are available specifically addressing satisfaction with treatment-related care. Patients and Methods CaPSURE comprises participants from 40 US sites who were monitored during and after their treatment course. Participants who were diagnosed with clinically localized prostate cancer after 1999 underwent radical prostatectomy, radiation therapy or primary androgen deprivation, and those who also completed the satisfaction questionnaire within 2 years of treatment were included in the present study. Satisfaction was measured using a validated instrument that assesses contact with providers, confidence in providers, communication skills, humanness and overall satisfaction. Multivariable linear regression analysis were performed to evaluate the independent relationships between demographic, clinical, treatment and patient-reported parameters and satisfaction. Results Of the 3056 participants, 1927 (63%) were treated with radical prostatectomy, 843 (28%) were treated with radiation therapy and 286 (9%) were treated with primary androgen deprivation. Multivariable analysis showed that multiple patient-reported factors were independently associatedwith satisfaction, whereas clinical, demographic and treatment parameters were not. Baseline health-related quality of life, measured by the 36-item short-form health survey, baseline fear of cancer recurrence (all P < 0.01) and declines in the sexual (P = 0.03), urinary (P < 0.01) and bowel (P = 0.02) function domains of the University of California Los Angeles Prostate Cancer Index were all independently associated with satisfaction. Patient-reported outcomes were more strongly associated with satisfaction in the low-risk subgroup. Conclusions Patient-reported factors such as health-related quality of life and fear of cancer recurrence are independently associated with satisfaction with care. Pretreatment parameters should be used to identify populations at-risk for dissatisfaction to allow for intervention and/or incorporation into treatment decision-making

Author(s): Reese, Adam C; Cowan, Janet E; Brajtbord, Jonathan S; Harris, Catherine R; Carroll, Peter R; Cooperberg, Matthew R | Abstract: BackgroundIn the current study, the authors propose the quantitative Gleason score (qGS), a modification of the current Gleason grading system for prostate cancer, based on the weighted average of Gleason patterns present in the pathology specimen. They hypothesize that the qGS can improve prostate cancer risk stratification and help prevent the overtreatment of patients with clinically indolent tumors.MethodsThe qGS was applied to patients in the University of California San Francisco urologic oncology database with tumors determined to have a GS of 7 on prostate biopsy or final pathology after radical prostatectomy (RP). Using multivariable logistic regression, Cox proportional hazards regression, receiver operating characteristic (ROC), and decision curve analyses, the ability of qGS to predict pathological GS and the risk of disease recurrence after RP was assessed.ResultsA total of 225 men were included in the analysis of biopsy specimens and 618 men were included in the assessment of RP specimens. Compared with traditional Gleason scoring, the qGS improved concordance between biopsy and pathological GS on decision curve and ROC analyses (area under the curve ROC curve, 0.79 vs 0.71). On regression analysis, the qGS of biopsy specimens was found to be significantly associated with pathological grade after RP (hazard ratio [HR], 1.78; 95% confidence interval [95% CI], 1.49-2.12) and the qGS of RP specimens was significantly associated with the risk of biochemical disease recurrence after RP (HR, 1.13; 95% CI, 1.04-1.24).ConclusionsThe qGS, a simple modification of the current Gleason system, appears to improve the correlation between biopsy and pathological GS, as well as the prediction of biochemical disease recurrence after RP. This scoring system may allow more men to pursue active surveillance, thereby avoiding the morbidity of prostate cancer treatment modalities.

Aim: The aim of this study was to compare the characteristics of older and younger patients with suspected paracetamol toxicity. Methods: A retrospective audit of the medical records of older (≥65 years, n= 25) and younger (20–30 years, n= 50) patients with a detectable paracetamol level at a Sydney hospital. Results: Older patients showed a different clinical pattern of suspected paracetamol toxicity and were more likely than younger patients to have multifactorial elevation of liver function tests. Additionally, older age was more likely to be associated with chronic therapeutic paracetamol dosing (71% older, 6% younger, P < 0.001), or with accidental toxic exposure (90% older, 29% younger, P < 0.001), while younger patients were more likely to have a deliberate high-dose exposure (10% older, 71% younger, P < 0.001). Conclusions: The age-related differences in paracetamol exposure, paracetamol levels and liver function tests described in this population should be considered when ordering and interpreting paracetamol levels.

UNLABELLED Study Type - Diagnostic (exploratory cohort) Level of Evidence 2b What's known on the subject? and What does the study add? The widespread use of serum PSA testing followed by TRUS-guided biopsy have resulted in profound prostate cancer stage migration with many patients presenting with focal rather than multifocal disease. There is increasing interest in the use of focal rather than whole-gland treatment. However, current biopsy schemes may still miss cancer or, even when cancer is identified, its extent or grade might not be accurately characterized. In order for focal therapy to be effective, the area of highest tumour volume and/or grade needs to localized accurately. The aim of this study was to assess how well biopsy, as currently performed, locates the focus of highest prostate cancer volume and/or grade. OBJECTIVE To evaluate the ability of transrectal ultrasonography (TRUS)-guided extended core biopsy to identify the dominant tumour accurately in men with early stage prostate cancer. PATIENTS AND METHODS Patients with early stage, low-risk prostate cancer who subsequently underwent radical prostatectomy (RP) and had complete surgical specimens were identified. Re-review was performed by a single uropathologist using ImageJ software to identify tumour location, dominant grade (DG) and dominant volume (DV). Pathology findings were then compared with biopsy results. RESULTS A total of 51 men with early stage, low-risk prostate cancer, who had undergone RP, had complete specimens for review and a median of 15 biopsy cores taken for diagnosis and grading. Sixteen men had a single diagnostic biopsy, 21 had one repeat biopsy, and 14 had two or more repeat biopsies. Compared with surgical findings, biopsy correctly identified the sextant with the largest tumour volume in 55% (95% CI 0.5-0.6) of specimens and the highest grade in 37% (95 CI 0.3-0.5). No demographic or clinical factors were significantly associated with identification of DG. Interval between last biopsy and RP, total tissue length taken and total length of tumour identified were significantly associated with correct identification of DV. CONCLUSIONS Our findings show that TRUS-guided biopsy detects and localizes DV better than it does DG. Even with an extended scheme, TRUS-guided biopsy does not reliably identify dominant cancer location in this low-risk cohort of men with early stage prostate cancer. TRUS-guided biopsy may perform better in similar men with low stage, but higher volume disease.

OBJECTIVE To determine whether the current definition of potency, inclusive of phosphodiesterase inhibitor (PDEi) use, is valid with respect to sexual bother (SB). This will be assessed by characterizing the effect of PDEi use on SB scores in men who are potent post radical prostatectomy. PATIENTS AND METHODS The study population consisted of patients who were potent both before and after radical prostatectomy, with at least 2 years of follow-up. Disease-specific quality of life data were evaluated by the University of California, Los Angeles, Prostate Cancer Index (PCI) survey. The relationships between changes in sexual function (SF) and SB and use of PDEi over time were evaluated by mixed model analysis controlling for age, clinical risk group, marital status, and time of PCI assessment. RESULTS Of the 246 patients who met the study criteria, 39% reported PDEi use at some point after treatment. PDEi use was not associated with improved SF (P = 0.81). Furthermore, PDEi use was not associated with a change in SB (P = 0.36). Both SF and SB were significantly associated with time of assessment and age, and SF and SB each improved over time. In addition, SB was significantly associated with marital status. CONCLUSION In this analysis, there was no difference in SF scores between men who were potent with or without the use of PDEi. Furthermore, there was no difference in SB scores between men who were potent with or without the use of PDEi. This suggests that the current, inclusive, definition of potency is valid with respect to SB. Keywords: radical prostatectomy, phosphodiesterase inhibitors, sexual bother, CaPSURE INTRODUCTION For men with localized prostate cancer, radical prostatectomy achieves excellent cancer control [1,2]. However, surgery is known to impact sexual function (SF) and sexual bother (SB) [3–6]. The use of phosphodiesterase inhibitors (PDEi) improves SF – specifically erectile function – in patients after surgery for prostate cancer [7,8]. Potency following surgery is most commonly defined as having erections sufficient for intercourse with or without the use of PDEi [9]. However, this definition – inclusive of medication use – does not consider the extent to which men who are potent after surgery with the use of PDEi may be bothered by having to take a medication. Previous studies have suggested a complex relationship between SF and SB, with findings of inconsistent correlation between the two domains [10–12]. For example, a recent study showed that even men with good erectile function post surgery were troubled by their broader sexual outcomes, resulting in worsening SB and quality of life [11]. Therefore, it may not be sufficient to assume patients with good erections post radical prostatectomy have no SB. More than half of patients typically use PDEi to improve their SF post surgery [13–15]. However, no study has assessed whether the use of PDEi in potent men affects SB. Without knowing the impact of PDEi use on SB in potent men, we cannot assume that the current definition of potency, inclusive of PDEi use, is valid with respect to SB. Therefore, this study aimed to characterize the effect of PDEi use on SF and SB scores in men who were potent before and following prostatectomy in a large national prostate cancer registry.

BACKGROUND: As androgen deprivation therapy (ADT) becomes a standard of treatment for men with recurrent or metastatic prostate cancer, evaluation of adverse effects associated with this treatment is needed. In this study, the authors evaluated the effect of ADT administered as monotherapy and in combination with local treatment on physical well-being in a longitudinal sample of men with prostate cancer. METHODS: Exposure to ADT was defined by 3 groups: local (local treatment only), combination (local treatment with adjuvant and/or neoadjuvant ADT), and primary ADT. Associations between exposure to ADT and physical well-being measured by self-reported health-related quality of life outcomes over time were evaluated by repeated measures analysis using mixed modeling. Estimates adjusted for various clinical and demographic variables are reported. RESULTS: A total of 2922 men, who completed both pretreatment and follow-up health-related quality of life assessment, were identified from the CaPSURE (Cancer of the Prostate Strategic Urologic Research Endeavor) registry. During 24 months of follow-up, exposure to ADT was associated with worse physical well-being compared with local treatment at all time points (P < .001). Being exposed to ADT as primary therapy was associated with more severe declines compared with combination therapy. CONCLUSIONS: The potential consequence of decline in physical well-being in patients exposed to ADT has to be included in treatment decision making. Cancer 2011;. © 2011 American Cancer Society.

The goals of cancer therapy are either to cure or con-trol disease while minimizing side effects to the pa-tient.Onemustbalancethenumberoflifeyearsgained(quantity) with the risk of morbidity and mortality ofa given treatment technique (quality). The ultimategoal is to match treatment type with the biological ag-gressiveness of the disease in an individual patient. Adifficult initial hurdle is predicting disease aggressive-ness.Radiographicstaginghasbeenthecornerstoneinrenal cancer prediction, while nomograms incorporat-ing multiple pathologic, laboratory, and clinical mea-sures have become the basis for prostate cancer pre-diction. The predictions made from this informationhave, to a substantial extent, guided modern treat-ment. In modern urologic oncology practice, a con-tinuing movement toward maximizing survival whileminimizing morbidity has been seen.This movement is seen clearly when examiningthe increasing use of laparoscopic and, more re-cently, robot-assisted laparoscopic techniques in thetreatment of renal and prostate cancers as well asconformal and intensity-modulated radiation therapy(IMRT), cryotherapy, high-intensity focused ultra-sound (HIFU), and brachytherapy in the treatment ofprostate cancer. More recent interest in focal, percuta-neous techniques (i.e., radiofrequency or cryotherapy)reflects this evolution in management.Minimally invasive interventional techniques areattractive since the risks of local progression andthus metastasis are, in theory, decreased comparedto surveillance, while the morbidity associated withradical (partial or complete) resection are also de-creased. Other advantages regarding localized renaltumor management include technical ease comparedto minimally invasive partial nephrectomy, no renalischemia requirement, relative ease in locating endo-phytic lesions, the unique opportunity for retreatmentwith no significant increased morbidity of a secondprocedure and, finally, decreased convalescence.The morbidity associated with radical prostatec-tomyandradiotherapyiswelldescribedandisprimar-ily a result of treatment effects on adjacent structures[1]. Therefore, minimally invasive interventional tech-niques stand to have the greatest impact with respectto cavernosal nerve preservation, and limitation of ex-traprostatic radiation leading to advantages in erectilefunction preservation, improved continence, as wellas hospital stay and return to normal daily activitiesand work. These techniques hold similar advantagesto those for renal cell carcinoma with the added ben-efits of relatively easy access to the gland and discreteablation that could facilitate less than whole-glandtreatment.Renal and prostate tumors are biologically uniqueand demand individual consideration for possiblesurveillance, local tumor treatment, or radical tumor

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Gentamicin pharmacokinetics show wide inter-individual variability across all age groups and impaired gentamicin clearance is associated with impaired creatinine clearance in older people. • Changes in body composition and renal function with old age and frailty are likely to affect the pharmacokinetics of gentamicin. • There is current debate on whether the Modification of Diet in Renal Disease (MDRD) equation estimate of glomerular filtration rate (GFR) should replace the Cockcroft Gault equation estimate of creatinine clearance for calculation of doses of renally excreted drugs. WHAT THIS STUDY ADDS • The volume of distribution of gentamicin is not significantly lower in frail than in non frail older people. • The correlation between volume of distribution of gentamicin and actual bodyweight is poor in frail and moderate in non frail older people. • Gentamicin clearance is significantly lower in frail than in non frail older people. • The Cockcroft Gault calculation of creatinine clearance, calculated using ideal bodyweight, gave the best estimate of gentamicin clearance in this population of frail and non frail older people. • The MDRD estimate of GFR and Cockcroft Gault estimate of creatinine clearance, calculated using actual bodyweight, overestimate gentamicin clearance in frail and non frail older people. AIMS Frailty, a syndrome of decreased physiological reserve that is prevalent in old age, impacts on clinical pharmacology. The aims of the study were to (1) determine whether frailty affects the pharmacokinetics of gentamicin and (2) assess the accuracy of different estimates of body size and renal clearance as estimates of gentamicin pharmacokinetics in older inpatients. METHODS This was an observational study of gentamicin pharmacokinetics in a cohort of Australian hospital inpatients aged ≥65 years, who were administered prophylactic intravenous gentamicin. RESULTS Of the 31 participants, 14 were frail and 17 non frail on the Reported Edmonton Frail Scale. The mean volume of distribution of gentamicin was 14.8 ± 1.4 l in frail participants and 15.3 ± 2.2 l in non frail (NS). Volume of distribution correlated best with lean bodyweight. Gentamicin clearance was significantly lower in frail participants (46.6 ± 10.7 ml min−1) than in non frail (58.2 ± 12.4 ml min−1, P= 0.01). The Cockcroft Gault estimate of creatinine clearance calculated using ideal bodyweight gave the best estimate of gentamicin clearance (mean error – 0.15 ml min−1, 95% CI −2.67, 2.39). The Cockcroft Gault creatinine clearance calculated using actual bodyweight and the estimated glomerular filtration rate from the modified diet in renal disease equation overestimated gentamicin clearance, with mean errors of −10.15 ml min−1 (95%CI −13.60, −6.71) and −18.86 ml min−1 (95% CI −22.45, −15.27), respectively. The Cockcroft Gault creatinine clearance calculated using lean bodyweight underestimated gentamicin clearance (mean error 6.54 ml min−1, 95% CI 4.18, 8.90). CONCLUSIONS Frail older people have significantly lower gentamicin clearance than non frail. The best estimate of gentamicin clearance is obtained from the Cockcroft Gault creatinine clearance calculated using ideal bodyweight.

Study Type – Therapy (case series) Level of Evidence 4 OBJECTIVE To evaluate the incidence and risk factors for bladder neck contracture (BNC) in men treated with robot-assisted laparoscopic radical prostatectomy (RALP) and open radical prostatectomy (ORP), as BNC is a well-described complication of ORP and may be partially attributable to technique. PATIENTS AND METHODS The University of California San Francisco Urologic Oncology Database was queried for patients undergoing RALP or ORP from 2002 to 2008. Patient demographics, prostate cancer-specific information, surgical data, and follow-up were collected. For each surgical approach, multivariate Cox proportional hazards regression was performed to evaluate associations of demographics and clinical characteristics with BNC. Time to BNC after RP was evaluated using life table and Kaplan–Meier methods. RESULTS From 2002 to 2008, 988 patients underwent RP as primary treatment and had at least 12 months of follow-up. Of these men, 695 underwent ORP and 293 underwent RALP. The mean (sd) age was 59.3 (6.80) years and 91% of men were Caucasian. D’Amico risk groups at diagnosis were low (38%), intermediate (38%), and high (24%). The BNC incidence was 2.2% (22 cases) overall, 1.4% (four) for RALP, and 2.6% (18) for ORP (P= 0.12). Patients with BNC were diagnosed a median (range) of 4.7 (1–15) months after surgery. At 18 months after surgery, the BNC-free rate was 97% for ORP and 99% for RALP (log-rank P= 0.13). The most common presenting complaint was slow stream, followed by urinary retention. In Cox proportional hazards regression analysis, earlier year of surgery, older age at diagnosis and higher PSA level at diagnosis were significantly associated with BNC among ORP patients. In the RALP group, none of the covariates were associated with BNC. CONCLUSIONS The overall incidence of BNC was low in both RALP and ORP groups. Technical factors such as enhanced magnification and a running bladder anastomosis may explain the lower BNC incidence in the RALP group.

Study Type – Therapy (outcomes research) Level of Evidence 2c OBJECTIVE To quantitatively assess the effect of radical prostatectomy (RP) on the specific domains that comprise overall sexual function (SF), focusing on the relationships among these domains and overall SF, and to identify predictors for recovery of SF over time, as a decline in SF and sexual bother (SB) are known potential complications of treatment for prostate cancer. PATIENTS AND METHODS Within the Cancer of the Prostate Strategic Urologic Research Endeavor database, we identified men diagnosed between 1995 and 2001 with localized prostate cancer treated with RP. SF and SB outcomes, measured using the University of California Los Angeles Prostate Cancer Index, were assessed at 6-month intervals for 4 years after RP. RESULTS In all, 620 men met the study criteria; at 6 months after RP, overall and all the specific domains of SF declined, with improvement in most specific domains by 2 years after RP. The greatest declines were in the ability to achieve erections, high-quality erections, and frequent erections; these domains were also most strongly correlated with overall SF. Sexual desire was relatively preserved, and there was a weak correlation between overall SF and sexual desire after RP, when there was the greatest discrepancy between sexual desire and other domains of function. SB showed continued improvement over time to 4 years but was not well correlated with any measurements of SF assessed. Younger age, college education, sexual aid and medication use, the absence of comorbid conditions, and nerve-sparing surgery were predictive of significant recovery of function in several specific domains of SF. CONCLUSIONS RP affects specific domains of SF to differing degrees. Compromised erectile function is most commonly reported among these specific domains and seems to play a more dominant role in determining overall SF, but notably none of the domains of function were closely linked to SB. Because education is protective in the perception of bother, appropriate counselling and the setting of expectations for outcomes in overall and specific domains of SF might lead to improved quality of life after treatment for prostate cancer.

Study Type – Therapy (case control) Level of Evidence 3b What's known on the subject? and What does the study add? The risks of delayed radical prostatectomy for men who progress on active surveillance are largely unknown. Two series have reported that prostatectomy after active surveillance has similar results to immediate therapy. Our data add to this growing body of evidence that appropriately selected men with prostate cancer can undergo active surveillance with delayed prostatectomy without added risk of missing an opportunity for cure as the majority of tumours remain organ confined. OBJECTIVE • To compare the pathological outcomes of men undergoing radical prostatectomy (RP) after a period of active surveillance (AS) with those of a similar risk group undergoing immediate surgery. PATIENTS AND METHODS • We identified men through our institutional database who underwent RP within 6 months of diagnosis or after a period of AS. The primary outcome of the present study was Gleason upgrade to ≥7 after prostatectomy. • Pathological stage and positive surgical margin rate were assessed as secondary outcomes. Binomial logistic regression models were used to determine associations of treatment subgroups with pathological upgrade, upstage and positive margins. RESULTS • Thirty-three men with initially low-risk cancer features underwent RP after a median (range) of 18 (7–76) months of AS. A total of 278 men with low-risk disease features underwent immediate RP within 6 months of diagnosis. Rates of Gleason upgrading to ≥7, pathological category pT3 and positive surgical margins did not differ significantly from the immediate RP group. • On multivariate analysis of low-risk patients, adjusting for baseline pathological features, treatment group (AS followed by prostatectomy vs immediate prostatectomy) was not associated with Gleason upgrading (odds ratio, OR, 0.35; 95% CI, 0.12–1.04), non-organ-confined disease (OR, 1.67; 95% CI, 0.32–8.65) or positive surgical margins at prostatectomy (OR, 0.95; 95% CI, 0.16–5.76). CONCLUSION • The present analysis did not show an association between RP after a period of AS and adverse pathological features for men with low-risk disease.

OBJECTIVE To determine whether 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) and nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with the risk of prostate cancer and improved survival in men with prostate cancer. PATIENTS AND METHODS We retrospectively examined the association between NSAID and statin use among 7042 men who underwent radical prostatectomy (RP, 4611) or radiotherapy (RT, 2431) for prostate cancer between 1990 and 2003 identified in the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE), a primarily community-based national prostate cancer registry. We compared clinical and sociodemographic variables by statin and NSAID use, using chi-square tests and multinomial logistic regression. We examined associations between medications and comorbid illness with mortality using unadjusted and adjusted Cox proportional hazard models. RESULTS The median (range) follow-up from treatment was 4 (0-16) years. In multivariate survival analysis, statin 'ever-use' was associated with a reduced risk of all-cause mortality (ACM) after RP (hazard ratio, HR, 0.35, 95% confidence interval, CI, 0.21-0.58) and RT (0.59, 0.37-0.94). NSAID ever-use was also associated with a reduced risk of ACM after RP (HR 0.47, 95% CI 0.30-0.75) and RT (0.39, 0.25-0.59). CONCLUSIONS In a population of men with prostate cancer, statin and NSAID ever-use were associated with a reduced risk of ACM. Our study highlights the importance of multidisciplinary survivorship care for men with prostate cancer.

BACKGROUND: Extended pelvic lymphadenectomy (PLND) during radical cystectomy (RC) reportedly improves bladder cancer-specific survival. Lymph node counts are often a proxy for the extensiveness of a dissection. In the current study, the impact of an institutional policy requiring a minimum number of lymph nodes was assessed. METHODS: Patients undergoing RC and PLND for invasive bladder cancer between March 2000 and February 2008 were retrospectively reviewed at the study institution. Beginning March 1, 2004, a policy was established that at least 16 lymph nodes had to be examined. Specimens with

Study Type – Prognosis (risk model) Level of Evidence 2a OBJECTIVE To design a decision-support tool to facilitate evidence-based treatment decisions in clinically localized prostate cancer, as individualized risk assessment and shared decision-making can decrease distress and decisional regret in patients with prostate cancer, but current individual models vary or only predict one outcome of interest. METHODS We searched Medline for previous reports and identified peer-reviewed articles providing pretreatment predictive models that estimated pathological stage and treatment outcomes in men with biopsy-confirmed, clinical T1-3 prostate cancer. Each model was entered into a spreadsheet to provide calculated estimates of extracapsular extension (ECE), seminal vesicle invasion (SVI), and lymph node involvement (LNI). Estimates of the prostate-specific antigen (PSA) outcome after radical prostatectomy (RP) or radiotherapy (RT), and clinical outcomes after RT, were also entered. The data are available at http://www.capcalculator.org. RESULTS Entering a patient’s 2002 clinical T stage, Gleason score and pretreatment PSA level, and details from core biopsy findings, into the CaP Calculator provides estimates from predictive models of pathological extent of disease, four models for ECE, four for SVI and eight for LNI. The 5-year estimates of PSA relapse-free survival after RT and 10-year estimates after RP were available. A printout can be generated with individualized results for clinicians to review with each patient. CONCLUSIONS The CaP Calculator is a free, online ‘clearing house’ of several predictive models for prostate cancer, available in an accessible, user-friendly format. With further development and testing with patients, the CaP Calculator might be a useful decision-support tool to help doctors promote evidence-based shared decision-making in prostate cancer.

Study Type – Therapy (case series) Level of Evidence 4 OBJECTIVE To compare rates of lymph node dissection (LND) and nodal yields between patients treated with open radical retropubic prostatectomy (ORRP) and robot-assisted RRP (RARP) in a contemporary single-institution series. PATIENTS AND METHODS Data from 1278 consecutive patients (716 ORRP and 562 RARP) from one institution were accrued prospectively in an institutional database, and the data analysed retrospectively. Disease risk was assessed using the Cancer of the Prostate Risk Assessment (CAPRA) score. The likelihood of LND, nodal yield, and likelihood of node positivity were compared between ORRP and RARP. RESULTS Of patients treated with ORRP and RARP, 47.8% and 31.8% had LND, respectively, with more receiving LND over time in both surgical approaches. Men undergoing LND had a higher disease risk than those not undergoing LND (mean CAPRA score 4.3 vs 2.1, P

The impact of high-resolution magic angle spinning (HR-MAS) spectroscopy on the histopathologic and mRNA integrity of human prostate tissues was evaluated. Forty prostate tissues were harvested at transrectal ultrasound (TRUS) guided biopsy (n = 20) or radical prostatectomy surgery (n = 20), snap-frozen on dry ice, and stored at −80°C until use. Twenty-one samples (n = 11 biopsy, n = 10 surgical) underwent HR-MAS spectroscopy prior to histopathologic and cDNA microarray analysis, while 19 control samples (n = 9 biopsy, n = 10 surgical) underwent only histopathologic and microarray analysis. Frozen tissues were sectioned at 14-µm intervals and placed on individual histopathology slides. Every 8th slide was stained with hematoxylin and eosin (HE however, one pathologist's scores were significantly lower for biopsy tissues following HR-MAS while the other pathologist's scores were not. mRNA integrity assays were performed using an Agilent 2100 Bioanalyzer and the electrophoretic traces were scored with an RNA integrity number (RIN) from 1 (degraded) to 10 (intact). RIN scores were not significantly different for surgical tissues, but were significantly lower for biopsy tissues following HR-MAS spectroscopy. The isolated mRNA then underwent two rounds of amplification, conversion to cDNA, coupling to Cy3 and Cy5 dyes, microarray hybridization, imaging, and analysis. Significance analysis of microarrays (SAM) identified no significantly over- or under-expressed genes, including 14 housekeeping genes, between HR-MAS and control samples of surgical and biopsy tissues (5% false discovery rate). This study demonstrates that histopathologic and genetic microarray analysis can be successfully performed on prostate surgical and biopsy tissues following HR-MAS analysis; however, biopsy tissues are more fragile than surgical tissues. Copyright © 2009 John Wiley & Sons, Ltd.

Treatment decision-making can be difficult and complex for patients with low-risk prostate cancer. To the authors' knowledge, there is no consensus regarding an optimal treatment strategy and the choice of therapy involves tradeoffs between differing harms and benefits that are sensitive to patient values. In such situations, patients are often asked to participate actively in the decision-making process, and high-quality decisions require a well-informed patient whose values and preferences have been taken into consideration. Prior studies have indicated that patients have poor knowledge and unrealistic expectations regarding treatment, and physician judgments concerning patient preferences are often inaccurate. Decision aids (DAs) have been developed to help inform patients with low-risk prostate cancer about treatment options and assist in the decision-making process; however, little is currently known regarding the effects of such programs in this population. Thirteen studies of DAs for patients with prostate cancer were reviewed and it was found that the use of DAs can improve knowledge, encourage more active patient involvement in decision-making, and decrease levels of anxiety and distress. The effect of DAs on treatment choice was less clear, although fewer patients chose surgery compared with historical controls, particularly in Europe. Further studies are needed to determine how best to implement DAs into practice, and whether they improve the consistency between patient preferences and treatment choice.

BACKGROUND: Virtually all patients with prostate cancer who receive androgen deprivation therapy (ADT) will ultimately develop evidence of resistance to treatment. The prognosis for patients who develop metastatic castrate-resistant disease is reported to be poor, with overall survival historically estimated to be 24 to 36 months. The goal of the current study was to identify predictors of clinical disease progression in patients with prostate cancer who were receiving ADT. METHODS: Of the 13,740 men with biopsy–proven prostate cancer who were enrolled in the Cancer of the Prostate Strategic Urological Research Endeavor (CaPSURE) database from 1995 to 2007, 4003 men treated with ADT after diagnosis without evidence of metastases at treatment initiation were identified. The primary endpoint was the development of bone metastasis. Clinical and pathologic characteristics were compared between patients who developed metastasis and those who did not using chi-square tests in a Cox proportional hazards regression model. RESULTS: The mean age of the men in the cohort was 70 years (range, 39-94 years). One hundred ninety-one men (4.8%) progressed to metastatic disease at a median of 18 months from the initiation of ADT (range, 1-139 months). On multivariate analyses, risk category (hazards ratio [HR], 2.58; P 33% (HR, 3.36; P = .003), age ≤65 years at diagnosis (HR, 2.11; P = .001, and prostate–specific antigen velocity on ADT (HR, 1.04; P < .001) were found to be significantly associated with the development of metastatic disease after ADT. CONCLUSIONS: Younger men with high–risk disease appear to have worse prognosis than older men with similar disease. This, along with the other prognostic variables established in the current study, may help identify candidates for clinical trials evaluating secondary treatments for patients with castrate-resistant disease. Cancer 2009. © 2009 American Cancer Society.

BACKGROUND. Active surveillance followed by selective treatment for men who have evidence of disease progression may be an option for select patients with early-stage prostate cancer. In this article, the authors report their experience in a contemporary cohort of men with prostate cancer who were managed with active surveillance. METHODS. All men who were managed initially with active surveillance were identified through the authors' institutional database. Selection criteria for active surveillance included: prostate-specific antigen (PSA) 0.75 ng/mL per year), was a secondary outcome. Chi-square and log-rank tests were used to compare groups. The association between clinical characteristics and receipt of active treatment was analyzed by using Cox proportional hazards regression. RESULTS. Three hundred twenty-one men (mean age [±standard deviation]: 63.4 ± 8.5 years) selected active surveillance as their initial management. The overall median follow-up was 3.6 years (range, 1-17 years). The initial mean PSA level was 6.5 ± 3.9 ng/mL. One hundred twenty men (37%) met at least 1 criterion for progression. Overall, 38% of men had higher grade on repeat biopsy, and 26% of men had a PSA velocity >0.75 ng/mL per year. Seventy-eight men (24%) received secondary treatment at a median 3 years (range, 1-17 years) after diagnosis. Approximately 13% of patients with no disease progression elected to obtain treatment. PSA density at diagnosis and rise in Gleason score on repeat biopsy were associated significantly with receipt of secondary treatment. The disease-specific survival rate was 100%. CONCLUSIONS. Selected individuals with early-stage prostate cancer may be candidates for active surveillance. Specific criteria can be and need to be developed to select the most appropriate individuals for this form of management and to monitor disease progression. A small attrition rate can be expected because of men who are unable or unwilling to tolerate surveillance. © 2008 American Cancer Society.

BACKGROUND. The authors report the likelihood of treatment failure and the outcomes after salvage therapy among men with prostate cancer who initially either received external-beam radiation therapy (EBRT) or underwent radical prostatectomy (RP). METHODS. Using a national disease registry, the Cancer of the Prostate Strategic Urological Research Endeavor (CaPSURE) database, 5277 men with prostate cancer were identified who initially either underwent RP (4342 men) or received EBRT (935 men). Outcomes after disease recurrence and subsequent salvage therapy were assessed. RESULTS. Recurrent disease developed in 1590 men (30%), including 1003 patients (23%) in the RP group and 587 patients (63%) in the EBRT group, at a mean of 34 months and 38 months, respectively (P = .003). Patients who had recurrent disease had greater rates of overall death (19% vs 3%; P < .01) and bone metastases (15% vs 1%; P < .01). Data after salvage therapy were available for 1050 patients (620 men in the RP group and 430 men in the EBRT group). Androgen-deprivation therapy (ADT) was the most common salvage treatment in both groups. Overall, 420 men in the RP group (68%) and 319 men in the EBRT group (74%) failed salvage therapy at mean of 43.6 months and 43.8 months, respectively (P = .95). These patients had a greater overall death rate than the 311 patients who did not fail salvage therapy (24.8% vs 6.9%, respectively; P < .001). No survival benefit in terms of prostate cancer-related death (P = .91) was identified with any particular combination of primary and salvage therapy. CONCLUSIONS. Disease recurrence developed in 30% of patients who were treated for prostate cancer, and ADT was the most common salvage therapy used. Patients who failed salvage therapy had worse overall survival, and no survival benefit was noted for any particular combination of primary and salvage therapy. Cancer 2008. © 2007 American Cancer Society.

A method was developed to quantify prostate metabolite concentrations using (1)H high-resolution magic angle spinning (HR-MAS) spectroscopy. T(1) and T(2) relaxation times (in milliseconds) were determined for the major prostate metabolites and an internal TSP standard, and used to optimize the acquisition and repetition times (TRs) at 11.7 T. At 1 degrees C, polyamines (PAs; T(1mean) = 100 +/- 13, T(2mean) = 30.8 +/- 7.4) and citrate (Cit; T(1mean) = 237 +/- 39, T(2mean) = 68.1 +/- 8.2) demonstrated the shortest relaxation times, while taurine (Tau; T(1mean) = 636 +/- 78, T(2mean) = 331 +/- 71) and choline (Cho; T(1mean) = 608 +/- 60, T(2mean) = 393 +/- 81) demonstrated the longest relaxation times. Millimolal metabolite concentrations were calculated for 60 postsurgical tissues using metabolite and TSP peak areas, and the mass of tissue and TSP. Phosphocholine plus glycerophosphocholine (PC+GPC), total choline (tCho), lactate (Lac), and alanine (Ala) concentrations were higher in prostate cancer ([PC+GPC](mean) = 9.34 +/- 6.43, [tCho](mean) = 13.8 +/- 7.4, [Lac](mean) = 69.8 +/- 27.1, [Ala](mean) = 12.6 +/- 6.8) than in healthy glandular ([PC+GPC](mean) = 3.55 +/- 1.53, P < 0.01; [tCho](mean) = 7.06 +/- 2.36, P < 0.01; [Lac](mean) = 46.5 +/- 17.4, P < 0.01; [Ala](mean) = 8.63 +/- 4.91, P = 0.051) and healthy stromal tissues ([PC+GPC](mean) = 4.34 +/- 2.46, P < 0.01; [tCho](mean) = 7.04 +/- 3.10, P < 0.01; [Lac](mean) = 45.1 +/- 18.6, P < 0.01; [Ala](mean) = 6.80 +/- 2.95, P < 0.01), while Cit and PA concentrations were significantly higher in healthy glandular tissues ([Cit](mean) = 43.1 +/- 21.2, [PAs](mean) = 18.5 +/- 15.6) than in healthy stromal ([Cit](mean) = 16.1 +/- 5.6, P < 0.01; [PAs](mean) = 3.15 +/- 1.81, P < 0.01) and prostate cancer tissues ([Cit](mean) = 19.6 +/- 12.7, P < 0.01; [PAs](mean) = 5.28 +/- 5.44, P < 0.01). Serial spectra acquired over 12 hr indicated that the degradation of Cho-containing metabolites was minimized by acquiring HR-MAS data at 1 degree C compared to 20 degrees C.

BACKGROUND Aberrant CpG methylation profiles of gene promoters and their correlation with advanced pathologic features have been well investigated in prostate carcinoma (PC). Several case–control and prospective studies have revealed a positive association between current smoking and PC. The authors hypothesized that smoking influences both progression and prognosis of PC through CpG hypermethylation of related genes. METHODS A total of 164 PC patients (52 current, 30 former, and 82 never smokers) and 69 benign prostatic hyperplasia (BPH) patients were examined by methylation-specific PCR (MSP) for 3 genes: adenomatous polyposis coli (APC), glutathione S-transferase pi (GSTP1), and multidrug resistance one (MDR1). The methylation status of representative samples was confirmed by bisulfite DNA sequencing analysis. The newly defined methylation score (M-score) of each sample is the sum of the corresponding log hazard ratio (HR) coefficients derived from multivariate logistic regression analysis for pathology (BPH vs. PC), and was related to clinical and pathologic outcome including smoking status. RESULTS The M-score was significantly higher in the current smokers than in never smokers (P = 0.008). Spearman rank correlation test demonstrated a significant correlation between pack-years smoked and M-score in PCs (P = 0.039). Significant correlation of the M-score methylation was observed with high pT category (P < 0.001), high Gleason sum (P < 0.001), high preoperative prostate-specific antigen (PSA) (P = 0.041), and advanced pathologic features. In addition, Gleason sum was significantly associated with PSA failure-free probability as a poor outcome (P = 0.020). CONCLUSIONS This is the first study to demonstrate significant correlation of the methylation status of multigenes with smoking status in PC. Smoking status may influence both progression and prognosis of PC through CpG hypermethylation of related genes. Cancer 2006. © 2005 American Cancer Society.

BACKGROUND Prostate cancer incidence and mortality rates vary widely among individuals of different ethnic/racial groups. We identified a relationship between a subset of genes and race/ethnicity using gene expression profiling. Estrogen receptor α (ERα) was selected for confirmation due to its plausible biological role in cancer susceptibility. METHODS Quantitative polymerase chain reaction (Q-PCR) was used to verify gene expression results. Protein levels of ERα were determined by quantitative immunohistochemistry in a large-scale tissue microarray study (n = 183). RESULTS ERα was significantly higher in stroma of Hispanic and Asian men than in Caucasian (P

BACKGROUND The action of transforming growth factor β (TGF-β) is mediated through type 1 (TβRI) and type 2 (TβRII) receptors. Prostate cancer cells are often resistant to TGF-β signaling due to loss of TβRII expression. The authors of the current study hypothesized that CpG methylation of the TβRII promoter at the Sp1 binding site −140 mediates this loss of TβRII expression in prostate cancer. METHODS Sixty-seven prostate cancer (PC) samples, 8 benign prostatic hyperplasia (BPH) samples, and 4 prostate cancer cell lines (DUPro, LNCaP, ND-1 and PC-3) were analyzed for 1) TβRII mRNA expression by semiquantitative RT-PCR, 2) TβRII protein expression by immunohistochemistry, and 3) TGFβRII promoter methylation at CpG site −140 by methylation specific PCR and bisulfite DNA sequencing. Prostate cancer cell lines were treated with the demethylating agent 5aza2′deoxycytidine to determine if TβRII gene expression could be increased by blocking promoter methylation. RESULTS mRNA and protein expression of TβRII was lower in the PC samples than in the BPH samples. CpG methylation at site −140 was higher in PC than in BPH (P < 0.01). Promoter methylation was inversely correlated with TβRII mRNA expression in the PC and BPH samples (P < 0.0001). PC3, ND1, and DUPro TβRII mRNA expression increased following treatment of cells with 5-aza-2′-deoxycytidine. CONCLUSION CpG methylation of the TβRII promoter at CPG site −140 leads to functional loss of the TβRII gene in prostate cancer. Treatment with 5-aza-2′ deoxycytidine can restore gene expression. The current study results report the first association between prostate cancer and loss of the TGF- β signaling pathway by TβRII DNA promoter methylation. Cancer 2005;. © 2005 American Cancer Society.