Search

Background: Although diabetes is inversely related to prostate cancer (PC) risk, to the authors' knowledge the impact of glycemic control on PC progression is unknown. In the current study, the authors tested the association between hemoglobin A1c (HbA1c) and long-term PC outcomes among diabetic men undergoing radical prostatectomy (RP).Methods: The authors retrospectively reviewed data regarding men undergoing RP from 2000 to 2017 at 8 Veterans Affairs hospitals. Diabetic patients were identified using International Classification of Diseases, Ninth Revision (ICD-9) codes (250.x) or by an HbA1c value >6.5% at any time before RP. Cox models tested the association between HbA1c and biochemical disease recurrence (BCR), castration-resistant PC (CRPC), metastases, PC-specific mortality, and all-cause mortality. The model for BCR was adjusted for multiple variables. Due to limited events, models for long-term outcomes were adjusted for biopsy grade and prostate-specific antigen only.Results: A total of 1409 men comprised the study population. Of these, 699 patients (50%) had an HbA1c value <6.5%, 631 (45%) had an HbA1c value of 6.5% to 7.9%, and 79 (6%) had an HbA1c value ≥8.0%. Men with an HbA1c value ≥8.0% were younger (P < .001) and more likely to be black (P = .013). The median follow-up after RP was 6.8 years (interquartile range, 3.7-10.6 years). On multivariable analysis, HbA1c was not found to be associated with BCR. However, a higher HbA1c value was associated with metastasis (hazard ratio [HR], 1.21; 95% CI, 1.02-1.44 [P = .031]) and CRPC (HR, 1.27; 95% CI, 1.03-1.56 [P = .023]). Although not statistically significant, there were trends between higher HbA1c and risk of PC-specific mortality (HR, 1.24; 95% CI, 0.99-1.56 [P = .067]) and all-cause mortality (HR, 1.09; 95% CI, 0.99-1.19 [P = .058]).Conclusions: Among diabetic men undergoing RP, a higher HbA1c value was associated with metastases and CRPC. If validated in larger studies with longer follow-up, future research should test whether better glycemic control improves long-term PC outcomes. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the relationship between periprostatic adipose tissue (PPAT) adipokine expression and prostate cancer (PCa) aggressiveness using both pathological features of radical prostatectomy (RP) and multiparametric magnetic resonance imaging (MRI) variables. Patients and Methods: Sixty‐nine men were recruited to assess immunohistochemical expression of tumour necrosis factor (TNF)α and vascular endothelial growth factor (VEGF) of periprostatic fat of RP specimens. Per cent immunopositivity was quantified on scanned slides using the Aperio Positive Pixel Count algorithm for PPAT TNFα, VEGF and androgen receptors. Periprostatic fat volume (PFV) was segmented on contiguous T1‐weighted axial MRI slices from the level of the prostate base to apex. PFV was normalized to prostate volume (PV) to account for variations in PV (normalized PFV = PFV/PV). MRI quantitative values (Kep, Ktrans and apparent diffusion coefficient) were measured from the PCa primary lesion using Olea Sphere software. Patients were stratified into three groups according to RP Gleason score (GS): ≤6, 7(3 + 4) and ≥7(4 + 3). Results: The mean rank of VEGF and TNFα was significantly different between the groups [H(2) = 11.038, P = 0.004] and [H(2) = 13.086, P = 0.001], respectively. Patients with stage pT3 had higher TNFα (18.2 ± 8.95) positivity than patients with stage pT2 (13.27 ± 10.66; t [67] = −2.03, P = 0.047). TNFα expression significantly correlated with Ktrans (ρ = 0.327, P = 0.023). TNFα (P = 0.043), and VEGF (P = 0.02) correlated with high grade PCa (GS ≥ 7) in RP specimens and also correlated significantly with upgrading of GS from biopsy to RP histology. Conclusions: The expression levels of TNFα and VEGF on immunostaining significantly correlated with aggressivity of PCa. As biomarkers, these indicate the risk of having high grade PCa in men undergoing RP. [ABSTRACT FROM AUTHOR]

Introduction: Prostate cancer is the most common cancer among men, but overall mortality rates remain low, due to the preponderance of low-risk disease. Over the last decade, there has been a shift toward more conservative management in low-risk prostate cancer, in order to minimize unnecessary intervention. This study aimed to evaluate the number of low-risk radical prostatectomies (RPs) being performed at the Southern Alberta Institute of Urology over a 10-year period. Methods: We retrospectively reviewed all patients who underwent RP from 2005 to 2014 at our institution. Patients were stratified by D'Amico risk classification and grade group based on 12-core transrectal ultrasound–guided biopsy (TRUS-bx) results. RP findings are reported from February 2005 to October 2014 to describe concordance between TRUS-bx and RPs. Basic descriptive analyses were used for this study. Results: Over the study period, 2,310 RPs were performed in our institution. Overall, 35.2% of these were performed on men with low-risk prostate cancer. From 2005 to 2014, the proportion of RPs performed for low-risk prostate cancer dropped from 54.0% to 8.9%, and 49.8% of patients who underwent RP for low-risk disease experienced pathologic upgrading, though only 3.8% were upgraded to grade group 3 or greater. Other adverse pathological findings were uniformly low among the low-risk group. Conclusion: The proportion of patients undergoing RP at our center for low-risk prostate cancer decreased significantly over the 10 years evaluated in this study, reflecting current global trends toward active surveillance in the management of low-risk prostate cancer. [ABSTRACT FROM AUTHOR]

Abstract Psychological distress is prevalent among men with prostate cancer (PCa). However, the variation in antidepressant use among individuals throughout the survivorship period is unknown. We sought to examine the variation and trends in receipt of antidepressants after PCa treatment, among patients with nonmetastatic PCa. Using population-based linked administrative data, we identified men ≥66 yr old who underwent surgery (n = 4952), radiotherapy (n = 4994), or surveillance (n = 2136), and these men were matched to general population controls (n = 57 127). One year prior to PCa treatment, 7.7% of men received an antidepressant prescription, which increased to 10.5% in the year after treatment. In difference-in-differences analysis, adjusted for demographic and health characteristics, men had increased odds of antidepressant receipt up to 5 yr after surgery (odds ratio [OR] 1.49; 95% confidence interval [CI] 1.35–1.64; p ≤ 0.0001) or radiotherapy (OR 1.33; 95% CI 1.21–1.47; p ≤ 0.0001). Men did not have an increased risk of antidepressant receipt up to 5 yr after surveillance (OR 1.15; 95% CI 0.94–1.41; p = 0.16). Limitations include the potential for selection bias and misclassification due to the retrospective design of the study and the use of administrative databases. Thus, men with nonmetastatic PCa who initially receive surgery or radiotherapy, but not those who initially undergo surveillance, have an increased risk of antidepressant receipt after treatment. Patient summary In this report, we examined antidepressant prescription for men after treatment of nonmetastatic prostate cancer across the entire population of men ≥66 yr in Ontario, Canada, from 2002 to 2009. For men diagnosed with nonmetastatic prostate cancer, the risk of antidepressant receipt at 5 yr after treatment was significantly increased after surgery or radiotherapy, but not after surveillance. Providers and patients should consider the psychological effects of prostate cancer treatment during the survivorship period. Take Home Message Patients treated for nonmetastatic prostate cancer with surgery or radiation have an increased risk of receiving antidepressant prescriptions for at least 5 yr, whereas patients undergoing surveillance do not. Thus, psychological support after treatment is an important part of prostate cancer care. [ABSTRACT FROM AUTHOR]

Abstract Background Intermediate clinical endpoints (ICEs) prognostic for overall survival (OS) are needed for men receiving postprostatectomy radiation therapy (PORT) to improve clinical trial design. Objective To identify a potential ICE for men receiving PORT. Design, setting, and participants We performed an institutional review board–approved multi-institutional retrospective study of 566 men consecutively treated with PORT at tertiary care centers from 1986 to 2013. The median follow-up was 8.2 yr. Outcome measurements and statistical analysis Biochemical failure (BF), distant metastases (DM), and castrate-resistant prostate cancer (CRPC) were evaluated for correlation with OS and assessed as time-dependent variables in a multivariable Cox proportional hazards model and in landmark analyses at 1, 3, 5, and 7 yr after PORT. Cross-validated concordance (c) indices were used to assess model discrimination. Results and limitations OS at 1, 3, 5, and 7 yr after PORT was 98%, 95%, 90%, and 82%, respectively. In a time-varying model controlling for clinical and pathologic variables, BF (hazard ratio [HR] 2.32, 95% confidence interval [CI] 1.45–3.71; p < 0.001), DM (HR 6.52, 95% CI 4.20–10.1; p < 0.001), and CRPC (HR 2.47, 95% CI 1.56–3.92; p < 0.001) were associated with OS. In landmark analyses, 5-yr DM had the highest c index when adjusting for baseline covariates (0.78), with 5-yr DM also providing the greatest increase in discriminatory power over a model only including baseline covariates. These findings require validation in prospective randomized data. Conclusions While limited by the retrospective nature of the data, 5-yr DM is associated with lower OS following PORT, outperforming the prognostic capability of BF and CRPC at 1, 3, 5, or 7 yr after treatment. Confirmation of this ICE as a surrogate for OS is needed from randomized trial data so that it can be incorporated into future clinical trial design. Patient summary We assessed potential intermediate clinical endpoints prognostic for overall survival in a cohort of men receiving radiotherapy after prostatectomy. We identified the development of metastatic disease within 5 yr after treatment as the strongest predictor of overall survival. Take Home Message We assessed potential intermediate clinical endpoints prognostic for overall survival in a cohort of men receiving radiotherapy after prostatectomy. We identified the development of metastatic disease within 5 yr after treatment as the strongest predictor of overall survival. [ABSTRACT FROM AUTHOR]

Abstract Background Among men with clinically low-risk prostate cancer, we have previously documented heterogeneity in terms of clinical characteristics and genomic risk scores. Objective To further study the underlying tumor biology of this patient population, by interrogating broader patterns of gene expression among men with clinically low-risk tumors. Design, setting, and participants Prostate biopsies from 427 patients considered potentially suitable for active surveillance underwent central pathology review and genome-wide expression profiling. These cases were compared with 1290 higher-risk biopsy cases with diverse clinical features from a prospective genomic registry. Outcome measurements and statistical analysis Average genomic risk (AGR) was determined from 18 published prognostic signatures, and MSigDB hallmark gene sets were analyzed using bootstrapped clustering methods. These sets were examined in relation to clinical variables and pathological and biochemical outcomes using multivariable regression analysis. Results and limitations A total of 408 (96%) biopsies passed RNA quality control. Based on AGR quartiles defined by the high-risk multicenter cases, the University of California, San Francisco (UCSF) low-risk patients were distributed across the quartiles as 219 (54%), 107 (26%), 61 (15%), and 21 (5%). Unsupervised clustering analysis of the hallmark gene set scores revealed three clusters, which were enriched for the previously described PAM50 luminal A, luminal B, and basal subtypes. AGR, but not the clusters, was associated with both pathological (odds ratio 1.34, 95% confidence interval [CI] 1.14–1.58) and biochemical outcomes (hazard ratio 1.53, 95% CI 1.19–1.93). These results may underestimate within-prostate genomic heterogeneity. Conclusions Prostate cancers that are homogeneously low risk by traditional characteristics demonstrate substantial diversity at the level of genomic expression. Molecular substratification of low-risk prostate cancer will yield a better understanding of its divergent biology and, in the future may help personalize treatment recommendations. Patient summary We studied the genomic characteristics of tumors from men diagnosed with low-risk prostate cancer. We found three main subtypes of prostate cancer with divergent tumor biology, similar to what has previously been found in women with breast cancer. In addition, we found that genomic risk scores were associated with worse pathology findings and prostate-specific antigen recurrence after surgery. These results suggest even greater genomic diversity among low-risk patients than has previously been documented with more limited signatures. Take Home Message In a large cohort of men who were candidates for active surveillance, genomic profiling finds a high degree of heterogeneity in biological pathway activation and genomic risk scores that predict adverse outcomes after radical prostatectomy. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) is one of the most prevalent cancer types in men. Biochemical recurrence continues to occur in a large proportion of patients after radical prostatectomy. Thus, prognostic biomarkers are required to determine which treatment is suitable. In the present study, RNA‑sequencing gene expression data from The Cancer Genome Atlas was used in order to develop a risk‑score staging system based on the expression of eight genes. Cox multivariate regression was used to predict the outcome of patients with PCa. The biomedical recurrence‑free survival of patients with low‑risk scores was significantly longer compared with patients with high‑risk scores (P=5x10‑7). This result was further validated using another dataset, GSE70769, from the National Center for Biotechnology Information. The prognostic values of other clinical information and risk scores were evaluated for 5‑year biochemical recurrence. The prognostic value of the risk score was determined using an area under curve value of 0.819, predicting the 5‑year biochemical recurrence of patients with PCa. The risk score was identified to be significantly associated with primary tumor stage (P<0.01), Gleason score (P<0.01), and lymph node invasion (P<0.05), but was independent of age. Cox multivariate regression revealed that the risk score was an indicator for prediction of biochemical recurrence. Thus, the risk score is a valuable and robust indicator for predicting the biochemical recurrence of patients with PCa. [ABSTRACT FROM AUTHOR]

Objective: To investigate the association between benign prostatic hyperplasia (BPH) patterns, classified by magnetic resonance imaging (MRI), with lower urinary tract symptoms (LUTS) or continence, preoperatively and after robot-assisted laparoscopic radical prostatectomy (RARP).Materials and Methods: This retrospective study included 49 prostate cancer patients, with prostate size >47 cm3, who underwent an endorectal MRI followed by RARP. Five BPH patterns were identified according to Wasserman, and additional prostate measurements were recorded. LUTS were assessed using the International Prostate Symptom Score and the PR25-LUTS-Questionnaire score. Continence was assessed using the International Consultation of Incontinence Questionnaire-Short Form.Results: BPH pattern 3 (44.9%) was identified most common, followed by pattern 5 (26.6%), 1 (24.5%), and 2 and 4 (both 2%). BPH patterns were significant predictors of preoperative LUTS, with pedunculated with bilateral transition zone (TZ) and retrourethral enlargement (pattern 5) causing more severe symptoms compared with bilateral TZ and retrourethral enlargement (pattern 3) and bilateral TZ enlargement (pattern 1), whereas pattern 3 was additionally associated with more voiding symptoms compared with pattern 1. None of the BPH patterns was predictive of postoperative LUTS and continence. Independent predictors of continence at 12 months were lower preoperative PR25-LUTS score (P = .022) and longer membranous urethral length (P = .025).Conclusion: MRI is useful for classifying patients in BPH patterns which are strongly associated with preoperative LUTS. However, BPH patterns did not predict remnant LUTS or postoperative incontinence. Postoperative continence status was only associated with preoperative LUTS and membranous urethra length. [ABSTRACT FROM AUTHOR]

Purpose While prostate cancer is primarily a disease of older men, young age prostate cancer represents an important clinical subgroup which has not been adequately studied. We evaluated the histopathological features and associated clinical behavior of prostate cancer in a cohort of younger men treated with radical prostatectomy. Materials and Methods The study included 171 men younger than 50 years with prostate cancer who were treated with radical prostatectomy at an academic institution between 2001 and 2015. Comprehensive pathology review was performed. Clinical and followup data were obtained from a prospectively maintained institutional database. Results Median age was 43 years (range 38 to 49). Of the tumors 42% were Gleason score 3 + 3 and 45% were 3 + 4 while Gleason score 4 + 3, 4 + 4 and 4 + 5 disease comprised 10.5%, 0.5% and 1% of cases, respectively. Mucinous carcinoma (greater than 25% extracellular mucin), an uncommon histological variant which comprises 0.2% of prostate cancers, was noted in 11 of our cases (6%). A further 21 cases (12%) of acinar adenocarcinoma had a less than 25% mucinous component. Followup data were available on 156 men (91%). Biochemical recurrence developed in 12 patients (19%) but there was no documented postoperative metastasis or death from disease in the cohort. All cases of mucinous carcinoma were associated with favorable clinicopathological characteristics. Conclusions Our findings provide additional evidence that younger men with prostate cancer who are treated with radical prostatectomy mostly have favorable disease characteristics and outcomes. While the histopathological features in our series were generally comparable to those of older onset carcinoma, our cohort was enriched for tumors with a mucinous phenotype. Correlation with molecular-genetic analysis in this subset of tumors may be valuable. [ABSTRACT FROM AUTHOR]

Purpose: We characterized factors related to nondefinitive management (NDM) of patients with high-risk prostate cancer and assessed impact from race, insurance status, and facility-level volume of technologically advanced prostate cancer treatments (i.e., intensity-modulated radiation therapy, robotic-assisted laparoscopic radical prostatectomy) on this outcome.Methods: We identified men with high-risk localized prostate cancer (based on D׳Amico criteria) in the National Cancer Database (2010-2012). Primary outcome was NDM (i.e., delayed/no treatment with prostatectomy/radiation therapy or androgen-deprivation monotherapy). Treating facilities were classified by quartiles of proportions of patients treated with advanced technology. Multivariable regression estimated odds of primary outcome based on race, insurance status, and facility-level technology use, and evaluated for interactions between these covariates.Results: Among 60,300 patients, 9,265 (15.4%) received NDM. This was more common among non-White men (P<0.001), Medicaid/uninsured patients (P<0.001), and those managed at facilities in the lowest quartile of technology use (25.1% vs. 11.0% highest, P<0.001). Though NDM was common among non-White men with Medicaid/no insurance treated at low-technology centers (43% vs. 10% White, private/Medicare, high-tech facility; adjusted odds ratios = 7.18, P<0.001), this was less likely if this group was managed at a high-tech hospital (22% vs. 43% low-tech, P<0.001).Conclusions: Technology use at a facility correlates with high-quality prostate cancer care and is associated with diminished disparities based on insurance status and patient race. More research is required to characterize other facility-level factors explaining these findings. [ABSTRACT FROM AUTHOR]

Purpose The impact of African-American race on oncologic outcomes for low risk prostate cancer is unclear due to conflicting data. We investigated the effect of African-American race on pathological upgrading and/or up staging at prostatectomy in men with clinically low risk prostate cancer. Materials and Methods We queried the National Cancer Database for men with low risk prostate cancer (clinical stage T2a or less, Gleason score 6 or less, prostate specific antigen less than 10 ng/ml) treated with radical prostatectomy between 2010 and 2013. The outcomes were pathological upgrading to Gleason score greater than 6 (primary) or Gleason score greater than 3+4=7 (secondary) and/or up staging (pathological T3-4 or N1 disease). The association between race and the end points was assessed using multivariable logistic regression. To further adjust for potential confounders, stratification by urban residence and comorbidity score, and subgroup analyses were performed. Results With adjustment for age, comorbidity, income, urban residence, T stage, prostate specific antigen and percentage of positive biopsy cores, African-American race conferred 1.2-fold higher odds of pathological upgrading to Gleason score greater than 6 and/or up staging (OR 1.2, 95% CI 1.1–1.3, p <0.01). African-American race also was an independent predictor of pathological upgrading to Gleason score greater than 3+4=7 and/or up staging (p=0.03). Conclusions African-American men with low risk prostate cancer are more likely to harbor higher risk disease, which may lead to adverse outcomes. This finding alone does not preclude active surveillance. However, race should be considered as men weigh the risks and benefits of active surveillance vs treatment. [ABSTRACT FROM AUTHOR]

Purpose: Prostate cancer (CaP) in younger men (age ≤50 years) appears to present differently compared with older men. This study describes CaP characteristics and outcomes in Australian young men. Methods: The South Australian Prostate Cancer Clinical Outcomes Collaborative database was used to identify men diagnosed with CaP 1998-2012. Men were stratified by age at diagnosis into groups ≤50, 50-70 and ≥70 years. Primary outcomes of cumulative biochemical recurrence (BCR) and cumulative prostate cancer-specific mortality (PCSM) were assessed at 5 and 10 years. Results: In total, 7018 men were included. At time of diagnosis, 182 (2.6 %) were aged ≤50 years. Median follow-up exceeded 4 years. Younger men had a greater proportion of T stage <2 disease, lower median PSA and higher rates of Gleason score <7 (all p < 0.001). They were more likely to experience active surveillance (AS) (4.9, 3.1, 1.5 %) or radical prostatectomy (RP) (70, 55, 8 %) and less likely radiotherapy (13, 24, 29 %) as their principal modality (all p < 0.001). Although only 4.9 % underwent AS, 48 % of men ≤50 years were eligible for AS. Men ≤50 years had both the lowest unadjusted cumulative BCR and PCSM at 10 years. After multivariate analysis, BCR was not significantly different. Sample size limited multivariate analysis of PCSM. Conclusions: In our cohort, men ≤50 years with CaP had less aggressive clinical characteristics, but were more likely to undergo RP. They appear to experience lower unadjusted PCSM, but similar rates of adjusted BCR. Further studies are needed to assess whether AS is appropriately utilised in these men. [ABSTRACT FROM AUTHOR]

Purpose Prostate cancer is clinically and molecularly heterogeneous. We determined the prognosis of men with ERG-ETS fusions and SPINK1 over expression. Materials and Methods Men were identified with intermediate or high risk localized prostate cancer treated with radical prostatectomy and no therapy before metastasis. A case-cohort design sampled a cohort (262) enriched with metastasis from the entire cohort and a cohort (213) enriched with metastasis from patients with biochemical recurrence. We analyzed transcriptomic profiles and subtyped tumors as m-ERG + , m-ETS + , m-SPINK1 + or Triple Negative (m-ERG ─ /m-ETS ─ /m-SPINK1 ─ ), and multivariable logistic regression analyses, Kaplan-Meier and multivariable Cox models were used to evaluate subtypes as predictors of clinical outcomes. Results Overall 36%, 13%, 11% and 40% of prostate cancer was classified as m-ERG + , m-ETS + , m-SPINK1 + and Triple Negative, respectively. Univariable analysis demonstrated that m-SPINK1 + tumors were more common in African-American men (OR 5, 95% CI 1.6–16) but less commonly associated with positive surgical margins (OR 0.16, 95% CI 0.03–0.69) compared to the m-ERG + group. Compared to the Triple Negative group, m-SPINK1 + showed similar associations with race and surgical margins in univariable and multivariable analyses across the entire cohort. Survival analyses did not show significant differences among m-ERG + , m-ETS + and Triple Negative cases. m-SPINK1 + independently predicted prostate cancer specific mortality after metastasis (HR 2.48, 95% CI 0.96–6.4) and biochemical recurrence (HR 3, 95% CI 1.1–8). Conclusions SPINK1 over expression is associated with prostate cancer specific mortality in at risk men with biochemical and clinical recurrence after prostatectomy. ERG-ETS alterations are not prognostic for outcome. [ABSTRACT FROM AUTHOR]

Purpose We compared pathological outcomes after radical prostatectomy for a population based sample of men with low risk prostate cancer initially on active surveillance and undergoing delayed prostatectomy vs those treated with immediate surgery in order to better understand this expectant management approach outside of the context of academic cohorts. We hypothesized that delays in surgery due to initial surveillance would not impact surgical pathological outcomes. Materials and Methods We performed a prospective cohort study of 2 groups of patients with NCCN low risk prostate cancer from practices in the Michigan Urological Surgery Improvement Collaborative, that is 1) men who chose initial active surveillance and went on to delayed prostatectomy and 2) men who chose immediate prostatectomy. Diagnoses occurred from January 2011 through August 2015. For these 2 groups we compared radical prostatectomy Gleason scores, and rates of extraprostatic disease, positive surgical margins, seminal vesicle invasion and lymph node metastases. Results During a median followup of 506 days 79 (6%) of 1,359 low risk men choosing initial surveillance transitioned to prostatectomy. Compared to those treated with immediate prostatectomy (778), men undergoing delayed surgery were more likely to have Gleason score 7 or greater disease (69.2% vs 48.8%, respectively, p=0.004), but were no more likely to have positive margins, extraprostatic extension, seminal vesicle invasion or lymph node metastases. Conclusions Patients with low risk prostate cancer who enter active surveillance have higher grade disease at prostatectomy compared to those undergoing immediate surgery. However, the lack of difference in other adverse pathological outcomes suggests preservation of the window of curability. [ABSTRACT FROM AUTHOR]

Background: We propose to improve the prognostic assessment after radical prostatectomy (RP) by dividing high-risk prostate cancer (hrPCa) (according to the d'Amico classification) into subgroups combining 1, 2 or 3 criteria of aggressiveness (cT2c-T3a, PSA >20 ng/ml, Gleason score (GS) > 7).Methods: Data from 4795 hrPCa patients who underwent RP in two French university hospitals from 1991 to 2013 were analyzed. Subgroups were formed to determine whether an increasing number (1, 2 or 3) of criteria of tumor aggressiveness was associated with poorer oncological results and early biochemical recurrence (BCR) (PSA > 0.2 ng/ml). These results were compared using Fisher's exact test and BCR was compared according to the Kaplan-Meier method.Results: Eight hundred fifteen patients were treated by RP for hrPCa (8 %). Four hundred eleven patients (79.5 %) presented 1 RF (Risk Factor), 93 (18.0 %) 2 RF and 13 (2.5 %) 3 RF. Lymph node invasion and positive margin rates were 12.4 and 44.1 %, respectively. The prognostic sub-stratification based on these 3 factors was significantly predictive for adverse pathologic features and for oncologic outcomes. BCR free survival was respectively 56.4, 27.06 and 18.46 % for 1RF, 2RF and 3RF (p < 0.0001). However, no predominant negative criterion was found.Conclusion: Oncologic results after RP are heterogenous within the hrPCa risk group. Sub-stratification based on three well-defined criteria leads to a better identification of the most aggressive cancers. On the other hand, RP provides both effective cancer control and satisfactory survival rates in patients with only one risk factor. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to assess postprostatectomy erectile function compared to preoperative status by subjective patient perception and the abbreviated International Index of Erectile Function (IIEF-5) questionnaire.Materials and methods: The study used data from a prospectively collected database and a cross-sectional, questionnaire-based study in patients following radical prostatectomy. Erectile function was assessed with the IIEF-5 and the question “Is your erectile functionas goodas before the surgery (yes/no)”. Patients were included if they were sexually active before surgery and had at least 1 year of follow-up. The main outcome measure was the proportion of patients returning to self-perceived baseline erectile function. Secondary outcome measures included the proportion of patients returning to baseline erectile function according to the IIEF-5 and predictors of return to baseline function.Results: Questionnaires from 210 patients were available. Overall, 14 patients (6.7%) reported that their erections were as good as before surgery. Bilateral nerve-sparing was the only significant predictor of a return to baseline erectile function (p = 0.004). Forty-three patients (20.5%), who did not report use of erectile aids, showed no decline in IIEF-5 score. When including patients who used erectogenic aids, 69 (32.9%) maintained their preoperative IIEF-5 score. On multivariate analysis a low preoperative IIEF-5 score was a significant predictor of return to baseline IIEF-5 score (p < 0.0001).Conclusions: Return to subjective baseline erectile function following radical prostatectomy is rare. The IIEF-5 questionnaire may not adequately reflect patients’ experience. This should be considered in preoperative patient counselling. [ABSTRACT FROM PUBLISHER]

Purpose: A radical prostatectomy might lead to an impaired quality of life. Aim of the study was to analyse the impact of inpatient and outpatient rehabilitation on psychosocial and physical outcomes in patients after surgery.Methods: Six hundred nineteen inpatients and 95 outpatients, treated for localized prostate cancer by prostatectomy, completed the Hospital Anxiety and Depression Scale (HADS) and two quality-of-life questionnaires (EORTC QLQ-C30 and EORTC QLQ-PR25) at the beginning and end of rehabilitation as well as 12 months after rehabilitation. Data were analysed by using t-tests, chi(2) - tests and analyses of variance with repeated measures.Results: Compared to a population sample, patients reported a significantly worse quality of life (EORTC QLQ-C30) and more anxiety (HADS) at the beginning of rehabilitation. Physical, role and social functioning increased significantly over time for in- and outpatients. Patients still reported lower emotional functioning (EORTC QLQ-C30), anxiety (HADS) and prostate cancer-specific physical symptoms (EORTC QLQ-PR25) 1 year after rehabilitation, although symptom levels decreased significantly over time. The setting did not have an independent significant effect in the multivariate model.Conclusions: In- and outpatients reported an increased quality of life 1 year after rehabilitation with respect to their physical constitution and their reintegration into social life. Nonetheless, both groups still struggled with problems due to surgery. The results indicated that both settings seem to be supportive in the recovery process but that patients seem to require additional support with aftercare for treating surgery-related problems as well as emotional discomfort. [ABSTRACT FROM AUTHOR]

Purpose We assessed the pathological outcomes after radical prostatectomy in men with favorable risk prostate cancer diagnosed on first/initial biopsy compared to those of men who were diagnosed on a subsequent/repeat prostate biopsy. Materials and Methods We identified 422 patients who met National Comprehensive Cancer Network® very low (199) and low risk (223) prostate cancer definitions who instead underwent radical prostatectomy. In each risk category we compared adverse pathological outcomes, defined as Gleason score upgrading, extraprostatic extension, seminal vesicle invasion and positive surgical margins, between men diagnosed on initial prostate biopsy vs repeat/subsequent prostate biopsy after a negative biopsy(-ies). Results There were no significant differences in the baseline clinical and demographic characteristics between the groups. However, men who were diagnosed on initial prostate biopsy demonstrated a higher median maximum cancer percent per single core (p <0.001) and higher median percent of positive cores (p <0.001). Compared to repeat/subsequent prostate biopsy, men diagnosed on initial prostate biopsy had a higher Gleason score upgrade (7 or greater) (57.7% vs 42.1%, p=0.005) and extraprostatic extension (14.1% vs 5.4%, p=0.01). On stratified analysis comparing initial prostate biopsy to repeat/subsequent prostate biopsy, very low risk disease was associated with Gleason score upgrade (49.3% vs 31.8%, p=0.02) and low risk disease demonstrated higher rates of extraprostatic extension (19.9% vs 6.0%, p=0.02). Conclusions The likelihood of adverse pathological outcomes at radical prostatectomy is lower in men diagnosed with favorable risk prostate cancer on repeat/subsequent prostate biopsy than in men diagnosed on initial prostate biopsy, and may represent an important consideration in risk stratifying cases of favorable risk prostate cancer. [ABSTRACT FROM AUTHOR]

As the most common noncutaneous malignancy in American men, prostate cancer currently accounts for 29% of all diagnosed cancers, and ranks second as the cause of cancer fatality in American men. Prostatic cancer is rarely symptomatic early in its course and therefore disease presentation often implies local extension or even metastatic disease. Thus, it is extremely critical to detect and diagnose prostate cancer in its earliest stages, often prior to the presentation of symptoms. Three of the most common techniques used to detect prostate cancer are the digital rectal exam, the transrectal ultrasound, and the use of biomarkers. This review presents an update regarding the field of prostate cancer biomarkers and comments on future biomarkers. Although there is not a lack of research in the field of prostate cancer biomarkers, the discovery of a novel biomarker that may have the advantage of being more specific and effective warrants future scientific inquiry. [ABSTRACT FROM AUTHOR]

Background Radical prostatectomy (RP) is a primary treatment option for men with intermediate- and high-risk prostate cancer. Although many are effectively cured with local therapy alone, these men are by definition at higher risk of adverse pathologic features and clinical disease recurrence. It has been shown that the Decipher test predicts metastatic progression in cohorts that received adjuvant and salvage therapy following RP. Objective To evaluate the Decipher genomic classifier in a natural history cohort of men at risk who received no additional treatment until the time of metastatic progression. Design, setting, and participants Retrospective case-cohort design for 356 men who underwent RP between 1992 and 2010 at intermediate or high risk and received no additional treatment until the time of metastasis. Participants met the following criteria: (1) Cancer of the Prostate Risk Assessment postsurgical (CAPRA-S) score ≥3; (2) pathologic Gleason score ≥7; and (3) post-RP prostate-specific antigen nadir <0.2 ng/ml. Outcome measurements and statistical analysis The primary endpoint was defined as regional or distant metastases. Time-dependent receiver operating characteristic (ROC) curves, extension of decision curve analysis to survival data, and univariable and multivariable Cox proportional-hazards models were used to measure the discrimination, net benefit, and prognostic potential of genomic and pathologic risk factors. Cumulative incidence curves were constructed using Fine-Gray competing-risks analysis with appropriate weighting of the controls to account for the case-cohort study design. Results and limitations Ninety six patients had unavailable tumor blocks or failed microarray quality control. Decipher scores were then obtained for 260 patients, of whom 99 experienced metastasis. Decipher correlated with increased cumulative incidence of biochemical recurrence, metastasis, and prostate cancer–specific mortality ( p < 0.01). The cumulative incidence of metastasis was 12% and 47% for patients with low and high Decipher scores, respectively, at 10 yr after RP. Decipher was independently prognostic of metastasis in multivariable analysis (hazard ratio 1.26 per 10% increase; p < 0.01). Decipher had a c -index of 0.76 and increased the c -index of Eggener and CAPRA-S risk models from 0.76 and 0.77 to 0.86 and 0.87, respectively, at 10 yr after RP. Although the cohort was large, the single-center retrospective design is an important limitation. Conclusions In a patient population that received no adjuvant or salvage therapy after prostatectomy until metastatic progression, higher Decipher scores correlated with clinical events, and inclusion of Decipher scores improved the prognostic performance of validated clinicopathologic risk models. These results confirm the utility already reported for Decipher. Patient summary The Decipher test improves identification of patients most at risk of metastatic progression and death from prostate cancer after radical prostatectomy. [ABSTRACT FROM AUTHOR]

Background: The role and type of pelvic lymph node dissection for clinically localized prostate cancer is controversial in Australia. Our study aims to determine the incidence of pelvic lymph node involvement and the complication rate of extended lymphadenectomy in a group of West Australian patients who underwent a robotic assisted radical prostatectomy plus extended pelvic lymph node dissection. Method: Forty-nine patients underwent a robotic assisted radical prostatectomy with extended pelvic lymph node dissection between 2008 and 2012 by a single private urological surgeon. The inclusion criteria for the extended lymph node dissection were clinical localized, intermediate and high-risk prostate cancer based on preoperative D'Amico classification. Results: Of the 49 patients, eight patients had positive nodes giving a nodal positivity rate of 16.33%. Six patients had a complication giving a total complication rate of 12.24%. Three of these complications have been attributed to the nodal dissection, thus giving an extended pelvic lymph node dissection complication rate of 6.12%. Conclusion: Rates of nodal involvement in our West Australian cohort are in keeping with those published in the literature. Extended pelvic lymph node dissection can be performed with an acceptable complication rate. Further research is required to investigate the therapeutic role of pelvic lymph node dissection. [ABSTRACT FROM AUTHOR]

Objective To identify an appropriate risk stratification system for intermediate-risk prostate cancer ( PCa). Patients and Methods We reviewed the data on 1559 patients who were treated with radical prostatectomy ( RP) at our institution between 2005 and 2013 and classified them according to National Comprehensive Cancer Network ( NCCN) risk groups. For our analyses, intermediate-risk PCa was designated as unfavourable intermediate-risk PCa if it met at least one of the following two criteria: biopsy Gleason score 4 + 3 and/or presence of ≥2 intermediate-risk criteria. All other men with intermediate-risk PCa were designated as having favourable intermediate-risk disease. Postoperative outcomes, including biochemical recurrence ( BCR)-free survival, were calculated and compared using the log-rank test and Cox proportional hazards model. Results In multivariable analysis, biopsy Gleason score 4 + 3 and multiple (≥2) intermediate-risk criteria were observed to be independent predictors of BCR risk among men in the intermediate-risk group undergoing RP. The favourable intermediate-risk group had a significantly higher 5-year BCR-free survival compared with the unfavourable intermediate-risk group (87.5 vs 66.5%; P < 0.001). The unfavourable intermediate-risk group had significantly higher 5-year BCR-free survival than the high-risk group (66.5 vs 47.9%; P < 0.001) while the favourable intermediate-risk group had significantly lower 5-year BCR-free survival than the low-risk group (87.5 vs 93.5%; P = 0.002). Conclusions A marked heterogeneity exists in the biochemical outcomes of contemporary patients with intermediate-risk PCa who undergo definitive RP. According to biopsy Gleason score and number of intermediate-risk criteria present, the intermediate-risk group should be sub-divided into those with favourable and unfavourable intermediate-risk disease. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) is the most common malignancy affecting men in the western world. Although radical prostatectomy and radiation therapy can successfully treat PCa in the majority of patients, up to ~30% will experience local recurrence or metastatic disease. Prostate carcinogenesis and progression is typically an androgen-dependent process. For this reason, therapies for recurrent PCa target androgen biosynthesis and androgen receptor function. Such androgen deprivation therapies (ADT) are effective initially, but the duration of response is typically ≤24 months. Although ADT and taxane-based chemotherapy have delivered survival benefits, metastatic PCa remains incurable. Therefore, it is essential to establish the cellular and molecular mechanisms that enable localized PCas to invade and disseminate. It has long been accepted that metastases require angiogenesis. In the present review, we examine the essential role for angiogenesis in PCa metastases, and we focus in particular on the current understanding of the regulation of vascular endothelial growth factor (VEGF) in localized and metastatic PCa. We highlight recent advances in understanding the role of VEGF in regulating the interaction of cancer cells with tumor-associated immune cells during the metastatic process of PCa. We summarize the established mechanisms of transcriptional and post-transcriptional regulation of VEGF in PCa cells and outline the molecular insights obtained from preclinical animal models of PCa. Finally, we summarize the current state of anti-angiogenesis therapies for PCa and consider how existing therapies impact VEGF signaling. [ABSTRACT FROM AUTHOR]

Prostate cancer affects couples' sexual intimacy, but men rarely use recommended proerectile aids. This mixed-methods study aimed to identify couples' preprostatectomy barriers to sexual recovery. Interviews about anticipated sexual recovery were paired with surveys: the Dyadic Assessment Scale, the Protective Buffering Scale, the Expanded Prostate Cancer Index Composite, the Sexual Experience Questionnaire (men), and the Female Sexual Function Index. Potential barriers were derived using Grounded Theory. Quantitative data triangulated qualitative findings. Heterosexual couples (N = 28) participated. Men's average age was 62 years and their partners' average age was 58 years. Preexisting and diagnosis-related barriers included aging-related sexual dysfunction, inadequate sexual problem-solving skills, stressors, worry, avoidance of planning for sexual recovery, and dislike of artificially assisted sex. Participants endorsed moderate/high marital satisfaction (DAS: for men, M = 110.0, SD = 11.4; for partners, M = 114.1, SD = 12.1) and communication (PBS: for men, M = 24.5.2, SD = 6.1; for partners, M = 25.1, SD ± 6.2). Men reported mild erectile dysfunction and incontinence (EPIC sexual function M = 76.6, SD = 21.5, urinary incontinence M = 88.4, SD = 18.2). Men's couple sexual satisfaction was lowest (Sexual Experience Questionnaire: M = 60.1, SD = 26.9). Mean total Female Sexual Function Index was low (M = 21.6, SD = 7.8). Heterosexual couples face prostatectomy-related sexual side-effects having experienced developmental sexual losses. Couples use avoidant strategies to defend against worry about cancer and anticipated prostatectomy-related sexual changes. These potential barriers are modifiable if couples can learn to cope with sexual losses and accept sexual rehabilitation strategies. [ABSTRACT FROM AUTHOR]

Objective To evaluate preoperative predictors of positive surgical margins and their location in Korean men undergoing radical prostatectomy. Methods A total of 3227 patients who had undergone radical prostatectomy (open, robotic or laparoscopic) for clinically localized prostate cancer at three centers between 2000 and 2010 were analyzed. Patients were stratified by using the D' Amico risk criteria. Positive surgical margins were categorized according to their location. Patients were divided depending on their prostate volume: <29, 29-36, 36-46 and ≥46 mL. All of the patients had a minimum of six. A total of 2041 patients (84.9%) underwent 12-14 core biopsies. In each patient, the number and location of positive cores with cancer were assessed. In the analysis of predictive factors for positive surgical margin locations, regression analysis was carried out using only open and robotic prostatectomy. Results The preoperative prostate-specific antigen, prostate volume, biopsy Gleason scores and clinical stage were significantly associated with an increased risk of positive surgical margins. The predictive variables for positive apical margin were small prostate volume (less than 29 mL) and positive apical biopsy. There were no statistically significant predictors for positive posterolateral or basal margin. Positive apical biopsy was the predictor of positive apical margin in open (odds ratio 1.7, P = 0.009) and robotic prostatectomy (odds ratio 2.2, P = 0.041). Small prostate volume was the predictor of positive apical margin in open prostatectomy (odds ratio 1.6, P = 0.012), but for positive basal margin in robotic radical prostatectomy (odds ratio 4.5, P < 0.001). In survival analysis, positive basal margin showed worse prognoses on biochemical recurrence than positive apical margin. Conclusions High prostate-specific antigen and small prostate volume are predictive factors of positive surgical margin in Korean patients undergoing radical prostatectomy. Apical positivity on extended transrectal biopsy represents a predictive factor of positive surgical margin. Small prostate volume is associated with higher risk of positive surgical margins at the apex in open radical prostatectomy and at the base in robotic-assisted laparoscopic radical prostatectomy. [ABSTRACT FROM AUTHOR]

Objective To determine the relationship between prostate gland and tumor volume in men undergoing radical prostatectomy (RP) for prostate cancer. We hypothesized that larger tumors within smaller prostate glands are associated with more aggressive disease characteristics. Methods Records of patients undergoing RP from 2000-2008 at a single institution were reviewed retrospectively. The dominant nodule was considered to be the largest focus of cancer within the prostate, and the dominant nodule-to-prostate volume ratio (DNVR) was calculated according to the ratio of the dominant nodule volume to the gland weight. Cox regression was performed to assess the relationship between DNVR and both pathologic outcomes (Cancer of the Prostate Risk Assessment post-Surgical score) and biochemical recurrence (BCR). Results At a median follow-up of 3.7 years, 174 patients (7.2%) suffered BCR. There was no linear correlation between tumor volume and gland size (R = -0.09). DNVR above the median (≥0.033 cc/gm) was closely associated with high clinicopathologic risk as measured by Cancer of the Prostate Risk Assessment post-Surgical score (hazard ratio, 35.53; 95% confidence interval, 14.42-87.55 for high- vs low-risk groups). In the univariable analysis, both tumor diameter and DNVR were associated with increased risk of BCR. However, in the multivariable model, only tumor diameter remained a significant predictor of BCR (hazard ratio, 2.02; 95% confidence interval, 1.04-3.91). Conclusion Increased DNVR appears to be a characteristic of aggressive prostate tumors, although it did not predict BCR in the present study. However, these data support the association between tumor diameter and BCR after RP for prostate cancer independent of other key clinicopathologic features. [ABSTRACT FROM AUTHOR]

The current management of patients with high‐risk prostate cancer is hampered by overstaging. This editorial reviews the referenced article as well as outlines the treatment strategies for patients with aggressive disease. [ABSTRACT FROM AUTHOR]

Abstract: Background: Few data exist regarding the impact on survival of definitive treatment of the prostate in men diagnosed with metastatic prostate cancer (mPCa). Objective: To evaluate the survival of men diagnosed with mPCa based on definitive treatment of the prostate. Design, setting, and participants: Men with documented stage IV (M1a–c) PCa at diagnosis identified using Surveillance Epidemiology and End Results (SEER) (2004–2010) and divided based on definitive treatment of the prostate (radical prostatectomy [RP] or brachytherapy [BT]) or no surgery or radiation therapy (NSR). Outcome measurements and statistical analysis: Kaplan-Meier methods were used to calculate overall survival (OS). Multivariable competing risks regression analysis was used to calculate disease-specific survival (DSS) probability and identify factors associated with cause-specific mortality (CSM). Results and limitations: A total of 8185 patients were identified: NSR (n =7811), RP (n =245), and BT (n =129). The 5-yr OS and predicted DSS were each significantly higher in patients undergoing RP (67.4% and 75.8%, respectively) or BT (52.6 and 61.3%, respectively) compared with NSR patients (22.5% and 48.7%, respectively) (p <0.001). Undergoing RP or BT was each independently associated with decreased CSM (p <0.01). Similar results were noted regardless of the American Joint Committee on Cancer (AJCC) M stage. Factors associated with increased CSM in patients undergoing local therapy included AJCC T4 stage, high-grade disease, prostate-specific antigen ≥20 ng/ml, age ≥70 yr, and pelvic lymphadenopathy (p <0.05). The major limitation of this study was the lack of variables from SEER known to influence survival of patients with mPCa, including treatment with systemic therapy. Conclusions: Definitive treatment of the prostate in men diagnosed with mPCa suggests a survival benefit in this large population-based study. These results should serve as a foundation for future prospective trials. Patient summary: We used a large population-based cancer database to examine survival in men diagnosed with metastatic prostate cancer (mPCa) undergoing definitive therapy for the prostate. Local therapy (LT) appeared to confer a survival benefit. Therefore, we conclude that prospective trials are needed to further evaluate the role of LT in mPCa. [Copyright &y& Elsevier]

Background:Identification of men harbouring insignificant prostate cancer (PC) is important in selecting patients for active surveillance. Tools have been developed in PSA-screened populations to identify such men based on clinical and biopsy parameters.Methods:Prospectively collected case series of 848 patients was treated with radical prostatectomy between July 2007 and October 2011 at an English tertiary care centre. Tumour volume was assessed by pathological examination. For each tool, receiver operator characteristics were calculated for predicting insignificant disease by three different criteria and the area under each curve compared. Comparison of accuracy in screened and unscreened populations was performed.Results:Of 848 patients, 415 had Gleason 3+3 disease on biopsy. Of these, 32.0% had extra-prostatic extension and 50.2% were upgraded. One had positive lymph nodes. Two hundred and six (24% of cohort) were D'Amico low risk. Of these, 143 had more than two biopsy cores involved. None of the tools evaluated has adequate discriminative power in predicting insignificant tumour burden. Accuracy is low in PSA-screened and -unscreened populations.Conclusions:In our unscreened population, tools designed to identify insignificant PC are inaccurate. Detection of a wider size range of prostate tumours in the unscreened may contribute to relative inaccuracy. [ABSTRACT FROM AUTHOR]

Abstract: Context: The role of robot-assisted radical prostatectomy (RARP) for men with high-risk (HR) prostate cancer (PCa) has not been well studied. Objective: To evaluate the indications for surgical treatment, technical aspects such as nerve sparing (NS) and lymph node dissection (LND), and perioperative outcomes of men with HR PCa treated with RARP. Evidence acquisition: A systematic expert review of the literature was performed in October 2012, searching the Medline, Web of Science, and Scopus databases. Studies with a precise HR definition, robotic focus, and reporting of perioperative and pathologic outcomes were included. Evidence synthesis: A total of 12 papers (1360 patients) evaluating RARP in HR PCa were retrieved. Most studies (67%) used the D’Amico classification for defining HR. Biopsy Gleason grade 8–10 was the most frequent HR identifier (61%). Length of follow-up ranged from 9.7 to 37.7 mo. Incidence of NS varied, although when performed did not appear to compromise oncologic outcomes. Extended LND (ELND) revealed positive nodes in up to a third of patients. The rate of symptomatic lymphocele after ELND was 3%. Overall mean operative time was 168min, estimated blood loss was 189ml, length of hospital stay was 3.2 d, and catheterization time was 7.8 d. The 12-mo continence rates using a no-pad definition ranged from 51% to 95% with potency recovery ranging from 52% to 60%. The rate of organ-confined disease was 35%, and the positive margin rate was 35%. Three-year biochemical recurrence–free survival ranged from 45% to 86%. Conclusions: Although the use of RARP for HR PCa has been relatively limited, it appears safe and effective for select patients. Short-term results are similar to the literature on open radical prostatectomy. Variability exists for NS and the template of LND, although ELND improves staging and removes a higher number of metastatic nodes. Further study is required to assess long-term outcomes. [Copyright &y& Elsevier]

Abstract: Background: Urinary incontinence is a common short-term complication of radical prostatectomy (RP). Little is known about the long-term impact of RP on continence. Objective: To elucidate the long-term progression of continence after RP. Design, setting, and participants: From October 2000 through September 2012, 1788 men undergoing open RP for clinically localized prostate cancer by a single surgeon at an urban tertiary care center prospectively signed consent to be followed before RP and at 3, 6, 12, 24, 96, and 120 mo after RP. A consecutive sampling method was used and all men were included in this study. Intervention: Men underwent open RP. Outcome measurements and statistical analysis: Regression models controlled for preoperative University of California, Los Angeles–Prostate Cancer Index urinary function score (UCLA-PCI-UFS), age, prostate-specific antigen level, Gleason score, stage, nerve-sparing status, race, and marital status were used to evaluate the association of time since RP with two dependent variables: UCLA-PCI-UFS and continence status. Results and limitation: The mean UCLA-PCI-UFS declined between 2 yr and 8 yr (83.8 vs 81.8; p =0.007) and marginally between 8 yr and 10 yr (81.8 vs 79.6; p =0.036) after RP, whereas continence rate did not significantly change during these intervals. Men ≥60 yr old experienced a decline in mean UCLA-PCI-UFS between 2 yr and 8 yr (p =0.002) and a marginal decline in continence rate between 2 yr and 10 yr (p =0.047), whereas these variables did not change significantly in men <60 yr old. These outcomes are for an experienced surgeon, so caution should be exercised in generalizing these results. Conclusions: Between 2 yr and 10 yr after RP, there were slight decreases in mean UCLA-PCI-UFS and continence rates in this study. Men aged <60 yr had better long-term outcomes. These results provide realistic long-term continence expectations for men undergoing RP. [Copyright &y& Elsevier]

Background: Prostate cancer is the most common cancer in men. Radical prostatectomy is the best method of treatment with curative intent, however, there are several types of approach for its removal, laparoscopic radical prostatectomy offers a similar incidence recurrence with conventional open surgery approach. Objective: Determine recurrence of prostate cancer comparing open radical prostatectomy with laparoscopic in Specialty Hospital Medical Center "La Raza", in the period of January 2006 to December 2010. Material and methods: Observational, retrospective, descriptive and transversal study in Specialty Hospital National Medical Center "La Raza". 118 patients with documented prostate cancer by transrectal biopsy were studied and who underwent surgery for open and laparoscopic radical prostatectomy. Results: 32 patients who underwent laparoscopic radical prostatectomy and 86 with open approach were studied. It was found that the overall recurrence in patients undergoing LRP and ORP was 43.75 and 50.0%, respectively. Conclusions: There is no statistically significant difference in overall recurrence rate when comparing both surgical techniques, having the laparoscopic approach with a difference of 6.25% in favor. There is evidence of better functional results and long term benefits related to sexual perfomance and urinary continence. [ABSTRACT FROM AUTHOR]

Purpose: Of men with very low risk prostate cancer at biopsy recent evidence shows that black American men are at greater risk for adverse oncologic outcomes after radical prostatectomy. We studied radical prostatectomy specimens from black and white men at very low risk to determine whether there are systematic pathological differences. Materials and Methods: Radical prostatectomy specimens were evaluated in men with National Comprehensive Cancer Network® (NCCN) very low risk prostate cancer. At diagnosis all men underwent extended biopsy sampling (10 or more cores) and were treated in the modern Gleason grade era. We analyzed tumor volume, grade and location in 87 black and 89 white men. For each specimen the dominant nodule was defined as the largest tumor with the highest grade. Results: Compared to white men, black men were more likely to have significant prostate cancer (61% vs 29%), Gleason 7 or greater (37% vs 11%, each p <0.001) and a volume of greater than 0.5 cm3 (45% vs 21%, p = 0.001). Dominant nodules in black men were larger (median 0.28 vs 0.13 cm3, p = 0.002) and more often anterior (51% vs 29%, p = 0.003). In men who underwent pathological upgrading the dominant nodule was also more frequently anterior in black than in white men (59% vs 0%, p = 0.001). Conclusions: Black men with very low risk prostate cancer at diagnosis have a significantly higher prevalence of anterior cancer foci that are of higher grade and larger volume. Enhanced imaging or anterior zone sampling may detect these significant anterior tumors, improving the outcome in black men considering active surveillance. [ABSTRACT FROM AUTHOR]

Major clinical trials using prostate-specific antigen (PSA) as the screening test to detect localized early-stage prostate cancer and to attempt to change its natural history with early intervention have yielded conflicting interpretations. The US Prostate, Lung, Colorectal, and Ovarian (US PLCO) cancer screening trial concluded that PSA-based screening conferred no meaningful survival benefit, whereas the European Randomized Study of Screening for Prostate Cancer (ERSPC) and the GOTEBORG clinical trial (GOTEBORG) trials claimed statistically significant life-saving benefits. These divergent outcomes have not provided physicians with clarity on the best evidence-based treatment. To determine the extent to which these divergent outcomes are clinically meaningful, we evaluated these data and those of a long-term prospective cohort study in the context of the clinically documented harms of androgen deprivation therapy (ADT). We noted the unheralded fact that in both European trials far more patients received hormonal treatment in the control than the prostatectomy arm, whereas hormonal therapy in the US trial was balanced between arms. We examined this imbalance in ADT treatment and prostate cancer–related deaths in the contexts of contamination, stage migration, and attribution of cause of death, all of which impinge on data interpretation. The ERSPC and GOTEBORG data are compatible with the hypothesis that ADT treatment contributes differentially to an increase in prostate cancer deaths in control patients. If so, the claim of a reduction in prostate cancer deaths in the screened cohort requires reappraisal. The conventional interpretation that PSA screening and radical treatment intervention are the major contributors to the results of these two studies needs more rigorous scientific scrutiny, as does the role of ADT treatment of nonmetastatic disease. [ABSTRACT FROM PUBLISHER]

Abstract: Background: Multiple large epidemiologic studies have examined the relationship between smoking and prostate cancer incidence and mortality only to arrive at contradictory results. In this series, we studied the effect of smoking on pathologic outcomes and biochemical recurrence in a cohort of men undergoing radical prostatectomy. Methods: We identified 630 men who underwent radical prostatectomy between 1989 and 2005 who had detailed smoking histories. There were 321 smokers and 309 nonsmokers. Pathologic outcomes included prostate weight, volume of cancer, volume of high grade cancer, margin status, seminal vesicle involvement, extraprostatic extension, perineural invasion, angiolymphatic invasion, and the presence of nodal metastasis. Biochemical recurrence was defined as a postoperative PSA ≥ 0.1 ng/ml. Univariate analysis and multivariate linear and Cox regression were used to study the impact of smoking on these outcomes. Results: The volume of cancer (2.54 vs. 2.16 ml, P = 0.016) and the volume of high grade cancer (0.58 vs. 0.28 ml, P = 0.004) were greater in smokers compared with nonsmokers. Smoking independently predicted greater volumes of cancer and high grade cancer in multivariate analysis. Heavy smokers (≥20 pack-year history) had a greater risk of biochemical recurrence on univariate survival analysis. Smoking also predicted a greater risk of biochemical recurrence on Cox regression, the magnitude of which was approximately 1% per pack-year smoked. Conclusions: Smoking is associated with adverse pathologic features and a higher risk of biochemical recurrence in men undergoing radical prostatectomy. If confirmed by additional studies, smoking history may need to be included into risk assessment models. [Copyright &y& Elsevier]

Abstract: Objectives: Prostate cancer (CaP) in the aging male will become an increasingly important and controversial health care issue. We evaluated the outcomes between a variety of treatments for low-risk CaP in patients 70 years of age and older. Methods and materials: A total of 3,650 men diagnosed with CaP between 1989 and 2009 were identified in the Center for Prostate Disease Research database to be 70 years of age or older at time of diagnosis. Of these patients, 770 men met the D'Amico criteria [13] for low-risk disease and were treated with radical prostatectomy, external beam radiation therapy, or watchful waiting. Cox proportional hazard models were used to compare clinicopathologic features across treatment groups. Kaplan-Meier analysis was used to compare biochemical recurrence-free, progression-free, and overall survival. Results: Of the 770 patient cohort, 194 (25%) chose radical prostatectomy, 252 (33%) chose external beam radiation therapy, and 324 (42%) were initially managed by watchful waiting with 110 (34%) of this subset ultimately undergoing secondary treatment. The median follow-up was 6.4 years. There were no significant differences in distributions of race/ethnicity, number of medical comorbidities, or clinical stage across the treatment groups. Patients managed on watchful waiting without secondary treatment had the poorest overall survival on Kaplan-Meier analysis (P = 0.0001). Additionally, multivariate analysis confirmed this result for watchful waiting without secondary treatment as being a statistically significant predictor of overall mortality (HR 1.938, P = 0.0084). [Copyright &y& Elsevier]

Background: Robot-assisted radical prostatectomy (RARP) has emerged in the last decade as an alternative to open radical prosta-tectomy for men with localized prostate cancer. The increased cost of this technique has been justified by its ability to reduce blood loss, and to provide improved vision, less postoperative pain and more rapid recovery from surgery, while maintaining satisfactory oncological and functional outcomes. Given the increasing diffu-sion of robotic surgical technology within Canada and its associ-ated high capital and operating costs, we review the clinical out-comes and complications from 305 consecutive cases performed at our Canadian institution. Methods: A consecutive cohort of 305 patients with a mean follow-up of 30 months was analyzed with institutional ethics approval. All patients were treated and reviewed postoperatively by a sin-gle surgeon (SP). The primary aim of the study was to assess the incidence and type of complications associated with RARP in a Canadian setting. Our prospective database captured preoperative, intra-operative and postoperative data and was maintained by an individual independent of the robotic program. We report com-plications categorized according to the Clavien system. Multiple complications seen in an individual were recorded separately for the purposes of our analysis. Results: Between April 2005 and October 2010, 305 patients underwent RARP at our institution. A total of 70 complications were identified, with 47 (67.1%) requiring only conservative or pharmacological management (Clavien l-ll). Twenty-three patients were found to have a major complication (Clavien lll-V). Of the 1 6 who required intervention under general anesthesia, 3 required emergency treatment and the remaining patients underwent elec-tive surgery. Conclusions: RARP has been incorporated at our institution with an acceptably low rate of intra-operative and postoperative complica-tions. We have found that the database was effective in providing patients with outcome-related information, which in turn helped us gain patient consent with regard to the institution-specific risks of RARP. [ABSTRACT FROM AUTHOR]

Objectives Benzothiazoles ( BZTs) represent organic compounds with different biological actions. In this study we aimed to investigate ten newly synthesized BZT derivatives as potential anti-tumour agents against prostate cancer in vitro and in vivo. Methods The cytotoxic effect of these compounds was screened on the human prostate cancer cell lines PC-3 and LNCaP. The most effective compound, N′-formyl-2-(5-nitrothiophen-2-yl)benzothiazole-6-carbohydrazide, was further characterized regarding its dose- and time-dependent effects on cell viability and proliferation ( XTT test) as well as on adhesion and spreading (real-time cell analyzer x Celligence), migration (scratch-wound repair assay) and invasion ( Boyden chamber) of the cells. This BZT derivative was also tested as an inhibitor of angiogenesis (chicken chorioallantoic membrane assay), clonogenic activity (soft agar) and matrix metalloproteinase 9 (gelatin zymography). Key findings N′-Formyl-2-(5-nitrothiophen-2-yl)benzothiazole-6-carbohydrazide significantly inhibited all tested properties of the prostate cancer cell lines and showed low toxic in vitro and in vivo effects. The in vitro anti-tumour activity of this compound was confirmed by the in vivo effects on PC-3 xenografts in nude mice. Tumour growth was decreased in treated compared with untreated mice. Conclusions These results suggest the potential capacity of BZTs and in particular N′-formyl-2-(5-nitrothiophen-2-yl)benzothiazole-6-carbohydrazide as anti-tumour agents for the treatment of prostate cancer. [ABSTRACT FROM AUTHOR]

Purpose: Radical prostatectomy has decreased prostate cancer specific mortality in men with clinically localized prostate cancer. We report oncological outcomes of the longest running series of nerve sparing radical retropubic prostatectomy on the 30th anniversary of the inaugural operation. Materials and Methods: A total of 4,478 men underwent anatomical radical retropubic prostatectomy, as performed by a single surgeon (PCW), at the Johns Hopkins Medical Institutions from 1982 to 2011, without neoadjuvant or adjuvant therapy. During a median followup of 10 years (range 1 to 29), we examined progression-free, metastasis-free and cancer specific survival. Results: The overall 25-year progression-free, metastasis-free and cancer specific survival rates were 68%, 84% and 86%, respectively, although there were significant differences in treatment outcomes between men treated in the pre-PSA and PSA eras. In each era, there were significant differences in progression-free, metastasis-free and cancer specific survival by D''Amico risk groups. In multivariable models considering prostatectomy features, pathological stage and grade were significantly associated with the risk of metastatic progression and disease specific mortality. Conclusions: Excellent prostate cancer specific survival was demonstrated up to 30 years after surgery. Clinical risk categories and pathological tumor features were significant predictors of long-term disease specific outcomes, supporting their ongoing use in risk stratification and management decisions. Anatomical radical retropubic prostatectomy continues to represent the gold standard in the surgical management of clinically localized prostate cancer to which alternate treatment options should be compared. [Copyright &y& Elsevier]

Study Type - Diagnostic (exploratory cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Men with high-risk prostate cancer experience recurrence, metastases and death at the highest rate in the prostate cancer population. Pathological stage at radical prostatectomy (RP) is the greatest predictor of recurrence and mortality in men with high-grade disease. Preoperative models predicting outcome after RP are skewed by the large proportion of men with low- and intermediate-risk features; there is a paucity of data about preoperative criteria to identify men with high-grade cancer who may benefit from RP. The present study adds comprehensive biopsy data from a large cohort of men with high-grade prostate cancer at biopsy. By adding biopsy parameters, e.g. number of high-grade cores and >50% involvement of any core, to traditional predictors of outcome (prostate-specific antigen concentration, clinical stage and Gleason sum), we can better inform men who present with high-grade prostate cancer as to their risk of favourable or unfavourable disease at RP. OBJECTIVE To investigate preoperative characteristics that distinguish favourable and unfavourable pathological and clinical outcomes in men with high biopsy Gleason sum (8-10) prostate cancer to better select men who will most benefit from radical prostatectomy (RP)., PATIENTS AND METHODS The Institutional Review Board-approved institutional RP database (1982-2010) was analysed for men with high-Gleason prostate cancer on biopsy; 842 men were identified., The 10-year biochemical-free (BFS), metastasis-free (MFS) and prostate cancer-specific survival (CSS) were calculated using the Kaplan-Meier method to verify favourable pathology as men with Gleason <8 at RP or ≤ pT3a compared with men with unfavourable pathology with Gleason 8-10 and pT3b or N1., Preoperative characteristics were compared using appropriate comparative tests., Logistic regression determined preoperative predictors of unfavourable pathology., RESULTS There was favourable pathology in 656 (77.9%) men. The 10-year BFS, MFS and CSS were 31.0%, 60.9% and 74.8%, respectively., In contrast, men with unfavourable pathological findings had significantly worse 10-year BFS, MFS and CSS, at 4.3%, 29.1% and 52.3%, respectively (all P < 0.001)., In multivariable logistic regression, a prostate-specific antigen (PSA) concentration of >10 ng/mL (odds ratio [OR] 2.24, 95% confidence interval [CI] 1.38-3.62, P= 0.001), advanced clinical stage (≥ cT2b; OR 2.55, 95% CI 1.55-4.21, P < 0.001), Gleason pattern 9 or 10 at biopsy (OR 2.55, 95% CI 1.59-4.09, P < 0.001), increasing number of cores positive with high-grade cancer (OR 1.16, 95% CI 1.01-1.34, P= 0.04) and >50% positive core involvement (OR 2.25, 95% CI 1.17-4.35, P= 0.015) were predictive of unfavourable pathology., CONCLUSIONS Men with high-Gleason sum at biopsy are at high risk for biochemical recurrence, metastasis and death after RP; men with high Gleason sum and advanced pathological stage (pT3b or N1) have the worst prognosis., Among men with high-Gleason sum at biopsy, a PSA concentration of >10 ng/mL, clinical stage ≥ T2b, Gleason pattern 9 or 10, increasing number of cores with high-grade cancer and >50% core involvement are predictive of unfavourable pathology. [ABSTRACT FROM AUTHOR]

ABSTRACT Introduction. Erectile dysfunction (ED) is one of the most frequent sources of distress after treatment for prostate cancer (PCa), yet evidence suggests that men do not easily adjust to loss of sexual function over time. A hypothesized determinant of men's adaptation to ED is the degree to which they experience a loss of masculine identity in the aftermath of PCa treatment. Aims. The aims of this study were (i) to describe the prevalence of concerns related to diminished masculinity among men treated for localized PCa; (ii) to determine whether diminished masculinity is associated with sexual bother, after controlling for sexual functioning status; and (iii) to determine whether men's marital quality moderates the association between diminished masculinity and sexual bother. Methods. We analyzed cross-sectional data provided by 75 men with localized PCa who were treated at one of two cancer centers. Data for this study were provided at a baseline assessment as part of their enrollment in a pilot trial of a couple-based intervention. Main Outcome Measures. The sexual bother subscale from the Prostate Health-Related Quality-of-Life Questionnaire and the Masculine Self-Esteem and Marital Affection subscales from Clark et al's PCa-related quality-of-life scale. Results. Approximately one-third of men felt they had lost a dimension of their masculinity following treatment. Diminished masculinity was the only significant, independent predictor of sexual bother, even after accounting for sexual functioning status. The association between diminished masculinity and sexual bother was strongest for men whose spouses perceived low marital affection. Conclusions. Diminished masculinity is a prominent, yet understudied concern for PCa survivors. Regardless of functional status, men who perceive a loss of masculinity following treatment may be more likely to be distressed by their ED. Furthermore, its impact on adjustment in survivorship may rely on the quality of their intimate relationships. Zaider T, Manne S, Nelson C, Mulhall J, and Kissane D. Loss of masculine identity, marital affection, and sexual bother in men with localized prostate cancer. J Sex Med **;**:**-**. [ABSTRACT FROM AUTHOR]

What's known on the subject? and What does the study add? Over the last decade, the surgical treatment of prostate cancer has evolved towards minimal access surgery, particularly via a robot-assisted technique. However, there is still debate regarding the true benefit for patients with respect to a functional outcome such as erectile function. The present prediction model provides a reliable estimation of the likelihood of regaining erectile function after prostatectomy. OBJECTIVE To identify the reported rates of potency after prostatectomy in the recent literature for men without preoperative erectile dysfunction (ED) and to develop a statistical model for predicting the expected potency after prostatectomy., MATERIALS AND METHODS A Medline search was conducted with the keywords 'potency' and 'prostatectomy' from 2003 to 2009., In total, 33 studies in the English language reporting pre- and postoperative erectile function were identified., Data from studies reporting outcome after open, laparoscopic and robot-assisted prostatectomy were analyzed separately., Only data obtained from potent men before surgery were included in the analysis., RESULTS In potent men before surgery, the main predictors of post-treatment erectile function are age and time after treatment., The cumulative range of potency rates at 48 months for all ages (45-75 years) was 49-74% for open, 58-74% for laparoscopic and 60-100% for robotic prostatectomy., The predicted outcome differs by type of operation and patient age., CONCLUSIONS Men aged <60 years have a significant likelihood of regaining erectile function after radical prostatectomy., The reported statistical model provides a reliable estimation of erectile function outcome after prostatectomy for men with localized prostate cancer and intact erectile function. [ABSTRACT FROM AUTHOR]

Study Type - Outcomes (cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Several comorbidity classifications have been investigated for their suitability to assist treatment decision-making in men with early prostate cancer. In unselected patients, some serious comorbidities have been shown to be associated with a 10-year competing mortality rate clearly superseding the 50% level. The present study shows that it is hardly possible to discern meaningful subsets of patients with a 10-year risk of competing mortality of >50% by using comorbidity classifications. This finding suggests that the selecting clinicians did well in estimating the medium-term survival probability in men referred for radical prostatectomy. OBJECTIVE To identify subsets of patients who are most likely to die from competing causes ≤10 years after radical prostatectomy (RP)., PATIENTS AND METHODS In all, 2205 consecutive patients who underwent RP for clinically localized prostate cancer between 1992 and 2005 were studied. The 10-year cumulative competing mortality rates were determined in several worst-case scenarios formed by using comorbidity classifications and combinations of them., RESULTS In this sample of men selected for RP, even those with the most severe comorbidity level had a competing mortality risk of <50% ≤10 years after RP., Depending on the comorbidity classification used, the 10-year cumulative competing mortality rates differed between 16 and 39% in the whole sample and between 18 and 48% in men aged ≥65 years., CONCLUSION Clinicians do well in estimating the further life span in candidates for RP. Comorbidity classifications may assist treatment choice in this population but are not able to discern meaningful subsets to be excluded from curative treatment because of a life expectancy falling below a limit of 10 years. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Prostate cancer is an underreported and emerging problem in China. Here we summarize the data for Chinese patients with prostate cancer (PCa), describe available treatment options, and report 5-year outcomes at multiple tertiary care institutions. Patients and methods: A series of 1611 patients (mean age 76.51years) diagnosed with PCa were enrolled. Survival rates for patients were analyzed using the Kaplan–Meier method. Prognostic factors for disease-specific survival were analyzed using the log-rank test and Cox proportional hazards model. Results: Seven hundreds and thirty-two patients with a prostate tumor clinical stage of III or IV and 879 with a tumor clinical stage of I or II were diagnosed. The disease-specific survival rates at 1, 3 and 5years were 94.6%, 81.3% and 72.6%, respectively. Five-year disease-specific survival rates were 99.2% for patients with low clinical stage PCa who underwent radical prostatectomy, 76.5% for those who underwent transurethral resection of the prostate plus hormone therapy, 38% for those who received hormone therapy plus radiation therapy and 29% for those that received hormone therapy alone. Conclusions: In keeping with a lack of prostate-specific antigen (PSA)-based screening, Chinese men present later in life and course of their disease, with over 27% men dying of PCa at five years. Debulking of tumors by surgery and radiation therapy for high grade tumor may provide some survival benefit in the senior men but further study is required to validate these findings. It is important of the annual use of PSA test for men over 50years old to detect the PCa in the early stage in this nation. [Copyright &y& Elsevier]

Prostate-specific antigen screening has significantly increased the percentage of men who are diagnosed with low-risk prostate cancer. All men undergoing retropubic radical prostatectomy for primary treatment of prostate cancer from April 2004 to September 2010 in our hospital were examined in order to determine whether active surveillance criteria could be applied to Japanese men. From pathological data of prostate biopsies, whether these men met five published criteria for active surveillance (Johns Hopkins Medical Institution, Prostate Cancer Research International: Active Surveillance Study, University of California, San Francisco, Toronto and Kakehi criteria) was evaluated. Men who met any of the criteria had a statistically significant lower extracapsular extension rate and organ-confinement rate. From the view of the possibility of Gleason upgrading and organ-confinement rate, the Johns Hopkins Medical Institution and Prostate Cancer Research International: Active Surveillance Study criteria showed to be appropriate for Japanese patients. However, the present study had limitations of selection bias and a limited number of cases. [ABSTRACT FROM AUTHOR]

Prostate adenocarcinoma is present in over 80% of men over the age of 80 and is by far the most common cancer of men. Although radical prostatectomy is curative in early disease, the risks of incontinence and impotence can affect the quality of life of patients. Early intervention with localized immunotherapy represents a potential solution as lymphocyte infiltration does occur in prostate cancer lesions, and immunotherapy with dendritic cell vaccines can significantly increase survival in late stage disease. However, lymphocytic infiltrates in the cancerous prostates have an anergic character arising from the suppressive effects of the microenvironment resulting from a conversion of effector cells into regulatory T-cells. Although TGFβ (transforming growth factor β) and IL-10 (interleukin-10) are known to be strong suppressor molecules associated with prostate cancer, they are among many possible suppressive factors. We discuss the possible role of alternative suppressor molecules, including the WAP (whey acidic protein) homologue ps20 that is expressed on prostate stroma and other WAP domain-containing proteins in the immunosuppressive prostate cancer milieu and discuss novel immunotherapeutic strategies to combat this disease. [ABSTRACT FROM AUTHOR]

Study Type - Diagnostic (exploratory cohort) Level of Evidence 2b What's known on the subject? and What does the study add? It has been reported that patients with Gleason 6 prostate cancer detected in a single microfocal positive core may actually harbour more aggressive disease. Meanwhile, several studies analyzing cases of single microfocal prostate cancer included a significant number of patients with serum PSA ≥ 10 ng/mL. Also, significant proportions of currently available published data on actual pathological characteristics of prostate cancer with favourable biopsy features were obtained from patients who underwent prostate biopsies performed in non-systematic fashion at different institutions and/or via non-contemporary scheme, such as sextant biopsy. Although PSA density can be considered an independent predictor of pathologically insignificant tumour among the patients with PSA ≤ 10 ng/mL and only a single microfocal tumour detected via multi (≥12)-core biopsy, clinical and biopsy-related parameters currently available have limited value in predicting pathologically insignificant or unfavourable prostate cancer in such patients. OBJECTIVE • To examine potential predictors of pathological outcomes for a single microfocal (≤3 mm) positive prostate cancer detected via contemporary biopsy scheme in patients presenting with prostate-specific antigen (PSA) ≤10 ng/mL. PATIENTS AND METHODS • We reviewed the data of 119 patients who had prebiopsy PSA ≤ 10 ng/mL and a single microfocal (≤3 mm) Gleason ≤6 prostate cancer identified via multicore (≥12) biopsy and who subsequently underwent radical prostatectomy (RP). • We assessed the rates of insignificant prostate cancer (organ-confined and pathological Gleason ≤6 with tumour volume <0.5 mL) and unfavourable prostate cancer (upstaging and/or upgrading) by analysing pathological findings. • Potential preoperative predictors of insignificant or unfavourable prostate cancer were analysed. Multivariable models for predicting insignificant and unfavourable tumours were devised and evaluated. RESULTS • Overall rates of insignificant and unfavourable prostate cancer were 44.5% and 24.4%, respectively. In multivariate analysis, only PSA density was an independent predictor of insignificant prostate cancer. • Predictive accuracies of multivariable models for predicting insignificant prostate cancer did not exceed 68.2%. No significant predictor for pathologically unfavourable tumour was found in multivariate analysis. • All versions of the multivariable model devised for prediction of unfavourable tumour showed predictive accuracies ≤66.9%. CONCLUSION • Although PSA density can be considered an independent predictor of pathologically insignificant tumour among patients with PSA ≤10 ng/mL and only a single microfocal tumour detected via multicore (≥12) biopsy, the clinical and biopsy-related parameters that are currently available have limited value in predicting pathologically insignificant or unfavourable prostate cancer in such patients. [ABSTRACT FROM AUTHOR]

Background: In 2008, we reported that radical prostatectomy, as compared with watchful waiting, reduces the rate of death from prostate cancer. After an additional 3 years of follow-up, we now report estimated 15-year results. Methods: From October 1989 through February 1999, we randomly assigned 695 men with early prostate cancer to watchful waiting or radical prostatectomy. Follow-up was complete through December 2009, with histopathological review of biopsy and radical-prostatectomy specimens and blinded evaluation of causes of death. Relative risks, with 95% confidence intervals, were estimated with the use of a Cox proportional-hazards model. Results: During a median of 12.8 years, 166 of the 347 men in the radical-prostatectomy group and 201 of the 348 in the watchful-waiting group died (P=0.007). In the case of 55 men assigned to surgery and 81 men assigned to watchful waiting, death was due to prostate cancer. This yielded a cumulative incidence of death from prostate cancer at 15 years of 14.6% and 20.7%, respectively (a difference of 6.1 percentage points; 95% confidence interval [CI], 0.2 to 12.0), and a relative risk with surgery of 0.62 (95% CI, 0.44 to 0.87; P=0.01). The survival benefit was similar before and after 9 years of follow-up, was observed also among men with low-risk prostate cancer, and was confined to men younger than 65 years of age. The number needed to treat to avert one death was 15 overall and 7 for men younger than 65 years of age. Among men who underwent radical prostatectomy, those with extracapsular tumor growth had a risk of death from prostate cancer that was 7 times that of men without extracapsular tumor growth (relative risk, 6.9; 95% CI, 2.6 to 18.4). Conclusions: Radical prostatectomy was associated with a reduction in the rate of death from prostate cancer. Men with extracapsular tumor growth may benefit from adjuvant local or systemic treatment. (Funded by the Swedish Cancer Society and the National Institutes of Health.) N Engl J Med 2011;364:1708-17. [ABSTRACT FROM AUTHOR]