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Purpose Metformin is commonly prescribed for patients with type 2 diabetes mellitus. We hypothesized that metformin plus androgen deprivation therapy may be beneficial in combination. Our objective was to assess this combination in a retrospective cohort of patients with advanced prostate cancer. Materials and Methods Using national Veterans Affairs databases we identified all men diagnosed with prostate cancer between 2000 and 2008 who were treated with androgen deprivation therapy with followup through May 2016. Study exclusions included treatment with androgen deprivation therapy for 6 months or longer, or receipt of androgen deprivation therapy concurrently with localized radiation. Three patient cohorts were developed, including no diabetes mellitus, diabetes mellitus with no metformin and diabetes mellitus with metformin. Cox proportional HRs were calculated for overall survival, skeletal related events and cancer specific survival. Results After exclusions the cohort consisted of 87,344 patients, including 61% with no diabetes mellitus, 22% with diabetes mellitus and no metformin, and 17% with diabetes mellitus on metformin. Cox proportional hazard analysis of overall survival showed improved survival in men with diabetes mellitus on metformin (HR 0.82, 95% CI 0.78–0.86) compared to those with diabetes mellitus who were not on metformin (HR 1.03, 95% CI 0.99–1.08). The reference group was men with no diabetes mellitus. Cox proportional hazard analysis of predictors of skeletal related events revealed a HR of 0.82 (95% CI 0.72–0.93) in men with diabetes mellitus on metformin. Cox proportional hazard analysis of cancer specific survival showed improved survival in men with diabetes mellitus on metformin (HR 0.70, 95% CI 0.64–0.77) vs those with diabetes mellitus without metformin (HR 0.93, 95% CI 0.85– 1.00). The reference group was men with no diabetes mellitus. Conclusions Metformin use in veterans with prostate cancer who receive androgen deprivation therapy is associated with improved oncologic outcomes. This association should be evaluated in a prospective clinical trial. [ABSTRACT FROM AUTHOR]

Purpose With the aim of developing a noninvasive test to detect clinically significant prostate cancer we investigated the potential of capturing cells from urine by microfiltration coupled with analysis of DNA methylation biomarkers. Materials and Methods In this prospective study urine from men suspected of having prostate cancer who were scheduled for transrectal ultrasound guided biopsy of the prostate was collected before digital rectal examination in 99, after digital rectal examination in 58 and from a urethral catheter in 7. Cells were isolated from whole volume voided urine using a filtration device containing a membrane filter with a pore size of 8 μm. Ten additional men provided 4 or 5 urine cell samples by self-collection prior to biopsy. Cellular DNA was analyzed for 5 methylation biomarkers using ddPCR™ (droplet digital polymerase chain reaction). Results Prostate cancer was diagnosed in 117 patients (71%). Across all tumor grades the sensitivity of urine DNA testing was 81% and 60% in samples obtained before and after digital rectal examination, respectively. In a prediction model including prostate specific antigen, patient age and the result of urine DNA analysis to detect high grade disease (Gleason score 7 or greater) an AUC of 0.95 (95% CI 0.90–1.00) was obtained for post-digital rectal examination samples. Analysis of repeat samples demonstrated substantial intraindividual variation in the shedding of cancerous cells in urine. Conclusions Capturing cells from urine by microfiltration provides a novel tool to detect prostate cancer noninvasively with high sensitivity for high grade disease. Repeat sampling may increase sensitivity, particularly when urine is obtained without prior physical manipulation of the prostate. [ABSTRACT FROM AUTHOR]

Purpose We sought to determine long-term outcomes after deferred radical prostatectomy. Materials and Methods The study population consisted of all 132 men with screening detected prostate cancer who underwent deferred radical prostatectomy from January 1, 1995 to December 31, 2014 after active surveillance in the Göteborg Randomized, Population-based Prostate Cancer Screening Trial. The last date of followup was May 15, 2017. Followup during active surveillance was performed with prostate specific antigen tests every 3 to 6 months and repeat biopsies every 2 to 4 years. Triggers for radical prostatectomy were disease progression based on prostate specific antigen, grade and/or stage, or patient request. Outcomes included adverse pathology findings at radical prostatectomy, defined as Gleason score greater than 3 + 4, extraprostatic extension, positive margins, seminal vesicle invasion and/or N+, whether the index tumor at radical prostatectomy was identified at biopsy and prostate specific antigen relapse-free survival. Kaplan-Meier analysis was performed. Results Median time from diagnosis to surgery was 1.9 years (IQR 1.2–4.2) and median postoperative followup was 10.9 years (IQR 7.5–14.5). A total of 52 men (39%) experienced at least 1 unfavorable pathology feature at radical prostatectomy. The 10-year prostate specific antigen relapse-free survival was 79.5%. The index tumor was not identified in the diagnostic biopsy in 38 of the 132 men (29%) or at the last repeat biopsy that preceded radical prostatectomy 22 of 105 (21%). Conclusions A large proportion of men had unfavorable pathology findings at deferred radical prostatectomy and the index tumor was frequently not identified. There is a clear need for better risk classification and protocols to determine disease progression during active surveillance. [ABSTRACT FROM AUTHOR]

Purpose We assessed the predictive value of prostate specific antigen density to detect clinically significant prostate cancer, defined as prostate cancer grade group 2 or greater, in a series of men undergoing prostate biopsy with prostate specific antigen 4 to 10 ng/ml. We sought to define an optimum cutoff point for prostate specific antigen density and assess how race and body mass index affects prostate specific antigen density performance. Materials and Methods We analyzed data on 2,162 men, of whom 56% were African American, with serum prostate specific antigen 4 to 10 ng/ml who underwent prostate biopsy. We compared the AUC between prostate specific antigen and prostate specific antigen density to predict clinically significant and any prostate cancer vs no cancer. We calculated the negative predictive value of prostate specific antigen density cutoff points ranging from 0.05 to 0.15 by every 0.01 step. We a priori defined the optimal cutoff point of prostate specific antigen density as a negative predictive value of 95% and tested whether the cutoff was sensitive to body mass index and race by comparing the negative predictive value across strata. Results Median prostate specific antigen was 5.6 ng/ml (IQR 4.8–7) and median prostate specific antigen density was 0.15 ng/ml/cc (IQR 0.1–0.22). Prostate specific antigen density improved the performance of prostate specific antigen to detect significant cancer (AUC 0.58 to 0.68) and any cancer (AUC 0.55 to 0.69, each p <0.001). We identified a prostate specific antigen density cutoff point of less than 0.08 ng/ml/cc with a 96% negative predictive value for grade group 2 or greater. This was largely unchanged among different races and body mass indexes. Conclusions Regardless of race or body mass index men with prostate specific antigen density less than 0.08 were unlikely to harbor grade group 2 or greater disease when prostate specific antigen was 4 to 10 ng/ml. If validated, prostate specific antigen density is a simple inexpensive and available tool that can be used to identify men who can likely forego prostate biopsies, thus reducing the over detection and morbidity of unnecessary biopsies. [ABSTRACT FROM AUTHOR]

Purpose The prospective PCM301 trial randomized 413 men with low risk prostate cancer to partial gland ablation with vascular targeted photodynamic therapy in 207 and active surveillance in 206. Two-year outcomes were reported previously. We report 4-year rates of intervention with radical therapy and further assess efficacy with biopsy results. Materials and Methods Prostate biopsies were mandated at 12 and 24 months. Thereafter patients were monitored for radical therapy with periodic biopsies performed according to the standard of care at each institution. Ablation efficacy was assessed by biopsy results overall and in field in the treated lobe or the lobe with index cancer. Results Conversion to radical therapy was less likely in the ablation cohort than in the surveillance cohort, including 7% vs 32% at 2 years, 15% vs 44% at 3 years and 24% vs 53% at 4 years (HR 0.31, 95% CI 0.21–0.46). Radical therapy triggers were similar in the 2 arms. Cancer progression rates overall and by grade were significantly lower in the ablation cohort (HR 0.42, 95% CI 0.29–0.59). End of study biopsy results were negative throughout the prostate in 50% of patients after ablation vs 14% after surveillance (risk difference 36%, 95% CI 28–44). Gleason 7 or higher cancer was less likely for ablation than for surveillance (16% vs 41%). Of the in field biopsies 10% contained Gleason 7 cancer after ablation vs 34% after surveillance. Conclusions In this randomized trial of partial ablation of low risk prostate cancer photodynamic therapy significantly reduced the subsequent finding of higher grade cancer on biopsy. Consequently fewer cases were converted to radical therapy, a clinically meaningful benefit that lowered treatment related morbidity. [ABSTRACT FROM AUTHOR]

Purpose We evaluated the diagnostic accuracy of multiparametric magnetic resonance imaging to diagnose clinically significant prostate cancer and compared it with the diagnostic accuracy of transperineal saturation prostate biopsy. Materials and Methods From January 2011 to February 2018 repeat saturation prostate biopsy (the reference test) was done due to suspicion of cancer in 1,032 men with a median age of 63 years in whom median prostate specific antigen was 8.6 ng/ml. All patients underwent 3.0 Tesla pelvic multiparametric magnetic resonance imaging before saturation prostate biopsy. Additional targeted fusion prostate biopsy was done of lesions with a PI-RADS™ (Prostate Imaging Reporting and Data System) score of 3 or greater. Results T1c prostate cancer was found in 372 of the 1,032 patients (36%). Of these cases 272 (73.1%) were classified as clinically significant prostate cancer. Saturation prostate biopsy vs targeted fusion prostate biopsy and a PI-RADS score of 3 or greater vs targeted fusion prostate biopsy and a PI-RADS score of 4 or greater diagnosed 95.6% vs 83.8% vs 60.3% of clinically significant prostate cancers (p <0.0001). Saturation prostate biopsy missed 12 of 272 clinically significant prostate cancers (4.5%) vs 44 (16.2%) and 108 of 272 (39.7%) missed by targeted fusion prostate biopsy and a PI-RADS score of 3 or greater and a score of 4 or greater, respectively (p <0.0001). As a triage test multiparametric magnetic resonance imaging would have spared 49.3% vs 73.6% of patients using a PI-RADS cutoff of 3 or greater vs 4 or greater. Conclusions Multiparametric magnetic resonance imaging could significantly reduce the number of unnecessary repeat prostate biopsies in about 50% of cases in which a PI-RADS score of 3 or greater is used. At the same time patients should be informed of the 16.2% and 39.7% false-negative rates of clinically significant prostate cancer for targeted fusion prostate biopsy of PI-RADS 3 or greater and 4 or greater lesions, respectively. [ABSTRACT FROM AUTHOR]

Purpose The second version of the PI-RADS™ (Prostate Imaging Reporting and Data System) was introduced in 2015 to standardize the interpretation and reporting of prostate multiparametric magnetic resonance imaging. Recently low cancer detection rates were reported for PI-RADS version 2 category 4 lesions. Therefore the aim of the study was to evaluate the cancer detection rate of PI-RADS version 2 in a large prospective cohort. Materials and Methods The study included 704 consecutive men with primary or prior negative biopsies who underwent magnetic resonance imaging/ultrasound fusion guided targeted biopsy and 10-core systematic prostate biopsy between September 2015 and May 2017. All lesions were rated according to PI-RADS version 2 and lesions with PI-RADS version 2 category 3 or greater were biopsied. An ISUP (International Society of Urological Pathology) score of 2 or greater (ie Gleason 3 + 4 or greater) was defined as clinically significant prostate cancer. Results The overall cancer detection rate of PI-RADS version 2 categories 3, 4 and 5 was 39%, 72% and 91% for all prostate cancer, and 23%, 49% and 77% for all clinically significant prostate cancer, respectively. If only targeted biopsy had been performed, 59 clinically significant tumors (16%) would have been missed. The PI-RADS version 2 score was significantly associated with the presence of prostate cancer (p <0.001), the presence of clinically significant prostate cancer (p <0.001) and the ISUP grade (p <0.001). Conclusions PI-RADS version 2 is significantly associated with the presence of clinically significant prostate cancer. The cancer detection rate of PI-RADS version 2 category 4 lesions was considerably higher than previously reported. When performing targeted biopsy, the combination with systematic biopsy still provides the highest detection of clinically significant prostate cancer. [ABSTRACT FROM AUTHOR]

Purpose Clinical trials in men initiating intermittent androgen deprivation therapy have used a range of induction durations between 3 and 12 months. We sought to determine whether the duration of induction androgen deprivation therapy would influence the duration of the off treatment interval and the recovery of serum testosterone. Materials and Methods This was a prospective, randomized, open label study. Men with biochemical recurrence after local therapy for prostate cancer and a negative bone scan were randomized to 4 and 10 months of monthly degarelix. The first dose was 240 mg and subsequent doses were 80 mg per month. Quality of life was evaluated by the I-PSS (International Prostate Symptom Score), the PAS-SFI (Problem Assessment Scale of the Sexual Function Index) and the FACT-P (Functional Assessment of Cancer Therapy-Prostate). Results A total of 90 patients were randomized, including 43 to 4 months and 47 to 10 months of treatment. There was no difference in any relevant baseline laboratory parameter, including prostate specific antigen and testosterone. There was no difference between the 2 treatment groups in time off treatment (HR 1.51, 95% CI 0.60–3.84, p = 0.38). Actuarial median time to testosterone recovery to 8.0 nmol/l or greater was 8.05 months (95% CI 4.34–39.89) in the 10-month treatment arm and 6.24 months (95% CI 5.45–15.90) in the 4-month treatment arm. The log rank test showed no statistical significance between the 2 treatment groups in time to testosterone recovery (p = 0.8392). There was no difference in the testosterone recovery rate between the 2 arms. Men younger than 65 years had a considerably shorter interval off treatment and time to testosterone recovery. There was a lesser adverse effect on quality of life at the end of treatment in the 4-month than in the 10-month arm. Conclusions In men with biochemical recurrence who initiated intermittent androgen deprivation therapy with degarelix no difference was observed in the duration of the off treatment interval or the rate of testosterone recovery whether they received 4 or 10 months of induction androgen deprivation therapy. [ABSTRACT FROM AUTHOR]

Purpose We sought to develop a core set of clinical indicators to enable international benchmarking of localized prostate cancer management using data available in the TrueNTH Global Registry. Materials and Methods An international expert panel completed an online survey and participated in a face-to-face meeting. Participants included 3 urologists, 3 radiation oncologists, 2 psychologists, 1 medical oncologist, 1 nurse and 1 epidemiologist with prostate cancer expertise from a total of 7 countries. Current guidelines on prostate cancer treatment and potential quality indicators were identified from a literature review. These potential indicators were refined and developed through a modified Delphi process during which each panelist independently and repeatedly rated each indicator based on importance (satisfying the indicator demonstrated a provision of high quality care) and feasibility (the likelihood that data used to construct the indicator could be collected at a population level). The main outcome measure was items with panel agreement indicated by a disagreement index less 1, median importance 8.5 or greater and median feasibility 9 or greater. Results The expert panel endorsed 33 indicators. Seven of these 33 prostate cancer quality indicators assessed care relating to diagnosis, 7 assessed primary treatment, 1 assessed salvage treatment and 18 assessed health outcomes. Conclusions We developed a set of quality indicators to measure prostate cancer care using numerous international evidence-based clinical guidelines. These indicators will be pilot tested in the TrueNTH Global Registry. Reports comparing indicator performance will subsequently be distributed to groups at participating sites with the purpose of improving the consistency and quality of prostate cancer management on a global basis. [ABSTRACT FROM AUTHOR]

Purpose Although androgen deprivation therapy is widely used to treat prostate cancer, its effects on cognitive function are unclear. To our knowledge no prior report has examined the impact of androgen deprivation therapy on self-reported cognitive function. Materials and Methods Three groups of men 50 years old or older who were matched on age and education were enrolled in the study, including 81 with prostate cancer starting on continuous androgen deprivation therapy, 84 controls with prostate cancer not receiving androgen deprivation therapy and 85 healthy controls. Two scales from the FACT-Cog (Functional Assessment of Cancer Therapy-Cognitive subscale) version 3 were used to assess self-reported cognitive function. Changes in cognitive scores with time were analyzed by 2 approaches, including 1) multivariable regression and 2) calculation of the proportion of subjects per group with a decrease of 1 SD or more. Multivariable regression was applied to assess predictors of a decline in self-reported cognitive function. We also examined relationships between the FACT-Cog and a neuropsychological battery of 15 tests. Results Mean participant age was 69 years (range 50 to 87). The mean educational level was 15 years (range 8 to 24). FACT-Cog scores were similar at baseline across the cohorts. Neither analytical approach revealed that androgen deprivation therapy was associated with changes in self-reported cognitive function on either FACT-Cog scale. Mood and fatigue correlated with changes in self-reported cognitive function. The relationship between self-reported and objective cognitive measures was weak (maximum Spearman correlation coefficient 0.14) and only 2 of 30 correlations were statistically significant. Conclusions A total of 12 months of androgen deprivation therapy were not associated with self-reported cognitive function changes in older men with nonmetastatic prostate cancer. [ABSTRACT FROM AUTHOR]

Purpose We evaluated the effect of transitioning from a prostate cancer specific treatment program to comprehensive insurance under the ACA (Patient Protection and Affordable Care Act) on the physical, mental and prostate cancer related health of poor, previously uninsured men. Materials and Methods We assessed general and prostate cancer specific health related quality of life using the RAND SF-12v2™ (12-Item Short Form Survey, version 2) and the UCLA PCI (Prostate Cancer Index) at 3 time points in 24 men who transitioned to comprehensive insurance as the insured group relative to 39 who remained in the prostate cancer program as the control group. We used mixed effects models controlling for treatment and patient factors to measure health differences between the groups during the transition period. Results Demographics, prostate cancer treatment patterns, and mental, physical and general health were similar before transition in the control and insured groups. After transition men who gained insurance coverage reported significantly worse physical health than men who remained in the prostate cancer program (p = 0.0038). After adjustment in the mixed effects model physical health remained worse in men who gained insurance (p = 0.0036). Mental health and prostate cancer related quality of life did not differ with time between the groups. Conclusions Compared to controls who remained in the state funded prostate cancer treatment program for poor, uninsured men, newly insured men reported worse physical health after transitioning to ACA coverage. Providers and policy makers may draw important lessons from understanding the mechanisms of this paradoxical worsening in physical health after gaining insurance. These results inform the development of disease specific models of care in the broader health insurance context. [ABSTRACT FROM AUTHOR]

Purpose Definitive therapy for prostate cancer (eg surgery or radiotherapy) often has side effects, including urinary, sexual and bowel dysfunction. The purpose of this study was to test whether urinary, sexual and bowel functions contribute to emotional distress during the first 2 years after treatment and whether distress may in turn decrease function. Materials and Methods The study participants were 1,148 men diagnosed with clinically localized disease who were treated with surgery (63%) or radiotherapy (37%). Urinary, sexual and bowel functions were assessed with EPIC (Expanded Prostate Cancer Index Composite). Emotional distress was assessed with the NCCN ® (National Comprehensive Cancer Network®) Distress Thermometer. Assessment time points were before treatment, and 6 weeks, and 6, 12, 18 and 24 months after treatment. We used time lagged multilevel models to test whether physical function predicted emotional distress and vice versa. Results Men with worse urinary, bowel and sexual functions reported more emotional distress than others at subsequent time points. The relationships were bidirectional. Men who reported worse distress also reported worse urinary, bowel and sexual functions at subsequent time points. Conclusions Clinicians supported by practice and payer policies should screen for and facilitate the treatment of side effects and heightened emotional distress to improve well-being in survivors of prostate cancer. These interventions may be cost-effective, given that emotional distress can negatively impact functioning across life domains. [ABSTRACT FROM AUTHOR]

Purpose Prostate cancer over diagnosis and overtreatment are concerns for clinicians and policy makers. Multiparametric magnetic resonance imaging and the PCA3 (prostate cancer antigen 3) urine test select for clinically significant cases. We explored how well the tests performed together with previous biopsies. Materials and Methods In accordance with ethics committee approval we collected clinicopathological data on all patients in whom a PCA3 test was done from January 2011 to June 2016. This included patients on active surveillance for low risk prostate cancer and those without prostate cancer who had previous negative biopsies and suspicion of occult disease. We explored whether age, prostate specific antigen, PCA3 score, multiparametric magnetic resonance imaging, digital rectal examination, family history and prostate size would predict clinically significant prostate cancer on repeat biopsy. The negative predictive value of multiparametric magnetic resonance imaging and PCA3 score was calculated. Results A total of 470 patients were included in study. The PCA3 score was abnormal at 35 or greater in 32.5% of cases. In the multivariate model including 154 men only age (OR 1.08, 95% CI 1.01–1.16), multiparametric magnetic resonance imaging PI-RADS™ (Prostate Imaging-Reporting and Data System) score 4 (OR 16.6, 95% CI 3.9–70.0) or 5 (OR 28.3, 95% CI 5.7–138) and PCA3 score (OR 2.9, 95% CI 1.0–8.8) predicted clinically significant cancer on biopsy. No patient with negative multiparametric magnetic resonance imaging and a normal PCA3 score had clinically significant prostate cancer on biopsy for a negative predictive value of 100% (p <0.0001). Conclusions In patients with dual negative tests (multiparametric magnetic resonance imaging and PCA3 score) clinically significant prostate cancer was never found on biopsy, which may be unnecessary in this group. This study was limited by its retrospective design, selection bias and lack of cost-effectiveness data. [ABSTRACT FROM AUTHOR]

Purpose We performed a comprehensive literature review and meta-analysis to evaluate the association of inflammation on prostate needle biopsies and prostate cancer risk. Materials and Methods We searched Embase®, PubMed® and Web of Science™ from January 1, 1990 to October 1, 2016 for abstracts containing the key words prostate cancer, inflammation and biopsy. Study inclusion criteria were original research, adult human subjects, cohort or case-control study design, histological inflammation on prostate needle biopsy and prostate cancer on histology. Two independent teams reviewed abstracts and extracted data from the selected manuscripts. Combined ORs and 95% CIs of any, acute and chronic inflammation were calculated using the random effects method. Results Of the 1,030 retrieved abstracts 46 underwent full text review and 25 were included in the final analysis, comprising a total of 20,585 subjects and 6,641 patients with prostate cancer. There was significant heterogeneity among studies (I 2 = 84.4%, p <0.001). The presence of any inflammation was significantly associated with a lower prostate cancer risk in 25 studies (OR 0.455, 95% CI 0.337–0.573). There was no evidence of publication bias (p >0.05). When subanalyzed by inflammation type, acute inflammation in 4 studies and chronic inflammation in 15 were each associated with a lower prostate cancer risk (OR 0.681, 95% CI 0.450–0.913 and OR 0.499, 95% CI 0.334–0.665, respectively). Conclusions In a meta-analysis of 25 studies inflammation on prostate needle biopsy was associated with a lower prostate cancer risk. Clinically the presence of inflammation on prostate needle biopsy may lower the risk of a subsequent prostate cancer diagnosis. [ABSTRACT FROM AUTHOR]

Purpose Data on the incidence, mortality and burden of prostate cancer as well as changing trends are necessary to provide policy makers with the evidence needed to allocate resources appropriately. This study presents estimates of prostate cancer incidence, mortality and burden from 1990 to 2015 by patient age, country and developmental status using the results of the Global Burden of Disease 2015 study. Materials and Methods Data from vital registration systems and cancer registries were used to generate mortality estimates. Cause specific mortality served as the basis for estimating incidence, prevalence and disability adjusted life years. The global number of incident cases, deaths and disability adjusted life years attributable to prostate cancer are reported as well as age standardized rates. Results Incident cases of prostate cancer increased 3.7-fold from 1990 to 2015. The age standardized incidence rate also increased 1.7-fold during the study period and in 2015 it reached 56.71/100,000 person-years (95% uncertainty interval 45.86-78.45). Global estimates of the age standardized death rate decreased slightly to 14.24 deaths (95% uncertainty interval 11.8-17.95) per 100,000 person-years in 2015. The decline in the age standardized death rate was more prominent in high income countries. Disability adjusted life years attributable to prostate cancer increased by 90% during the study period. Conclusions The prostate cancer mortality rate is decreasing in high income countries. However, the incidence and burden of disease are steadily increasing globally, resulting in further challenges in the allocation of limited health care resources. The current study provides comprehensive knowledge of the local burden of disease and help with appropriate allocation of resources for prostate cancer prevention, screening and treatment. [ABSTRACT FROM AUTHOR]

Purpose We compared pathological and biochemical outcomes after radical prostatectomy in patients at favorable intermediate risk who fulfilled current NCCN ® (National Comprehensive Cancer Network®) Guidelines® for active surveillance criteria to outcomes in patients who met more traditional criteria for active surveillance. Materials and Methods We queried our institutional review board approved prostate cancer database for patients who met NCCN criteria for very low risk (T1c, Grade Group 1, 3 or fewer of 12 cores, 50% or less core volume and prostate specific antigen density less than 0.15 ng/ml), low risk (T1-T2a, Grade Group 1 and prostate specific antigen less than 10 ng/ml) or favorable intermediate risk (major pattern grade 3 and less than 50% positive biopsy cores) and who had 1 intermediate risk factor, including T2b/c, Grade Group 2 or prostate specific antigen 10 to 20 ng/ml. Men at intermediate risk who did not meet favorable criteria were labeled as being at unfavorable intermediate risk. Patients at favorable intermediate risk were compared to those at very low and low risk, and those at unfavorable intermediate risk to identify differences in rates of adverse pathological findings at radical prostatectomy, including Gleason score Grade Group 3-5, nonorgan confined disease or nodal involvement. Time to biochemical recurrence was compared among the groups using Cox regression. Results A total of 3,686 patients underwent radical prostatectomy between January 1, 2014 and December 31, 2015. Of these men 1,454, 250 and 1,362 fulfilled the criteria for low, favorable intermediate and unfavorable intermediate risk, respectively. The rate of adverse pathological findings in favorable intermediate risk cases was significantly higher than in low risk cases and significantly lower than in unfavorable intermediate risk cases (27.4% vs 14.8% and 48.5%, respectively, each p <0.001). Time to biochemical recurrence differed significantly among the risk groups (p <0.001). Conclusions Relative to men at low risk those at favorable intermediate risk represent a distinct group. Care should be taken when selecting these patients for active surveillance and monitoring them once they are in an active surveillance program. [ABSTRACT FROM AUTHOR]

Purpose Nerve sparing contributes to the recovery of sexual and urinary function after radical prostatectomy but it may be ineffective in some patients or carry the risk of a positive surgical margin. We evaluated sexual and urinary function outcomes according to the degree of nerve sparing in patients with prostate cancer treated with radical prostatectomy. Materials and Methods The CEASAR (Comparative Effectiveness Analysis of Surgery and Radiation) study is a prospective, population based, observational study of men diagnosed with localized prostate cancer in 2011 to 2012. Patient reported sexual and urinary functions were measured using the 26-item Expanded Prostate Index Composite at baseline within 6 months after diagnosis, and 6, 12 and 36 months after enrollment. Study inclusion criteria included radical prostatectomy as primary treatment, documentation of nerve sparing status and absent androgen deprivation therapy. Nerve sparing status was defined as none, unilateral or bilateral according to the operative report. Results The final analytical cohort included 991 men. The 11 men treated with unilateral nerve sparing and the 75 treated with a nonnerve sparing procedure were grouped together. In the multivariable model there was a significant difference in the sexual function score 3 years after radical prostatectomy in the bilateral nerve sparing group compared with the unilateral and nonnerve sparing group (6.1 points, 95% CI 2.0–10.3, p = 0.004). This was more pronounced in men with high baseline sexual function (8.23 points, 95% CI 1.6–14.8, p = 0.014) but not in those with low baseline function (4.0 points, 95% CI –0.6–8.7, p = 0.090). Similar effects were demonstrated on urinary incontinence scores. Conclusions Bilateral nerve sparing resulted in better sexual and urinary function outcomes than unilateral or nonnerve sparing but the difference was not significant in men with low baseline sexual function. [ABSTRACT FROM AUTHOR]

Background In order to prevent over treatment of prostate cancer and significant adverse effects after surgical intervention, active surveillance was suggested in low risk or very low risk patients. This study aimed to retrospectively analyze the adverse pathological results of candidates eligible for active surveillance. Methods A total of 904 patients underwent robot-assisted laparoscopic radical prostatectomy in this single institute, from 2005 to April 2014. One hundred and thirty-two patients were eligible for active surveillance (AS). Candidates for active surveillance were defined as low risk (T1/T2a, prostate specific antigen 10 ng/ml or less, and Gleason score 6 or less) and very low risk (T1c, prostate specific antigen density 0.15 or less, Gleason score 6 or less, 2 or fewer positive biopsy cores, 50% or less cancer involvement per core) patients. Adverse pathological results were defined as Gleason sum more than 6, and non-organ-confined disease. Results There were 132 patients eligible for active surveillance. One hundred and thirteen (85.6%, 113/132) patients had low risk disease and nineteen (14.4%, 19/132) patients had very low risk disease. The adverse pathological results of low risk disease were upgrading Gleason sum and non-organ-confined disease, 41.6% (47/113) and 28.3% (32/113), respectively. The adverse pathological results of very low risk disease were upgrading Gleason sum and non-organ-confined disease, 15.8% (3/19) and 15.8% (3/19), respectively. Conclusion We conclude that although AS may prevent over treatment and significant adverse effects after surgical intervention, stratification of patients with low risk prostate cancer is of paramount importance when choosing appropriate candidate for AS. The risk of adverse pathological results should be well informed in the pretreatment counseling. [ABSTRACT FROM AUTHOR]

Purpose This guideline is structured to provide a clinical framework stratified by cancer severity to facilitate care decisions and guide the specifics of implementing the selected management options. The summary presented represents Part I of the two-part series dedicated to Clinically Localized Prostate Cancer: AUA/ASTRO/SUO Guideline discussing risk stratification and care options by cancer severity. Materials and Methods The systematic review utilized in the creation of this guideline was completed by the Agency for Healthcare Research and Quality and through additional supplementation by ECRI Institute. This review included articles published between January 2007 and March 2014 with an update search conducted through August 2016. When sufficient evidence existed, the body of evidence for a particular treatment was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. Additional information is provided as Clinical Principles and Expert Opinions ( table 2 in supplementary unabridged guideline, http://jurology.com/ ). Results The AUA (American Urological Association), ASTRO, and SUO (Society of Urologic Oncology) formulated an evidence-based guideline based on a risk stratified clinical framework for the management of localized prostate cancer. Conclusions This guideline attempts to improve a clinician’s ability to treat patients diagnosed with localized prostate cancer, but higher quality evidence in future trials will be essential to improve the level of care for these patients. In all cases, patient preferences should be considered when choosing a management strategy. [ABSTRACT FROM AUTHOR]

Purpose We describe anatomical sites of recurrence in patients with prostate cancer who had biochemical recurrence following radical prostatectomy and who received radiotherapy and/or androgen deprivation therapy postoperatively. We performed 11 C-choline positron emission tomography/computerized tomography and multiparametric magnetic resonance imaging. Materials and Methods After radiotherapy and/or androgen deprivation therapy patients who underwent radical prostatectomy were evaluated by 11 C-choline positron emission tomography/computerized tomography and multiparametric magnetic resonance imaging to determine recurrence patterns and clinicopathological features. Recurrent sites were described as local only (seminal vesicle bed/prostate fossa, vesicourethral anastomosis and bladder neck) or distant metastatic disease. Features associated with the identification of any distant metastatic disease were evaluated by multivariable logistic regression. Results A total of 550 patients were identified. Treatment included androgen deprivation therapy in 108, radiotherapy in 201, and androgen deprivation therapy and radiotherapy in 241. Median prostate specific antigen at evaluation was 3.9, 3.6 and 2.8 ng/ml in patients treated with androgen deprivation therapy, radiotherapy and a combination, respectively. Recurrence developed locally in 77 patients (14%), as distant metastasis only in 411 (75%), and as local and distant metastatic disease in 62 (11%). On multivariable analysis treatment with radiotherapy (OR 7.18, 95% CI 2.92–17.65), and radiotherapy and hormonal therapy (OR 9.23, 95% CI 3.90–21.87, all p <0.01) was associated with increased odds of distant failure at evaluation. Conclusions The combination of 11 C-choline positron emission tomography/computerized tomography and multiparametric magnetic resonance imaging successfully identified patterns of recurrence after postoperative radiotherapy and/or androgen deprivation therapy at a median prostate specific antigen of less than 4 ng/ml. Half of this cohort had local only recurrence and/or a low disease burden limited to pelvic lymph nodes. These patients may benefit from additional local therapy. These data and this analysis may facilitate the evaluation of such patients with biochemically recurrent prostate cancer. [ABSTRACT FROM AUTHOR]

Purpose Serum testosterone suppression during androgen deprivation therapy has been reported to affect the efficacy of androgen deprivation therapy. However, the factors impacting hormonal variations during androgen deprivation therapy remain unclear. Therefore, in this study we investigated the significance of missense polymorphisms in the gene encoding GNRH in men treated with primary androgen deprivation therapy for metastatic prostate cancer. Materials and Methods This study included 80 Japanese patients with metastatic prostate cancer with available serum testosterone levels during androgen deprivation therapy. We examined the association of GNRH1 (rs6185, S20W) and GNRH2 (rs6051545, A16V) gene polymorphisms with clinicopathological parameters, including serum testosterone levels during androgen deprivation therapy, as well as prognosis, including progression-free and overall survival. Results The CT and CT/TT alleles in the GNRH2 gene (rs6051545) were associated with higher serum testosterone during androgen deprivation therapy compared with those of the CC allele. Consequently the CT alleles were associated with a higher risk of progression after adjustment for age and serum testosterone during androgen deprivation therapy (HR 1.73, 95% CI 1.00–3.00, p = 0.049). Conclusions Taken together these findings suggest that rs6051545 ( GNRH2 ) genetic variation may result in inadequate suppression of serum testosterone during androgen deprivation therapy. This may lead to detrimental effects of androgen deprivation therapy on prognosis in men with metastatic prostate cancer. [ABSTRACT FROM AUTHOR]

Purpose We assessed the rate and predictors of depressive symptoms and impaired sexual desire in patients who underwent open or robot-assisted radical prostatectomy. Materials and Methods A total of 811 patients completed IIEF (International Index of Erectile Function) and BDI (Beck Depression Inventory) preoperatively, and 6, 12, 24 and 36 months postoperatively. Rates and predictors of depressive symptoms and impaired sexual desire were assessed with descriptive statistics and logistic regression models. Results We analyzed data on 416 patients treated with robot-assisted radical prostatectomy and 395 who underwent open radical prostatectomy. Overall the incidence of patients with postoperative BDI scores suggestive of depressive symptoms ranged between 26.3% at 6 months and 36.7% at 36 months. BDI scores were significantly higher in open than in robot-assisted radical prostatectomy cases at every analyzed postoperative time point (all p <0.01). Patients treated with robot-assisted radical prostatectomy showed higher IIEF-EF (Erectile Function) domain scores and a greater proportion of them experienced erectile function recovery at each time point compared to those treated with open radical prostatectomy (all p <0.005). Postoperatively the rate of impaired sexual desire ranged between 40.9% at 6 months and 34.1% at 24 months. IIEF-SD (Sexual Domain) scores were significantly lower in open radical prostatectomy cases at every followup (all p <0.02). Age, open radical prostatectomy and postoperative erectile dysfunction were independent predictors of BDI scores and impaired sexual desire. Conclusions One of 3 men surgically treated for prostate cancer still report depressive symptoms months after surgery. Patients who undergo robot-assisted radical prostatectomy reported lower depressive symptoms than those treated with open radical prostatectomy. Sexual desire was highly affected after radical prostatectomy with greater impairment reported by patients who underwent open radical prostatectomy. [ABSTRACT FROM AUTHOR]

Purpose A phase 2 study of enzalutamide monotherapy in patients with hormone naïve prostate cancer demonstrated high prostate specific antigen response rates at 25 weeks, 1 year and 2 years with minimal effects on total body bone mineral density and favorable safety. In this followup analysis we evaluated enzalutamide antitumor activity and safety at 3 years. Materials and Methods In a single arm analysis 67 patients with hormone naïve prostate cancer and noncastrate testosterone (230 ng/dl or greater) received enzalutamide 160 mg per day orally until disease progression or unacceptable toxicity. The primary end point was the prostate specific antigen response (80% or greater decline from baseline). Results No patients discontinued treatment during year 3. Of 42 patients with prostate specific antigen assessments at 3 years 38 (90.5%, 95% CI 77.4–97.3) maintained a prostate specific antigen response. Of 26 patients with metastases at baseline 17 (65.4%) had a complete or partial response as the best overall response during 3 years. In patients who completed the 3-year visit minimal mean changes from baseline were observed in total body bone mineral density or bone mineral density of the femoral neck, trochanter, spine L1–L4 or forearm (range –2.7% to –0.1%). At 3 years total body fat had increased a mean of 16.5%, total lean body mass had decreased a mean of –6.5% and global health status had minimally decreased from baseline. Common adverse events were gynecomastia, fatigue, hot flush and nipple pain. Conclusions Enzalutamide antitumor activity was maintained in patients with hormone naïve prostate cancer at 3 years. Overall bone mineral density, global health status and safety results were similar to those at 2 years. [ABSTRACT FROM AUTHOR]

Purpose Although lower urinary tract symptoms and sleep problems often develop together, to our knowledge it is unknown whether sleep disturbances are linked to lower urinary tract symptoms development and progression. As measured by the 6-item MOS-Sleep (Medical Outcomes Study Sleep Scale) survey we examined the relationship between sleep problems, and the development and progression of lower urinary tract symptoms in the REDUCE (Reduction by Dutasteride of Prostate Cancer Events) study. Materials and Methods REDUCE was a randomized trial testing prostate cancer chemoprevention with dutasteride in men with prostate specific antigen 2.5 to 10 ng/ml and a negative biopsy. At baseline men completed MOS-Sleep and a scaled average was used to calculate the sleep score. Men were followed for 4 years and I-PSS (International Prostate Symptom Score) was completed at baseline and every 6 months. Asymptomatic men had I-PSS less than 8 while symptomatic men had I-PSS 8 or greater. In the placebo arm of 2,588 men not receiving α-blockers or 5α-reductase inhibitors at baseline we tested the association between sleep problems and lower urinary tract symptom development and progression using Cox models. Results During followup lower urinary tract symptoms developed in 209 of 1,452 asymptomatic men (14%) and 580 of 1,136 (51%) with lower urinary tract symptoms demonstrated progression. On multivariable analysis higher sleep scores were suggestively associated with increased lower urinary tract symptoms in asymptomatic men (quartile 4 vs 1 HR 1.41, 95% CI 0.92–2.17, p = 0.12) and with lower urinary tract symptom progression in symptomatic men (per 10 points of sleep score HR 1.06, 95% CI 1.01–1.12, p = 0.029). Conclusions Among men with lower urinary tract symptoms worse sleep scores were associated with the progression of lower urinary tract symptoms and among asymptomatic men worse sleep scores were suggestively associated with the development of lower urinary tract symptoms. If confirmed, these data suggest that sleep problems may precede such symptoms. Whether treating sleep problems would improve lower urinary tract symptoms requires further testing. [ABSTRACT FROM AUTHOR]

Purpose We assessed focal therapy eligibility in men who underwent multiparametric magnetic resonance imaging and targeted biopsy with correlation to whole mount histology after radical prostatectomy. Materials and Methods Subjects were selected from among the 454 men in whom targeted biopsy proven prostate cancer was derived from regions of interest on multiparametric magnetic resonance imaging from 2010 to 2016. Focal therapy eligibility was limited to a maximum Gleason score of 4 + 3 in regions of interest with or without other foci of low risk prostate cancer (Gleason score 3 + 3 and less than 4 mm). Men who did not meet NCCN® intermediate risk criteria were classified as ineligible for focal therapy. Of the 454 men 64 underwent radical prostatectomy and biopsy findings were compared to final pathology findings. Results Of the 454 men with a biopsy proven region of interest 175 (38.5%) were eligible for focal therapy. Fusion biopsy, which combined targeted and template biopsy, had 80.0% sensitivity (12 of 15 cases), 73.5% specificity (36 of 49) and 75.0% accuracy (48 of 64) for focal therapy eligibility. Targeted cores alone yielded 73.3% sensitivity (11 of 15 cases), 47.9% specificity (23 of 48) and 54.7% accuracy (35 of 64). Gleason score and extension across the midline differed in 4 and 9, respectively, of the 13 cases that showed discordant biopsy and whole mount histology. Conclusions Using intermediate risk eligibility criteria more than a third of men with a targeted biopsy proven lesion identified on multiparametric magnetic resonance imaging would have been eligible for focal therapy. Eligibility determined by fusion biopsy was concordant with whole mount histology in 75% of cases. Improved selection criteria are needed to reliably determine focal therapy eligibility. [ABSTRACT FROM AUTHOR]

Purpose We examined the clinical features and outcomes associated with delayed biochemical recurrence after radical prostatectomy, specifically among men with more than 20 years of followup. Materials and Methods A total of 16,720 men underwent radical prostatectomy and 2,699 experienced biochemical recurrence. We determined predictors of delayed biochemical recurrence as well as metastasis-free and cancer specific survival rates for recurrence at various time points after radical prostatectomy. We performed subset analysis of the 732 men with 20 or more years of recurrence-free followup. Cumulative incidence curves for metastasis and prostate cancer death were calculated and stratified by biochemical recurrence time points. Results Predictors of delayed biochemical recurrence included elevated prostate specific antigen at radical prostatectomy, higher clinical and pathological stage, and positive surgical margins. Delayed biochemical recurrence was associated with favorable cumulative incidence curves for metastasis and prostate cancer death compared to early biochemical recurrence. Among the 732 men with undetectable prostate specific antigen at 20 years biochemical recurrence developed in 17 (2.3%), metastatic disease developed in a single patient and none died of prostate cancer. The actuarial probability of biochemical recurrence among men with undetectable prostate specific antigen at 20 years increased with adverse pathological features. Conclusions Men with delayed biochemical recurrence have favorable clinical features and improved survival. Men with undetectable prostate specific antigen 20 years after radical prostatectomy had a low rate of recurrence and no deaths from prostate cancer. This suggests that 20 years is a reasonable time to discontinue prostate specific antigen testing. [ABSTRACT FROM AUTHOR]

Purpose Defining biochemical failure as nadir + 2 may overestimate cure after radiotherapy. We assessed long-term prostate specific antigen stability after low dose rate prostate brachytherapy and predictors of biochemical failure when prostate specific antigen was slowly rising below the nadir + 2 ng/ml threshold. Materials and Methods A total of 2,339 patients with low or intermediate risk prostate cancer received 125 iodine brachytherapy from 1998 to 2010 with a minimum 3-year followup. In addition, 49.7% of the patients received 6 months of androgen deprivation. Clinical, dosimetric and prostate specific antigen data were retrieved from a prospective database. Biochemical results were classified as stable or rising prostate specific antigen (0.2 ng/ml or greater and increased 0.1 ng/ml or greater during the preceding 2 years), or biochemical failure (defined as nadir + 2). Multivariate analysis was done to identify predictors of failure used to create logistic regression models. Results At a median followup of 89 months (range 37 to 199) prostate specific antigen was stable (nadir 0.03 ng/ml and at 60 months 0.04 ng/ml) in 2,004 patients (86%) and rising (nadir 0.16 ng/ml and at 60 months 0.29 ng/ml) in 145 (6%) while biochemical failure (nadir 0.51 ng/ml, p <0.001) was noted in 190 (8%). When there was no prior androgen deprivation therapy, the prostate specific antigen nadir and prostate specific antigen at 60 months were the strongest predictors of failure (OR 20.6 and 18.3, respectively, each p <0.0001). The logistic regression model had 85% sensitivity and 98% specificity, and predicted failure in 8 of 82 men (9.8%). A second model was created for the group with androgen deprivation therapy and rising prostate specific antigen using the predictive factors prostate specific antigen at 60 months (OR 53.9, p <0.0001) and T stage (OR 0.25, p = 0.0008). This model predicted biochemical failure in 30 of 56 men (54%) with 85% sensitivity and 93% specificity. The 2 predictive models yield an anticipated 90% cure rate in the entire cohort. Conclusions Brachytherapy is highly curative with stable prostate specific antigen at a surgical ablation level in 86% of patients. Rising prostate specific antigen is rare at a 6% incidence and often innocuous. [ABSTRACT FROM AUTHOR]

Purpose We determined whether men on continuous androgen deprivation therapy who achieve testosterone less than 0.7 nmol/l demonstrate subsequent testosterone elevations during followup and whether such events predict worse oncologic outcomes. Materials and Methods We evaluated a random, retrospective sample of 514 patients with prostate cancer treated with continuous androgen deprivation therapy in whom serum testosterone was less than 0.7 nmol/l at University Health Network between 2007 and 2016. Patients were followed from the date of the first testosterone measurement of less than 0.7 nmol/l to progression to castrate resistance, death or study period end. Study outcomes were the development of testosterone elevations greater than 0.7, greater than 1.1 and greater than 1.7 nmol/l, and progression to a castrate resistant state. Survival curves were constructed to determine the rate of testosterone elevations. Multivariate Cox regression analysis was done to assess whether elevations predicted progression to castrate resistance. Results Median patient age was 74 years and median followup was 20.3 months. Within 5 years of followup 82%, 45% and 18% of patients had subsequent testosterone levels greater than 0.7, greater than 1.1 and greater than 1.7 nmol/l, respectively. In 96% to 100% of these patients levels less than 0.7 nmol/l were subsequently reestablished within 5 years. No patient baseline characteristic was associated with elevations and elevations were not a significant predictor of progression to a castrate resistant state. Conclusions Men on continuous androgen deprivation therapy in whom initial testosterone is less than 0.7 nmol/l frequently show subsequent elevations in serum testosterone. Such a development should not trigger an immediate response from physicians as these events are prognostically insignificant with regard to oncologic outcomes. Levels are eventually reestablished at less than 0.7 nmol/l. [ABSTRACT FROM AUTHOR]

Purpose Enzalutamide significantly prolonged median progression-free survival vs bicalutamide in chemotherapy naïve men with metastatic castration resistant prostate cancer in the TERRAIN (Enzalutamide versus Bicalutamide in Castrate Men with Metastatic Prostate Cancer) trial. In this post hoc analysis we investigated the influence of age on the efficacy and safety of enzalutamide vs bicalutamide in this population. Materials and Methods Patients were randomized 1:1 to enzalutamide 160 mg per day or bicalutamide 50 mg per day. Progression-free survival, time to prostate specific antigen progression and safety were analyzed post hoc in younger (age less than 75 years) and older (age 75 years or greater) subgroups. Results Enzalutamide significantly reduced the risk of disease progression or death vs bicalutamide in patients younger than 75 years (HR 0.38, 95% CI 0.27–0.52, p <0.0001) and 75 years old or older (HR 0.59, 95% CI 0.37–0.92, p = 0.018). Time to prostate specific antigen progression was also significantly prolonged with enzalutamide vs bicalutamide in each subgroup. The adverse event distribution between treatments was similar in each subgroup except for more (5% or greater difference between subgroups) atrial fibrillation, urinary tract infections, falls and decreased appetite as well as less extremity pain and hot flushing in enzalutamide treated patients 75 years old or older, and less back pain and hot flushing in bicalutamide treated patients 75 years old or older. Grade 3 or greater cardiac events were more frequent in enzalutamide treated and bicalutamide treated patients who were 75 years old or older vs younger than 75 years. Fatigue was more frequent in enzalutamide treated patients with a similar distribution in each age subgroup. Conclusions Enzalutamide improved clinical outcomes vs bicalutamide irrespective of age. Increased falls and cardiac events suggest caution when prescribing to older patients (age 75 years or greater) with significant comorbidity. [ABSTRACT FROM AUTHOR]

Purpose We analyzed the oncologic and functional outcomes of partial gland ablation compared with robot-assisted radical prostatectomy in patients with low and intermediate risk prostate cancer. Materials and Methods A total of 1,883 patients underwent robot-assisted radical prostatectomy and 373 underwent partial gland ablation from July 2009 to September 2015. We selected 1,458 of these participants for analysis, including 1,222 and 236 treated with robot-assisted radical prostatectomy and partial gland ablation, respectively. Patients had a Gleason score of 3 + 3 or 3 + 4, clinical stage T2b or less, prostate specific antigen 15 ng/dl or less, unilateral disease and life expectancy greater than 10 years. Propensity score matching analysis (1:2) was applied in the overall robot-assisted radical prostatectomy sample, which selected 472 patients for comparison. For partial gland ablation 188 men underwent high intensity focused ultrasound and 48 underwent cryotherapy. Oncologic outcomes were analyzed in terms of the need for salvage treatment. Partial gland ablation failure was defined as any positive control biopsy after treatment. Functional outcomes were assessed by validated questionnaires. Results Matching was successful across the 2 groups, although men treated with partial gland ablation were older (p <0.001). Mean followup in the partial gland ablation group was 38.44 months. Partial gland ablation failure was observed in 68 men (28.8%), including 53 (28.1%) treated with high intensity focused ultrasound and 15 (31.2%) treated with cryotherapy. Partial gland ablation was associated with a higher risk of salvage treatment (HR 6.06, p <0.001). Complications were comparable between the groups (p = 0.06). Robot-assisted radical prostatectomy was associated with less continence recovery and a lower potency rate 3, 6 and 12 months after surgery (p <0.001). Conclusions In select patients with organ confined prostate cancer partial gland ablation offered good oncologic control with fewer adverse effects that required additional treatments. Potency and continence appeared to be better preserved after partial gland ablation. [ABSTRACT FROM AUTHOR]

Purpose We prospectively evaluated the diagnostic performance of prostate specific membrane antigen targeted 18 F-DCFPyL positron emission tomography/computerized tomography in the preoperative staging of men at high risk for harboring metastatic prostate cancer despite a negative conventional staging evaluation. Materials and Methods Men with clinically localized high or very high risk prostate cancer were imaged with 18 F-DCFPyL positron emission tomography/computerized tomography before undergoing radical prostatectomy with standardized pelvic lymph node dissection. The scans were interpreted by 2 blinded nuclear medicine readers and assessed for interreader variability as well as diagnostic accuracy for pelvic lymph node staging. Surgical pathology served as the reference standard to which 18 F-DCFPyL scan findings were compared. Results A total of 25 men contributed analyzable data to this study. Seven of these patients (28%) were found to have 1 or more positive lymph nodes on surgical pathology. Sites of radiotracer uptake were identified in the prostate of all imaged patients. The 2 readers identified the same number of prostatic lesions in 22 patients (88%), of whom all had at least 1 intraprostatic lesion in common between the 2 reads. Additionally, the readers assigned the same N stage to 46 of 50 individual lymph node packets (92%). Following reconciliation of the relatively few discordant imaging reads, 7 patients (28%) were found to have 1 or more sites of radiotracer uptake in the pelvis consistent with N1 disease, resulting in 71.4% sensitivity (95% CI 29.0–96.3) and 88.9% specificity (95% CI 65.3–98.6). Analysis at the level of individual nodal packets resulted in 66.7% sensitivity (95% CI 29.9–92.5) and 92.7% specificity (95% CI 80.1–98.5). Three men (12%) had evidence of M1a disease. Conclusions 18 F-DCFPyL positron emission tomography/computerized tomography allowed for accurate detection of prostate cancer sites in men believed to have clinically localized disease based on conventional imaging. Our results support the need for a larger study to more precisely define the diagnostic accuracy of this novel molecular imaging test. [ABSTRACT FROM AUTHOR]

Purpose We investigated the tolerability, safety and antitumor effects of a novel intraprostatic depot formulation of antiandrogen 2-hydroxyflutamide (in NanoZolid®) in men with localized prostate cancer. Materials and Methods Two clinical trials, LPC-002 and LPC-003, were performed in a total of 47 men. The formulation was injected transrectally into the prostate under ultrasound guidance. In LPC-002 the effects on prostate specific antigen and prostate volume were measured for 6 months in 24 patients. In LPC-003 antitumor effects were evaluated by histopathology and magnetic resonance imaging including spectroscopy during 6 or 8 weeks in 23 patients. In each study testosterone and 2-hydroxyflutamide in plasma were measured as well as quality of life parameters. Results In LPC-002 (mean dose 690 mg) a reduction was observed in prostate specific antigen and prostate volume. Average nadir prostate specific antigen and prostate volume were 24.9% and 14.0% below baseline, respectively. When increasing the dose in LPC-003 to 920 and 1,740 mg, average prostate specific antigen decreased 16% and 23% after 6 and 8 weeks, respectively. Magnetic resonance imaging and magnetic resonance spectroscopy showed morphological changes and a global reduction in metabolite concentrations following treatment, indicating an antitumor response. Injections did not result in hormone related side effects. Three serious adverse events were reported and all resolved with oral antibiotic treatment. Conclusions Intraprostatic injections of 2-hydroxyflutamide depot formulations showed antitumor effects, and proved to be safe and tolerable. However, for better anticancer effects higher doses and better dose distribution are suggested. [ABSTRACT FROM AUTHOR]

Background Our objective in this study was to evaluate the role and benefits in terms of local toxicity and biochemical disease-free survival (bDFS) following escalated-dose conformal radiation therapy in prostate adenocarcinoma. Methods The study population was composed of 53 patients with histologically proven T1b-T4, NO, MO prostate adenocarcinoma, having any Gleason score with prostate-specific antigen (PSA) of less than 50 ng/mL at diagnosis, given escalated dose EBRT (74 Gy) during the period between January 2011 and December 2013, retrospectively and evaluated for a period of 2 years post-radiation. Patients were followed up for a period of 2 years, beginning after completion of escalated dose external beam radiotherapy (EBRT) for biochemical failure as defined in ASTRO consensus committee guidelines 1996 and investigated for gastrointestinal, genitourinary skin toxicity. Results Out of 53 patients, 35 showed no biochemical failure at the end of 2 years following the completion of definitive escalated dose conformal radiotherapy while 18 were observed to have biochemical relapse. Acute gastrointestinal grade 1 toxicity was found in 26 patients, grade 2 in 24, and grade 3 only in 3 patients. Late gastrointestinal grade 0 toxicity was found in 16 patients, grade 1 in 28, grade 2 in 7 and grade 3 only in 2 patients. Grade 1 acute genitourinary toxicity was the highest in frequency observed in 28 of the total population followed by grade 2 in 21, grade 0 and grade 3 each, only in 2 patients. Late genitourinary Grade 0 toxicity was observed in 32 patients, grade 1 in 19, grade 2 and 3 only in 1 patient of the total population, respectively. Conclusion Our data were comparable to international studies of dose escalation using 3D and beneficial as compared to conventional radiation therapy delivered by 2D in terms of biochemical failure rate and treatment related toxicity. [ABSTRACT FROM AUTHOR]

Purpose We summarize published data on associations between cavernous neurovascular bundle preservation (nerve sparing) during prostatectomy and positive surgical margins, erectile function, urinary function and other patient reported outcomes. Materials and Methods A systematic literature search of MEDLINE®, Embase® and Cochrane Reviews databases was performed for interventional or observational studies published between 2000 and 2014. English language articles that compared clinical outcomes of patients undergoing nerve sparing and nonnerve sparing radical prostatectomy were included. Meta-analyses were performed to calculate pooled relative risk estimates for positive surgical margins, erectile dysfunction and urinary incontinence in nerve sparing and nonnerve sparing groups. Sensitivity analyses compared outcomes among unilateral and bilateral nerve sparing vs nonnerve sparing groups. Results Of the 1,883 articles identified, 124 studies (73,448 patients) were included in the analysis. Nerve sparing did not increase the risk of positive surgical margins in patients with pT2 (RR 0.92, 95% CI 0.75–1.13) or pT3 disease (RR 0.83, 95% CI 0.71–0.96), potentially due to appropriate patient selection. The risk of incontinence was lower in nerve sparing cases (RR 0.75, 95% CI 0.65–0.85 and RR 0.61, 95% CI 0.44–0.84) at 3 and 12 months, respectively. The relative risk of erectile dysfunction with nerve sparing was 0.77 (95% CI 0.70–0.85) at 3 months and 0.53 (95% CI 0.39–0.71) at 12 months. Subgroup analyses of unilateral and bilateral nerve sparing approaches demonstrated similar results. Conclusions Among cohort studies nerve sparing was not associated with worse cancer outcomes. Nerve sparing is associated with better urinary and erectile function. These results should be interpreted with caution given the potential for selection bias and unadjusted confounding factors. [ABSTRACT FROM AUTHOR]

Purpose Focal laser ablation is a potential treatment in some men with prostate cancer. Currently focal laser ablation is performed by radiologists in a magnetic resonance imaging unit (in bore). We evaluated the safety and feasibility of performing focal laser ablation in a urology clinic (out of bore) using magnetic resonance imaging-ultrasound fusion for guidance. Materials and Methods A total of 11 men with intermediate risk prostate cancer were enrolled in this prospective, institutional review board approved pilot study. Magnetic resonance imaging-ultrasound fusion was used to guide laser fibers transrectally into regions of interest harboring intermediate risk prostate cancer. Thermal probes were inserted for real-time monitoring of intraprostatic temperatures during laser activation. Multiparametric magnetic resonance imaging (3 Tesla) was done immediately after treatment and at 6 months along with comprehensive fusion biopsy. Results Ten of 11 patients were successfully treated while under local anesthesia. Mean procedure time was 95 minutes (range 71 to 105). Posttreatment magnetic resonance imaging revealed a confined zone of nonperfusion in all 10 men. Mean zone volume was 4.3 cc (range 2.1 to 6.0). No CTCAE grade 3 or greater adverse events developed and no changes were observed in urinary or sexual function. At 6 months magnetic resonance imaging-ultrasound fusion biopsy of the treatment site showed no cancer in 3 patients, microfocal Gleason 3 + 3 in another 3 and persistent intermediate risk prostate cancer in 4. Conclusions Focal laser ablation of prostate cancer appears safe and feasible with the patient under local anesthesia in a urology clinic using magnetic resonance imaging-ultrasound fusion for guidance and thermal probes for monitoring. Further development is necessary to refine out of bore focal laser ablation and additional studies are needed to determine appropriate treatment margins and oncologic efficacy. [ABSTRACT FROM AUTHOR]

Purpose Prostate cancer screening with prostate specific antigen reduces prostate cancer mortality but leads to over diagnosis of indolent prostate cancer. The use of 5α-reductase inhibitors lowers prostate specific antigen and in theory could affect the performance of prostate specific antigen based screening. We evaluated the outcomes of prostate cancer screening in 5α-reductase inhibitors users. Materials and Methods The study was performed in FinRSPC (Finnish Randomized Study of Screening for Prostate Cancer). Of 80,454 men 31,866 were randomized to be screened at 4-year intervals during 1996 to 2004. Information on 5α-reductase inhibitors reimbursements before prostate cancer during 1995 to 2009 was collected from the national prescription database for 78,615 men. We evaluated the effect of screening on prostate cancer risk and mortality by 5α-reductase inhibitors using Cox regression. Results Men receiving 5α-reductase inhibitors had higher median prostate specific antigen and were more often screen positive than nonusers. Despite this, screening did not significantly affect prostate cancer detection (HR 0.89, 95% CI 0.79–1.01) or mortality (HR 0.82, 95% CI 0.51–1.32) compared to findings in the control arm among men on 5α-reductase inhibitors. On ROC analysis prostate specific antigen and age did not predict Gleason 7-10 prostate cancer as accurately in 5α-reductase inhibitors users as it did among nonusers (first screening round AUC 0.79 vs 0.88). Conclusions Prostate specific antigen based screening among men receiving 5α-reductase inhibitors did not improve the detection of high grade or metastatic prostate cancer, or prevent prostate cancer death. [ABSTRACT FROM AUTHOR]

Purpose In this white paper update we identify and discuss the prevalence and prevention of common complications of prostate needle biopsy. Materials and Methods A literature review was performed on prostate biopsy complications via queries of PubMed and EMBASE ® databases for prostate biopsy complications from January 1, 2010 until June 1, 2015. We focused on infection, bleeding, urinary retention, needle tract seeding and erectile dysfunction. A total of 346 articles were identified for full text review and 119 are included in the final data synthesis. Results Infection is the most common complication of prostate biopsy with fluoroquinolone resistant Escherichia coli having a prominent role. Reported rates of infectious complications range from 0.1% to 7.0%, and sepsis rates range from 0.3% to 3.1% depending on antibiotic prophylaxis regimens. Mild, self-limiting and transient bleeding is also a common complication. Other complications are extremely rare. Conclusions This white paper provides a concise reference document for the more common prostate biopsy complications and prevention strategies. Risk assessment should be performed for all patients to identify known risk factors for harboring fluoroquinolone resistance. If infection incidence increases check the local antibiogram, current equipment and cleaning practices, and consider alternate approaches to antibiotic prevention such as needle cleaning, risk basked augmentation, rectal culture with targeted prophylaxis and transperineal biopsy. If infection occurs, actively re-situate the patient and start empiric intravenous treatment with carbapenems, amikacin or second and third generation cephalosporins. [ABSTRACT FROM AUTHOR]

Purpose We examined rebiopsies in MUSIC (Michigan Urological Surgery Improvement Collaborative) to understand adherence to guidelines recommending repeat prostate biopsy in patients with multifocal high grade prostatic intraepithelial neoplasia or atypical small acinar proliferation. Materials and Methods We analyzed data on men undergoing repeat biopsy, practice patterns and cancer detection rates. Multivariate regression modeling was used to calculate the proportion of patients undergoing rebiopsy. We used claims data to validate the treatment classification in MUSIC. To understand reasons for not performing rebiopsy we reviewed records of a sample of patients with atypical small acinar proliferation. Results We identified 5,375 men with a negative biopsy, of whom 411 (7.6%) underwent repeat biopsy. In 718 men with high grade prostatic intraepithelial neoplasia, 350 with atypical small acinar proliferation and 587 with high grade prostatic intraepithelial neoplasia and atypical small acinar proliferation or atypical small acinar proliferation alone at initial biopsy the rebiopsy rate was 20.7%, 42.5% and 55.6%, respectively. The adjusted proportion of patients with rebiopsy in each practice ranged from 0% to 17.2% (p <0.001). The overall cancer detection rate at rebiopsy was 39.3%. It was highest after atypical small acinar proliferation (adjusted probability 0.39, 95% CI 0.30–0.48), and after high grade prostatic intraepithelial neoplasia and atypical small acinar proliferation (adjusted probability 0.50, 95% CI 0.35–0.65). The greatest Gleason 7 or greatest detection rate of 41.1% was found in patients with high grade prostatic intraepithelial neoplasia and atypical small acinar proliferation. Chart review revealed that 45.5% of patients with atypical small acinar proliferation underwent prostate specific antigen testing instead of rebiopsy while 36% failed to undergo rebiopsy despite a recommendation. Conclusions Rebiopsy rates vary in Michigan practices with relatively low use in men with high grade prostatic intraepithelial neoplasia and atypical small acinar proliferation or atypical small acinar proliferation alone. Quality improvement strategies should target patients with atypical small acinar proliferation and high grade prostatic intraepithelial neoplasia as they have the highest likelihood of cancer detection. [ABSTRACT FROM AUTHOR]

Purpose We assessed the midterm oncologic outcomes of vascular targeted photodynamic therapy with padeliporfin for low risk prostate cancer treatment. Materials and Methods We prospectively assessed all patients treated with vascular targeted photodynamic therapy for low risk prostate cancer at our center. Patients were followed every 6 months. All patients underwent prostate biopsies 6 months after treatment or when there was biological or clinical progression. The primary end point was progression-free survival. Secondary end points were absent clinically significant cancer in the treated lobes, radical therapy and the prostate specific antigen rate. Variables were compared with the chi-square, Mann-Whitney or Wilcoxon test. Progression-free survival is reported with Kaplan-Meier curves. Results A total of 82 men were treated with vascular targeted photodynamic therapy. Median followup was 68 months (range 6 to 89). Median progression-free survival was 86 months (95% CI 82–90). Median prostate specific antigen decreased significantly by 41% 6 months after treatment and it remained stable during followup (p <0.001). A total of 115 lobes were treated and absent clinically significant cancer was achieved in 94 (82%). Of the 82 patients 20 (24%) underwent radical therapy, including radical prostatectomy in 18 and brachytherapy in 2, at a median of 22 months (range 6 to 86). Study limitations include a single arm design, small population size and midterm followup. Conclusions Padeliporfin vascular targeted photodynamic therapy for low risk prostate cancer achieved an 82% rate of absent clinically significant cancer in treated lobes and 76% of patients avoided radical therapy at a median followup of 68 months. However, longer followup is required to determine long-term outcomes. [ABSTRACT FROM AUTHOR]

Purpose Long-term data supporting the role of primary tumor resection in node positive prostate cancer are lacking. We evaluated the impact of adding radical retropubic prostatectomy to surgical castration on long-term oncologic outcomes in pathological node positive prostate cancer. Materials and Methods We identified men who underwent pelvic lymphadenectomy and orchiectomy within 90 days for pathological node positive prostate cancer from 1966 to 1995. Men treated with radical retropubic prostatectomy in addition to orchiectomy were matched 1:1 to men who underwent orchiectomy alone based on age, year of surgery, clinical grade, clinical T stage, number of positive nodes and preoperative serum prostate specific antigen, the latter from 1987 and thereafter. Kaplan-Meier and Cox regression analyses were done to compare cancer specific and overall survival. Results The matched cohort included 158 men with 79 in each group. Of men who underwent orchiectomy alone 76 died, including 60 of prostate cancer. Of patients treated with radical retropubic prostatectomy plus orchiectomy 70 died, including 28 of prostate cancer. On Kaplan-Meier analyses prostatectomy plus orchiectomy vs orchiectomy alone was associated with prolonged cancer specific survival (at 20 years 59% vs 18%, log rank p <0.001) and overall survival (at 20 years 22% vs 9%, log rank p <0.001). In Cox models prostatectomy plus orchiectomy vs orchiectomy alone was associated with improved cancer specific survival (HR 0.28, 95% CI 0.17–0.46, p <0.001) and overall survival (HR 0.48, 95% CI 0.34–0.66, p <0.001). Findings were similar in the subset with available preoperative prostate specific antigen values. Conclusions With lifelong followup in nearly the entire cohort, this study demonstrates that adding radical retropubic prostatectomy to surgical castration for pathological node positive prostate cancer is associated with improved cancer specific and overall survival. When technically feasible in well selected patients, aggressive locoregional resection should be considered for node positive prostate cancer as part of a multimodal approach. [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 Robot-assisted radical prostatectomy has undergone rapid dissemination driven in part by market forces to become the most frequently used surgical approach in the management of prostate cancer. Accordingly, a critical analysis of its volume-outcome relationship has important health policy implications. Therefore, we evaluated the association of hospital robot-assisted radical prostatectomy volume with perioperative outcomes, and examined the distribution of hospital procedure volume to contextualize the volume-outcome relationship. Materials and Methods We identified 140,671 men who underwent robot-assisted radical prostatectomy from 2009 to 2011 in NIS (Nationwide Inpatient Sample). The associations of hospital volume with perioperative outcomes and total hospital costs were evaluated using multivariable logistic regression and generalized linear models. Results In 2011, 70% of hospitals averaged 1 robot-assisted radical prostatectomy per week or less, accounting for 28% of surgeries. Compared to patients treated at the lowest quartile hospitals, those treated at the highest quartile hospitals had significantly lower rates of intraoperative complications (0.6% vs 1.4%), postoperative complications (4.8% vs 13.9%), perioperative blood transfusion (1.5% vs 4.0%), prolonged hospitalization (4.3% vs 13.8%) and mean total hospital costs ($12,647 vs $15,394, all p trend <0.001). When modeled as a nonlinear continuous variable, increasing hospital volume was independently associated with improved rates of each perioperative end point up to approximately 100 robot-assisted radical prostatectomies per year, beyond which there appeared to be marginal improvement. Conclusions Increasing hospital robot-assisted radical prostatectomy volume was associated with improved perioperative outcomes up to approximately 100 surgeries per year, beyond which there appeared to be marginal improvement. A substantial proportion of these procedures is performed at low volume hospitals. [ABSTRACT FROM AUTHOR]

Purpose Androgen deprivation therapy is often used as salvage treatment in men with rising prostate specific antigen after initial radical prostatectomy or radiotherapy for clinically localized prostate cancer. Given the lack of evidence from general practice, we examined the association of salvage androgen deprivation therapy with mortality in an observational cohort study. Materials and Methods From 3 managed care organizations we assembled a retrospective cohort of all 5,804 men with newly diagnosed localized prostate cancer from 1995 to 2009 who had a prostate specific antigen increase (biochemical recurrence) after primary radical prostatectomy or radiotherapy. The main outcomes were all-cause and prostate cancer specific mortality. We used Cox proportional hazards models to estimate mortality with salvage androgen deprivation therapy as a time dependent predictor. Results Overall salvage androgen deprivation therapy was not associated with all-cause or prostate cancer specific mortality in the prostatectomy cohort (HR 0.97, 95% CI 0.70–1.35 or HR 1.18, 95% CI 0.68–2.07) or in the radiotherapy cohort (HR 0.84, 95% CI 0.70–1.01 or HR 1.06, 95% CI 0.80–1.40, respectively). Among men with prostate specific antigen doubling time less than 9 months after the prostate specific antigen rise, salvage androgen deprivation therapy was statistically significantly associated with a decreased risk of all-cause and prostate cancer specific mortality in the prostatectomy cohort (HR 0.35, 95% CI 0.20–0.63 and HR 0.43, 95% CI 0.21–0.91) and in the radiotherapy cohort (HR 0.62, 95% CI 0.48–0.80 and HR 0.65, 95% CI 0.47–0.90, respectively). Conclusions We found no association of salvage androgen deprivation therapy with all-cause or cause specific mortality in most men with biochemical recurrence after primary radical prostatectomy or radiotherapy for clinically localized prostate cancer. Men with quickly progressed disease may derive a clinical benefit from salvage androgen deprivation therapy. [ABSTRACT FROM AUTHOR]

Purpose Dutasteride, which is licensed for symptomatic benign prostatic hyperplasia, has been associated with a lower progression rate of low risk prostate cancer. We evaluated the effect of dutasteride on prostate cancer volume as assessed by T2-weighted magnetic resonance imaging. Materials and Methods In this randomized, double-blind, placebo controlled trial, men with biopsy proven, low-intermediate risk prostate cancer (up to Gleason 3 + 4 and PSA up to 15 ng/ml) who had visible lesion of 0.2 ml or greater on T2-weighted magnetic resonance imaging sequences were randomized to daily dutasteride 0.5 mg or placebo for 6 months. Lesion volume was assessed at baseline, and 3 and 6 months with image guided biopsy to the lesion at study exit. The primary end point was the percent reduction in lesion volume over 6 months. This trial was registered with the European Clinical Trials register (EudraCT 2009-102405-18). Results A total of 42 men were recruited between June 2010 and January 2012. In the dutasteride group, the average volumes at baseline and 6 months were 0.55 and 0.38 ml, respectively and the average reduction was 36%. In the placebo group, the average volumes at baseline and 6 months were 0.65 and 0.76 ml, respectively, and the average reduction was −12%. The difference in percent reductions between the groups was 48% (95% CI 27.4–68.3, p <0.0001). The most common adverse event was deterioration in erectile function, which was 25% in men randomized to dutasteride and 16% in men randomized to placebo. Conclusions Dutasteride was associated with a significant reduction in prostate cancer volume on T2-weighted magnetic resonance imaging compared to placebo. [ABSTRACT FROM AUTHOR]

Purpose Current clinicopathological parameters are insufficient to predict the likelihood of biochemical recurrence in patients with prostate cancer after radical prostatectomy. Such information may help identify patients who would likely benefit from adjuvant radiotherapy rather than active surveillance. A multiplex proteomic assay, previously tested on biopsies and found to be predictive of favorable or unfavorable pathology at radical prostatectomy, was assessed for its predictive value to identify patients at higher risk for biochemical relapse. Materials and Methods Proteomic assays from core needle biopsies of 288 men who subsequently underwent radical prostatectomy at CHUM (Centre hospitalier de l’Université de Montréal) were evaluated for the prediction of subsequent biochemical recurrence. Results Of the 288 men, biochemical relapse was observed in 47 (16.3%) and metastases were found in 5 (1.7%). Median followup was 68.5 months. The proteomic assay clearly separated patients into 3 categories, including those at low, intermediate and high risk for biochemical relapse (p = 0.0007). Assay scores predicted biochemical relapse on univariate analysis (HR 1.724, p = 0.0002 per 20% change in score), significantly better than other preoperative prognostic parameters. Additionally, the assay score had a significantly higher p value when combined with clinical National Comprehensive Cancer Network® stage compared to stage alone (HR 1.579, p = 0.0017 per 20% change in score). Conclusions A protein based assay score derived from diagnostic needle biopsy has strong predictive ability for biochemical relapse after surgery. These results suggest that this assay score can be used at the diagnostic stage to identify patients in whom prostate cancer is potentially more biologically aggressive and active treatment should be considered. [ABSTRACT FROM AUTHOR]

Purpose To our knowledge the optimal treatment of patients following a negative prostate biopsy is unknown. Consequently, resources are increasingly being directed toward risk stratification in this cohort. However, the risk of prostate cancer mortality in this group before the introduction of supplemental biomarkers and imaging techniques is unclear. Materials and Methods The PLCO (Prostate, Lung, Colorectal and Ovarian Cancer) Screening Trial provides survival data prior to the implementation of new diagnostic interventions. We divided men with an initial positive screen and a subsequent prostate biopsy into cohorts based on positive or negative results. Prostate cancer specific mortality was then compared to that in the trial control arm to estimate the prognostic significance of biopsy results relative to the general population. Results A total of 36,525 and 36,560 patients comprised the screening and control arms, respectively. Of 4,064 subjects with a positive first screen 1,233 underwent a linked biopsy, of which 473 were positive and 760 were negative. At a median followup of 12.9 years, 1.1% of men in the negative biopsy cohort had died of prostate cancer. The difference in mortality rates between the negative biopsy and control arms was 0.734 deaths per 1,000 person-years. The proportional subhazard ratios of prostate cancer specific mortality for negative biopsy and positive biopsy relative to the control arm were 2.93 (95% CI 1.44–5.99) and 18.77 (95% CI 12.62–27.93), respectively. Conclusions After a negative prostate biopsy, men face a relatively low risk of death from prostate cancer when followed with traditional markers and biopsy techniques. This suggests limited potential for new diagnostic interventions to improve survival in this group. [ABSTRACT FROM AUTHOR]

Purpose Docetaxel is the first line chemotherapy currently used to treat patients with symptomatic metastatic castration resistant prostate cancer. Although it provides survival benefits, it is associated with significant side effects. Novel therapeutic options are needed for patients with metastatic castration resistant prostate cancer and an approach is combining docetaxel with chemosensitizing agents. Metformin has been shown to improve the survival of patients with breast, lung and endometrial cancer receiving chemotherapy, and enhance chemotherapeutic efficacy in breast cancer and colon cancer cells. However, to our knowledge the chemosensitizing effect of metformin in prostate cancer has not been explored. Therefore, the hypothesis for our study was that diabetic patients with metastatic castration resistant prostate cancer who were administered metformin during docetaxel chemotherapy would have improved prostate cancer specific and overall survival. Materials and Methods This retrospective cohort study used data from several Ontario administrative health care databases. Men older than 65 years diagnosed with metastatic castration resistant prostate cancer and treated with docetaxel were stratified into groups based on diabetes status and use of antidiabetic medications. We evaluated the effect of metformin use with docetaxel on prostate cancer specific survival and overall survival using Kaplan-Meier survival curves, the log rank test and multivariate Cox proportional HRs. Results Survival curves showed that metformin use with docetaxel did not improve prostate cancer specific survival (p = 0.9562) or overall survival (p = 0.9927). HRs showed no significant effect of metformin use with docetaxel on prostate cancer specific survival (HR = 0.96, p = 0.66) or overall survival (HR = 0.94, p = 0.39). Conclusions Metformin use during docetaxel chemotherapy did not significantly improve prostate cancer specific or overall survival in diabetic patients with metastatic castration resistant prostate cancer. This study indicates that metformin may not be an effective chemosensitizer for metastatic castration resistant prostate cancer. [ABSTRACT FROM AUTHOR]

Purpose Men with intermediate risk prostate cancer have widely variable outcomes. Some suggest that active surveillance or less invasive therapies (brachytherapy or focal therapy) may be appropriate for some men with Gleason score 3 + 4 = 7 disease. Molecular markers may help further distinguish prostate cancers with aggressive behavior. We tested whether loss of the PTEN (phosphatase and tensin homolog) tumor suppressor in 3 + 4 = 7 tumor biopsies is associated with adverse pathology at prostatectomy. Materials and Methods We queried prostate needle biopsies from 2000 to 2014 with a maximum Gleason score of 3 + 4 = 7 followed by prostatectomy. A total of 260 cases had PTEN status evaluable by clinical grade immunohistochemistry. Biopsy PTEN status was correlated with preoperative and postoperative clinicopathological parameters. Results PTEN loss was detected in 27% of 3 + 4 = 7 biopsies. Loss of PTEN was less common in tumors of African American men compared to European American men (9% vs 31%, p = 0.002). At prostatectomy, tumors with PTEN loss were more likely to show nonorgan confined disease compared to those with PTEN intact (52% vs 27%, p <0.001). In logistic regression models including age, race, prostate specific antigen, clinical stage and biopsy tumor involvement, PTEN loss at biopsy remained significantly associated with an increased risk of nonorgan confined disease (HR 2.46, 95% CI 1.34–4.49, p = 0.004). On ROC analysis, the AUC for models including prostate specific antigen and clinical stage was increased from 0.61 to 0.67 upon inclusion of PTEN status. Conclusions PTEN loss in a Gleason score 3 + 4 = 7 biopsy is independently associated with an increased risk of nonorgan confined disease at prostatectomy. It adds to the preoperative parameters commonly used to predict pathological stage. [ABSTRACT FROM AUTHOR]