The impact of obesity on the predictive accuracy of PSA in men undergoing prostate biopsy.

PURPOSE: Obese men have been reported to have lower serum PSA values relative to normal-weight men in population-based studies, screening cohorts, and in men with prostate cancer (CaP) treated with surgery. There are concerns that PSA may be less accurate in detecting prostate cancer in men with increased body mass index (BMI). We determine whether the diagnostic potential of PSA is negatively influenced by obesity by comparing its operating characteristics across BMI categories among men undergoing prostate biopsy. METHODS: Demographic, clinical, and histopathological data on 917 men who underwent trans-rectal ultrasound-guided prostate needle biopsy from 2002 to 2010 at a University hospital in Italy were used in the study. Men were categorized for BMI as follows: <25 kg/m(2) (normal weight), 25-29.9 kg/m(2) (overweight), and ≥ 30 kg/m(2) (obese). Receiver operator characteristics (ROC) curves were used to assess PSA accuracy for predicting prostate cancer overall and then stratified according to digital rectal examination (DRE) findings using the area under the ROC curve (AUC). RESULTS: The obesity rate of the study cohort was 21 %. There was no statistically significant difference in the overall AUCs of PSA for predicting CaP among normal-weight (AUC = 0.56), overweight (AUC = 0.60), and obese men (AUC = 0.60; p = 0.68) in either DRE-positive or negative men. CONCLUSIONS: In a cohort of Italian men undergoing prostate biopsy, the performance accuracy of PSA as a predictor of CaP is not significantly altered by BMI. Obesity does not negatively impact the overall ability of PSA to discriminate between CaP and benign conditions.

Does the multidisciplinary approach improve oncological outcomes in men undergoing surgical treatment for prostate cancer?

OBJECTIVES: To determine whether oncological outcomes are improved in prostate cancer patients by using a multidisciplinary strategy as compared with a standard clinic paradigm, and whether time to treatment is delayed when using a multidisciplinary approach. METHODS: We retrospectively analyzed patients who were evaluated and pursued radical prostatectomy as primary treatment, by the same surgeons, in the prostate cancer multidisciplinary clinic (n = 194) and standard urology clinic (n = 741) at Duke University Medical Center from 2005 to 2009. Comparisons of baseline characteristics were examined using rank sum and χ(2) -tests. Differences in time to radical prostatectomy and oncological outcomes were evaluated using multivariate linear and Cox regression, respectively. RESULTS: A greater proportion of high-risk patients (D'Amico criteria) were evaluated at the multidisciplinary clinic compared with the urology clinic (23.2% vs 15.6%, P = 0.014). Mean-adjusted time from biopsy to radical prostatectomy was shorter for multidisciplinary clinic patients (85.6 vs 96.8 days, P = 0.006). After a median follow up of 21 months, no significant difference was found between the multidisciplinary clinic and urology clinic in the risk of biochemical recurrence after radical prostatectomy, whether controlling for clinical (hazard ratio 0.71, P = 0.249) or pathological variables (hazard ratio 0.75, P = 0.349). CONCLUSIONS: Despite higher-risk disease, men evaluated using the multidisciplinary approach have similar oncological outcomes compared with men undergoing standard evaluation. Furthermore, time to radical prostatectomy is not delayed by the multidisciplinary management of these patients.

Association between exercise and primary incidence of prostate cancer: does race matter?

BACKGROUND: Exercise is a modifiable lifestyle risk factor associated with prostate cancer risk reduction. However, whether this association is different as a function of race is unclear. In the current study, the authors attempted to characterize the link between exercise and prostate cancer (CaP) in white and black American men. METHODS: Using a prospective design, 307 men (164 of whom were white and 143 of whom were black) who were undergoing prostate biopsy completed a self-reported survey that assessed exercise behavior (metabolic equivalent [MET] hours per week). Crude and adjusted logistic regression analyses were used to estimate the risk of prostate cancer controlling for age, body mass index, digital rectal examination findings, previous biopsy, Charlson comorbidity score, and family history of CaP stratified by self-reported race. RESULTS: There was no significant difference noted with regard to the amount of exercise between racial groups (P = .12). Higher amounts of MET hours per week were associated with a decreased risk of CaP for white men in both crude (P = .02) and adjusted (P = .04) regression models. Among whites, men who exercised ≥ 9 MET hours per week were less likely to have a positive biopsy result compared with men exercising < 9 MET hours per week (odds ratio, 0.47; 95% confidence interval, 0.22-0.99 [P = .047]). There was no association noted between MET hours per week and risk of CaP among black men in both crude (P = .79) and adjusted (P = .76) regression models. CONCLUSIONS: In a prospective cohort of men undergoing biopsy, increased exercise, measured as MET hours per week, was found to be associated with CaP risk reduction among white but not black men. Investigating race-specific mechanisms by which exercise modifies CaP risk and why these mechanisms disfavor black men in particular are warranted.

Androgenetic alopecia at various ages and prostate cancer risk in an equal-access multiethnic case-control series of veterans.

PURPOSE: Epidemiological data are conflicting regarding the association between androgenetic alopecia (AA) and prostate cancer (CaP). We examined the relationship between these two conditions. MATERIALS AND METHODS: We performed a case-control study at a Veterans Affairs Hospital among 708 men: 312 healthy controls, 167 men with CaP, and 229 men without CaP on prostate biopsy. Participants were asked to self-describe hair patterns at ages 30 and 40 and at study enrollment. We tested the association between hair pattern (overall, vertex, or frontal) and CaP status using logistic regression analysis adjusting for multiple clinical features. Disease grade was similarly examined as a secondary outcome. RESULTS: Relative to healthy controls, younger age of AA onset was significantly associated with increased CaP risk (p = 0.008). Similar patterns were noted for frontal (p = 0.005) and not vertex balding (p = 0.22). When compared with biopsy-negative men, a similar pattern was seen with younger age of AA onset having higher risk of CaP, though this was not significant (p = 0.07). A suggestion for younger age of AA onset for frontal (p = 0.07) being associated with CaP versus biopsy-negative men was also observed. Overall balding (yes/no) was associated with greater than twofold increase in high-grade disease (p = 0.02). CONCLUSIONS: Men reporting earlier AA onset were at increased CaP risk and suggestively had more aggressive disease. Contrary to other studies, frontal balding was the predominant pattern associated with elevated CaP risk. Further study is required to confirm these findings in a larger sample and to better understand the role of AA, androgens, and CaP biology.

Emergent ureteric stent vs percutaneous nephrostomy for obstructive urolithiasis with sepsis: patterns of use and outcomes from a 15-year experience.

OBJECTIVES: To characterize the use of emergent JJ ureteric stent placement and percutaneous nephrostomy (PCN) for patients with obstructive urolithiasis with sepsis, and to determine whether outcomes differ between the two treatment methods. PATIENTS AND METHODS: A total of 130 patients with obstructive urolithiasis and systemic inflammatory response syndrome criteria were identified retrospectively from a single health system database from 1995 to 2011. Primary outcomes included stone-related and clinical variables which predicted the use of each treatment method. Secondary outcomes included the length of hospital stay, risk of intensive care unit (ICU) admission, and surgical approach used for definitive stone management. RESULTS: The overall rate of failed procedures was 2.3% (3/130), with one in-hospital death (0.8%). Patients treated with PCN had larger stones (10 vs 7 mm, P = 0.031), and were more acutely ill (acute physiology, age, chronic health evaluation [APACHE] II scores of 15 vs 11, P = 0.036) than those treated with JJ stent placement. Patients treated with PCN were more likely to require ICU admission (odds ratio: 3.23, 95% confidence interval [CI]: 1.24-8.41, P = 0.016), and demonstrated longer length of hospital stay (ß: 0.47, 95% CI: 0.20-0.74, P = 0.001), even when adjusting for age, APACHE II score, and Charlson Comorbidity Index score. After resolution of sepsis, patients treated with PCN were more likely to be treated definitively with a percutaneous approach, while patients treated with JJ stent placement were more likely to be treated ureteroscopically. CONCLUSIONS: Both JJ stent placement and PCN drainage appear effective. Patients with larger stones and who are more acutely ill are more likely to be treated with PCN. Additional randomized clinical trials of adequate power are warranted to define the optimum management of these often complex cases.

Intratumoral inflammation is associated with more aggressive prostate cancer.

PURPOSE: Inflammation may play a role in the development and progression of many cancers, including prostate cancer. We sought to test whether histological inflammation within prostate cancer was associated with more aggressive disease. METHODS: The slides of prostatectomy specimens were reviewed by a board-certified pathologist on 287 men from a Veterans Affairs Medical Center treated with radical prostatectomy from 1992 to 2004. The area with the greatest tumor burden was scored in a blinded manner for the degree of inflammation: absent, mild, or marked. We used logistic and Cox proportional hazards regression analysis to examine whether categorically coded inflammation score was associated with adverse pathology and biochemical progression, respectively. RESULTS: No inflammation was found in 49 men (17%), while 153 (53%) and 85 (30%) had mild and marked inflammation. During a median follow-up of 77 months, biochemical recurrence occurred among 126 (44%) men. On multivariate analysis, more inflammation was associated with greater risk of positive margins, capsular penetration, and seminal vesicle invasion (all p < 0.05). Marked inflammation was associated with increased PSA recurrence risk when adjusting for preoperative features only (HR 2.08, 95% CI 1.02-4.24), but not after adjusting for pathologic features. CONCLUSIONS: Inflammation within prostate cancer was associated with more advanced disease, although it is unclear whether aggressive disease caused increased inflammation or inflammation caused aggressive disease.

High serum folate is associated with reduced biochemical recurrence after radical prostatectomy: results from the SEARCH Database.

INTRODUCTION: To analyze the association between serum levels of folate and risk of biochemical recurrence after radical prostatectomy among men from the Shared Equal Access Regional Cancer Hospital (SEARCH) database. MATERIALS AND METHODS: Retrospective analysis of 135 subjects from the SEARCH database treated between 1991-2009 with available preoperative serum folate levels. Patients' characteristics at the time of the surgery were analyzed with ranksum and linear regression. Uni- and multivariable analyses of folate levels (log-transformed) and time to biochemical recurrence were performed with Cox proportional hazards. RESULTS: The median preoperative folate level was 11.6 ng/mL (reference = 1.5-20.0 ng/mL). Folate levels were significantly lower among African-American men than Caucasians (P = 0.003). In univariable analysis, higher folate levels were associated with more recent year of surgery (P < 0.001) and lower preoperative PSA (P = 0.003). In univariable analysis, there was a trend towards lower risk of biochemical recurrence among men with high folate levels (HR = 0.61, 95 %CI = 0.37-1.03, P = 0.064). After adjustments for patients characteristics' and pre- and post-operative clinical and pathological findings, higher serum levels of folate were independently associated with lower risk for biochemical recurrence (HR = 0.42, 95 %CI = 0.20-0.89, P = 0.023). CONCLUSION: In a cohort of men undergoing radical prostatectomy at several VAs across the country, higher serum folate levels were associated with lower PSA and lower risk for biochemical failure. While the source of the folate in the serum in this study is unknown (i.e. diet vs. supplement), these findings, if confirmed, suggest a potential role of folic acid supplementation or increased consumption of folate rich foods to reduce the risk of recurrence.

Outcomes of metallic stents for malignant ureteral obstruction.

PURPOSE: Malignant ureteral obstruction often necessitates chronic urinary diversion and is associated with high rates of failure with traditional ureteral stents. We evaluated the outcomes of a metallic stent placed for malignant ureteral obstruction and determined the impact of risk factors previously associated with increased failure rates of traditional stents. MATERIALS AND METHODS: Patients undergoing placement of the metallic Resonance® stent for malignant ureteral obstruction at an academic referral center were identified retrospectively. Stent failure was defined as unplanned stent exchange or nephrostomy tube placement for signs or symptoms of recurrent ureteral obstruction (recurrent hydroureteronephrosis or increasing creatinine). Predictors of time to stent failure were assessed using Cox regression. RESULTS: A total of 37 stents were placed in 25 patients with malignant ureteral obstruction. Of these stents 12 (35%) were identified to fail. Progressive hydroureteronephrosis and increasing creatinine were the most common signs of stent failure. Three failed stents had migrated distally and no stents required removal for recurrent infection. Patients with evidence of prostate cancer invading the bladder at stent placement were found to have a significantly increased risk of failure (HR 6.50, 95% CI 1.45-29.20, p = 0.015). Notably symptomatic subcapsular hematomas were identified in 3 patients after metallic stent placement. CONCLUSIONS: Failure rates with a metallic stent are similar to those historically observed with traditional polyurethane based stents in malignant ureteral obstruction. The invasion of prostate cancer in the bladder significantly increases the risk of failure. Patients should be counseled and observed for subcapsular hematoma formation with this device.

Pretreatment expectations of patients undergoing robotic assisted laparoscopic or open retropubic radical prostatectomy.

PURPOSE: We previously found that patients undergoing robotic assisted laparoscopic radical prostatectomy vs radical retropubic prostatectomy had a higher likelihood of not being satisfied, independent of side effect profile. We hypothesized that differential preoperative expectations might contribute to this finding. In the current study we compared expectations of patients undergoing robotic assisted laparoscopic radical prostatectomy vs radical retropubic prostatectomy. MATERIALS AND METHODS: A questionnaire on expectations regarding recovery was administered to 171 patients electing to undergo robotic assisted laparoscopic radical prostatectomy or radical retropubic prostatectomy from 2008 to 2010. We prospectively collected data on patient expectations before surgery. Differences between patients undergoing robotic assisted laparoscopic radical prostatectomy vs radical retropubic prostatectomy were assessed with adjusted proportional odds models. RESULTS: Patients who underwent robotic assisted laparoscopic radical prostatectomy (97) did not differ significantly from those treated with radical retropubic prostatectomy (74) in age, race, income, time between survey and surgery, and prostate specific antigen (p ≥0.4). Patients who underwent radical retropubic prostatectomy had significantly higher clinical stage and Gleason grade disease (p ≤0.007). After adjusting for socioeconomic factors, clinical stage and grade on multivariate analysis, patients who underwent robotic assisted laparoscopic radical prostatectomy expected a significantly shorter length of stay (OR 0.07, p <0.001) and earlier return to physical activity (OR 0.36, p = 0.005). The choice of robotic assisted laparoscopic radical prostatectomy (OR 0.41, p = 0.012), younger age (OR 0.49, p = 0.001) and higher preoperative International Index of Erectile Function-5-item version score (OR 0.60, p = 0.017) were independently associated with the expectation of earlier return of erections but not of continence on multivariate analysis. CONCLUSIONS: The body of evidence surrounding robotic assisted laparoscopic radical prostatectomy supports shorter hospitalization but there is no conclusive evidence that the robotic approach results in earlier return to physical activity or improved disease specific outcomes. Nonetheless we found that patients who underwent robotic assisted laparoscopic radical prostatectomy had higher expectations regarding these outcomes, particularly that of erectile function recovery, than did their radical retropubic prostatectomy counterparts.

Utilization trends at a multidisciplinary prostate cancer clinic: initial 5-year experience from the Duke Prostate Center.

PURPOSE: The multidisciplinary approach is becoming increasingly encouraged but little is known about the multidisciplinary experience compared to routine care. For patients with prostate cancer the goal is to provide evaluations by urologists, medical and radiation oncologists at a single visit. Although additional resources are required, this strategy may enhance the overall health care experience. We compared utilization determinants between a multidisciplinary and a urology prostate cancer clinic at Duke University Medical Center and identified factors associated with pursuing treatment at the university medical center for multidisciplinary clinic patients. MATERIALS AND METHODS: We retrospectively analyzed data on patients referred for primary prostate cancer treatment evaluation at Duke University Medical Center from 2005 to 2009. Comparisons between 701 multidisciplinary clinic and 1,318 urology prostate cancer clinic patients were examined with the rank sum and chi-square tests. Predictive factors for pursuing treatment at the university medical center were assessed using multivariate adjusted logistic regression. RESULTS: Compared to patients at the urology prostate cancer clinic those at the multidisciplinary clinic were more likely to be younger and white, have a higher income and travel a longer distance for evaluation. Of multidisciplinary clinic patients 58% pursued primary treatment at the university medical center. They were more likely to be younger, black and physician referred, have a lower income and reside closer to the medical center. Factors predictive of pursuing treatment at the medical center included high risk disease and physician referral. Factors predictive of not receiving care at the university medical center were income greater than $40,000 and a distance traveled of greater than 100 miles. CONCLUSIONS: A different patient demographic is using the multidisciplinary approach. However, when treatment is pursued at the institution providing multidisciplinary services, the patient demographic resembles that of the treating institution.

Predicting participation in and successful outcome of a penile rehabilitation programme using a phosphodiesterase type 5 inhibitor with a vacuum erection device after radical prostatectomy.

UNLABELLED: Study Type--Therapy (case series) Level of Evidence 4. What's known on the subject? and What does the study add? The role of the vacuum erection device (VED) has increased with its use in combined therapy with a phosphodiesterase type 5 inhibitor (PDE5i) for penile rehabilitation after radical prostatectomy (RP) and radiotherapy. The advantages of the VED are non-invasive, cost-effective, and a possibility of preventing shrinkage of penis length. Albeit current widespread use of penile rehabilitation programmes for post-RP erectile dysfunction, independent predictors for the rehabilitation participants, as well as for its treatment success have not been fully investigated. In the present study, we have added several new predictors for rehabilitation participation, e.g. African-Americans and higher preoperative sexual function. Conversely, higher preoperative PSA concentrations and the presence of positive surgical margins were predictors for avoidance of rehabilitation. Notably, there was a primary surgeon difference, which had a trend for predicting outcome of the rehabilitation among the participants, implying their surgical technique and follow-up might influence success of the rehabilitation. OBJECTIVES: • To investigate baseline demographic and clinicopathological characteristics of men who participate in our penile rehabilitation programme after radical prostatectomy (RP). • To determine predictors for participation in rehabilitation, as well as successful rehabilitation outcome using multivariable logistic regression analyses. PATIENTS AND METHODS: • We analysed data on 2345 consecutive patients who underwent RP between 2001 and 2009 in our institution. • The decision to participate in penile rehabilitation using phosphodiesterase type 5 inhibitor (PDE5i) with a vacuum erection device (VED) was based on the patient's choice after post-RP discussions. • Rehabilitation success was defined using the following criteria: (i) patients who continued the penile rehabilitation programme and did not switch treatment from PDE5i to other erectile aids, (ii) success was noted in men who had an Expanded Prostate Cancer Index Composite (EPIC) sexual function (SF) score of >75% of the patient's baseline EPIC score, and (iii) patients who answered that they achieved adequate erections with a PDE5i. • Logistic regression analysis was used to identify factors associated with treatment participation and its success. RESULTS: • Of 676 patients, 354 (53.2%) men participated in a penile rehabilitation programme. Among 329 rehabilitation participants with available data, 96 (29.2%) had treatment success. • In multivariable regression analysis, African-Americans (odds ratio [OR] 3.47, P < 0.001), and higher preoperative SF (OR 1.02, P < 0.001) were associated with participation in rehabilitation. • Higher preoperative PSA concentration (OR 0.50, P = 0.004) and presence of positive surgical margins (OR 0.68, P = 0.042) were found to be independent predictors for non-participation in the rehabilitation. • For rehabilitation outcomes, being older at surgery (OR 0.93, P = 0.001) and adjuvant therapy (OR 0.34, P = 0.047) had a negative association with successful outcome. • There was a trend in the relationship between primary surgeon and rehabilitation success (OR 1.05, P = 0.053) CONCLUSIONS: • Those patients who have risk factors, e.g. adverse prostate cancer features, need to be carefully counselled and encouraged to participate in the penile rehabilitation programme. • Clinicians could lead patients toward successful outcomes if appropriate surgical techniques and rehabilitation are provided.

Association between preoperative erectile dysfunction and prostate cancer features--an analysis from the Duke Prostate Center Database.

INTRODUCTION: Erectile dysfunction (ED) is related to several co-morbidities including obesity, metabolic syndrome, cigarette smoking, and low testosterone, all of which have been reported to be associated with adverse prostate cancer features. AIM: To examine whether preoperative ED has a relationship with adverse prostate cancer features in patients who underwent radical prostatectomy (RP). METHODS: We analyzed data from our institution on 676 patients who underwent RP between 2001 and 2010. Crude and adjusted logistic regression models were used to investigate the association between preoperative ED and several pathological parameters. The log-rank test and multivariate proportional hazards model were conducted to determine the association of preoperative ED with biochemical recurrence (BCR). MAIN OUTCOME MEASURES: The expanded prostate cancer index composite (EPIC) instrument was used to evaluate preoperative erectile function (EF). Preoperative normal EF was defined as EPIC-SF ≥ 60 points while ED was defined as preoperative EPIC-SF lower than 60 points. RESULTS: Preoperatively, a total of 343 (50.7%) men had normal EF and 333 (49.3%) men had ED. After adjusting for covariates, preoperative ED was identified a risk factor for positive extracapsular extension (OR 1.57; P = 0.029) and high percentage of tumor involvement (OR 1.56; P = 0.047). In a Kaplan-Meier curve, a trend was identified that patients with ED had higher incidence of BCR than men with normal EF (P = 0.091). Moreover, using a multivariate Cox model, higher preoperative EF was negatively associated with BCR (HR 0.99; P = 0.014). CONCLUSIONS: These results suggest that the likelihood for adverse pathological outcomes as well as BCR following prostatectomy is higher among men with preoperative ED, though these results require validation in larger datasets. The present study indicates that preoperative ED might be a surrogate for adverse prostate cancer outcomes following RP.

Preoperative predictors of pathologic stage T2a in low-risk prostate cancer: implications for focal therapy.

OBJECTIVE: To assess preoperative parameters that may be predictive of pathologic stage T2a disease in low-risk prostate cancer patients. METHODS: Data from a cohort of 1,495 consecutive men with low-risk prostate cancer who underwent a radical prostatectomy between 1993 and 2009 were evaluated. Preoperative parameter assessment focused on age, race, clinical stage, diagnostic PSA level, biopsy tumor laterality and diagnostic Gleason score. Preoperative parameters were analyzed by univariate and multivariate methods. Kaplan-Meier method was used to evaluate the biochemical disease-free survival. RESULTS: Among the 1,495 men, 236 (15.8%) had pT2a disease. In univariate analysis, biopsy tumor unilaterality (p < 0.001), diagnostic PSA ≤ 4 ng/ml (p < 0.001) and non-African-American race (p = 0.009) were significant variables. In multivariate analysis, biopsy tumor laterality (OR 0.377; p < 0.001), diagnostic PSA ≤ 4 ng/ml (OR 0.621; p = 0.002) and race (OR 0.583; p = 0.029) were independent predictors. Low-risk patients with pT2a disease showed a better PSA recurrence-free survival rate, compared with men with >pT2a diseases (p = 0.012). CONCLUSIONS: Biopsy tumor unilaterality, diagnostic PSA ≤ 4 ng/ml and race are independent predictors of pT2a in low-risk prostate cancer. These three preclinical variables may be a useful reference to begin the selection process for focal therapy in men with low-risk prostate cancer.

Association of prostate-specific antigen doubling time and cancer in men undergoing repeat prostate biopsy.

OBJECTIVES: To analyze the association between prostate-specific antigen doubling time with prostate cancer risk and grade among men with prostate-specific antigen levels ≥4.0 ng/mL undergoing repeat prostate biopsy. METHODS: A total of 286 patients with prostate-specific antigen ≥4 ng/mL and available prostate-specific antigen doubling time data, who underwent repeat prostate biopsy from 1996-2009, were included in this analysis. Prostate-specific antigen doubling time was divided into three groups: >9 years, 3-9 years and <3 years. Multivariate analyses of prostate-specific antigen doubling time with cancer risk and grade (≤3 + 4 vs ≥4 + 3) were carried out using logistic regression adjusting for prebiopsy prostate-specific antigen, race, age, digital rectal examination, year of biopsy and number of prior negative biopsies. RESULTS: The median prostate-specific antigen doubling time before biopsy was 4.5 years (interquartile range = 2.5-10). Shorter prostate-specific antigen doubling time was associated with higher prostate-specific antigen (P < 0.001), but it was unrelated to age, digital rectal examination or race. Shorter prostate-specific antigen doubling time as a continuous variable was associated with greater prostate cancer risk in both uni- (hazard ratio = 0.99, 95% confidence interval = 0.98-0.99, P = 0.001) and multivariate analysis (hazard ratio = 0.99, 95% confidence interval = 0.98-0.99, P = 0.004). The prevalence of cancer among prostate-specific antigen doubling time groups (>9, 3-9, <3 years) was 17%, 37% and 40%, respectively. Shorter prostate-specific antigen doubling time groups were associated with higher cancer risk (P = 0.001). Stratified by grade, short prostate-specific antigen doubling time as a continuous variable significantly predicted both low- (P = 0.010) and high-grade disease (P = 0.049). The inclusion of prostate-specific antigen doubling time groups in a multivariate model to predict biopsy positivity increased its accuracy from 0.69 to 0.74. CONCLUSION: Prostate-specific antigen doubling time seems to provide further cancer risk assessment in men undergoing repeat biopsy for prostate-specific antigen ≥4.0 ng/mL. If validated in future studies, the present findings support the use of prostate-specific antigen doubling time in the risk stratification of this patient population.

Inclusion of nonrandomized studies of interventions in systematic reviews of interventions: updated guidance from the Agency for Health Care Research and Quality Effective Health Care program.

OBJECTIVES: We developed guidance to inform decisions regarding the inclusion of nonrandomized studies of interventions (NRSIs) in systematic reviews (SRs) of the effects of interventions. STUDY DESIGN AND SETTING: The guidance workgroup comprised SR experts and used an informal consensus generation method. RESULTS: Instead of recommending NRSI inclusion only if randomized controlled trials (RCTs) are insufficient to address the SR key question, different topics may require different decisions regarding NRSI inclusion. We identified important considerations to inform such decisions from topic refinement through protocol development. During topic scoping and refinement, considerations were related to the clinical decisional dilemma, adequacy of RCTs to address the key questions, risk of bias in NRSIs, and the extent to which NRSIs are likely to complement RCTs. When NRSIs are included, during SR team formation, familiarity with topic-specific data sources and advanced analytic methods for NRSIs should be considered. During protocol development, the decision regarding NRSI inclusion or exclusion should be justified, and potential implications explained. When NRSIs are included, the protocol should describe the processes for synthesizing evidence from RCTs and NRSIs and determining the overall strength of evidence. CONCLUSION: We identified specific considerations for decisions regarding NRSI inclusion in SRs and highlight the importance of flexibility and transparency.

The association of diabetes mellitus and high-grade prostate cancer in a multiethnic biopsy series.

OBJECTIVE: To analyze the association of diabetes mellitus (DM) with risk of prostate cancer and cancer grade among men undergoing prostate biopsy and to analyze how obesity and race modify these associations. MATERIALS AND METHODS: Retrospective analysis of 998 men from the Durham VA undergoing first prostate biopsy between 2001 and 2009 with complete data available. History of DM was determined by chart review. Patients' characteristics at biopsy were analyzed with chi-square and ranksum. Multivariable analyses of DM and risk of cancer and cancer grade were done using logistic regression adjusting for PSA, body mass index, race, age, year, and digital rectal exam. RESULTS: At biopsy, 284 (28%) men had DM. DM was associated with African American (AAM; p = 0.010) and higher BMI (p < 0.001). DM was not associated with prostate cancer risk on either bivariate (p = 0.600) or multivariate analysis (p = 0.485). Similar results were found after stratification by race and obesity. In multivariable analysis, DM was associated with greater risk of high-grade disease (RR = 2.13, p = 0.024). The association was stronger among obese men (RR = 3.84, p = 0.020) and null in non-obese subjects (RR = 1.39, p = 0.460). After further stratification by race, DM was associated with high-grade disease only in obese Caucasian men (CM; RR = 5.81, p = 0.025) but not in obese AAM. DM was not associated with risk of low-grade disease in all men together or after stratification by obesity or race. CONCLUSION: History of DM was associated with greater risk of high-grade disease. The association was strongest among obese CM suggesting the effect of DM on high-grade prostate cancer is modified by race and obesity.

Risk of death from prostate cancer after radical prostatectomy or brachytherapy in men with low or intermediate risk disease.

PURPOSE: Radical prostatectomy and brachytherapy are widely used treatments for favorable risk prostate cancer. We estimated the risk of prostate cancer specific mortality following radical prostatectomy or brachytherapy in men with low or intermediate risk prostate cancer using prospectively collected data. MATERIALS AND METHODS: The study cohort comprised 5,760 men with low risk prostate cancer (prostate specific antigen 10 ng/ml or less, clinical category T1c or 2a and Gleason score 6 or less), and 3,079 with intermediate risk prostate cancer (prostate specific antigen 10 to 20 ng/ml, clinical category T2b or T2c, or Gleason score 7). Competing risks multivariable regression was performed to assess the risk of prostate cancer specific mortality after radical prostatectomy or brachytherapy, adjusting for age, year of treatment, cardiovascular comorbidity and known prostate cancer prognostic factors. RESULTS: After a median followup of 4.2 years (IQR 2.0-7.4) for low risk and 4.8 years (IQR 2.2-8.1) for intermediate risk men, there was no significant difference in the risk of prostate cancer specific mortality among low risk (adjusted hazard ratio 1.62, 95% CI 0.59-4.45, p = 0.35) or intermediate risk men (AHR 2.30, 95% CI 0.95-5.58, p = 0.07) treated with brachytherapy compared with radical prostatectomy. The only factor associated with an increased risk of prostate cancer specific mortality (AHR 1.05, 95% CI 1.01-1.10, p = 0.03) was increasing age at treatment in intermediate risk men. CONCLUSIONS: The risk of prostate cancer specific mortality in men with low or intermediate risk prostate cancer was not significantly different following radical prostatectomy vs brachytherapy.

Factors predicting early and late phase decline of sexual health-related quality of life following radical prostatectomy.

INTRODUCTION: The association between early and late phase sexual health-related quality of life (HRQoL) following radical prostatectomy (RP) is unclear. Moreover, factors that predict either early or late sexual HRQoL decline have not been fully investigated. AIM: The aim of this study was to evaluate the correlation between early and late phase sexual HRQoL decline, and identify clinical parameters that predict substantial sexual HRQoL decline after surgery in the early phase (3 months) and late phase (20 months) following RP. METHODS: We analyzed data on 2,345 consecutive patients who underwent radical retropubic prostatectomy, radical perineal prostatectomy, or robotic-assisted laparoscopic prostatectomy between 2001 and 2009 from the Duke Prostate Center database. MAIN OUTCOME MEASURE: Sexual HRQoL was assessed using the Expanded Prostate Cancer Index Composite instrument at baseline, early and late phase after surgery. The Spearman rank test was used to calculate correlation coefficients between early and late phase sexual HRQoL decline. Logistic regression analysis was performed to identify factors associated with substantial sexual HRQoL decline during both phases. RESULTS: Of 406 men who met our criteria, 217 (53.5%) men had normal erectile function, whereas 189 (46.5%) men had erectile dysfunction at baseline. Declines of sexual HRQoL during early phase had a significant association with that of a decline during late phase (r = 0.48, P < 0.001). In logistic regression, older age at surgery (odds ratio [OR], 1.06; P = 0.007 and OR, 1.08; P = 0.001), African-American race (OR, 4.32; P = 0.001 and OR, 3.13; P = 0.017), and overall comorbidity (OR, 1.43; P = 0.072 and OR, 1.72; P = 0.010) were consistently associated with substantial decline of sexual HRQoL in both early and late phases. CONCLUSIONS: Sexual HRQoL at early and late phases after RP were strongly correlated. Additionally, several factors were identified to be a predictor for decline of sexual HRQoL. Our findings may be used to advise patients who possess aforementioned risk factors during both phases.

Factors affecting patient radiation exposure during percutaneous nephrolithotomy.

PURPOSE: We identified patient and stone characteristics that may contribute to increased radiation exposure during percutaneous nephrolithotomy and offer technique modifications to limit the radiation dose. MATERIAL AND METHODS: We reviewed the records of 96 patients who underwent percutaneous nephrolithotomy in the last 2 years. The effective radiation dose was calculated using accepted conversion tables. We performed multivariate linear regression to determine the association of the effective radiation dose with specific patient, stone and procedural characteristics. RESULTS: Mean±SD patient age was 51.5±13.4 years and 62.5% of the patients were female. Median body mass index was 32.0±9.7 kg/m2 (range 16.2 to 59.6) and the median stone burden was 4 cm2. Increased body mass index (p<0.001), higher stone burden (p=0.013), stone nonbranched configuration (p=0.002) and a greater number of percutaneous access tracts (p=0.040) were significantly associated with an increased effective radiation dose. Specifically obese patients with a body mass index of 30 to 39.9 kg/m2 had a more than 2-fold increase in the mean adjusted effective radiation dose and morbidly obese patients with a body mass index of 40 kg/m2 or greater had a greater than 3-fold increase vs that in normal weight patients with a body mass index of less than 25 kg/m2 (6.49 and 9.13 mSv, respectively, vs 2.66, p<0.001). Other stone specific parameters, including site and composition, percutaneous access site and estimated blood loss were not associated with the effective radiation dose. CONCLUSIONS: Patients with higher body mass index, greater stone burden, nonbranched stones and multiple nephrostomy access tracts are at risk for increased radiation exposure during percutaneous nephrolithotomy. Urologists must seek alternative strategies to minimize radiation exposure, such as tighter collimation to the region of interest, judicious use of magnification and the acquisition of as few images as possible during stone removal.

Multicenter clinical validation of PITX2 methylation as a prostate specific antigen recurrence predictor in patients with post-radical prostatectomy prostate cancer.

PURPOSE: Radical prostatectomy is potentially curative in patients with clinically localized prostate cancer. However, biochemical recurrence affects 15% to 30% of men who undergo radical prostatectomy. We previously reported the prognostic potential of PITX2 gene promoter methylation using conventional assays. In the current study we validated PITX2 methylation status as a biochemical recurrence predictor after radical prostatectomy using a novel microarray based platform in a multi-institutional setting. MATERIALS AND METHODS: PITX2 methylation status was assessed in formalin fixed, paraffin embedded prostatectomy tumor tissue samples from 476 patients from a total of 4 institutions on customized EpiChip PITX2 microarrays. Associations between PITX2 methylation and biochemical recurrence were assessed using the log rank test and Cox regression controlling for prostate cancer features. RESULTS: On multivariate analysis men with high methylation status were at significantly higher risk for biochemical recurrence than those with low methylation status (HR 3.0, 95% CI 2.0-4.5, p <10(-5)). The biochemical recurrence-free survival rate 5 years after surgery was 85% and 61% in the low and high methylation groups, respectively. In men with pathological Gleason 7 tumors the relative risk of biochemical recurrence was twice as high for high than for low PITX2 methylation (HR 2.0, 95% CI 1.2-3.3, p = 0.005). CONCLUSIONS: PITX2 methylation status assessed by EpiChip PITX2 identifies patients with prostate cancer who are most likely to have biochemical recurrence. This test independently adds to the prognostic information provided by standard clinicopathological analysis, improving prostatectomy case stratification into those at high and low risk for biochemical recurrence. This new clinical tool would be of particular benefit to assess intermediate risk cases (Gleason 7) in which risk stratification remains a challenge.