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We developed guidance to inform decisions regarding the inclusion of nonrandomized studies of interventions (NRSIs) in systematic reviews (SRs) of the effects of interventions.The guidance workgroup comprised SR experts and used an informal consensus generation method.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.We identified specific considerations for decisions regarding NRSI inclusion in SRs and highlight the importance of flexibility and transparency.

Introduction: Nonrandomized studies of interventions (NRSIs) are observational or experimental studies of the effectiveness and/or harms of interventions, in which participants are not randomized to intervention groups. There is increasingly widespread recognition that advancements in the design and analysis of NRSIs allow NRSI evidence to have a much more prominent role in decision making, and not just as ancillary evidence to randomized controlled trials (RCTs). Objective: To guide decisions about inclusion of NRSIs for addressing the effects of interventions in systematic reviews (SRs), this chapter updates the 2010 guidance on inclusion of NRSIs in Agency for Healthcare Research and Quality (AHRQ) Evidence-based Practice Center (EPC) SRs. The chapter focuses on considerations for decisions to include or exclude NRSIs in SRs. Methods: In November 2020, AHRQ convened a 20-member workgroup that comprised 13 members representing 8 of 9 AHRQ-appointed EPCs, 3 AHRQ representatives, 1 independent consultant with expertise in SRs, and 3 representatives of the AHRQ-appointed Scientific Resource Center. The workgroup received input from the full EPC Program regarding the process and specific issues through discussions at a virtual meeting and two online surveys regarding challenges with NRSI inclusion in SRs. One survey focused on current practices by EPCs regarding NRSI inclusion in ongoing and recently completed SRs. The other survey focused on the appropriateness, completeness, and usefulness of existing EPC Program methods guidance. The workgroup considered the virtual meeting and survey input when identifying aspects of the guidance that needed updating. The workgroup used an informal method for generating consensus about guidance. Disagreements were resolved through discussion. Results: We outline considerations for the inclusion of NRSIs in SRs of intervention effectiveness. We describe the strengths and limitations of RCTs, study design features and types of NRSIs, and key considerations for making decisions about inclusion of NRSIs (during the stages of topic scoping and refinement, SR team formation, protocol development, SR conduct, and SR reporting). We discuss how NRSIs may be applicable for the decisional dilemma being addressed in the SR, threats to the internal validity of NRSIs, as well as various data sources and advanced analytic methods that may be used in NRSIs. Finally, we outline an approach to incorporating NRSIs within an SR and key considerations for reporting. Conclusion: The main change from the previous guidance is the overall approach to decisions about inclusion of NRSIs in EPC SRs. Instead of recommending NRSI inclusion only if RCTs are insufficient to address the Key Question, this updated guidance handles NRSI evidence as a valuable source of information and lays out important considerations for decisions about the inclusion of NRSIs in SRs of intervention effectiveness. Different topics may require different decisions regarding NRSI inclusion. This guidance is intended to improve the utility of the final product to end-users. Inclusion of NRSIs will increase the scope, time, and resources needed to complete SRs, and NRSIs pose potential threats to validity, such as selection bias, confounding, and misclassification of interventions. Careful consideration must be given to both concerns.

Objectives Systematic reviews should provide balanced assessments of benefits and harms, while focusing on the most important outcomes. Selection of harms to be reviewed can be a challenge due to the potential for large numbers of diverse harms. Study Design and Setting A workgroup of methodologists from Evidence-based Practice Centers (EPCs) developed consensus-based guidance on selection and prioritization of harms in systematic reviews. Recommendations were informed by a literature scan, review of Evidence-based Practice Center reports, and interviews with experts in conducting reviews or assessing harms and persons representing organizations that commission or use systematic reviews. Results Ten recommendations were developed on selection and prioritization of harms, including routinely focusing on serious as well as less serious but frequent or bothersome harms; routinely engaging stakeholders and using literature searches and other data sources to identify important harms; using a prioritization process (formal or less formal) to inform selection decisions; and describing the methods used to select and prioritize harms. Conclusion We provide preliminary guidance for a more structured approach to selection and prioritization of harms in systematic reviews.

Importance Cutaneous chronic graft-vs-host disease (cGVHD) is common after allogeneic hematopoietic stem cell transplant and is often associated with poor patient outcomes. A reliable and practical method for assessing disease severity and response to therapy among these patients is urgently needed. Objective To evaluate the interrater agreement and reliability of skin-specific and range of motion (ROM) variables of the 2014 National Institutes of Health (NIH) response criteria for cGVHD and a skin sclerosis grading scale (SSG). Design, Setting, and Participants In this observational study performed at a single tertiary academic center, 6 academic blood and marrow transplant specialists and 4 medical dermatologists examined 8 patients with diagnosed cutaneous cGVHD on July 10, 2015. The patient cohort was enriched for patients with sclerotic features. Each patient was evaluated by using the skin-specific and ROM criteria of the 2014 NIH response criteria for cGVHD and an SSG ranging from 0 to 3. Each patient was also asked to complete quality-of-life scoring instruments. Interrater agreement and reliability were estimated by calculating the Krippendorff α and Cohen κ statistics. Data were analyzed from September 29, 2015, through November 22, 2018. Main Outcomes and Measures Estimation of interrater agreement by interclass coefficient (Krippendorff α and Cohen κ statistics) for the skin-specific and ROM components of the 2014 NIH Response Criteria for Chronic GVHD and for the SSG. Results The median age of the patients evaluated was 54 years (range, 46-58 years). Patients were predominantly male (6 [75%]). Six of the 8 patients had a predominantly sclerotic cutaneous phenotype. Interrater agreement among our experts was acceptable for NIH skin feature score (0.68; 95% CI, 0.30-0.86) and good for NIH ROM scoring (0.80; 95% CI, 0.68-0.86). Dermatologists had acceptable agreement for NIH skin GVHD score (0.69; 95% CI, 0.25-0.82) and skin feature score (0.78; 95% CI, 0.17-0.98), good agreement in ROM grading (0.85; 95% CI, 0.69-0.90), and near perfect agreement in identifying sclerosis (0.82; 95% CI, 0.27-0.97). Conclusions and Relevance Although dermatologists had acceptable agreement in NIH skin GVHD score and skin features score, near perfect agreement in identifying cutaneous sclerosis, better agreement in grading severity of cutaneous cGVHD, especially in the intermediate grades, appears to be needed.

Background Rituximab is a promising steroid sparing agent used in the treatment of moderate to severe pemphigus vulgaris. Its exact place in the algorithm of pemphigus treatment, vis-a-vis other, conventional adjuvant therapy (CAT) is not known. Objective To describe and compare disease course outcomes and morbidity among patients with moderate to severe pemphigus who received rituximab therapy (RT) in addition to prednisone and CAT, versus those who were treated with prednisone and CAT alone. Methods A 16-year retrospective case control study was designed with adult patients who were seen at the Duke University Dermatology Immunodermatology clinic from 1999–2015, who had a diagnosis of pemphigus vulgaris, and required prednisone and at least 1 systemic CAT. All patients had at least 6 months follow up from the initial visit. Interventions included RT, systemic CAT, and prednisone. The main outcome measured was prednisone intake. Secondary outcomes were complete remission (CR) and partial remission (PR). Results 40 patients were included in the study. All initially received prednisone and at least 1 systemic CAT. 13/40 eventually went on to receive RT, while 27/40 remained on CAT (CAT-only). Patients in the RT group, pre-RT, had a median prednisone intake of 658.57 mg/month. Rituximab treatment significantly reduced this to 177.22 mg/month (p = 0.002). Median prednisone intake of the CAT-only group was 141.33 mg/month. This was significantly less than Pre-RT (p = 0.01) and on par with Post-RT intake (p = 0.58). 54% of patients in the RT group and 64% of those in the CAT-only group achieved CR. All patients in the RT group and 96% of those in the CAT-only group achieved at least PR. Conclusions 32.5% of our patients with moderate to severe pemphigus vulgaris failed prednisone and traditional CAT treatment and required rituximab therapy. Rituximab reduced the monthly prednisone intake in these patients by 73%. This suggests that a subset of patients with moderate to severe pemphigus may benefit from early institution of rituximab therapy. Rituximab significantly reduces the monthly prednisone requirement among CAT-resistant pemphigus vulgaris patients to levels on par with CAT-responsive patients.

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 χ2-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.

Introduction:The US Agency for Healthcare Research and Quality (AHRQ) Evidence-based Practice Center (EPC) program sponsors the development of systematic reviews to inform clinical policy and practice. The EPC program sought to better understand how health systems identify and use this evidence.Methods:Representatives from eleven EPCs, the EPC Scientific Resource Center, and AHRQ developed a semi-structured interview script to query a diverse group of nine Key Informants (KIs) involved in health system quality, safety and process improvement about how they identify and use evidence. Interviews were transcribed and qualitatively summarized into key themes.Results:All KIs reported that their organizations have either centralized quality, safety, and process improvement functions within their system, or they have partnerships with other organizations to conduct this work. There was variation in how evidence was identified, with larger health systems having medical librarians and central bureaus to gather and disseminate information and smaller systems having local chief medical officers or individual clinicians do this work. KIs generally prefer guidelines, especially those with treatment algorithms, because they are actionable. They like systematic reviews because they efficiently condense study results and reconcile conflicting data. They prefer information from systematic reviews to be presented as short digestible summaries with the full report available on demand. KIs preferred systematic reviews from reputable entities and those without commercial bias. Some of the challenges KIs reported include how to resolve conflicting evidence, the generalizability of evidence to local needs, determining whether the evidence is up-to-date, and the length of time required to generate reviews. The topics of greatest interest included predictive analytics, high-value care, advance care planning, and care coordination. To increase awareness of AHRQ EPC reviews, KIs suggest alerting people at multiple levels in a health-system when new evidence reports are available and making reports easier to find in common search engines.Conclusions:Systematic reviews are valued by health system leaders. To be most useful they should be easy to locate and available in different formats targeted to the needs of different audiences.

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 (β: 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.

Statins are associated with lower PSA levels. As PSA is the primary method for prostate cancer (PC) screening, this confounds any associations between statins and risk of being diagnosed with PC. Thus, we examined the association between statins and cancer and high-grade cancer in REDUCE, where biopsies were largely PSA-independent.Post-hoc secondary analysis of REDUCE, which was a prospective multinational randomized controlled trial of dutasteride vs placebo for 4 years among men aged 50-75 years with PSA of 2.5-10.0 ng ml(-1) and a negative biopsy at baseline, and included PSA-independent biopsies mandated at 2- and 4-years. Analyses were limited to men who underwent at least one biopsy while under study (n=6729). The association between baseline statin use and risk of overall, high-grade (Gleason ≥ 7) or low-grade (Gleason ≤ 6) PC vs no cancer was examined using multinomial logistic regression adjusting for age, race, baseline PSA, prostate volume, rectal examination findings, body mass index (BMI), comorbidities, smoking, alcohol intake and treatment arm.Of 6729 men who had at least one biopsy while on study, 1174 (17.5%) were taking a statin at baseline. Men taking statins were older, had lower PSA levels, higher BMI values and lower serum testosterone and dihydrotestosterone levels, though differences, were slight. Statin use was not associated with overall PC diagnosis (multivariable OR 1.05, 95% CI 0.89-1.24, P=0.54). When stratified by grade, statin use was not associated with low-grade (multivariable OR 1.03, 95% CI 0.85-1.25, P=0.75) or high-grade cancer (multivariable OR 1.11, 95% CI 0.85-1.45, P=0.46). The major limitation is the inclusion of only men with a negative baseline biopsy.Among men with a negative baseline biopsy and follow-up biopsies largely independent of PSA, statins were not associated with cancer or high-grade cancer.

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.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.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 p0.05). 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.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.

Prostate cancer is the most common cancer among men. The prospective discrimination of aggressive and clinically insignificant tumors still poses a significant and, as yet, unsolved problem. PITX2 DNA methylation is a strong prognostic biomarker in prostate cancer. Recently, a diagnostic microarray for prostate cancer prognosis based on PITX2 methylation has been developed and validated. Because this microarray requires nonstandard laboratory equipment, its use in a diagnostic setting is limited. This study aimed to develop and validate an alternative quantitative real-time PCR assay for measuring PITX2 methylation that can easily be established in clinical laboratories, thereby facilitating the implementation of this biomarker in clinical practice. A methylation cut-off for patient stratification was established in a training cohort (n = 157) and validated in an independent test set (n = 523) of men treated with radical prostatectomy. In univariate Cox proportional hazards analysis, PITX2 hypermethylation was a significant predictor for biochemical recurrence (P < 0.001, hazard ratio = 2.614). Moreover, PITX2 hypermethylation added significant prognostic information (P = 0.003, hazard ratio = 1.814) to the Gleason score, pathological T stage, prostate-specific antigen, and surgical margins in a multivariate analysis. The clinical performance was particularly high in patients at intermediate risk (Gleason score of 7) and in samples containing high tumor cell content. This assay might aid in risk stratification and support the decision-making process when determining whether a patient might benefit from adjuvant treatment after radical prostatectomy.

Changes in sexual bother (SB) following radical prostatectomy (RP) negatively affect health-related quality of life (HRQoL) of prostate cancer survivors. However, post-operative SB tends to be neglected whereas sexual function (SF) is thoroughly assessed in clinical practice and few studies have focused on and evaluated patients' SB. We retrospectively reviewed 2 345 consecutive patients who underwent RP between 2001 and 2009 at a single institution. SF and SB were assessed using Expanded Prostate Cancer Index Composite (EPIC) questionnaires. We stratified our cohort by SB recovery and post-operative SF status, including a subset of men who recovered SB despite persistent post-RP sexual dysfunction. Multivariable logistic regression analyses were conducted to identify factors for men who have SB recovery. Of 319 eligible patients, 133 (41.7%) recovered their SB at a mean of 20 months after RP. Among the 133 men who demonstrated SB recovery, 109 had post-operative sexual dysfunction. Patients with SB recovery despite post-RP sexual dysfunction were more likely to be old (p = 0.004), to have higher clinical T stage (p < 0.001), to have more non-nerve-sparing RP (p < 0.001), to have lower pre-operative EPIC-SF/SB scores (p < 0.001), to have more extracapsular extension (p = 0.031) and to be PDE5i non-users after surgery (p < 0.001). In multivariable analysis, predictors for this subset were lower comorbidity (OR 0.62, p = 0.043), higher clinical cancer stage (OR 2.35, p = 0.026), worse pre-operative SF (OR 0.98, p = 0.010), SB (OR 0.98, p < 0.010) and no PDE5i use (OR 0.37, p = 0.002); age was not related (OR 0.99, p = 0.555). As SB can influence patients' overall HRQoL, expectations of SB recovery should be provided to patients in the same way that SF recovery is presented. This study may help clinicians to discuss SB with patients and assess their potential for SB recovery following RP.

• The Agency for Healthcare Research and Quality Evidence-based Practice Center program recently published a methods white paper on the effectivehealthcare.ahrq.gov web site which focused on a preliminary exploration of the use of text-mining in evidence synthesis.

Active surveillance (AS) is increasingly utilized in low-risk prostate cancer (PC) patients. Although black race has traditionally been associated with adverse PC characteristics, its prognostic value for patients managed with AS is unclear.A retrospective review identified 145 patients managed with AS at the Duke Prostate Center from January 2005 to September 2011. Race was patient-reported and categorized as black, white or other. Inclusion criteria included PSA10 ng ml(-1), Gleason sum ≤ 6, and ≤ 33% of cores with cancer on diagnostic biopsy. The primary outcome was discontinuation of AS for treatment due to PC progression. In men who proceeded to treatment after AS, the trigger for treatment, follow-up PSA and biopsy characteristics were analyzed. Time to treatment was analyzed with univariable and multivariable Cox proportional hazards models and also stratified by race.In our AS cohort, 105 (72%) were white, 32 (22%) black and 8 (6%) another race. Median follow-up was 23.0 months, during which 23% percent of men proceeded to treatment. The demographic, clinical and follow-up characteristics did not differ by race. There was a trend toward more uninsured black men (15.6% black, 3.8% white, 0% other, P = 0.06). Black race was associated with treatment (hazard ratio (HR) 2.93, P = 0.01) as compared with white. When the analysis was adjusted for socioeconomic and clinical parameters at the time of PC diagnosis, black race remained the sole predictor of treatment (HR 3.08, P = 0.01). Among men undergoing treatment, the trigger was less often patient driven in black men (8 black, 33 white, 67% other, P = 0.05).Black race was associated with discontinuation of AS for treatment. This relationship persisted when adjusted for socioeconomic and clinical parameters.

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.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.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.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.

Objective To analyze the serum androgen concentrations in men who underwent an initial prostate biopsy, focusing on the percent-free testosterone (%FT) as a predictor of low- and high-grade prostate cancer (PCa). Most studies have suggested that the absolute serum testosterone and free testosterone levels are not related to PCa risk. However, to date, the concurrent effect of free and total testosterone levels has not been evaluated. In particular, the association of the %FT (free testosterone/total testosterone) with PCa risk has not been explored. Methods From 2006 to 2010, we collected data on 812 white Italian men with no history of PCa who underwent 12-core biopsy. The testosterone, free testosterone, and %FT (free testosterone/total testosterone) were examined as predictors of low-grade (Gleason score of ≤6) and high-grade (Gleason score ≥7) PCa using crude and adjusted multinomial logistic regression analysis. Results On multivariate analysis, testosterone ( P ≥ .11) and free testosterone ( P ≥ .45) were not significantly associated with low- or high-grade PCa. A greater %FT level significantly predicted high-grade PCa on both crude ( P = .01) and multivariate ( P = .02) analysis but not low-grade PCa ( P ≥ .38). When examined in tertiles, men in the greatest %FT tertile had a significant twofold increased risk of high-grade PCa (odds ratio 2.04, 95% confidence interval 1.23-3.37, P = .005). Conclusion In white Italian men, a greater %FT level was associated with an increased risk of high-grade PCa on initial prostate biopsy. These findings suggest that a high %FT level, rather than the absolute androgen levels, might be associated with high-grade PCa. Additional studies are needed to confirm our findings.

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

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. Kimura M, Banez LL, Gerber L, Qi J, Tsivian M, Freedland SJ, Satoh T, Polascik TJ, Baba S, and Moul JW. Association between preoperative erectile dysfunction and prostate cancer features—An analysis from the Duke Prostate Center Database. J Sex Med 12;9:1174–1181.

Background: Coronary artery disease (CAD) and prostate cancer (PCa) are not only common diseases, but share many risk factors. To date, only a few studies have explored the relationship between CAD and PCa risk, with conflicting results. Methods: The four-year REDUCE study tested dutasteride 0.5 mg daily for PCa risk reduction in men with prostate specific antigen (PSA) of 2.5 to 10.0 ng/mL and a negative biopsy. Among men who underwent at least one on-study biopsy (n = 6,729; 82.8%), the association between CAD and overall PCa risk and disease grade was examined with logistic and multinomial logistic regression adjusting for clinicopathologic features, respectively. Results: Overall, 547 men (8.6%) had a history of CAD. Men with CAD were significantly older and had higher body mass index, PSA, and larger prostate volumes and were more likely to have diabetes, hypertension, and hypercholesterolemia and take aspirin and statins. On multivariate analysis, CAD was associated with a 35% increased risk of PCa diagnosis (OR = 1.35, 95% CI: 1.08–1.67, P = 0.007), while elevating risk of both low- (OR = 1.34, 95% CI: 1.05–1.73, P = 0.02) and high-grade disease (OR = 1.34, 95% CI: 0.95–1.88, P = 0.09). Conclusions: In a post hoc hypothesis developing secondary analysis of the REDUCE study, CAD was significantly associated with increased PCa diagnosis. Impact: If confirmed in other studies, this suggests CAD may be a novel PCa risk factor and suggests common shared etiologies. Whether lifestyle changes shown to reduce CAD risk (i.e., weight loss, exercise, cholesterol reduction, etc.) can reduce PCa risk, warrants further study. Cancer Epidemiol Biomarkers Prev; 21(4); 576–81. ©2012 AACR.

Thomas J-A II, Gerber L, Moreira DM, Hamilton RJ, Banez LL, Castro-Santamaria R, Andriole GL, Isaacs WB, Xu J, Freedland SJ (Durham VA Medical Center, Durham, NC, USA; Duke University School of Medicine, Durham, NC, USA; The Author Smith Institute for Urology, New Hyde Park, NY, USA; Memorial Sloan-Kettering Cancer Center, New York, NY, USA; GlaxoSmithKline, Research Triangle Park, NC, USA; Washington University School of Medicine, St. Louis, MO, USA; Johns Hopkins Hospital, Baltimore, MD, USA; Wake Forest University, Winston-Salem, NC, USA; and Duke University School of Medicine, Durham, NC, USA). Prostate cancer risk in men with prostate and breast cancer family history: results from the REDUCE study (R1). J Intern Med 2012; 272: 85–92. Background. To what degree the associations between PCa risk and family history of prostate cancer (PCa) and/or breast cancer (BCa) are attributable to screening biases is unclear. We examined these questions within the REDUCE study, where biopsies were largely independent of prostate specific antigen (PSA) minimizing screening biases. Methods. Data were from REDUCE, which tested dutasteride 0.5 mg daily for PCa risk reduction in men with PSA 2.5–10.0 ng mL−1 and a negative prestudy biopsy. Among men undergoing at least one on-study biopsy with complete data (n = 6415; 78.1%), the association between family history and PCa risk was tested using multivariate logistic regression adjusting for clinicodemographic characteristics. Results. A family history of PCa alone was associated with increased PCa diagnosis (OR: 1.47, 95%CI: 1.22–1.77). In North America, PCa family history was not related to PCa diagnosis (OR: 1.02, 95%CI: 0.73–1.44), whereas outside North America, PCa family history was significantly related to diagnosis (OR: 1.72, 95%CI: 1.38–2.15) (P-interaction = 0.01). A family history of both PCa and BCa (OR: 2.54, 95%CI: 1.72–3.75) but not BCa alone (OR: 1.04, 95%CI: 0.84–1.29) was associated with increased PCa risk versus no family history and irrespective of geographical region. Conclusions. In REDUCE, PCa family history was significantly related to PCa diagnosis, although only for men outside North America. The presence of both PCa and BCa family history significantly increased risk versus PCa family history alone, irrespective of geographical region. Ultimately, our observations may support the need for changes in how we address family history in terms of both risk of PCa diagnosis and general risk stratification.

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. 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. At biopsy, 284 (28%) men had DM. DM was associated with African American (AAM; p = 0.010) and higher BMI (p

A wide array of biomarkers is being investigated as predictors of prostate cancer (PCa) diagnosis and recurrence. We compared the expression of a small panel of these biomarkers as a function of race among men undergoing radical prostatectomy (RP). Prostate needle biopsy specimens from 131 patients treated with RP at the Durham Veterans Affairs Medical Center were hematoxylin and eosin stained and immunofluorescent assayed for α-methylacyl CoA racemase (AMACR), androgen receptor (AR) and Ki67. Proprietary image analysis was used to identify six biometric feature combinations that were significantly associated with progression in a previous study. Analysis of population characteristics, stratified by race, was performed using rank-sum and χ(2)-test. The effect of race on expression of these biomarker profiles was analyzed using multivariate linear regression. All six biomarker features were expressed at higher levels in black men than white men, with Norm AR (P=0.006) and Ki67 (P=0.02) attaining statistical significance. On multivariate analysis, all markers were expressed at higher levels in black men, with Norm AR (P=0.001), Ki67 (P=0.007) and Ki67/lum (P=0.022) reaching significance. These data support the hypothesis that PCa may be biologically more aggressive among black men.

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.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.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 (p0.001), 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, p0.001). Other stone specific parameters, including site and composition, percutaneous access site and estimated blood loss were not associated with the effective radiation dose.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.

Prostate growth is dependent on circulating androgens which can be influenced by hepatic function. Liver disease has been suggested to influence prostate cancer (CaP) incidence. However, the effect of hepatic function on CaP outcomes has not been investigated. A total of 1,181 patients who underwent radical prostatectomy (RP) between 1988 and 2008 at four Veterans Affairs hospitals that comprise the Shared Equal Access Regional Cancer Hospital (SEARCH) database and had available liver function test (LFT) data were included in the study. Independent associations of LFTs with unfavorable pathological features and biochemical recurrence were determined using logistic and Cox regression analyses. Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) levels were elevated in 8.2% and 4.4% of patients, respectively. After controlling for CaP features, logistic regression revealed a significant association between SGOT levels and pathological Gleason sum ≥7(4+3) cancer (odds ratio=2.12; 95% confidence interval=1.11-4.05; p=0.02). Mild hepatic dysfunction was significantly associated with adverse CaP grade but was not significantly associated with other adverse pathological features or biochemical recurrence in a cohort of men undergoing R. The effect of moderate to severe liver disease on disease outcomes in CaP patients managed non-surgically remains to be investigated.

Study Type – Diagnosis (exploratory cohort) Level of Evidence 2b OBJECTIVE To clarify the relationship between estimated blood loss (EBL) and biochemical recurrence, assessed by prostate-specific antigen (PSA) level, as blood loss is a long-standing concern associated with radical prostatectomy (RP), and no studies to date have examined the association between blood loss and cancer control. PATIENTS AND METHODS In all, 1077 patients were identified in the Shared Equal-Access Regional Cancer Hospital database who underwent retropubic RP (between 1998 and 2008) and had EBL and follow-up data available. We examined the relationship between EBL and recurrence using multivariate Cox regression analyses. RESULTS Increased EBL was correlated with PSA recurrence in a multivariate-adjusted model (P = 0.01). When analysed by 500-mL EBL categories, those with an EBL of

Preoperative prostate specific antigen is widely used to predict unfavorable pathological features and biochemical relapse after radical prostatectomy. Recent reports that hemodilution may be responsible for lower prostate specific antigen in obese men led to concerns that prostate specific antigen may be less effective for prognosticating in men with increased body mass index. We determined whether the clinical usefulness of prostate specific antigen is negatively impacted by obesity by examining its operating characteristics and predictive accuracy as a function of body mass index.We performed a multicenter retrospective analysis of the records of 11,705 men who underwent radical prostatectomy from 1988 to 2007 from Veterans Affairs hospitals of the Shared Equal Access Regional Cancer Hospital Database, the Duke Prostate Center and Johns Hopkins Hospital. ROC curve analysis, the concordance index and the test for interaction were used to compare the ability of prostate specific antigen to predict unfavorable tumor characteristics and biochemical recurrence across body mass index categories.There were no significant differences in the area under ROC curves across increasing body mass index categories for prostate specific antigen to predict pathological Gleason sum (7 or greater, 7 [4 + 3] or greater, or 8 or greater), positive surgical margins, extracapsular extension or seminal vesicle invasion in all 3 cohorts. There was no significant difference in prostate specific antigen accuracy to predict biochemical failure across increasing body mass index categories.In 3 cohorts of men treated with radical prostatectomy the ability of preoperative prostate specific antigen to predict adverse pathological features and posttreatment biochemical recurrence is not significantly affected by obesity. However, adjusting for obesity related hemodilution may still be required to properly interpret prostate specific antigen results in men with increased body mass index.

Obesity is associated with increased risk of positive surgical margins and prostate specific antigen (PSA) recurrence among men undergoing radical prostatectomy. To what degree positive margins contribute to poorer outcome is unclear. Thus, we sought to examine the association between body mass index (BMI) and more objective measures of tumor aggressiveness, tumor grade and size. We carried out a retrospective analysis of 2302 patients treated with radical prostatectomy at the Duke Prostate Center from 1988-2007. Tumor volume was calculated by multiplying prostate weight by percent of specimen involved with cancer. Associations between BMI and tumor volume and high-grade disease (Gleasonor=4+3) independent of pre-operative clinical characteristics of age, race, PSA, clinical stage, biopsy Gleason sum, and year of surgery were assessed using linear and logistic regression, respectively. Mean and median BMI among all subjects was 28.1 and 27.6 kg m(-2), respectively. Increased BMI was significantly associated with younger age (P0.001), black race (P0.001), more recent year of surgery (P0.001), and positive surgical margins (P0.001). After adjusting for multiple clinical pre-operative characteristics, higher BMI was associated with a greater percent of the prostate involved with cancer (P=0.003), increased tumor volume (P0.001), and high-grade disease (P=0.007). Men with a BMIor=35 kg m(2) had nearly 40% larger mean tumor volumes than normal weight men (5.1 versus 3.7 cc), after adjustment for multiple clinical characteristics. In this study, obese men undergoing radical prostatectomy had higher-grade and larger tumors, providing further evidence that obese men undergoing radical prostatectomy have more aggressive prostate cancers.

The literature contains conflicting data on preoperative predictors of estimated blood loss (EBL) at radical retropubic prostatectomy (RRP). We sought to examine preoperative predictors of EBL at the time of RRP among patients from the SEARCH database to lend clarity to this issue. A total of 1154 patients were identified in the SEARCH database who underwent RRP between 1988 and 2008 and had EBL data available. We examined multiple preoperative factors for their ability to predict EBL using multivariate linear regression analysis. Median EBL was 900 ml (s.d. 1032). The 25th and 75th percentile for EBL were 600 and 1500 ml, respectively. EBL increased significantly with increasing body mass index (BMI) and increasing prostate size and decreased with more recent year of RRP (all P0.001). The mean-adjusted EBL in normal-weight men (BMI25 kg/m(2)) was 807 ml compared to 1067 ml among severely obese men (BM Ior=35 kg/m(2)). Predicted EBL for men with the smallest prostates (20 g) was 721 ml, compared to 1326 ml for men with prostatesor=100 g. Finally, statistically significant differences between centers were observed, with mean-adjusted EBL ranging from 844 to 1094 ml. Both BMI and prostate size are predictors of increased EBL. Prostate size is of particular note, as a nearly twofold increased EBL was seen from the smallest (20 g) to the largest prostates (or=100 g). Over time, average EBL significantly decreased. Finally, significant differences in EBL were observed between centers. Patients with multiple risk factors should be forewarned they are at increased risk for higher EBL, which may translate into a greater need for blood transfusion.

Vascular endothelial growth factor (VEGF)-mediated angiogenesis is thought to play a critical role in tumor growth and metastasis. Consequently, anti-VEGF therapies are being actively investigated as potential anti-cancer treatments, either as alternatives or adjuncts to conventional chemo or radiation therapy. Among the techniques used to block the VEGF pathway are: 1) neutralizing monoclonal antibodies against VEGF or its receptor, 2) small molecule tyrosine kinase inhibitors of VEGF receptors, 3) soluble VEGF receptors which act as decoy receptors for VEGF, and 4) ribozymes which specifically target VEGF mRNA. Recent evidence from phase III clinical trials led to the approval of bevacizumab, an anti-VEGF monoclonal antibody, by the FDA as first line therapy in metastatic colorectal carcinoma in combination with other chemotherapeutic agents. However, may challenges still remain, and the role of anti-VEGF therapy in the treatment of other solid tumors remains to be elucidated. The aim of this article is to review the progress of clinical investigations involving VEGF inhibitors in the treatment of different types of solid tumors.

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.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.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).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.

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.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).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.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.

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.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.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 (β: 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.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.

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 11.6ng/mL (reference = 1.5-20.0ng/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.

To investigate racial differences in tumor burden (cancer volume, cancer percentage and cancer to PSA ratios) in a large cohort of men undergoing radical prostatectomy (RP).Demographic, clinical and pathological data of patients undergoing RP between 1993-2010 were reviewed and compared between African-American (AA) and non African-American (nAA) men. Further assessments of pathological tumor burden (estimated tumor volume, percent of cancer involvement, and estimated tumor volume/PSA ratios) were performed across Gleason score categories.Of 4157 patients in the analysis, 604 (14.5%) were AA. Overall, AA patients were younger, had higher Gleason scores, PSA levels and incidence of palpable disease (all P0.001). Despite comparable prostate weights (39.4 vs. 39.6 g), AA men had higher percent cancer involvement and estimated tumor volume (all P0.001) but similar estimated tumor volume/PSA ratios ( P0.05). When stratified by Gleason scores, prostate weights were comparable; however, estimated tumor volume, percent cancer involvement and estimated tumor volume/PSA ratios were higher in AA men with low grade (≤ 6) prostate cancer (PCa), similar in intermediate grade (7-8) and lower in high grade (9-10) PCa compared to nAA men.In this large series, AA patients had higher disease burden (estimated tumor volume, percent cancer involvement, estimated tumor volume/PSA ratios) compared to nAA but this association was especially pronounced in low grade (Gleason ≤ 6) cancers. These data depict a complex picture of relations between race and tumor burden across the spectrum of PCa aggressiveness. Further investigation is warranted to understand the mechanisms of racial disparities in PCa.

To assess preoperative parameters that may be predictive of pathologic stage T2a (pT2a) and pathologic Gleason score (pGS) ≤ 6 disease in low-risk prostate cancer patients considering active surveillance. A cohort of 1,495 men with low-risk prostate cancer between 1993 and 2009 was utilized. Preoperative assessment focused on patient age, race, diagnostic PSA level, clinical stage, diagnostic biopsy Gleason score, and prostate cancer laterality. Kaplan–Meier curves and a Cox regression model were used for analysis of PSA recurrence. Preoperative parameters were analyzed by univariate and multivariate logistic regression methods. Of 1,495 patients, 187 (12.5 %) were identified with pT2a and pGS ≤ 6 disease. Of the 187 men with pT2a and pGS ≤ 6 disease, only 6 (3.2 %) cases had PSA recurrence. Kaplan–Meier PSA recurrence-free survival curves identified a difference between prostate cancers with pT2a and pGS ≤ 6 and prostate cancers with >pT2a or pGS ≥ 7 disease (p = 0.002). Only biopsy tumor unilaterality (OR, 10.452; p ≤ 0.001) and low diagnostic PSA levels (OR, 0.887; p = 0.003) were independent predictors of prostate cancers with pT2a and pGS ≤ 6 disease on univariate and multivariate logistic regression. Biopsy tumor unilaterality and low diagnostic PSA levels are the independent predictors of pT2a and pGS ≤ 6 disease in low-risk prostate cancer patients. Unilateral cancer by prostate biopsy and low diagnostic PSA level may be the reference to improving the selection of appropriate candidates for active surveillance within a low-risk prostate cancer cohort.

To find the predictors of Gleason score upgrading in a cohort of low-risk prostate cancer patients, data were analyzed comprising 1,632 consecutive men with low-risk prostate cancer who underwent radical prostatectomy between 1993 and 2009. Assessment focused on preoperative parameters including patient age, race, diagnostic prostate-specific antigen (PSA) levels, clinical stage and biopsy Gleason score, along with pathological parameters including percentage of tumor involvement (PTI), tumor laterality, pathological stage, extra-capsular extension, seminal vesicle invasion, and surgical margins. These parameters were analyzed using univariate and multivariate methods. Kaplan–Meier curves compared differences in biochemical disease-free survival in men having cancers with and without Gleason score upgrading. Cases involving pathological Gleason score upgrading were identified in 723 (44.3 %) of 1,632 patients. Kaplan–Meier PSA recurrence-free survival curves showed a difference in outcome between men with and without Gleason score upgrading (p

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. Cancer 2013. © 2013 American Cancer Society.

Prostate-specific antigen (PSA) screening has increased the detection of small, organ-confined tumors, and studies suggest that these patients may have favorable outcomes following radical prostatectomy (RP). To date, there are limited data available on the outcomes of patients diagnosed with low PSA (≤ 4 ng/ml) who underwent RP. This study aimed to evaluate long-term oncological outcomes of patients undergoing RP with preoperative PSA2.5 and 2.5-4 ng/ml compared with PSA 4.1-10 ng/ml.Data were analyzed from 3,621 men who underwent RP between 1988 and 2010 at our institution. Patients were stratified into 3 PSA groups:2.5 ng/ml (n = 280), 2.5-4 ng/ml (n = 563), and 4.1-10 ng/ml (n = 2,778). Patient and disease characteristics were compared. Overall, biochemical disease-free (bDFS), and PCa-specific survivals were analyzed and compared between the groups. Multivariable analyses were conducted using proportional hazards model.Compared with the 4.1-10 ng/ml PSA group, Gleason score7, extracapsular extension, and non-organ-confined disease were less common in patients with PSA ≤ 4 ng/ml (all P0.001). The incidence of organ-confined disease was similar between the PSA2.5 and 2.5-4 ng/ml groups while perineural invasion (P = 0.050) and Gleason score ≥ 7 (P = 0.026) were more common in the 2.5-4 ng/ml PSA group. Estimated 10-year overall and PCa-specific survivals were comparable across all PSA groups, whereas bDFS was significantly lower in PSA 4.1-10 group (P0.001). bDFS was not statistically different between PSA2.5 and 2.5-4 groups (P = 0.300). 10-year bDFS were 59.0%, 70.1%, and 76.4% in PSA 4.1-10, 2.5-4, and2.5, respectively. For the PSA ≤ 4 ng/ml groups, age, race, margin status, pathologic stage, but not PSA were independent predictors of bDFS, whereas age, pathologic Gleason, and biochemical recurrence were associated with overall survival.Long-term oncological outcomes (overall, bDFS, PCa-specific survivals) of patients presenting with low PSA (≤ 4 ng/ml) were excellent in this study. Compared with PSA 4.1-10 ng/ml, patients presenting with PSA ≤ 4 ng/ml had better bDFS outcomes. However, there was no difference in long-term outcomes between PSA2.5 and 2.5-4 ng/ml.