Perceived barriers to the adoption of active surveillance in low-risk prostate cancer: a qualitative analysis of community and academic urologists.

BACKGROUND: Clinical practice guidelines recommend active surveillance as the preferred treatment option for low-risk prostate cancer, but only a minority of eligible men receive active surveillance, and practice variation is substantial. The aim of this study is to describe barriers to urologists' recommendation of active surveillance in low-risk prostate cancer and explore variation of barriers by setting. METHODS: We conducted semi-structured interviews among 22 practicing urologists, evenly distributed between academic and community practice. We coded barriers to active surveillance according to a conceptual model of determinants of treatment quality to identify potential opportunities for intervention. RESULTS: Community and academic urologists were generally in agreement on factors influencing active surveillance. Urologists perceived patient-level factors to have the greatest influence on recommendations, particularly tumor pathology, patient age, and judgements about the patient's ability to adhere to follow-up protocols. They also noted cross-cutting clinical barriers, including concerns about the adequacy of biopsy samples, inconsistent protocols to guide active surveillance, and side effects of biopsy procedures. Urologists had differing opinions on the impact of environmental factors, such as financial disincentives and fear of litigation. CONCLUSIONS: Despite national and international recommendations, both academic and community urologists note a variety of barriers to implementing active surveillance in low risk prostate cancer. These barriers will need to be specifically addressed in efforts to help urologists offer active surveillance more consistently.

Feasibility of a Weight Management Program Tailored for Overweight Men with Localized Prostate Cancer - A Pilot Study.

BACKGROUND: Overweight men with prostate cancer are more likely to suffer from recurrence and death following prostatectomy compared with healthy weight men. This study tested the feasibility of delivering a comprehensive program to foster weight loss before and weight maintenance after surgery in overweight men with localized prostate cancer. METHODS: Twenty overweight men scheduled for prostatectomy elected either the intervention (n = 15) or the nonintervention (n = 5). Anthropometrics, biomarkers, diet quality, nutrition literacy, quality of life, and long-term follow-up were assessed in both groups. RESULTS: The intervention led to 5.55 kg of weight loss including 3.88 kg of fat loss from baseline to surgery (mean = 8.3 weeks). The intervention significantly increased fiber, protein, fruit, nut, and vegetable intake; and decreased trans fats intake during weight loss. The intervention significantly reduced insulin, C-peptide, systolic blood pressure, leptin:adiponectin ratio, and visceral adiposity compared to the nonintervention. Post-surgically, weight loss was maintained. Changes in lipid profiles, nutrition literacy, and follow-up were not statistically significant in either group. CONCLUSION: Significant weight loss (≥5%) is feasible with a coaching intervention in overweight men preparing for prostatectomy and is associated with favorable cardiometabolic effects. This study is registered under NCT02252484 (www.clinicaltrials.gov).

GSK-3ß controls autophagy by modulating LKB1-AMPK pathway in prostate cancer cells.

BACKGROUND: Glycogen synthase kinase 3ß (GSK3B, GSK-3ß) is a multi-functional protein kinase involved in various cellular processes and its activity elevates after serum deprivation. We have shown that inhibition of GSK-3ß activity triggered a profound autophagic response and subsequent necrotic cell death after serum deprivation in prostate cancer cells. In this study, we dissected the mechanisms involved in GSK-3ß inhibition-triggered autophagy. METHODS: Prostate cancer PC-3 and DU145 cells were used in the study. Multiple GSK-3ß specific inhibitors were used including small chemicals TDZD8, Tideglusib, TWS119, and peptide L803-mts. Western blot assay coupled with phospho-specific antibodies were used in detecting signal pathway activation. ATP levels were assessed with ATPLite kit and HPLC methods. Autophagy response was determined by evaluating Microtubule-associated proteins 1A/1B light chain 3B (LC3B) processing and p62 protein stability in Western blot assays. Immunofluorescent microscopy was used to detect LKB1 translocation. RESULTS: Inhibition of GSK-3ß activity resulted in a significant decline of cellular ATP production, leading to a significant increase of AMP/ATP ratio, a strong trigger of AMP-activated protein kinase (AMPK) activation in prostate cancer PC-3 cells. In parallel with increased LC-3B biosynthesis and p62 protein reduction, the classical sign of autophagy induction, AMPK was activated after inhibition of GSK-3ß activity. Further analysis revealed that Liver kinase B1 (LKB1) but not Calcium/calmodulin-dependent protein kinase kinase ß (CaMKKß) is involved in AMPK activation and autophagy induction triggered by GSK-3ß inhibition. Meanwhile, GSK-3ß inhibition promoted LKB1 translocation from nuclear to cytoplasmic compartment and enhanced LKB1 interaction with its regulatory partners Mouse protein-25 (MO25) and STE20-related adaptor (STRAD). CONCLUSIONS: In conclusion, our data suggest that GSK-3ß plays an important role in controlling autophagy induction by modulating the activation of LKB1-AMPK pathway after serum deprivation.

Nanomicellar TGX221 blocks xenograft tumor growth of prostate cancer in nude mice.

BACKGROUND: Combination of androgen ablation along with early detection and surgery has made prostate cancer highly treatable at the initial stage. However, this cancer remains the second leading cause of cancer death among American men due to castration-resistant progression, suggesting that novel therapeutic agents are urgently needed for this life-threatening condition. Phosphatidylinositol 3-kinase p110ß is a major cellular signaling molecule and has been identified as a critical factor in prostate cancer progression. In a recent report, we established a nanomicelle-based strategy to deliver p110ß-specific inhibitor TGX221 to prostate cancer cells by conjugating the surface of nanomicelles with a RNA aptamer against prostate specific membrane antigen (PSMA) present in all clinical prostate cancers. In this study, we tested this nanomicellar TGX221 for its in vivo anti-tumor effect in mouse xenograft models. METHODS: Prostate cancer cell lines LAPC-4, LNCaP, C4-2 and 22RV1 were used to establish subcutaneous xenograft tumors in nude mice. Paraffin sections from xenograft tumor specimens were used in immunohistochemistry assays to detect AKT phosphorylation, cell proliferation marker Ki67 and proliferating cell nuclear antigen (PCNA), as well as 5-bromo-2-deoxyuridine (BrdU) incorporation. Quantitative PCR assay was conducted to determine prostate-specific antigen (PSA) gene expression in xenograft tumors. RESULTS: Although systemic delivery of unconjugated TGX221 significantly reduced xenograft tumor growth in nude mice compared to solvent control, the nanomicellar TGX221 conjugates completely blocked tumor growth of xenografts derived from multiple prostate cancer cell lines. Further analyses revealed that AKT phosphorylation and cell proliferation indexes were dramatically reduced in xenograft tumors received nanomicellar TGX221 compared to xenograft tumors received unconjugated TGX221 treatment. There was no noticeable side effect by gross observation or at microscopic level of organ tissue section. CONCLUSION: These data strongly suggest that prostate cancer cell-targeted nanomicellar TGX221 is an effective anti-cancer agent for prostate cancer.

A prospective study of erectile function after transrectal ultrasonography-guided prostate biopsy.

OBJECTIVE: To prospectively evaluate the effect of transrectal ultrasonography (TRUS)-guided prostate biopsy on erectile and voiding function at multiple time-points after biopsy. PATIENTS AND METHODS: All men who underwent TRUS-guided prostate biopsy completed a five-item version of the International Index of Erectile Function (IIEF-5) and the International Prostate Symptom Score (IPSS) before and at 1, 4 and 12 weeks after TRUS-guided biopsy. Statistical analyses used were a general descriptive analysis, continuous variables using a t-test and categorical data using chi-square analysis. A paired t-test was used to compare each patient's baseline score to their own follow-up survey scores. RESULTS: In all, 220 patients were enrolled with a mean age of 64.1 years and PSA level of 6.7 ng/dL. At initial presentation, 38.6% reported no erectile dysfunction (ED), 22.3% mild ED, 15.5% mild-to-moderate ED, 10% moderate ED, and 13.6% severe ED. On paired t-test there was a statistically significant reduction in IIEF-5 score at 1 week after biopsy compared with before biopsy (18.2 vs 15.5; P < 0.001). This remained significantly reduced at 4 (18.4 vs 17.3; P = 0.008) and 12 weeks (18.4 vs 16.9, P = 0.004) after biopsy. CONCLUSIONS: The effects of TRUS-guided prostate biopsy on erectile function have probably been underestimated. It is important to be aware of these transient effects so patients can be appropriately counselled. The exact cause of this effect is yet to be determined.

Modifier 22 on perioperative outcomes of robotic assisted laparoscopic prostatectomy.

INTRODUCTION: Robotic assisted laparoscopic prostatectomy (RALP) is a mainstay in the treatment of prostate cancer. Current procedure terminology (CPT) identifies a case that requires substantially greater effort than usual by using the modifier 22 code (M22). Our objective was to identify the most common etiologies leading to M22 at our institution and determine the effect on perioperative outcomes. MATERIALS AND METHODS: We retrospectively reviewed our prostatectomy database from 2009-2012 to identify patients who underwent RALP with and without M22. Reasons for M22 were determined by review of operative reports. Comparisons were made using Chi-square analysis and independent t-tests for continuous data. RESULTS: Of 579 patients identified from our database, 208 (36%) had a M22. Eighty-six (41%) patients had ≥ 2 documented reasons for M22. Adhesiolysis was the most common reason for M22 followed by large prostate and previous hernia mesh. Body mass index (BMI) (29.8 versus 28), prostate volume (53 g versus 44 g), operative time (259 minutes versus 234 minutes), and discharge from hospital with pelvic drain in place (6.7% versus 3%) were all significantly higher in the M22 group. Final pathological stage and positive margin rate were not increased in those with a M22. Complications were not different between those with and without M22. CONCLUSION: The M22 code is associated with longer operative times, larger prostates, and higher BMI. Adverse effects on final pathological stage, margin status and complications were not found in those with M22. Many patients with a M22 have more than one reason documented as for the explanation of the modifier.

GSK-3beta promotes cell survival by modulating Bif-1-dependent autophagy and cell death.

Glycogen synthase kinase 3 beta (GSK-3beta) is constantly active in cells and its activity increases after serum deprivation, indicating that GSK-3beta might play a major role in cell survival under serum starvation. In this study, we attempted to determine how GSK-3beta promotes cell survival after serum depletion. Under full culture conditions (10% FBS), GSK-3beta inhibition with chemical inhibitors or siRNAs failed to induce cell death in human prostate cancer cells. By contrast, under conditions of serum starvation, a profound necrotic cell death was observed as evidenced by cellular morphologic features and biochemical markers. Further analysis revealed that GSK-3beta-inhibition-induced cell death was in parallel with an extensive autophagic response. Interestingly, blocking the autophagic response switched GSK-3beta-inhibition-induced necrosis to apoptotic cell death. Finally, GSK-3beta inhibition resulted in a remarkable elevation of Bif-1 protein levels, and silencing Bif-1 expression abrogated GSK-3beta-inhibition-induced autophagic response and cell death. Taken together, our study suggests that GSK-3beta promotes cell survival by modulating Bif-1-dependent autophagic response and cell death.

Suppression of glycogen synthase kinase 3 activity reduces tumor growth of prostate cancer in vivo.

BACKGROUND: Glycogen synthase kinase 3 (GSK-3) has been regarded as a potential therapeutic target for multiple human cancers. We previously reported that suppression of GSK-3 activity with lithium chloride (LiCl) or small chemical inhibitors impaired cellular DNA synthesis and reduced cell proliferation in prostate cancer cells. Therefore, in this study, we extended this in vitro findings to in vivo settings in order to establish a proof of concept that inhibition of GSK-3 activity is feasible in suppressing tumor growth of prostate cancer in vivo. METHODS: In this study, we used three GSK-3 inhibitors, LiCl, TDZD-8, and L803-mts, which are structurally unrelated and non-ATP competitive. Human prostate cancer cell lines PC-3 and C4-2 were used for nude mouse xenograft models. The autochthonous transgenic prostate cancer TRAMP mice were used for testing GSK-3 inhibitor's effect on tumor development. Anti-Ki-67 and BrdU immunohistochemistry was used to determine cell proliferation. The pE2F-TA-LUC (E2F-LUC) luciferase reporter assay and gene specific small interferencing RNA technique were used to examine C/EBP involvement in GSK-3 inhibitor-induced E2F-1 suppression. RESULTS: Using mouse xenograft models, we demonstrated that LiCl and TDZD-8 significantly suppressed tumor development and growth of subcutaneous xenografts derived from human prostate cancer cells. Similarly, in the TRAMP mice, TDZD-8 and L803-mts reduced the incidence and tumor burden in the prostate lobes. Consistent with our previous in vitro findings, GSK-3 inhibitors significantly reduced BrdU incorporation and Ki67-positive cells in xenograft tumors and mouse cancerous prostates compared to the control. Further analysis revealed that following GSK-3 inhibition, C/EBPα, a negative cell cycle regulator, was remarkably accumulated in xenograft tumors or in cultured prostate cancer cells. Meanwhile, knocking down C/EBPα expression abolished GSK-3 inhibition-induced suppression of E2F1 transactivation, suggesting that C/EBPα accumulation is involved in GSK-3 inhibition-induced anti-tumor effect. CONCLUSION: Taken together, these results suggest that GSK-3 inhibition has the potential as a therapeutic strategy for prostate cancer intervention, although further pre-clinical and clinical testing are desirable.

A phase II clinical trial of neoadjuvant ketoconazole and docetaxel chemotherapy before radical prostatectomy in high risk patients.

PURPOSE: Patients with high risk prostate cancer (prostate specific antigen greater than 20 ng/ml, Gleason score greater than 7, or clinical stage T2b or greater) have been shown to have a 30% to 40% biochemical recurrence rate after definitive local therapy. Looking for improvement on these outcomes, we conducted a phase II clinical trial examining the combination of ketoconazole and docetaxel in the neoadjuvant setting before radical prostatectomy. MATERIALS AND METHODS: A total of 22 patients with clinically localized, high risk prostate cancer were enrolled in the study. For 12 weeks they were treated with neoadjuvant docetaxel and ketoconazole, with dosing based on phase I data. Patients were monitored for tolerance of therapy and dosing adjustments were made for significant toxicities. Radical prostatectomy with extended lymph node dissection was subsequently performed and patients were followed postoperatively for biochemical recurrence. RESULTS: At a median followup of 18 months 8 patients remained biochemically free of recurrence after surgery alone. An additional 6 patients received salvage therapy and had an undetectable prostate specific antigen. Of the 22 patients 16 experienced National Cancer Institute grade 3 or 4 toxicity at some point during the therapy. However, 16 patients completed all 4 cycles of chemotherapy. CONCLUSIONS: Neoadjuvant ketoconazole combined with docetaxel has appreciable but acceptable toxicity with 73% of the patients completing all 4 courses of therapy. Of those who underwent radical prostatectomy 36% remained continuously biochemically free of recurrence at a median followup of 18 months.

The American Board of Urology: In Pursuit of Diversity, Equity, and Inclusion.

INTRODUCTION: The purpose of this manuscript is to describe the methods we employ to build a foundation of diversity, quality and inclusion within the American Board of Urology and its certifying processes. METHODS: The American Board of Urology consists of 3 major committees: the Trustees of the Board and the Written and Oral Exam Committees. Yearly, before selecting new members to these committees, a Gap analysis is performed to evaluate discrepancies between the committee structure and the constituents we serve. The selection of new committee members is based on both the individual's merit and an attempt to match or supersede the diversity ratios described within the most current national census conducted by the American Urological Association. RESULTS: This year's evaluation revealed our committee structure consisting of 85% (98/115) male and 15% (17/115) women: National Census 90% and 10% respectively. Regarding race and ethnicity, White nonHispanic: 74% (85/115) compared to 81% (National Census); Hispanic: 1% (1/115) compared to 4%; Asian: 22% (25/115) compared to 12%; Black/African American 3% (4/115) compared to 2%. CONCLUSIONS: The American Board of Urology recognizes that the evaluation of ratios is an excellent initial step to establish diversity; however, ratios alone may not change behavior or attitudes. To reach our eventual goal, we must include educational efforts that inform our diplomates and committee members regarding the benefits of diversity. We also acknowledge that establishing and maintaining diversity within any governing board is an imperative that requires continuous and structural processes to be sustained.

Exploration of biomarkers from a pilot weight management study for men undergoing radical prostatectomy.

BACKGROUND: Several biologic mechanisms, including inflammation and immune changes, have been proposed to explain the role of obesity in prostate cancer (CaP) progression. Compared to men of a healthy weight, overweight and obese men are more likely to have CaP recurrence post-prostatectomy. Obesity is related to inflammation and immune dysregulation; thus, weight loss may be an avenue to reduce inflammation and reverse these immune processes. OBJECTIVES: This study explores the reversibility of the biological mechanisms through intentional weight loss using a comprehensive weight management program in men undergoing prostatectomy. Outcomes include blood and tissue biomarkers, microtumor environment gene expression, inflammation markers and Dietary Inflammatory Index (DII) scores. METHODS: Twenty overweight men undergoing prostatectomy participated in this study. Fifteen men chose the intervention and 5 men chose the nonintervention group. The intervention consisted of a comprehensive weight loss program prior to prostatectomy and a weight maintenance program following surgery. Prostate tissue samples were obtained from diagnostic biopsies before the intervention and prostatectomy samples after weight loss. Blood samples and diet records were collected at baseline, pre-surgery after weight loss and at study end after weight maintenance. Immunohistochemistry and NanoString analysis were used to analyze the tissue samples. Flow cytometry was used to assess circulating immune markers. Inflammation markers were measured using Luminex panels. RESULTS: The intervention group lost >5% body weight prior to surgery. DII scores improved during the weight loss intervention from baseline to pre-surgery (P = 0.002); and between group differences were significant (P = 0.02). DII scores were not associated with IL-6 nor hsCRP. In the intervention, CXCL12, CXCR7, and CXCR4 (C-X-C motif chemokine ligand/receptor) and Ki67 expression decreased in the prostate tissue from biopsy to surgery (P = 0.06), yet plasma CXCL12 increased during the same timeframe (P = 0.009). The downregulation of several genes (FDR<0.001) was observed in the intervention compared to the non-intervention. Changes in immune cells were not significant in either group. CONCLUSION: This feasibility study demonstrates that in overweight men with localized CaP, weight loss alters blood, and tissue biomarkers, as well as tumor gene expression. More research is needed to determine the biological and clinical significance of these findings.

Impact of Fellowship-Trained Andrology and Sexual Medicine Specialists on Performance on the Annual American Urological Association In-Service Examination.

OBJECTIVE: To demonstrate the distribution and impact of fellowship-trained andrology and/or sexual medicine urological specialists (FTAUS) on resident in-service examination (ISE) performance. METHODS: Residency program websites were accessed to create a database of FTAUS in the United States between 2007 and 2017. This database was reviewed by three separate FTAUS and cross referenced with membership lists to the Sexual Medicine of North America Society and the Society for the Study of Male Reproduction. De-identified ISE scores were obtained from the American Urological Association from 2007-2017 and scores from trainees at programs with a FTAUS were identified for comparison. Resident performance was analyzed using a linear model of the effect of a resident being at a program with an FTAUS, adjusting for post-graduate year. RESULTS: ISE data from 13,757 residents were obtained for the years 2007-2017. The number of FTAUS in the United States increased from 40-102 during this study period. Mean raw scores on the "Sexual Dysfunction, Endocrinopathy, Fertility Problems" (SDEFP) section of the ISE ranged from 52.1% ± 17.7% to 65.7% ± 16% (mean ± SD). Throughout the study period, there was no difference in performance within the SDEFP section (P < .01). Residents at a program with a FTAUS answered 0.95% more questions correctly in the SDEFP than those without a FTAUS (P < .001). For these residents, there was an improvement of approximately 0.66% on the percentage of questions answered correctly on the ISE overall (P < .001). Performance improved significantly as residents progressed from PGY-2-PGY-5. CONCLUSION: There is a small but statistically significant improvement in overall ISE and SDEFP sub-section performance.

Active surveillance for prostate cancer in a veteran population.

INTRODUCTION: Active surveillance for prostate cancer is a therapeutic option which is gaining more popularity. Implicit in this approach is careful monitoring to identify those with progression. Criteria for placing patients on active surveillance vary but generally include Gleason sum of 6 or less, prostate-specific antigen (PSA) less than 20, and a small volume of cancer in the biopsy specimen. We review our experience with active surveillance in a veteran population. MATERIALS AND METHODS: We conducted a retrospective review of patients from the Kansas City Veterans Affairs (KCVA) who met the requirements for active surveillance (Gleason sum 6, percent of cancer in the specimen less than 20%, and PSA less than 20 ng/dL) between January 2004 and December 2009. In the patient group who chose active surveillance (AS), we evaluated the rates of compliance with the protocol mandated PSA's and the 1 year biopsy. In the patient group who declined AS and underwent immediate prostatectomy, we reviewed the final pathology for stage, Gleason grade, percent of tissue involved with cancer, margin status, nodal status, and rates of biochemical recurrence. RESULTS: We identified 207 patients who met the requirements for active surveillance. Of these patients, 45 patients chose active surveillance while 66 patients underwent immediate radical prostatectomy at the KCVA. Of the 45 patients who went on active surveillance, all participants had at least one PSA drawn. However, only 24 (53.3%) patients complied with the protocol mandated prostate biopsy at 1 year. In the patient group who chose to undergo an immediate prostatectomy, 43 of 66 (65.2%) patients had upgrading of their Gleason score. This included 12 patients upgraded to Gleason sum 8 to 10 and two patients who were upstaged to T3 disease. Despite the significant upgrading, only two patients have had a biochemical recurrence at a median follow up of 30 months. CONCLUSIONS: Active surveillance is a viable option for patients with low risk prostate cancer. However, this study raises concerns about compliance with recommendations for active surveillance in a VA population. Furthermore, there was a significant risk in this study of under-grading in patients who underwent immediate prostatectomy. This emphasizes the need for better education of patients who enter into active surveillance protocols regarding the need for compliance, the risks of progression, and the chance of under grading.

Medical Professionalism Is Like Pornography: You Know it When You See it.

Addressing professionalism is a key role of Certification Boards, but how best to do this is not clear. This article describes a 360° approach to monitoring and enhancing professionalism taken by the American Board of Urology (ABU). In addition to monitoring full and active medical licenses, ABU has identified ethical issues specific to Urology, includes a position article on ethics in Urology on its Web site, and requires a completion of modules on ethics. As a part of its 10-year cycle, the Board requires peer evaluations from other urologists in the community. Finally, and most importantly, ABU uses a portfolio practice log to evaluate the candidates' use of procedures appropriate to their stated subspecialty area of expertise, evaluation of potential overuse or inappropriate use of procedures and a narrative that details any major complications associated with their procedures.

Eighteen-Year Review of Resident Performance on the American Urological Association In-Service Examination.

OBJECTIVE: To analyze national performance trends of urology residents on the American Urological Association In-Service Examination (ISE) over the last 18 years. METHODS: Trends in the national averages on the in-service examination for each year of residency training were collected and analyzed between the years 2000 and 2017. Mean and standard error were calculated for examination performance for each year of residency. Subject-specific performance was also determined for each given year of residency. Regression analysis was used to model trends in performance as a function of residency year. RESULTS: There was no significant difference in examination performance over 18 years with respect to each specific residency year. While there was an overall improvement in total scores with each advancing training year, year-over-year improvement in total examination performance began to plateau after Uro-2. Largest absolute performance improvement from Pre-Uro to Uro-4 were in subjects of "Urinary Diversion," "Obstructive Uropathy" and "Neoplasm." Scores in "Sexual Dysfunction, Endocrinopathy, Fertility Problems", and "Congenital Anomalies, Embryology, Anatomy" were consistently the lowest regardless of year of training. CONCLUSION: No significant change in performance was seen in each given year of residency over the 18-year period. There was improvement in overall scores as residents progressed through training, but scores plateaued after Uro-2 with minimal improvement between Uro-3 and Uro-4 years. Difference in subject scores suggests a disparity in educational focus in residency curricula and a potential need to improve the teaching strategies for subjects that tested less well throughout residency training.

Effects of short-term finasteride on apoptotic factors and androgen receptors in prostate cancer cells.

PURPOSE: We explored the molecular correlates of the effect of finasteride on prostate tissue in patients undergoing radical prostatectomy. MATERIALS AND METHODS: Patients undergoing radical prostatectomy for localized prostate cancer were eligible for study. After providing informed consent patients were randomized to receive 5 mg finasteride or placebo daily for at least 30 days before surgery. At surgery prostate tissue was harvested from the surgical specimen and sent for analysis. Tissue samples were analyzed for the pro-apoptotic factors caspase-3, caspase-7 and IGFBP-3. Samples were also analyzed for the tumor suppressor/proto-oncoproteins bcl-2, p53 and p21. Finally, tissues were analyzed for androgen receptor density and insulin growth factor-1. RESULTS: A total of 22 study and 20 placebo samples were collected and analyzed. Negligible staining for bcl-2 or caspase-3 was noted in each group. Statistical differences were not observed for bcl-2, p53, p21 or insulin growth factor-1 between the groups. There was a statistically significant difference in caspase-7 and IGFBP-3. A mean of 77% and 99.9% of cells stained for caspase-7 in the treatment and placebo groups, respectively (p = 0.007). In 3 patients caspase-7 staining disappeared completely and it was decreased by 70% and 50% in 1 patient each. Mean intensity staining for IGFBP-3 was 1.03 in the treatment group and 1.54 in the placebo group (p = 0.005). The staining intensity of nuclear androgen receptors on benign and cancerous cells was not significantly different between the treatment and placebo groups. However, there was a significant difference in androgen receptor staining between benign and cancer cells in the 2 populations. Mean nuclear androgen receptor staining intensity in all cancer and all benign tissue samples was 119.3 and 151.8, respectively (0.001). CONCLUSIONS: Finasteride administered 30 days before surgery appears to decrease the apoptotic factors caspase-7 and IGFBP-3 in cancer cells, while having little to no effect on caspase-3, insulin growth factor-1, bcl-2, p53 and p21. This short-term study may have interesting implications for interpreting Prostate Cancer Prevention Trial data on the molecular level. No differences were noted between the treatment and placebo groups in the expression of nuclear androgen receptor. However, decreased expression of androgen receptors was present in cancer cells compared to that in benign prostate cells in the 2 groups.

Predictors of positive surgical margins after radical perineal prostatectomy.

INTRODUCTION/OBJECTIVE: Margin positivity has been a well described adverse prognostic factor in patients undergoing radical prostatectomy. Previous studies with regards to predictors of margin positivity after prostatectomy have primarily focused on the retropubic or robotic approach. We sought to examine the predictors of margin positivity in a contemporary series of men undergoing radical perineal prostatectomy (RPP). MATERIALS AND METHODS: We reviewed the records of 103 patients who underwent RPP at our institution from July 1998 until May 2008. A positive surgical margin (PSM) was defined as the presence of cancer cells at the inked margin of the surgical specimen. Records were reviewed for the following preoperative parameters: age at operation, body mass index (BMI), preoperative PSA, clinical stage and biopsy Gleason sum score. Pathological data included prostate weight (PW) and tumor volume. RESULTS: Mean age was 60.9 (range 45-76). Mean BMI was 31.4 kg/m2 (20.9-51.6). The preoperative prevalence of palpable disease was 50.5%. A PSM was found in 23.3%. Age, BMI, clinical stage, biopsy Gleason sum score and preoperative PSA were not found to be independent predictors of a PSM after RPP. Only prostate weight was found to be a significant preoperative predictor of a PSM after RPP with men with smaller prostates at higher risk. CONCLUSIONS: Prostate weight was found to be significantly and inversely related to the PSM rate in this cohort of RPP patients. Patients with smaller volume prostates should be counseled preoperatively that they are at higher risk for a PSM when undergoing a RPP.

Science in the Heartland: Exploring determinants of offering cancer clinical trials in rural-serving community urology practices.

OBJECTIVE: Engaging community urologists in referring patients to clinical trials could increase the reach of cancer trials and, ultimately, alleviate cancer disparities. We sought to identify determinants of referring patients to clinical trials among urology practices serving rural communities. METHODS: We conducted semistructured qualitative interviews based on the Theoretical Domains Framework at nonmetropolitan urology practices located in communities offering urological cancer trials. Participants were asked to consider barriers and strategies that might support engaging their patients in discussions about urological cancer clinical trials and referring them appropriately. Recorded interviews were transcribed and coded using template analysis. RESULTS: Most participants were not aware of available trials and had no experience with trial referral. Overall, participants held positive attitudes toward clinical trials and recognized their potential roles in accrual, but limited local resources reduced opportunities for offering trials. Most participants expressed a need for increased human, financial, and other resources to support this role. Many participants requested information and training to increase their knowledge of clinical trials and confidence in offering them to patients. Participants highlighted the need to build efficient pathways to identify available trials, match eligible patients, and facilitate communication and collaboration with cancer centers for patient follow-up and continuity of care. CONCLUSIONS: With adequate logistical and informational support, community urology practices could play an important role in clinical trial accrual, advancing cancer research and increasing treatment options for rural cancer patients. Future studies should explore the effectiveness of strategies to optimize urology practices' role in clinical trial accrual.

Patient Factors That Influence How Physicians Discuss Active Surveillance With Low-Risk Prostate Cancer Patients: A Qualitative Study.

For men diagnosed with prostate cancer, making treatment decisions can be overwhelming. Navigating treatment options, along with potential treatment side effects, can be difficult, and patients often rely heavily on the advice of their physicians. This study was aimed at understanding more about the way urologists talk with their patients about one treatment option: active surveillance (AS), a recognized management strategy for men with low-risk prostate cancer that includes close observation and monitoring of the cancer. This study reports, through 22 interviews with urologists, that urologists believe patients are hesitant about AS for a number of reasons, including misperceptions about cancer severity, anxiety, aversion to repeated biopsies that accompany AS, or family member preferences. Because urologists play an influential role in educating patients about treatment options, the discussion around AS can be impacted by barriers that physicians believe matter for their patients. Improving awareness among urologists about what factors impact their patient education about low-risk prostate cancer is important. Identifying tools to improve shared decision making in this area could result in treatment decisions that are increasingly concordant with patients' values, concerns, and goals.