Faculty Bibliography

Context: The immunology of the prostate has developed into a new field of research in urology. The leukocyte population increases are not yet fully understood, but it has been demonstrated that most resected prostate tissue shows signs of inflammatory response. Objective: This article reviews recent findings and discusses the complex mechanisms involved in the prostatic inflammatory response and the immunologic functions of the prostate, and the roles the prostatic inflammatory response in the cause of prostate disease such as benign prostatic hyperplasia (BPH). Evidence acquisition: We performed a search of the medical literature with PubMed, using keywords such as prostate cancer, inflammation of the prostate, leukocytes, estrogen, and cytokine and genetic expression of inflammation. Articles and data were reviewed as to their relevance, and inclusion and exclusion criteria were determined prospectively. Evidence synthesis: Evidence showing that inflammation of the prostate plays a role in prostate cancer (PCa) is mounting. Different types of inflammation exist and are distinguished according to the distribution and location of leukocytes and the histology of the surrounding tissue. Most resected prostate tissue shows signs of inflammatory response, and a relationship between T-cell infiltration and stromal proliferation can be found. Evidence for the importance of estrogen and proinflammatory cytokine interleukin (IL; IL-6, IL-8, IL-15, IL-17) also can be found. Early stages of investigation of the immunologic function of the prostate show that both prostatic epithelial and stromal cells express members of the toll-like receptor family and are therefore capable of recognizing foreign incoming antigens. Conclusions: Although this area of study is new, the immunology and inflammatory responses of the prostate are seen as important components of further study of prostate diseases such as PCa and BPH. Data supporting the role of immunology and activated leukocytes in malignant cells are also an important finding and can possibly lead to new knowledge about malignant cells. (C) 2009 Published by Elsevier B. V. on behalf of European Association of Urology

OBJECTIVE: Prostate cancer is still the most frequent noncutaneous male malignancy and is the second most common cause of cancer death. Genetic factors have been extensively studied in different countries. In addition, numerous genome-wide association studies have been performed in developed countries. Genetic tests will be applied in the near future for diagnosis, therapeutic, and prognostic significance. Therefore, we reviewed the association of several important pathways and genes with critical functions in prostate cancer development or progression. MATERIALS AND METHODS: We performed a PubMed search using several key words such as prostate cancer, names of important genes with critical function, and polymorphisms. Then, we reviewed retrieved articles as well as relevant articles from 1997 to 2009. RESULTS: There are conflicting results of studies on some gene polymorphisms in association with prostate cancer. Most of the inconsistent results have been reported in studies investigating the vitamin D receptor gene polymorphism in association with prostate cancer. Genes related to angiogenesis and cell adhesion genes are more promising. Following results of future studies, the use of antibodies blocking over-expressed genes or proteins may be supported in patients with prostate cancer. CONCLUSIONS: The difference between the results of studies on gene polymorphisms in prostate cancer may be explained partly by ethnic differences, limited sample size, and other risk or protective factors modifying these effects. Genome-wide studies are currently performed in developed countries and extensive use of this type of analysis may merit consideration in other countries. Furthermore, future studies are needed to further investigate environmental and diet factors interactions with genetic factors

PURPOSE: Because many investigators have suggested that ideal candidates for focal therapy are those with unilateral prostate cancer, we evaluated whether these men are at decreased risk for adverse pathological and oncological outcomes. MATERIALS AND METHODS: We reviewed the charts of 1,458 consecutive patients who underwent open radical prostatectomy, as performed by a single surgeon. Patients were divided into 311 with unilateral (group 1) and 1,147 with bilateral (group 2) disease on final surgical pathology. They were also substratified by clinical risk into low risk (prostate specific antigen less than 10 ng/ml, clinical stage less than T2b or Gleason score less than 7) and high risk groups. The groups were compared with respect to extracapsular extension, seminal vesical invasion, percent of tumor involvement, pathological Gleason score and biochemical recurrence. RESULTS: Compared to patients with bilateral disease those with unilateral disease had a lower rate of extracapsular extension (p = 0.004), seminal vesical invasion (p = 0.003), greater than 10% tumor involvement (p <0.001) and Gleason score 7 or greater (p <0.001). At a median followup of 36 months 8.3% and 16.7% of the men in groups 1 and 2, respectively, experienced biochemical recurrence (p = 0.001). Low risk disease was more prevalent in those with unilateral disease than in those with bilateral disease. Of men with low risk disease the risk of adverse pathological features/biochemical recurrence did not differ between groups 1 and 2. CONCLUSIONS: Although men with unilateral prostate cancer have more favorable oncological outcomes than those with bilateral prostate cancer, this appears to be due to the higher prevalence of low risk disease. While focality/laterality may direct the method of subtotal gland treatment, clinical risk features may be adequate to select candidates for focal therapy

This study provides further insights into those preoperative parameters that predict side-specific risk of pathological stage in men undergoing radical prostatectomy (RP). The transrectal ultrasound-guided tissue biopsy cores obtained from the right and left sides of the prostate were collected in separate jars and examined independently according to the side of origin in 1250 men with clinically localized prostate cancer who underwent RP. The side-specific biopsy specimens were examined for Gleason score, number of positive cores, percentage of positive cores, percent tumor volume in the biopsy specimens and the presence of perineural invasion. All of the surgical specimens were processed and analyzed by pathologists at NYUMC using a standardized protocol. The surgical specimens were examined for side-specific extracapsular extension (ECE) and seminal vesicle invasion (SVI). Using a univariate analysis, age, serum prostate-specific antigen (PSA), prostate volume, clinical stage, Gleason score, number of positive biopsies, percent positive biopsy cores, percent volume of prostate cancer in cores and perineural invasion were all significant predictors of both ECE and SVI. A multivariate analysis was performed to determine the independent predictors of ECE and SVI. Serum PSA, biopsy Gleason score, percent volume of biopsy cores with cancer and perineural invasion were independent predictors of side-specific ECE. Age, serum PSA, Gleason score and prostate volume were independent predictors of side-specific SVI. Our study identified previously unrecognized independent predictors of side-specific ECE and SVI. Our study also provides evidence that the independent predictors of ECE and SVI are different

PURPOSE: The development of erectile dysfunction represents a major concern for potent men with localized prostate cancer undergoing open radical retropubic prostatectomy. We identified factors predicting the preservation of erectile function in men undergoing open radical retropubic prostatectomy. MATERIALS AND METHODS: Between October 2000 and September 2005 a total of 1,110 men underwent open radical retropubic prostatectomy by a single surgeon. The UCLA-PCI was self-administered at baseline, and at 3, 6, 12 and 24 months postoperatively. The 728 (66%) men who responded that they engaged in sexual intercourse with or without taking phosphodiesterase type 5 inhibitors in the month before surgery and who were not dependent on intracavernous injections, intraurethral suppositories, vacuum devices or penile prostheses were considered potent. Followup was available for 659 men. Of the evaluable men 25 received salvage radiation therapy, adjuvant chemotherapy or hormonal therapy and were excluded from the study. Univariate and multivariate analyses using a logistic regression model were used to identify factors predicting the preservation of potency. RESULTS: Age, coronary artery disease, diabetes mellitus, quality of preoperative erections, frequency of intercourse, hypertension, neurovascular bundle preservation and the use of phosphodiesterase type 5 inhibitors preoperatively predicted the preservation of potency. On multivariate analysis age, no history of diabetes mellitus and nerve sparing were independent predictors of the preservation of potency. CONCLUSIONS: We identified many factors that were predictors of the preservation of potency after open radical retropubic prostatectomy. Only age, no history of diabetes mellitus and neurovascular bundle preservation were independent predictors. These parameters should be considered when counseling surgical candidates so that erectile function expectations are realistic

OBJECTIVES: To assess the prevalence and pathologic features of men with unilateral prostate cancer at radical prostatectomy (RP), because it has recently been proposed that men with small-volume, well-differentiated, unilateral prostate cancer can be treated with focal therapy. METHODS: The records of 1467 consecutive men who underwent open RP by a single surgeon from January 2000 to June 2007 were reviewed after institutional review board approval. The RP pathologic reports were analyzed to determine the frequency of unilateral or bilateral disease, surgical margin status, presence of extracapsular extension, seminal vesicle invasion, Gleason score, percentage of tumor involvement (PTI), prostate-specific antigen (PSA) level, and prostate volume. Logistic regression analysis was performed to analyze the relationship between these factors and the detection of unilateral disease. RESULTS: Unilateral cancer was identified in 313 of 1467 patients (21.3%). Of these patients, 206 had a PTI of < or = 5%, 40 had a PTI of 5%-10%, 8 had a PTI of 10%-15%, and 40 had a PTI > 15%. The factors significantly associated with unilateral disease on univariate analysis were PTI, PSA level, pathologic Gleason score, seminal vesicle invasion, and extracapsular extension. The PSA level and seminal vesicle invasion remained significant predictors on multivariate analysis. Overall, 163 men (11.1%) had unilateral, low-risk disease (defined as a PSA level < 10 ng/mL, Gleason score < 7, and PTI < 10%). CONCLUSIONS: Although candidates for focal therapy exist among men undergoing RP within a contemporary cohort, they represent a small minority. Before proceeding with focal therapy, the urology community must identify accurate methods of candidate selection

PURPOSE: There is a paucity of information on changes in continence and erectile function beyond 2 years after radical prostatectomy. We prospectively examined changes in continence and erectile function between 2 and 4 years after radical prostatectomy. MATERIALS AND METHODS: Between October 2000 and August 2003, 731 consecutive men underwent open retropubic radical prostatectomy for clinically localized prostate cancer. Preoperative and postoperative continence, and erectile function were ascertained using the UCLA Prostate Cancer Index. The 48-month prospective self-assessment followup questionnaire captured changes in urinary control and erectile function between 24 and 48 months, including marked, moderate or slight improvement, no change or worsening. RESULTS: Overall between 24 and 48 months after radical prostatectomy 23.4% and 42.3% of men showed any degree of improvement in continence and erectile function, and 12.2% and 19.8% showed marked and moderate improvement in continence and erectile function, respectively. The probability of experiencing any qualitative improvement in urinary continence was not significantly different in men who were continent or incontinent at 24 months. The likelihood of experiencing any qualitative improvement in erectile function was significantly greater in men who were potent at 24 months compared to those who were impotent. CONCLUSIONS: Our study provides compelling evidence that clinically significant improvements in urinary control and erectile function occur beyond 2 years after radical prostatectomy. These qualitative improvements are greatest for erectile function in men who were potent at 2 years. Therefore, men should not be counseled that maximal urinary continence or erectile function are achieved by 24 months after radical prostatectomy

The medical treatment of benign prostatic hyperplasia (BPH) has its roots in the early 1970s. During this era, the first clinical trials investigating alpha-blockade and androgen deprivation therapy were reported for men with clinical BPH. The observation that clinical BPH was improved following administration of both alpha-blockers and androgen deprivation therapy supported the evolving paradigm that clinical BPH resulted from dynamic and static pathways. During the past several decades, the evolution of alpha-blockers for the treatment of BPH has been impacted by innovations targeted to simplify the administration and improve tolerability while maintaining their effectiveness