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: To determine whether the number and location of positive surgical margins (PSMs) in radical prostatectomy (RP) surgical specimens affect biochemical recurrence (BCR) rates. PATIENTS AND METHODS: The locations of PSMs were recorded for 1308 consecutive men who underwent RP between October 2000 and December 2006. BCR was defined as three consecutive prostate-specific antigen (PSA) level rises with the peak level >or=0.15 ng/mL. Multivariate regression analyses were used to identify preoperative predictors of PSMs and BCR. The estimated 5-year risk of BCR was calculated using the Kaplan-Meier method. RESULTS: In all, 128 (9.8%) men had one or more PSMs. The mean body mass index, mean preoperative serum PSA level, the distributions of clinical stage and biopsy Gleason scores, and the presence or absence of biopsy perineural invasion were significantly different between men with or with no PSMs. In multivariate analysis, baseline serum PSA level, Gleason score and perineural invasion were independent preoperative predictors of PSMs. The 5-year actuarial BCR rates were dependent on the site of the PSM (P = 0.035) and not the number of PSMs (P = 0.18). The rank order of estimated 5-year BCR rates according to the site of PSMs were base > anterior > posterolateral > apex approximately posterior. CONCLUSIONS: About half of the men with PSMs in the RP surgical specimen in our prospective series did not develop BCR. The risk of BCR was dependent on the site and not the number of PSMs. Adjuvant therapy should be considered in cases with anterior and basilar PSMs due to the very high risk of BCR

OBJECTIVES: To provide insights into the likelihood that benign prostatic tissue represents a source of measurable prostate-specific antigen (PSA) after radical prostatectomy. METHODS: From October 2000 to December 2006, 1308 consecutive men underwent open radical retropubic prostatectomy by a single surgeon. Of these 1308 men, 331 (25.3%) met our criteria for having 'extremely' low-risk disease as determined by the preoperative and pathologic factors, including a preoperative PSA level <10 ng/mL, clinical Stage T1c or T2a, a Gleason score of < or =6, an estimated cancer volume in the specimen of <5%, and no evidence of positive surgical margins. This cohort was selected because any measurable PSA level would be highly suspicious for a benign origin. Undetectable PSA was defined as a PSA level of < or =0.04 ng/mL. A measurable PSA level included values between 0.05 and 0.14 ng/mL on > or =2 consecutive measurements 6 months apart. Biochemical recurrence was defined as 3 consecutively increasing PSA levels with a peak level of > or =0.15 ng/mL. RESULTS: At 3 months to 6 years of follow-up (mean 36.2 months), 0.6% and 0.3% of patients had developed a measurable PSA level or biochemical recurrence, respectively. The single patient with biochemical recurrence responded to salvage radiotherapy, strongly suggesting a malignant etiology for the recurrence. CONCLUSIONS: A measurable PSA level or biochemical recurrence was an extraordinarily rare event in our select group of patients with extremely low-risk disease. These results provide compelling evidence that retained benign prostatic elements are an unlikely source of elevated PSA levels in men who have undergone radical prostatectomy

OBJECTIVE To determine if biopsy characteristics can be used to identify men with unilateral prostate cancer on radical prostatectomy (RP) pathological specimens, thereby selecting candidates for hemi-ablative focal therapy. PATIENTS AND METHODS Of 1458 men who had RP from January 2000 to June 2007, we identified 590 of 880 evaluable patients with unilateral disease on their preoperative biopsy. Charts were reviewed to record preoperative prostate-specific antigen (PSA) level, high-grade prostatic intraepithelial neoplasia (HGPIN), clinical stage, Gleason score, perineural invasion (PNI), prostate volume, number of positive cores, and percentage of positive cores. Final surgical pathology was evaluated for unilateral cancer. Univariate analysis was used (logistic regression method) to identify independent predictors of unilateral disease on the RP specimen. A subset analysis was done in men with low-risk disease, defined as clinical stage T1C, Gleason score <7 and a PSA level of <10 ng/mL. RESULTS Of 590 men with unilateral disease on biopsy, 163 (27.3%) had unilateral disease on the RP specimen. Pathological features, including HGPIN (P = 0.714), Gleason score (P > 0.608), PNI (P = 0.714), number of positive cores (P = 0.076), percentage of cores positive (P = 0.056), prostate volume (P = 0.285), and PSA level (P = 0.062) did not improve the prediction of unilateral disease. When men with unilateral cancer were further stratified to include only those with low-risk disease, 28.4% had unilateral disease on the RP specimen. None of the biopsy or clinical features evaluated were predictors of unilateral disease on the RP specimen. CONCLUSION Unilateral prostate cancer on biopsy predicts unilateral disease on RP pathology in only 27.6% of cases. The predictive ability is not improved by adding biopsy and clinical characteristics. Additional methods are needed to accurately identify men appropriate for focal therapy

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

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

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 advent of prostate-specific antigen (PSA) testing in the early 1980s revolutionized the diagnosis of prostate cancer. As a result of PSA testing, there has been a surge in the number of prostate cancer diagnoses. This review examines the results of 2 recent landmark trials that studied the effect of screening on prostate cancer mortality: the European Randomized Study of Screening for Prostate Cancer (ERSPC) and the US-based Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial