Faculty Bibliography

Open radical prostatectomy (ORP) is the reference standard for the surgical management of localized prostate cancer. With wider availability of minimally invasive radical prostatectomy techniques, there is a debate regarding the standard treatment of the management of localized prostate cancer. Therefore, we reviewed the current status of laparoscopic radical prostatectomy (LRP) and robotic-assisted laparoscopic radical prostatectomy (RALRP) as compared with ORP. Because no prospective, randomized trials comparing the different techniques have been performed, outcomes must be assessed from published series by centers that focus on ORP, LRP, and RALRP. Aside from reducing the amount of blood loss, current data suggest that the most significant outcomes (cure, continence, and potency) are no better with LRP or RALRP than with conventional ORP. Therefore, in experienced hands, ORP remains the gold standard procedure. However, there is a trend toward consistently better outcomes following RALRP in comparison with LRP. In the end, individual patient outcomes can be maximized by choosing the best modality based on the patient's comorbid medical conditions, cancer characteristics, and surgeon experience. Future studies are needed to further investigate long-term cancer control as well as functional outcomes for RALRP series

Defects in pRb tumor suppressor pathway occur in approximately 50% of the deadly muscle-invasive urothelial carcinomas in humans and urothelial carcinoma is the most prevalent epithelial cancer in long-term survivors of hereditary retinoblastomas caused by loss-of-function RB1 mutations. Here, we show that conditional inactivation of both RB1 alleles in mouse urothelium failed to accelerate urothelial proliferation. Instead, it profoundly activated the p53 pathway, leading to extensive apoptosis, and selectively induced pRb family member p107. Thus, pRb loss triggered multiple fail-safe mechanisms whereby urothelial cells evade tumorigenesis. Additional loss of p53 in pRb-deficient urothelial cells removed these p53-dependent tumor barriers, resulting in late-onset hyperplasia, umbrella cell nuclear atypia, and rare-occurring low-grade, superficial papillary bladder tumors, without eliciting invasive carcinomas. Importantly, mice deficient in both pRb and p53, but not those deficient in either protein alone, were highly susceptible to subthreshold carcinogen exposure and developed invasive urothelial carcinomas that strongly resembled the human counterparts. The invasive lesions had a marked reduction of p107 but not p130 of the pRb family. Our data provide compelling evidence, indicating that urothelium, one of the slowest cycling epithelia, is remarkably resistant to transformation by pRb or p53 deficiency; that concurrent loss of these two tumor suppressors is necessary but insufficient to initiate urothelial tumorigenesis along the invasive pathway; that p107 may play a critical role in suppressing invasive urothelial tumor formation; and that replacing/restoring the function of pRb, p107, or p53 could be explored as a potential therapeutic strategy to block urothelial tumor progression

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

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

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

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

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