Faculty Bibliography

Many clinically localized prostate cancers that are diagnosed today are low risk, and prevention of disease-specific mortality may only be realized decades after treatment. Radical prostatectomy (RP) may adversely impact health-related quality of life (HRQOL) by causing both transient or permanent urinary incontinence and erectile dysfunction. In contrast, RP may also improve HRQOL via relief of lower urinary tract symptoms in men suffering from these symptoms prior to surgery. Because the average man treated for prostate cancer has a life expectancy of approximately 14 years, it is imperative to consider the long-term impact of RP on both survival and HRQOL in treatment decision making. This comprehensive literature review examines short-, intermediate-, and long-term HRQOL following RP. In addition, the long-term results of RP are compared with other treatment modalities for treating clinically localized prostate cancer.

p44/MEP50/WDR77 has been identified as a coactivator of androgen receptor (AR), with distinct growth suppression and promotion function in gender specific endocrine organs and their malignancies. We dissected the functional domains of p44 for protein interaction with transcription factors, transcriptional activation, as well as the functional domains in p44 related to its growth inhibition in prostate cancer. Using a yeast two-hybrid screen, we identified a novel transcription complex AR-p44-Smad1, confirmed for physical interaction by co-immunoprecipitaion and functional interaction with luciferase assays in human prostate cancer cells. Yeast two-hybrid assay revealed that the N-terminal region of p44, instead of the traditional WD40 domain at the C-terminus, mediates the interaction among p44, N-terminus of AR and full length Smad1. Although both N and C terminal domains of p44 are necessary for maximum AR transcriptional activation, the N terminal fragment of p44 alone maintains the basic effect on AR transcriptional activation. Cell proliferation assays with N- and C- terminal deletion mutations indicated that the central portion of p44 is required for nuclear p44 mediated prostate cancer growth inhibition.

Study Type - Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Some studies have evaluated preoperative and intraoperative examination for inguinal hernias and their repair, noting a decrease in the rate of post-prostatectomy hernias. However, this did not eradicate post-prostatectomy hernias, indicating that this method probably missed subclinical hernias. Other studies looked at prophylactic procedures to prevent the formation of inguinal hernias at the time of prostatectomy and showed a decrease in the rate of postoperative hernias. To our knowledge this is the only series evaluating a multi-modal approach with magnetic resonance imaging, ultrasonography and examination to identify all clinical and subclinical hernias and repair them at the time of prostatectomy. This approach only subjects those patients at risk for symptomatic hernias to an additional procedure and decreases the post-prostatectomy hernia rate to <1%. OBJECTIVE: * To assess if a comprehensive evaluation to diagnose clinical and subclinical hernias and repair of these hernias at the time of open radical retropubic prostatectomy (ORRP) decreases the incidence of clinical inguinal hernias (IHs) after ORRP. PATIENTS AND METHODS: * Between 1 July 2007 and 31 July 2010, 281 consecutive men underwent ORRP by a single surgeon. * Of these men, 207 (74%) underwent comprehensive preoperative screening for IH, which included physical examination, upstanding ultrasonography and magnetic resonance imaging. * Between 12 and 24 months after ORRP, 178 (86%) of these men completed a questionnaire designed to capture development of clinical IHs. RESULTS: * Of the 178 evaluable patients, 92 (52%) were diagnosed preoperatively with IH by at least one diagnostic modality. * Forty-one and 51 of the men had bilateral or unilateral IHs, respectively for a total of 133 IHs. * No preoperative factor was significantly associated with the presence of an IH before prostatectomy. * No groin subjected to IH repair (IHR) at the time of ORRP developed a clinical IH compared with four of the 21 patients with postoperative IHs who did not undergo repair of their preoperatively diagnosed IH at the time of ORRP (P= 0.024). * Only one (0.4%) clinical IH developed in a groin that had no evidence of IH by physical examination, upstanding ultrasonography and magnetic resonance imaging before prostatectomy. CONCLUSIONS: * Our comprehensive evaluation increases the detection of IHs before ORRP. * Repair of these IHs at the time of ORRP significantly decreases the risk of developing post-prostatectomy clinical IHs.

Study Type - Therapy (outcomes) Level of Evidence 2c What's known on the subject? and What does the study add? In addition to a higher prevalence and biological aggressiveness of prostate cancer, African-Americans tend towards narrower pelvises than Caucasians resulting in a potentially more difficult surgical dissection doing radical prostatectomy and increased positive surgical margins. In this study, there was no difference in urinary or sexual HRQL or overall satisfaction between African-Americans and Caucasians 2 years after radical prostatectomy, suggesting that the potential technical challenges of a narrower pelvis do not translate into poorer outcomes for African-Americans. OBJECTIVE: * To determine if any differences exist in postoperative health-related quality-of-life (HRQL) outcomes, e.g. erectile function and continence, after radical prostatectomy (RP) in African-American (AA) vs Caucasian-American (CA) men. PATIENTS AND METHODS: * Between October 2000 and July 2008, 1338 CA and 56 AA men underwent open RP by a single surgeon and signed informed consent to participate in a prospective longitudinal outcomes study. * The American Urological Association Symptom Score (AUA-SS) and University of California, Los Angeles, Prostate Cancer Index (UCLA-PCI) and a global assessment of satisfaction were self-administered at baseline and after RP 24 months. * Urinary, sexual, and satisfaction outcomes were compared at 24 months. RESULTS: * AA men had significantly higher rates of hypertension and diabetes. * There were no other significant baseline differences in age, co-morbidities, body mass index, phosphodiesterase type 5 inhibitor use, preoperative prostate-specific antigen level, AUA-SS, and UCLA-PCI scores. * There were no differences in the percentage of men undergoing nerve-sparing procedures, estimated blood loss, transfusion rates, or complication rates between the groups. * At 24 months after RP the mean UCLA-PCI urinary and sexual function and bother scores and global satisfaction scores were similar between the groups. CONCLUSION: * AA and CA men experience no significant differences in urinary and sexual HRQL or overall satisfaction after open RP when performed by a single experienced surgeon.

PURPOSE: The effect of statins on prostate cancer recurrence has been investigated in several studies with inconsistent results. We investigated whether statins were associated with biochemical recurrence in a large cohort of men after radical prostatectomy. We also performed a meta-analysis of existing studies. MATERIALS AND METHODS: A total of 1,446 patients who underwent radical prostatectomy at New York University were followed a median of 57 months for biochemical recurrence events. Baseline demographic and clinical characteristics were compared between 437 statin users and 1,009 nonusers. Kaplan-Meier curves and Cox models were used to examine biochemical recurrence-free survival by statin use. A meta-analysis was performed with data from our cohort and 5 published studies using the random effects model. RESULTS: Statin users were slightly older and more likely to have diabetes (p <0.01). They were similar to nonusers in race and body mass index. Although preoperative prostate specific antigen and tumor stage were similar between the 2 groups, the proportion of patients with pathological Gleason score 7-10 tumors was slightly higher among statin users (p = 0.03). The biochemical recurrence-free survival rate was 87.4% and 89.0% for statin users and nonusers, respectively, at the end of followup (log rank p = 0.26). Overall biochemical recurrence was not associated with statin use (HR 1.15, 95% CI 0.82-1.61). Results were similar when patients were stratified by D'Amico low and intermediate or high risk groups. Meta-analysis revealed no overall association between statins and biochemical recurrence (pooled HR 1.00, 95% CI 0.80-1.19). CONCLUSIONS: Our findings are consistent with the results of the meta-analysis, which indicated that preoperative statin use does not impact the overall risk of biochemical recurrence.