Faculty Bibliography

PURPOSE: We evaluate the efficacy of medical therapy on nocturia in men with benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: We performed a secondary analysis of data from the VA Cooperative Study Program Trial in which 1,229 men with BPH 45 to 80 years old were randomly assigned to receive terazosin, finasteride, combination or placebo. RESULTS: The 1,078 men who completed 12 months of the trial are included in this study. Of those men 1,040 (96.5%) had at least 1 episode of nocturia at baseline and 38 (3.5%) had less than 1 episode (baseline nocturia is an average of 2 measures). Of those 1,040 men 788 (75.8%) had 2 or more nocturia episodes. Overall, nocturia decreased from a baseline mean of 2.5 to 1.8, 2.1, 2.0 and 2.1 episodes in the terazosin, finasteride, combination and placebo groups, respectively. Of men with 2 or more episodes of nocturia 50% reduction in nocturia was seen in 39%, 25%, 32% and 22% in the terazosin, finasteride, combination and placebo groups, respectively. Changes in nocturia were correlated with changes in reported bother from nocturia (Pearson correlation 0.48), BPH impact index (0.32) and overall satisfaction with urinary symptoms (0.33). CONCLUSIONS: Terazosin and combination therapy reduced nocturia in men with BPH, yet the net advantage of terazosin over placebo was a net reduction of 0.3 nocturia episode. For a person to reach a 50% or greater reduction in nocturia, the advantage of terazosin over placebo was 17 percentage points. Changes in nocturia had a moderate impact on symptom specific quality of life measures

PURPOSE: We developed an algorithm that prospectively defines when to excise the neurovascular bundles during radical retropubic prostatectomy with the goal of maximizing the performance of nerve sparing procedures while minimizing positive surgical margins. MATERIALS AND METHODS: From January 1 to December 31, 2000 a single surgeon performed 272 radical retropubic prostatectomies and 263 were performed from January 1 to December 31, 2001. A single pathologist analyzed all specimens with positive margins. There were no prospectively defined criteria to guide decisions regarding excision of the neurovascular bundles in the 2000 study cohort. Gleason score, percent tumor volume and perineural invasion were independently analyzed in the biopsy specimens according to the site of origin (right versus left side) for the 2001 group only. The ipsilateral neurovascular bundle was excised for Gleason 6 or less tumors when there were 50% or greater tumor volume in the biopsy specimen and perineural invasion, for Gleason 7 tumors when there was 30% or greater tumor volume, or perineural invasion and for Gleason 8 to 10 tumors when there was 10% or greater tumor volume, or perineural invasion. RESULTS: There were no statistically significant differences between the 2000 and 2001 groups in regard to preoperative prostate specific antigen, clinical and pathological stage, biopsy Gleason score and percent tumor volume in the surgical specimen. There was a statistically significant decrease in the incidence of positive margins between the 2000 and 2001 groups (14% versus 8%, p = 0.027). The lower positive margin rate was not achieved because of a tendency to excise more neurovascular bundles since a significantly greater percent of neurovascular bundles was preserved in the 2001 group. The sensitivity, specificity, positive and negative predictive values, and accuracy of our algorithm were 18%, 93%, 28%, 89% and 84%, respectively. In sides of the prostate with extraprostatic extension ipsilateral wide excision of the neurovascular bundle was associated with positive margins in 33% of cases compared with 22% when the neurovascular bundle was preserved (p = 0.42). CONCLUSIONS: The New York University nerve sparing algorithm prospectively defines when to excise the neurovascular bundle based on Gleason score, perineural invasion and tumor volume in the biopsy specimen. Use of this algorithm decreases positive surgical margin rates, while significantly increasing the preservation of neurovascular bundles

Overall, in the hands of an experienced surgeon, the outcomes following radical prostatectomy are excellent. Attention to patient selection, preoperative management, surgical technique, and postoperative management are essential factors contributing to favorable outcomes for men with a biologically significant cancer and 10-year life expectancy. For these men, radical prostatectomy represents the optimal management based on cure, morbidity, and quality of life

Alpha-blockers and 5-alpha-reductase inhibitors are medical therapies that are being used as alternatives to surgical interventions to relieve symptoms of benign prostatic hyperplasia (BPH). Taken as monotherapy, alpha-blockers and 5-alpha-reductase inhibitors have each been shown to provide relief from BPH symptoms. Treatment with finasteride over 4 years has been shown to reduce both BPH symptoms and the likelihood of acute urinary retention and the need for surgery. Direct comparison of the alpha-blocker terazosin with finasteride has been done, but only for a period of 1 year. The Medical Therapy of Prostatic Symptoms (MTOPS) trial is a multicenter, randomized, placebo-controlled, double-masked clinical trial designed to evaluate the long-term efficacy of the alpha-blocker doxazosin and the 5-alpha-reductase inhibitor finasteride, whether taken as a monotherapy or in combination, in preventing or delaying the progression of BPH. We describe in this paper the design of the MTOPS trial, the concept of BPH progression, the definition and methods of determining the primary outcome events and the proposed statistical analysis methods. A unique feature of MTOPS is the inclusion of prostate biopsies on a subgroup of randomized participants. Volunteers among randomized participants are to undergo a biopsy of the prostate at predetermined time points during the trial. Studies that will be conducted using the tissue specimens collected in MTOPS can potentially provide information at the molecular level on the natural history of BPH among medically treated and untreated men with moderate to severe symptoms of BPH

OBJECTIVES: To determine the influence of body weight and prostate volume on surgical outcomes after radical retropubic prostatectomy. METHODS: Between January 1994 and July 2000, 1024 men underwent radical retropubic prostatectomy by a single surgeon. Information was collected on body weight, prostate volume, operative time, estimated blood loss, allogenic transfusion rate, intraoperative complications, perioperative complications, postoperative complications, surgical margin status, and length of hospital stay. Postoperative continence and erectile function were assessed from self-administered questionnaires. RESULTS: Body weight was not significantly related to operative time (P = 0.09), estimated blood loss (P = 0.12), allogenic transfusion rate (P = 0.49), intraoperative complications (P = 0.37), perioperative complications (P = 0.84), postoperative complications (P = 0.44), positive margin rate (P = 0.07), length of hospital stay (P = 0.27), postoperative continence (P = 0.72), or postoperative erectile function (P = 0.92). The prostate volume was significantly and directly related to the estimated blood loss (P = 0.02), allogenic transfusion rate (P = 0.01), and length of hospital stay (P = 0.01). The prostate volume was significantly and inversely related to the positive surgical margin rate (P = 0.03). The prostate volume was not significantly related to the operative time (P = 0.12), intraoperative complications (P = 0.68), perioperative complications (P = 0.73), postoperative complications (P = 0.14), postoperative continence (P = 0.23), or postoperative erectile function (P = 0.90). CONCLUSIONS: No clinically relevant risks were associated with increasing body weight. Intraoperative bleeding resulting in higher transfusion rates represented the only clinically significant outcome that was adversely impacted by prostate volume. In the hands of experienced surgeons, radical retropubic prostatectomy can be performed in heavy men and in men with large prostates with excellent outcomes

BACKGROUND: One of the major constraints in elucidating the mechanisms involved in the etiology of benign prostatic hyperplasia (BPH) is the lack of suitable model systems that are readily manipulable in vitro and in vivo. To address this issue, we have used murine prostatic cell lines to establish a novel in vivo model for studying prostatic cell interactions. METHODS: Luminal, basal, and smooth muscle (SM) cell lines were inoculated alone or in combinations under the renal capsule of intact or castrated male mice, and the growth and composition of prostatic tissue in the absence or presence of doxazosin was determined. RESULTS: Both the luminal and basal cell lines reconstituted prostatic tissue if co-inoculated under the renal capsule with normal SM cells, whereas none of the lines formed significant tissue when inoculated alone. Luminal cells produced and secreted prostatic secretory products. The growth of prostatic tissue formed from co-inoculation of basal and SM cells was androgen responsive. In addition, a significant reduction in prostatic tissue was noted in animals treated with doxazosin. CONCLUSION: We have established an in vivo model that uses prostatic epithelial and SM cell lines for investigating cellular interactions between epithelial and SM cells that regulate prostatic growth and function. This model will be useful for delineating the mechanisms by which prostatic cells interact and in determining the efficacy of new approaches aimed at interfering with prostatic stromal/epithelial interactions that result in abnormal cellular proliferation

OBJECTIVES: To determine the feasibility and safety of removing the urinary catheter on postoperative day (POD) 3 or 4 after radical retropubic prostatectomy (RRP). METHODS: Between January 2001 and August 2001, gravity cystography was performed on POD 3 or 4 after RRP by a single surgeon (H.L.) on 151 men. The urinary catheter was removed on POD 3 or 4 providing no extravasation was evident on cystography. Urinary catheters were replaced over a guidewire placed into the bladder under flexible cystoscopic guidance in cases of acute urinary retention (AUR). Continence was assessed at 3 months after RRP. RESULTS: Of the 151 cystograms performed on POD 3 or 4, 116 (76.8%) revealed no evidence of extravasation. The indwelling catheters were removed in 114 of these cases (98.3%). Twenty-two (19.3%) of the 114 men whose catheters were removed on POD 3 or 4 developed AUR within 48 hours of catheter removal, requiring catheter replacement. Two of these patients required repeated surgery secondary to complications related to AUR. At 3 months after RRP, 75% of the men whose catheters were removed on POD 3 or 4 required no pads or a single pad during a 24-hour interval, and 77.6% reported none or slight bother from incontinence. Of the 37 men whose catheters were removed on POD 7 or later, 1 patient (2.7%) developed AUR, and the catheter was replaced without complications. At 3 months after RRP, 65.7% of men whose catheters were removed on POD 7 or later required no pads or a single pad during a 24-hour interval, and 71.4% reported none or slight bother from incontinence. The incidence of anastomotic stricture in men whose catheters were removed on POD 3 or 4 and POD 7 or later was 12.1% and 22.6%, respectively. CONCLUSIONS: Most men will have a watertight anastomosis on POD 3 or 4 after RRP. Early catheter removal does not have a negative impact on continence or the rate of anastomotic strictures. Because of the high incidence of AUR, requiring replacement of the urinary catheter, and the potential for disruption of the anastomosis or bladder neck reconstruction, we currently recommend delaying catheter removal until POD 7 or later

The treatment of benign prostatic hyperplasia (BPH) has changed dramatically over the past 10 years. Phase 3 studies of the safety and effectiveness of alpha-blockers (eg, terazosin and doxazosin) and 5-alpha-reductase inhibitors (eg, finasteride) for the treatment of BPH began to appear in the literature in 1992. This article reviews the results of landmark studies of these agents, either separately as monotherapy or as combined therapy, for the treatment of BPH. The relationship between prostate size and lower urinary tract symptoms (LUTS) is discussed. Although prostate volume is not as strongly correlated with these symptoms as was once believed, it has been shown to be an important predictor of risk for developing acute urinary retention. alpha-Blockers represent an effective treatment for LUTS independent of prostate volume; the clinical benefit of finasteride for LUTS is limited primarily to men with large prostates. Finasteride decreases the risk of progression to acute urinary retention and the requirement for surgical intervention; this benefit is greatest in men with enlarged prostates

The treatment of benign prostatic hyperplasia (BPH) has changed dramatically over the past 10 years. Phase 3 studies of the safety and effectiveness of alpha-blockers (eg, terazosin and doxazosin) and 5-alpha-reductase inhibitors (eg, finasteride) for the treatment of BPH began to appear in the literature in 1992. This article reviews the results of landmark studies of these agents, either separately as monotherapy or as combined therapy, for the treatment of BPH. The relationship between prostate size and lower urinary tract symptoms (LUTS) is discussed. Although prostate volume is not as strongly correlated with these symptoms as was once believed, it has been shown to be an important predictor of risk for developing acute urinary retention. alpha-Blockers represent an effective treatment for LUTS independent of prostate volume; the clinical benefit of finasteride for LUTS is limited primarily to men with large prostates. Finasteride decreases the risk of progression to acute urinary retention and the requirement for surgical intervention; this benefit is greatest in men with enlarged prostates