Faculty Bibliography

Critics of screening have stated that early detection of prostate cancer does not necessarily reflect a diminishing death rate from the disease. However, several recent reports have demonstrated that the death rate from prostate cancer is decreasing, representing the most compelling validation for aggressive screening. Prostate cancer can be halted only if there is no evidence of systemic or regional metastases and the disease is confined to the surgical field or the radiation template. Surgeons and radiation oncologists must make a concerted effort to exclude men with regional and systemic metastases who are unlikely to benefit from treatment. With the widespread acceptance of prostate-specific antigen screening, a greater proportion of men are being diagnosed with clinically localized prostate cancer. Both radical prostatectomy and radiation therapy are able to halt disease spread in this significant subset of men, but survival outcomes indicate that radical prostatectomy is a more reliable treatment than radiation therapy for clinically localized prostate cancer. Overall, the immediate treatment-related morbidity of radical prostatectomy and radiation therapy in the modern era is quite low. Radical prostatectomy and radiation therapy appear to have a similar impact on continence and erectile function. There is a need for neoadjuvant and adjuvant therapies that can be utilized in those cases where radical prostatectomy and radiation are less likely to completely eradicate or destroy the cancer

PURPOSE: Complexed (c) prostate specific antigen (PSA) has been shown to enhance specificity for prostate cancer (CaP) detection over total PSA (tPSA), although a large multi-institutional prospective evaluation was required to confirm these findings. We compared the clinical performance of cPSA with tPSA as a first line test for CaP detection and secondarily to determine if PSA ratios, namely percent free PSA (fPSA) and percent cPSA, can provide further enhancement in diagnostic performance over cPSA or tPSA. MATERIALS AND METHODS: Consecutive men scheduled for initial biopsy of the prostate were enrolled prospectively at each of 7 university centers and community based urology practices. Serum was collected and tested with the Immuno 1 (Bayer Diagnostics, Tarrytown, New York), tPSA and cPSA, and Access (Beckman, Inc., San Diego, California) fPSA and tPSA methods. RESULTS: A total of 831 patients were evaluated, of whom 313 (37.5%) were diagnosed with CaP. ROC curve analysis performed from the results of all samples and those within the clinically relevant cPSA ranges of 1.5 to 3.2, 1.5 to 5.1, 1.5 to 8.3 and 3.2 to 8.3 ng/ml (tPSA 2 to 4, 2 to 6, 2 to 10 and 4 to 10 ng/ml, respectively) indicated a significant improvement in the AUC ROC curve for cPSA compared with tPSA (p < or =0.001). Using cutoff points that provide a sensitivity of 80% to 95% for CaP detection within the 1.5 to 8.3 ng/ml cPSA range cPSA provided a statistically significant enhancement in specificity over tPSA of 6.2% to 7.9%. Within the cPSA range of 1.5 to 3.2 ng/ml using a cutoff point of 2.5 ng/ml for tPSA and 2.2 ng/ml for cPSA provided a specificity of 21.2% and 35%, respectively, and 85% sensitivity for CaP detection. PSA ratios provided no further enhancement in specificity over cPSA within these ranges. CONCLUSIONS: The use of cPSA as a single test provided improved specificity over tPSA. Percent fPSA and percent cPSA offered little to no additional benefit in the differentiation of benign and malignant disease at clinically relevant cPSA concentrations

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

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

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

Today, more men than ever before are being followed after radical prostatectomy. Prognosis and follow-up should be based on the pathologic specimen. Measurable prostate-specific antigen (PSA) after surgery defines failure, with time to detectable PSA and rate of PSA rise being useful prognostic factors. The natural history of untreated biochemical failure is protracted, a fact to be considered in discussions of adjuvant treatment. Early in disease recurrence, imaging studies to locate residual disease rarely are useful clinically. Both adjuvant and salvage radiation to the prostate bed have benefits and risks, but neither is superior in overall prostate cancer survival. The timing of hormone therapy remains largely empiric. The promise of effective cytotoxic chemotherapy still is greater than its actual benefits, although novel cytostatic agents are being developed. The future management of this disease will improve with better molecular definition of risk and therapeutic response

OBJECTIVES: To analyze the ability of volume-adjusted total, complexed, and free prostate-specific antigen (PSA) to predict organ-confined cancer at radical prostatectomy in patients with nonpalpable disease. METHODS: Collected sera were assayed for total PSA (tPSA), complexed PSA (cPSA), and free PSA (fPSA) in 78 men who underwent radical prostatectomy with nonpalpable prostate cancer. The pathologic results (organ-confined versus extraprostatic extension [EPE]), tPSA, cPSA, fPSA/tPSA ratio, cPSA/tPSA ratio, fPSA/cPSA ratio, tPSA density (tPSAD), cPSA density (cPSAD), and fPSA density (fPSAD) were compared by the Mann-Whitney U test and receiver operating characteristic curves. RESULTS: Fifteen men (19.2%) had pathologic EPE. After stratifying the patients on the basis of the Beckman tPSA, the cPSAD, tPSAD, and fPSAD were significant predictors of EPE when comparing their respective medians in individuals with tPSA greater than 4.0 ng/mL. Statistically significant differences were noted between patients with and without EPE for tPSAD (P = 0.0015), cPSAD (P = 0.0018), and fPSAD (P = 0.0022), but not for the fPSA/tPSA, cPSA/tPSA, and fPSA/cPSA ratios. The area under the receiver operating characteristic curve was similar for tPSA (0.539) and cPSA (0.542), as it was for tPSAD (0.708), cPSAD (0.700), and fPSAD (0.731). The specificity and diagnostic accuracy of tPSAD, cPSAD, and fPSAD were significantly greater than those of tPSA and cPSA (specificity P <0.001; diagnostic accuracy P <0.05). CONCLUSIONS: In men with nonpalpable prostate cancer, the density parameters of tPSA, cPSA, and fPSA performed equivalently and appeared to enhance the predictability of EPE