Faculty Bibliography

PURPOSE: We performed a global self-assessment of continence following radical retropubic prostatectomy (RRP) and determined how this global self-assessment of continence correlates with commonly used definitions of continence. MATERIALS AND METHODS: Between October 2000 and February 2002 all men who underwent RRP were encouraged to complete the University of California-Los Angeles Prostate Cancer Index 3, 6, 12 and 24 months postoperatively. Beginning October 2002 a single question capturing the patient global self-assessment of continence status was added to the postoperative continence assessment. The study design was cross-sectional since only continence surveys submitted between October 2002 through February 2003 were evaluated. Sensitivity, specificity and kappa coefficient was determined for the relationship between the patient global assessment of continence vs the definition of continence based on pad requirement, problem due to incontinence and frequency of incontinence. RESULTS: Continence progressively improved 3 to 24 months following RRP for all continence outcomes. At 24 months following RRP 97.1% of men considered themselves continent, while 97.1%, 94.1% and 97.1% were considered continent using continence definitions, including the requirement of no or 1 pad in a 24-hour interval, no or slight bother due to incontinence and total control or occasional dribbling, respectively. Our 3 definitions of continence derived from responses to the University of California-Los Angeles Prostate Cancer Index had excellent agreement with patient global self-assessment of continence (kappa coefficients between 0.76 and 0.83). CONCLUSIONS: The majority of men achieve continence without invasive intervention following RRP. Final continence status should be ascertained at 24 months. The patient global assessment of continence provides face validity for other definitions of continence based on responses to validated self-administered questionnaires

PURPOSE: We determined the impact of radical retropubic prostatectomy on continence and lower urinary tract symptoms (LUTS). MATERIALS AND METHODS: Between October 2000 and August 2002, 500 men with clinically localized prostate cancer underwent radical retropubic prostatectomy by a single surgeon, and completed the UCLA Prostate Cancer Index and American Urological Association (AUA) symptom index at baseline, 3, 6, 12 and 24 months after radical prostatectomy. Univariate analysis was performed to identify factors predisposing the early return of continence. RESULTS: A total of 100%, 98.3%, 97.1%, 94.2% and 98.6% of patients filled out the UCLA Prostate Cancer Index and AUA symptom index at baseline, and 3, 6, 12 and 24 months, respectively. Based on protective pad requirement or frequency of incontinence 100%, 90.9%, 87.2%, 92.1% and 98.5% vs 98.8%, 80.6%, 91.2%, 95.2% and 98.5% of men were continent at baseline, 3, 6, 12 and 24 months after surgery, respectively. Age, severity of lower urinary tract symptoms, Gleason score, nerve sparing status, blood loss or presence of benign prostatic tissue in the apical soft tissue margin did not predict early return of continence. All of the individual urinary symptoms captured by the AUA symptom score showed significant improvement after radical retropubic prostatectomy. Radical prostatectomy was associated with a mean 5.4 unit decrease in AUA symptom score (40% decrease) in men with baseline moderate/severe LUTS (AUA symptom score 8 or greater). CONCLUSIONS: The majority of men regain continence after radical retropubic prostatectomy and maximal continence is achieved by 24 months. No factors were identified that predicted early return of continence in our cohort of men undergoing radical prostatectomy. Radical prostatectomy has a clinically significant impact on improving LUTS

OBJECTIVES: To determine the value of intraoperative biopsy during radical retropubic prostatectomy. METHODS: Between October 2000 and August 2002, 500 men with clinically localized prostate cancer underwent radical retropubic prostatectomy by a single surgeon. A 2 to 3-mm circumferential biopsy was routinely obtained from the apical and bladder neck soft-tissue margin and submitted for frozen section examination. In selective cases suspicious for capsular incision, a biopsy was sent from what was believed to be the contiguous neurovascular bundle/lateral pedicle. RESULTS: Prostate cancer was observed in 4.5%, 0.8%, and 1.6% of the intraoperative biopsies sent from the apical, bladder neck, and neurovascular bundle/lateral pedicle soft-tissue margins, respectively. Patient age, Gleason score, perineural invasion on diagnostic prostate biopsy, and clinical stage were not associated with prostate cancer at the apical soft-tissue margin. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the surgical specimen to predict cancer in the apical soft-tissue margin was 57.7%, 98.2%, 62%, 97.7%, and 96%, respectively. Intraoperative biopsy of the apical soft-tissue margin reduced the positive margin rate by 3.8%. CONCLUSIONS: The yield of intraoperative biopsy of the bladder neck and neurovascular bundle/lateral pedicle is too low to justify it in routine practice. Biopsy of the apical soft tissue should be routinely performed to reduce the positive surgical margin rate

The clinical manifestations of benign prostatic hyperplasia (BPH) include lower urinary tract symptoms (LUTS), poor bladder emptying, urinary retention, detrusor instability, urinary tract infection, hematuria, and renal insufficiency. However, the majority of men with BPH present with LUTS only. Because LUTS can indicate a variety of conditions, evaluation of symptomatic men must first aim to identify or exclude BPH and, if present, assess its severity. It is important to assess symptom severity at baseline and during follow-up, using the American Urological Association Symptom Index or the International Prostate Symptom Score. Further testing can then be tailored to narrow the diagnosis and guide treatment decisions. Factors such as patient age and concomitant malignancy will also affect management, but the main goal of treatment remains the improvement of quality of life for the patient

The pathophysiology, epidemiology, and natural history of benign prostatic hyperplasia (BPH) are incompletely understood; however, the development of reliable instruments to measure symptom severity, prostatic enlargement, and bladder outlet obstruction has allowed major advances in their elucidation. The development of lower urinary tract symptoms (LUTS) in the aging male is influenced to some degree by the severity of bladder outlet obstruction and prostatic enlargement. Although the development of LUTS, bladder outlet obstruction, and BPH are age-dependent, they are not necessarily causally related; there are many other factors involved in the pathophysiology of LUTS. The clinically important parameters of disease progression in men with moderate to severe LUTS and low peak flow rates are symptom progression and the development of acute urinary retention (AUR). The risk of AUR is related to both baseline serum prostate-specific antigen level and prostate volume. In men with moderate prostate enlargement, the risk of AUR appears to be high enough to justify intervention with a 5alpha-reductase inhibitor in order to reduce this risk

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

BACKGROUND: Benign prostatic hyperplasia is commonly treated with alpha-adrenergic-receptor antagonists (alpha-blockers) or 5alpha-reductase inhibitors. The long-term effect of these drugs, singly or combined, on the risk of clinical progression is unknown. METHODS: We conducted a long-term, double-blind trial (mean follow-up, 4.5 years) involving 3047 men to compare the effects of placebo, doxazosin, finasteride, and combination therapy on measures of the clinical progression of benign prostatic hyperplasia. RESULTS: The risk of overall clinical progression--defined as an increase above base line of at least 4 points in the American Urological Association symptom score, acute urinary retention, urinary incontinence, renal insufficiency, or recurrent urinary tract infection--was significantly reduced by doxazosin (39 percent risk reduction, P<0.001) and finasteride (34 percent risk reduction, P=0.002), as compared with placebo. The reduction in risk associated with combination therapy (66 percent for the comparison with placebo, P<0.001) was significantly greater than that associated with doxazosin (P<0.001) or finasteride (P<0.001) alone. The risks of acute urinary retention and the need for invasive therapy were significantly reduced by combination therapy (P<0.001) and finasteride (P<0.001) but not by doxazosin. Doxazosin (P<0.001), finasteride (P=0.001), and combination therapy (P<0.001) each resulted in significant improvement in symptom scores, with combination therapy being superior to both doxazosin (P=0.006) and finasteride (P<0.001) alone. CONCLUSIONS: Long-term combination therapy with doxazosin and finasteride was safe and reduced the risk of overall clinical progression of benign prostatic hyperplasia significantly more than did treatment with either drug alone. Combination therapy and finasteride alone reduced the long-term risk of acute urinary retention and the need for invasive therapy

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

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