Potential benefit of transrectal saturation prostate biopsy as an initial biopsy strategy: decreased likelihood of finding significant cancer on future biopsy.

OBJECTIVE: To identify the ability of transrectal saturation prostate biopsy (SPBx) as the initial diagnostic approach to reduce the likelihood of finding previously unrecognized prostate cancer (PCa) during repeat prostate biopsy. MATERIALS AND METHODS: We reviewed PCa detection in 561 men who underwent first repeat SPBx after initial negative biopsy between March 2002 and April 2012. We divided the patients on the basis of the number of cores retrieved on initial biopsy (group 1, initial negative SPBx [n = 81] and group 2, initial negative extended prostate biopsy [n = 480]). The yield of repeat SPBx was compared between the 2 groups. Insignificant PCa and low-risk PCa were defined according to Epstein criteria and D'Amico risk criteria, respectively. RESULTS: PCa detection on first repeat SPBx was 43.1% lower in group 1 (19.8% vs 34.8%; P = .008). Moreover, lower rate of significant PCa (31.3% vs 74.3%; P <.001) and intermediate- and/or high-risk PCa (25.0% vs 50.9%; P = .048) in group 1. Multivariate analysis confirmed that initial negative SPBx decreased PCa detection on first repeat SPBx (odds ratio = 0.41, 95% confidence interval 0.22-0.78). CONCLUSION: Men whose initial biopsy was per transrectal saturation technique were less likely to have cancer identified during repeat biopsy. Furthermore, PCa diagnosed after negative initial SPBx was much more likely to be clinically insignificant. These findings suggest that SPBx may be less likely to miss clinically significant cancer during initial prostate biopsy. If confirmed in other studies, this suggests that initial biopsy by saturation technique may eliminate the need for most men to undergo repeat biopsy.

Vacuum erection devices revisited: its emerging role in the treatment of erectile dysfunction and early penile rehabilitation following prostate cancer therapy.

INTRODUCTION: Vacuum erection devices (VEDs) are becoming first-line therapies for the treatment of erectile dysfunction and preservation (rehabilitation) of erectile function following treatment for prostate cancer. Currently, there is limited efficacy of the use of phosphodiesterase type 5 inhibitors in elderly patients, or patients with moderate to severe diabetes, hypertension, and coronary artery disease. AIM: The article aims to study the role of VED in patients following prostate cancer therapy. RESULTS: Alternative therapies such as VED have emerged as one of the primary options for patients refractory to oral therapy. VED has also been successfully used in combination treatment with oral therapy and penile injections. More recently, there has been interest in the use of VED in early intervention protocols to encourage corporeal rehabilitation and prevention of postradical prostatectomy veno-occlusive dysfunction. This is evident by the preservation of penile length and girth that is seen with early use of the VED following radical prostatectomy. There are ongoing studies to help preserve penile length and girth with early use of VED following prostate brachytherapy and external beam radiation for prostate cancer. Recently, there has also been interest in the use of VED to help maintain penile length following surgical correction of Peyronie's disease and to increase penile size prior to implantation of the penile prosthesis. CONCLUSION: VEDs can be one of the options for penile rehabilitation after prostate cancer therapy.

Early intervention with phosphodiesterase-5 inhibitors after prostate brachytherapy improves subsequent erectile function.

OBJECTIVE: To examine the early use of phosphodiesterase-5 inhibitor (PDE-5i; sildenafil citrate) in preventing subsequent erectile dysfunction (ED) after (monotherapy) prostate brachytherapy (PB, an accepted option for Gleason 6 or low-volume Gleason 7 prostate cancer), as PB is currently being offered more frequently in younger patients, and ED can be a side-effect often within the first 12 months after treatment. PATIENTS AND METHODS: We examined a single-surgeon series of 69 patients who had been treated with PB from 2002 to 2005. All patients had a follow-up of ≥ 1 year; prospectively, and patients had baseline, 6- and 12-month assessments using the Sexual Health Inventory for Men (SHIM) and International Index of Erectile Function (IIEF)-6 scores. The 69 patients were divided into early treatment with PDE-5i (31) and not treated with PDE-5i (38), and their SHIM and IIEF-6 scores were compared at baseline, 6 and 12 months. Daily sildenafil (25-50 mg) was given immediately after PB for 12 months. Overall, for the entire group, the mean prostate-specific antigen (PSA) level was 6.8 ng/mL; 78% had Gleason 6 cancer and 20% had Gleason 7 (3 + 4) cancer. The mean age in the early PDE-5i group was 64.8 years, and was 66.0 years in the no-PDE-5i group. The mean radiation dose in the early PDE-5i group was 50.2 Gy, and 43.9 Gy in the other group (P= 0.08). RESULTS: In the no-PDE-5i group, the mean baseline SHIM score of 17.1 decreased rapidly to 9.1 at 6 months (P= 0.01) and stayed at 9.3 at 12 months (P= 0.01). In the early PDE-5i group, the mean baseline SHIM score of 21.8 decreased slightly to 17.6 at 6 months (P= 0.2), and was maintained at 17.9 at 12 months (P= 0.2). Using the Wilcoxon rank-sum test, the 6- and 12-month SHIM scores in the two groups (P < 0.001). The IIEF-6 questionnaire confirmed the SHIM analysis. CONCLUSIONS: After PB patients had a significant decline in SHIM/IIEF-6 scores at 6 and 12 months. Our results indicate a 50% decrease in the quality of their erections. This provides an opportunity to initiate early intervention with PDE-5i or perhaps vacuum constriction devices or intraurethral alprostadil. In this study, the early use of PDE-5i after PB maintained erectile function at both 6 and 12 months.

Long-term potency after early use of a vacuum erection device following radical prostatectomy.

OBJECTIVE: To evaluate the long-term potency after radical prostatectomy (RP) with the early use of a vacuum erection device (VED), and reasons for sexual inactivity and long-term attrition and maintenance of sexual activity, as RP is one of the most common treatments for prostate cancer but erectile dysfunction (ED) is a common side-effect. PATIENTS AND METHODS: We identified 141 sexually active patients who underwent RP at Cleveland Clinic Foundation. Patients were offered various non-oral treatment options to prevent ED and were also motivated for early penile rehabilitation. At 5 years 62% remained sexually active, of whom 71% had natural erections sufficient for intercourse without assistance, 8.5% were still using sildenafil, 10% were using combined therapy (sildenafil plus VED). At 5 years 38% (43/113) men were sexually inactive. The reasons included loss of interest in 17 (40%), cardiovascular/neurological diseases in 18 (42%), hormonal therapy in three (7%), loss of partner in three (7%) and two had other surgery. The natural rate of erections for sufficient vaginal penetration without an erection aid were preserved and maintained in the early-prophylaxis group, and almost 60% of them had used a VED as early prophylaxis. CONCLUSION: Despite current phosphodiesterase-5 inhibitor treatments for ED, VED is becoming recognized again as having a primary role in early penile rehabilitation in many patients, specifically those treated for prostate cancer.

Does transrectal ultrasound probe configuration really matter? End fire versus side fire probe prostate cancer detection rates.

PURPOSE: We compared prostate cancer detection rates for the 2 most commonly used transrectal ultrasound prostate biopsy probes, end fire and side fire, to determine whether the probe configuration affects detection rates. MATERIALS AND METHODS: We evaluated 2,674 patients who underwent initial prostate biopsy between 2000 and 2008 with respect to prostate specific antigen, biopsy technique and pathological findings. Patients were divided into 1,124 in whom biopsies were performed with an end fire probe and 1,550 in whom biopsies were performed with a side fire probe. RESULTS: There was a significant difference in the overall cancer detection rate in the end vs side fire arms (45.8% vs 38.5%, p <0.001). In the subsets of patients with prostate specific antigen greater than 4 to 10 ng/ml or less and greater than 10 ng/ml a significant difference persisted (46.4% vs 38.9% and 61.7% vs 49.1%, p <0.004 and <0.015, respectively). There was also a significant difference in detection rates between probes in those who underwent 8 to 19 biopsy cores (p <0.009). Biopsies of greater than 20 cores failed to attain statistical significance (p >0.105). We also found that prostate volume, patient age, prostate specific antigen and hypoechoic findings were independent variables for predicting cancer detection on multivariate analysis (p <0.001). CONCLUSIONS: The type of probe significantly affects the overall prostate cancer detection rate, particularly in patients with prostate specific antigen greater than 4 ng/ml and/or nonsaturation (8 to 19 cores) prostate biopsy. This may be because the end fire probe allows better mechanical sampling of the lateral and apical regions of the peripheral zone, where cancer is most likely to reside. We set the stage for a randomized, controlled trial to confirm our observations.

Vacuum erection devices to treat erectile dysfunction and early penile rehabilitation following radical prostatectomy.

Vacuum erection devices (VED) are becoming first-line therapies for erectile dysfunction and preservation (rehabilitation) of erectile function following treatment for prostate cancer. Currently, phosphodiesterase-5 inhibitors have limited efficacy in elderly patients or patients with moderate to severe diabetes, hypertension, and coronary artery disease. Alternative therapies, such as VED, have emerged as a primary option for patients refractory to oral therapy. VED has also been successfully used in combination treatment with oral therapy and penile injections. More recently, there has been interest in the use of VED in early intervention protocols to encourage corporeal rehabilitation and prevention of post-radical prostatectomy venoocclusive dysfunction. This is evident by the preservation of penile length and girth seen with the early use of the VED following radical prostatectomy. There are ongoing studies to help preserve penile length and girth with early use of VED following prostate brachytherapy and external beam radiation for prostate cancer. Recently, there has also been interest in VED to help maintain penile length following surgical correction of Peyronie's disease and to increase penile size before implantation of the penile prosthesis.

The clinical utility of atypical cytology is significantly increased in both screening and monitoring for bladder cancer when indexed with nuclear matrix protein-22.

OBJECTIVES: To assess atypical cytology as a positive bladder tumour marker and to determine if indexing atypical cytology to nuclear matrix protein-22 (NMP22) can decrease the false-positive results or increase the positive predictive value (PPV). PATIENTS AND METHODS: In all, 197 patients at risk of bladder cancer were identified as having atypical urine cytology; 126 were incident (screening) cases and 71 were prevalent (monitoring) cases of bladder cancer. All patients with atypical cytology were evaluated using office cystoscopy. All cancers were confirmed histologically and patients had a negative upper tract study within a 1-year interval. The atypical cytology was then indexed with NMP22 values in an effort to decrease the false-positive results. RESULTS: Atypical cytology detected 17 cancers in the 126 patients who were screened, giving a PPV of 13% (17/126). When stratified by NMP22, using a threshold of >10 U/mL, the PPV increased to 71% (15/21). In the 71 patients who were being monitored, atypical cytology detected 43 cancers, for a PPV of 61% (43/71). When stratified by NMP22 using a threshold of >6 U/mL, the PPV increased to 92% (35/38). CONCLUSIONS: The clinical utility of atypical cytology was significantly increased in both screening and monitoring for bladder cancer when indexed with NMP22 levels.

Saturation technique does not decrease cancer detection during followup after initial prostate biopsy.

PURPOSE: It has been reported that the prostate cancer detection rate in men with prostate specific antigen 2.5 ng/ml or greater undergoing saturation (20 cores or greater) prostate biopsy as an initial strategy is not higher than that in men who undergo 10 to 12 core prostate biopsy. At a median followup of 3.2 years we report the cancer detection rate on subsequent prostate biopsy in men who underwent initial saturation prostate biopsy. MATERIALS AND METHODS: Saturation prostate biopsy was used as an initial biopsy strategy in 257 men between January 2002 and April 2006. Cancer was initially detected in 43% of the patients who underwent saturation prostate biopsy. In the 147 men with negative initial saturation prostate biopsy followup including digital rectal examination and repeat prostate specific antigen measurement was recommended at least annually. Persistently increased prostate specific antigen or an increase in prostate specific antigen was seen as an indication for repeat saturation prostate biopsy. RESULTS: During the median followup of 3.2 years after negative initial saturation prostate biopsy 121 men (82%) underwent subsequent evaluation with prostate specific antigen and digital rectal examination. Median prostate specific antigen remained 4.0 ng/ml or greater in 57% of the men and it increased by 1 ng/ml or greater in 23%. Cancer was detected in 14 of 59 men (24%) undergoing repeat prostate biopsy for persistent clinical suspicion of prostate cancer. No significant association was demonstrated between cancer detection and initial or followup prostate specific antigen, or findings of atypia and high grade prostatic intraepithelial neoplasia on initial saturation prostate biopsy. Cancers detected on repeat prostate biopsy were more likely to be Gleason 6 and organ confined at prostatectomy than were those diagnosed on initial saturation prostate biopsy. CONCLUSIONS: Previous experience suggests that, while office based saturation prostate biopsy improves cancer detection in men who have previously undergone a negative prostate biopsy, it does not improve cancer detection as an initial biopsy technique. We now report that the false-negative rate on subsequent prostate biopsy after initial saturation prostate biopsy is equivalent to that following traditional prostate biopsy. These data provide further evidence against saturation prostate biopsy as an initial strategy.

Limited pelvic lymph node dissection does not improve biochemical relapse-free survival at 10 years after radical prostatectomy in patients with low-risk prostate cancer.

OBJECTIVES: To compare the long-term differences in actuarial biochemical relapse-free survival rates from a contemporary series of patients who underwent radical prostatectomy with and without pelvic lymph node dissection (PLND). METHODS: The records of 806 consecutive radical prostatectomy cases performed from January 1995 to June 1999 were reviewed. The entire subset of patients (n = 336) with low-risk disease, defined by a prostate-specific antigen level of 10 ng/mL or less, biopsy Gleason score of 6 or less, and clinical Stage T1 or T2a, who had not received adjuvant or neoadjuvant therapy were divided into two groups according to whether PLND was performed (PLND group, n = 140) or omitted (no-PLND group, n = 196). A Cox proportional hazards model was used to analyze the effect of demographic, pretreatment, surgical, and pathologic factors on the likelihood of biochemical failure. Biochemical relapse-free survival for each group was estimated by Kaplan-Meier analysis. The median prostate-specific antigen follow-up time for the entire group was 89.0 months, with a similar follow-up for both cohorts (PLND group 94.5 months and no-PLND group 88.0 months, Mann-Whitney U test, P = 0.14). RESULTS: The long-term biochemical relapse-free survival rate for the entire cohort was 86.1% at 10 years. The 10-year actuarial biochemical relapse-free rate for the PLND and no-PLND groups was 83.8% and 87.9%, respectively (log-rank, P = 0.33). On univariate analysis, PLND was not an independent predictor of outcome (Wald, P = 0.33). CONCLUSIONS: The results of our study have shown that the omission of limited PLND in patients with favorable tumor characteristics does not adversely affect biochemical relapse-free survival at 10 years. Such patients can be spared the morbidity and cost of PLND without affecting their chance for cure.

Urinary cytology and nuclear matrix protein 22 in the detection of bladder cancer recurrence other than transitional cell carcinoma.

OBJECTIVE: To assess the value of nuclear matrix protein-22 (NMP22), compared with urinary cytology, in predicting the recurrence of bladder cancer that is not transitional cell carcinoma (non-TCC). PATIENTS AND METHODS: We tested the sensitivity, specificity and the predictive accuracy of NMP22 in the context of non-TCC bladder cancer recurrence, and compared it to the performance of urinary cytology. The study group comprised 2687 patients with history of non-muscle-invasive bladder cancer from 10 centres across four continents. RESULTS: The mean patient age was 64.8 years and 75.4% were men; of all patients, 513 (19.1%) had positive urinary cytology, 906 (33.7%) had a positive NMP22 test (>or=10 units/mL) and 80 (3.0%) had non-TCC recurrence. Most of these, i.e. 60 (75%), were stage >or=T2. The sensitivity and specificity of urinary cytology were, respectively, 20.0% and 94.8%, vs 77.5% and 81.8% for NMP22 of >or=10 units/mL. The predictive accuracy of urinary cytology was 57.5%, vs 87.1% for NMP22 >or= 10 units/mL. A combined model that included dichotomized NMP22 and urinary cytology was 85.3% accurate. CONCLUSION: The ability of a NMP22 level of >or=10 units/mL to predict non-TCC recurrence was better than that of urinary cytology, suggesting that NMP22 might have a role in the surveillance of patients at risk of non-TCC recurrence.

Nerve-sparing surgery significantly affects long-term continence after radical prostatectomy.

OBJECTIVES: In this long-term prospective study we evaluated the factors affecting urinary continence after radical prostatectomy. METHODS: In this study, we recruited 156 patients (mean age, 64.1 +/- 6.7 years; follow-up, 7.8 +/- 1.3 years; prostate-specific antigen [PSA] level, 9.57 +/- 8.81 ng/mL) who underwent radical prostatectomy between 1995 and 1998. Long-term data were obtained on 152 patients, with 4 patients lost to follow-up. Incontinence was evaluated by the number of pads per day. Follow-up data were collected at 3, 6, 12, and 24 months and annually. The multivariate analysis included the following variables: preoperative PSA levels, nerve-sparing (NS) status (bilateral NS, unilateral NS, and non-NS), and age at the time of operation (< or = 65 or > 65 years). RESULTS: With a mean follow-up of 7.8 +/- 1.3 years, the overall incontinence rate was 17.7% (27 of 152). The incontinence rates were significantly higher in the non-NS group (18 of 61) compared with the bilateral NS group (6 of 66; P <0.05). No significant difference was seen between the unilateral NS and non-NS groups in terms of incontinence rates (P >0.05). When stratified by the NS status, the bilateral NS group had a significant improvement in overall continence. The association between age and incontinence was significant: P <0.05 for patients 65 years or younger (7 of 85) versus those older than 65 years (20 of 67). The association between the preoperative PSA levels and incontinence was not significant but showed a trend (the median PSA in the incontinence group was 8.75 ng/mL; in the continence group it was 5.9 ng/mL; P = 0.0534). CONCLUSIONS: Nerve-sparing radical prostatectomy improves the time interval to regain continence and long-term continence rates.

Penile rehabilitation following radical prostatectomy: role of early intervention and chronic therapy.

The increase in the number of prostate cancer survivors and their relatively young age has prompted many urologists to concentrate on early penile rehabilitation to improve potency rates following radical prostatectomy. Positive results from various procedures range from 14% to 81% following bilateral nerve-sparing laparoscopic radical prostatectomy, to 43% to 97% following robotic-assisted laparoscopic prostatectomy. An early program with an erectaid improves erectile physiology and performance and logistically, the combination of a 5-phosphodiesterase inhibitor and a vacuum constriction device may prove to be the most user-friendly, cost-effective, and patient-compliant. Other issues that affect patient compliance, such as loss of interest and fear of undertaking sexual activity, will only be revealed through long-term patient follow-up and care.

Female sexual dysfunction: classification, pathophysiology, and management.

Female sexual dysfunction is a prevalent problem in the general community; however, it has not been studied as extensively as male sexual dysfunction. Female sexual dysfunction is a common complication after most pelvic surgeries. With the introduction of screening programs, most pelvic malignancies are detected at earlier stages and in younger patients. Sexual dysfunction is a major quality-of-life issue in these young women. Hysterectomy (simple or radical) is the most common type of pelvic surgery in women and is one of the most important causes of female sexual dysfunction. Additionally, female sexual dysfunction is an important issue after urologic (radical cystectomy) and colorectal surgeries (simple and radical proctocolectomy). Sexual dysfunction is a common problem among postmenopausal women. Modifications in the surgical technique (nerve sparing) are rapidly evolving in the field of urology and colorectal surgery, which will be soon followed by modifications in the field of gynecologic surgery. In this article we summarize the pathophysiology and classification of female sexual dysfunction, with special emphasis on the relationship between female sexual dysfunction and pelvic surgeries.

The early use of transurethral alprostadil after radical prostatectomy potentially facilitates an earlier return of erectile function and successful sexual activity.

OBJECTIVE: To assess whether early introduction of the Medicated Urethral System for Erection (MUSE(TM), Vivus Inc., Mountain View, CA, USA) after radical prostatectomy (RP) results in a shorter recovery time for the return to functional erections and successful sexual activity. PATIENTS AND METHODS: In a prospective study of 91 sexually active men who had a nerve-sparing RP for prostate cancer, 56 were treated with MUSE (125 or 250 microg three times per week for 6 months) while the remaining 35 had no erectogenic aids, except as necessary when attempting sexual activity. Self-administration of MUSE was initiated approximately 3 weeks after RP. Treatment efficacy was analysed by the patient's response to the Sexual Health Inventory for Men (SHIM) questionnaire. RESULTS: The mean patient age was approximately 59 years and the median follow-up 6 months; the compliance rate was 68%. Patients reported a significant improvement in all domains of the SHIM questionnaire after using MUSE. At the end of 6 months 74% of the patients who remained on MUSE were able to have successful vaginal intercourse. Of patients who completed the 6-month course of MUSE, half were able to have successful vaginal intercourse by the end of treatment. Most of these patients reported the recovery of spontaneous erections and required no additional erectogenic aids for successful intercourse. They had a mean SHIM score of 18.9. All 56 patients who received MUSE reported mild penile aching or urethral burning, and of these, 32% discontinued treatment. In the untreated control group, 37% regained erections sufficient for vaginal intercourse at the 6-month follow-up, with a mean SHIM score of 15.8. Of the control patients who recovered penile function, 71% were dissatisfied with the quality of their erections and sought adjuvant therapy. CONCLUSIONS: Initiating MUSE shortly after RP is safe and tolerable, and appears to shorten the recovery time to reagin erectile function.

Long-term effectiveness of luteinizing hormone-releasing hormone agonist or antiandrogen monotherapy in elderly men with localized prostate cancer (T1-2): a retrospective study.

AIM: To evaluate the long-term effectiveness, side effects and compliance rates of two types of drugs (luteinizing hormone-releasing hormone [LHRH] agonist and antiandrogen) that were used individually to treat patients with localized prostate cancer (T1-2) at our institution. METHODS: Ninety-seven patients who were diagnosed in the period from April 1997 to January 2000 as having clinically localized prostate cancer (T1-2) received either LHRH agonist (leuprolide acetate 7.5 mg/month) monotherapy (group 1, n = 62) or antiandrogen monotherapy (group 2, n = 35; 18 received bicalutamide 50 mg q.d., 13 received nilutamide 150 mg t.i.d. and 4 received flutamide 250 mg t.i.d.). The mean age in both groups was 76 years. RESULTS: The mean follow-up time was (50.8 +/- 8.5) months in group 1 and (43.1 +/- 2.2) months in group 2. Prostate-specific antigen (PSA) levels rose in only 1 of the 62 patients (1.6%) in group 1, and in 20 of the 35 patients (57.1%) in group 2. In group 2, 10 of the 20 patients (50%) with increasing PSA levels were treated with LHRH salvage therapy, and eight (80%) responded. Hot flashes (54.8%) and lethargy (41.9%) were the most common side effects in group 1. In contrast, nipple-tenderness (40%) and light-dark adaptation (17.1%) were more often seen in group 2. Only 1 of the 62 patients (1.6%) in group 1 switched to another medication because of adverse side effects; whereas 8 of the 35 patients (22.9%) in group 2 did so. CONCLUSION: Unlike antiandrogen monotherapy, LHRH agonist monotherapy provided long-term durable control of localized prostate cancer (T1-2). It can also be an effective treatment option for patients whose disease failed to respond to antiandrogen monotherapy. The limitations of our study are the lack of health outcomes analysis and a small sample size.

The incidence of high-grade prostatic intraepithelial neoplasia and atypical glands suspicious for carcinoma on first-time saturation needle biopsy, and the subsequent risk of cancer.

OBJECTIVE: To investigate the detection rate and extent of high-grade prostatic intraepithelial neoplasia (HGPIN) and atypical glands (AG) suspicious for prostate cancer, and the cancer risk in subsequent biopsies, diagnosed by a first 24-core saturation biopsy, as although the optimum extent of biopsy is controversial there is a trend to increase the number of cores taken, and apart from detecting prostate cancer, identifying HGPIN and AG is associated with a greater risk of finding cancer in subsequent biopsies, thus warranting a closer follow-up. PATIENTS AND METHODS: The study included 100 men with consecutive first-time saturation biopsies; the indications for biopsy were an abnormal digital rectal examination and/or a serum prostate-specific antigen (PSA) level of >2.5 ng/mL. Each biopsy specimen was reviewed retrospectively by two pathologists to confirm the histological diagnosis. The number and percentage of cores positive for HGPIN, bilateral involvement and multifocality (HGPIN involving two or more cores) were recorded in each case. The presence of AG and cancer was also recorded. An extended (10-12 cores) repeat biopsy was available in 23 patients. RESULTS: The median (range) age and PSA level of the patients was 63 (41-80) years and 4.9 (1.5-67.0) ng/mL, respectively. Of the 100 patients, 34% had normal findings (benign prostatic tissue, BPT), 39% had cancer, 26% had HGPIN and cancer, 22% had HGPIN alone, and 5% had AG. Repeat biopsies were available in nine of the 22 (41%) patients with HGPIN, four of five with AG, and 10 of the 34 (29%) with BPT. The median (range) interval between the first and second biopsy was 13 (4-36) months. Prostate cancer was detected at the second biopsy in a third of patients with isolated HGPIN on the first biopsy, and one of the four with AG. None of the patients with BPT had cancer on re-biopsy. The cancer detection rate was significantly greater in patients with multifocal than in those with unifocal HGPIN (80% vs none, P = 0.010). The median number of cores and percentage of tissue involved by HGPIN was 3.5 (2-5) and 1.0 (0.5-1.2)%, respectively, in patients with cancer detected in repeat biopsies, compared to 1.0 (1-3) and 0.2 (0.2-0.6)% in patients without cancer on repeat biopsy (P = 0.023 and 0.015, respectively). CONCLUSION: Identifying multifocal HGPIN on first saturation biopsy is associated with an overall cancer detection rate of 80% on repeat 10-12-core biopsy. Although there were few patients, the detection of multifocal HGPIN warrants additional searches for concurrent invasive carcinoma by repeated biopsy.

Outcomes in patients with urothelial carcinoma of the bladder with limited pelvic lymph node dissection.

OBJECTIVES: To evaluate the rates of local and systemic progression (LP and SP), recurrence-free survival and overall survival for patients with urothelial carcinoma of the bladder with limited pelvic lymph node dissection (PLND) in 1987-2000. PATIENTS AND METHODS: A consecutive series was analysed of 385 patients (median age 61.9 years, range 30.7-83.8) treated by limited bilateral PLND and radical cystectomy (RC) between 1987 and 2000, with negative surgical margins on final pathology. All patients were staged N0M0 before RC, and none received neoadjuvant radiotherapy or chemotherapy. The boundaries of the limited PLND were the pelvic side-wall between the genitofemoral and obturator nerves, and bifurcation of iliac vessels to the circumflex iliac vein. LP was defined as a radiographic soft-tissue density of > or = 2 cm below the bifurcation of the aorta. Pathological characteristics, based on the 1997 Tumour-Nodes-Metastasis system, recurrence patterns, and recurrence-free and overall survival, were determined. RESULTS The median (range) overall follow-up was 45.1 (1.1-165.6) months; the number of lymph nodes (LNs) reported per patient was 12 (2-32). Of the 385 patients, 130 (33.8%) had evidence of LP and 60 (15.6%) of SP. The 5-year recurrence-free and overall survival rates were both 71% for patients with organ-confined, N0 tumours, and 23% and 26% for unconfined, N0 tumours. Positive LNs were found in 45 (12%) patients, who had a recurrence-free and overall survival rate of 9% at 5 years. CONCLUSION: Compared with published reports of similar cohorts of patients managed with RC and extended PLND, the present study suggests that limited PLND is associated with suboptimal staging, greater rates of LP, and lower rates of recurrence-free survival, particularly for patients with unconfined or LN-positive disease.

Variability in the performance of nuclear matrix protein 22 for the detection of bladder cancer.

PURPOSE: We assessed variability in the diagnostic performance of NMP22 for detecting recurrence and progression in patients with Ta, T1, and/or CIS transitional cell carcinoma of the bladder in a large international cohort. MATERIALS AND METHODS: NMP22 voided urine levels were measured in 2,871 patients who underwent office cystoscopy for monitoring previous stage Ta, T1 and/or CIS transitional cell carcinoma at 12 participating institutions. RESULTS: Patient characteristics varied considerably among institutions. Overall 1,045 patients (36.4%) had recurrent transitional cell carcinoma (range across institutions 13.6% to 54.3%). Median NMP22 was 5.5 U/ml (range across institutions 2.5 to 18.8). Of the patients 33.5% had grade III tumors (range across institutions 20.6% to 54.0%) and 22.4% had muscle invasive tumors (range across institutions 3.2% to 38.2%). Area under the ROC curve for bladder TCC detection was 0.735 (95% CI 0.715 to 0.755, range across institutions 0.676 to 0.889). The manufacturer recommended cutoff of 10 U/ml detected 57% of cases with a 19% false-positive rate. AUC for grade III and stage T2 or greater disease was 0.806 (95% CI 0.780 to 831) and 0.864 (95% CI 0.839 to 0.890), respectively. For each NMP22 cutoff NMP22 had higher sensitivity for detecting grade III and stage T2 or greater bladder transitional cell carcinoma than for detecting any cancer. No optimal cutoffs for detecting any or aggressive bladder transitional cell carcinoma could be derived based on NMP22 values. CONCLUSIONS: There is a substantial degree of heterogeneity in the diagnostic performance of NMP22 applied to populations from different institutions. There is no clearly defined NMP22 cutoff but there is a continuum of risk for recurrence and progression.

Institutional variability in the accuracy of urinary cytology for predicting recurrence of transitional cell carcinoma of the bladder.

OBJECTIVE: To assess the contemporary inter-institutional accuracy of urinary cytology in predicting the recurrence of transitional cell carcinoma (TCC) of the bladder, in a large multi-institutional cohort from four continents, as cystoscopy and urinary cytology represent the 'gold standards' for surveillance of TCC recurrences, but the ability of cytology to predict recurrence varies. PATIENTS AND METHODS: Ten institutions contributed 2542 patients with a history of superficial TCC, of whom 898 had TCC recurrence. Age- and gender-adjusted logistic regression models were used to evaluate the association between urine cytology and TCC recurrence. The predictive accuracy derived from the logistic regression model was tested using the area under the receiver operating characteristic curve. The resulting predictive accuracy estimates were internally validated with 200 bootstrap re-samples. RESULTS: The mean (range across institutions) age of the patients was 65 (48-69) years and 75 (67-87)% were men. Cytology was positive in 19 (10-38)% of patients; recurrence was identified in 35 (27-54)% of patients. The sensitivity was 38-65% across institutions. Urinary cytology varied significantly in its ability to predict recurrence of bladder cancer. Institution-specific predictive accuracy adjusted for gender and age was 0.627-0.893. Stratifying by grade and stage only partly attenuated the discrepancies between centres. CONCLUSIONS: The variability of urinary cytology results was very appreciable among the 10 centres and ranged from poor (63%) to excellent (89%).