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Objective: To assess the diagnostic and prognostic performance of a noninvasive FGFR3 mutation analysis. After transurethral resection (TUR) of noninvasive bladder transitional cell carcinoma (B-TCC), recurrence occurs in 70% of patients, thus justifying cystoscopic surveillance., Materials and Methods: A prospective multicenter study was carried out with a 2-year follow-up of patients with superficial B-TCC. Urine samples were collected before TUR and then before each cystoscopy during follow-up. Screening for the most prevalent FGFR3 mutations was done using urinary cells. The prognostic significance of an FGFR3 mutation at the time of the initial diagnosis was determined. The performance of the test in diagnosing and/or predicting recurrence during follow-up was assessed by calculating sensitivity and specificity., Results: Of 191 patients studied, 74 (39%) had a positive analysis before TUR (FGFR3 mutation group). The presence of an FGFR3 mutation at the time of diagnosis was associated with a shorter time to recurrence (P = .02). During follow-up, 68 patients from the FGFR3 mutation group were evaluated. FGFR3 mutation analysis showed a sensitivity of 0.73 and a specificity of 0.87 when compared with the results of cystoscopy. A positive urine test was predictive of recurrence either at the time of the positive result or later during the 2-year follow-up, with a sensitivity of 0.70 and a specificity of 0.87., Conclusion: Among patients with an FGFR3 mutation in the initial tumor, a noninvasive urine test during follow-up can be valuable in diagnosing or predicting subsequent recurrence., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: To assess the quality of specimens obtained from prostate biopsies performed by urology residents and evaluate the number of procedures required to perform high-quality transrectal ultrasound (TRUS)-guided prostate biopsies., Materials and Methods: Between 2006 and 2009, 770 patients underwent TRUS-guided prostate biopsies in our academic center. During the 6 semesters of this period, 24 residents (4 per semester) performed 1 session of 5.6±1.5 procedures each month for a total of 33.6±9 procedures during the study. The first session was performed with a senior urologist. Prostate cancer detection rate and standards of quality (average length of prostatic core biopsy specimens and absence of prostatic tissue) were retrospectively studied between the beginning and the end of each semester., Results: A total of 12,760 biopsy cores were performed for 770 procedures. Mean patient age (64.5±6.1 years), and median prostate-specific antigen (8.7±3.7 ng/mL) were comparable between the study periods. The average length of biopsy cores significantly improved (+10%) from the first (12±2.7 mm) to the last month (13.2±2.1 mm) with a plateau after 12 procedures. Overall, cancer detection rate was 47% and was stable during the semester (41.3% the first month vs 44.1% the last month; P=.39). On univariate and multivariate analysis the mean length of biopsy specimens was associated with the number of procedures (P<.001) and the number of cores performed (P<.001)., Conclusion: Twelve procedures are necessary to perform high-quality TRUS-guided prostate biopsies without compromising prostate cancer detection. In current training programs, we strongly recommend that residents have direct supervision for a minimum of 12 cases before they are allowed to perform TRUS-guided biopsies with indirect supervision., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objectives: To investigate the hypothesis that Northern Africans differ from Caucasians with regard to their PCa characteristics, using our 1988-2006 database we retrospectively reviewed the preoperative and pathological features of consecutive patients subjected to radical prostatectomy (RP) for localized prostate cancer (PCa) and stratified according to their ethnic origin., Methods: In 727 consecutive patients (616 Caucasians; 61 Blacks originating from Central Africa and the French West Indies; 50 Northern Africans from Morocco, Algeria, Tunisia), we preoperatively analyzed and compared age, clinical stage of the tumour, prostate-specific antigen (PSA), transrectal ultrasound prostate volume, PSA density (PSAD), biopsy Gleason score, number of positive cores (NPC), and percentage of tissue core invaded by cancer (PTIC); postoperatively, we determined the status of the capsule, seminal vesicles, and margins of the RP specimen, as well as Gleason score and prostate weight. Statistical analyses (chi-square test and ANOVA) were performed to compare the results between the three groups of patients. A multivariate analysis was carried out to test the independence of variables., Results: Black patients were the youngest at the time of surgery (by 3-4 yr) and had the highest rates of final Gleason score>or=8. The Northern Africans had more favourable features than did Caucasian and Black patients: mean PTIC was 7.1% versus 14.6% and 12.5%, respectively (p=0.005), mean NPC was 26.4% versus 34.7% and 36.4%, respectively (p=0.034), rates of biopsy and final Gleason score>or=8 were significantly lower (p=0.02 and p=0.028, respectively), and there were positive margins in 26% versus 36% and 35.6%, respectively (p>0.05)., Conclusions: This study showed that a French Black population is the most likely of those studied to have unfavourable PCa characteristics at the time of RP. Albeit in a limited series, we show for the first time that Northern Africans have significantly better features in this regard than Caucasians and Blacks. Although Northern Africans did not have a better pathological stage outcome, they did have a more favourable Gleason score.

Posterior urethral valves (PUVs) in patients with Down syndrome (DS) have been previously described. However, no case of PUVs has been reported in an adult patient with DS. We report on a 40-year-old man with DS, who presented with two severe urinary infections and obstructive symptoms. He was found to have type 3 PUVs associated with bladder neck sclerosis. PUV resection and bladder neck incision were done. Because PUVs seem to be more frequent in patients with DS, complete investigations should be performed, even in adults with DS, in the case of urinary infection or lower urinary tract symptoms.

Objectives: To study the pathologic features of radical prostatectomy (RP) specimens of patients operated on the basis of a potentially "Insignificant" prostate cancer (Ca P) characterized by one single focus (less than 3mm) of moderately differentiated adenocarcinoma - Gleason score < or =6, out of 6-10 biopsies and to determine which characteristics, if any, are predictive of the presence of a "non significant" prostate cancer in the specimen characterized by a low volume (<0.5 ml) moderately differentiated organ confined, cancer (Gleason score less than 6)., Patients and Methods: PSA, biopsy features, and surgical specimens of a series of 56 patients submitted to RP for "insignificant Ca P" on TRUS prostate biopsies between 1988 and 2004 were compared regarding the number of tumor foci, Gleason grade and score, tumor volume determined by the cylinder method, as well as extraprostatic extension (EPE) and positive surgical margins (P.SM.)., Results: 70% of the patients had multifocal microfocal cancer apart from the index tumor. The presence of grade 4 was ignored by the biopsy in 50% of the cases, however the primary grade was correctly evaluated in more than 70% of the biopsy sets. 42% of the patients had a cancer volume less than 0.5 ml and 29% met the definition of insignificant/unimportant cancer characterized by a moderately differentiated (Gleason score < or =6) of low volume (less than 0.5 ml) however no feature accurately predictive of insignificant cancer could be individualized. In this whole series, only 8% of the patients had EPE. When the pre-operative PSA was <10 ng/ml, 98% of the patients had an organ confined tumor., Conclusion: Patients diagnosed with prostate cancer on the basis of one single focus less than 3 mm of moderately differentiated (Gleason < or =6) prostate cancer have 30% of chances of harboring an insignificant tumor in their prostate and are therefore, at risk of being overtreated, however there is at this time no specific feature able to identify these patients pre operatively.

Objectives: Pathological and biochemical features of prostate cancers detected on repeat biopsies in men with total PSA level between 2.0 and 4 ng/ml were evaluated and compared to those cancers detected on first biopsy., Methods: 315 men with PSA level between 2.0 and 4 ng/ml underwent transrectal ultrasound guided sextant biopsy and two additional transition zone biopsies (Octant Biopsy). All subjects whose biopsy samples were negative for prostate cancer underwent a repeat biopsy after 6 weeks. Those with clinically localized cancers were offered surgery or radiation therapy. Pathological and clinical features of patients diagnosed with prostate cancer on initial and repeat biopsy were compared., Results: Cancer detection rates on first and second biopsy were 24% (75/315) and 13% (29/224), respectively. Overall, of patients with clinically localized disease (83% of cancers detected), 87% underwent radical prostatectomy, 11% opted for radiation therapy and 2% opted for watchful waiting. Cancers found in the first biopsy group were more multifocal (p = 0.01) while cancers found on second biopsy were more located in the apical-dorsal region (p = 0.003). No significant differences were noted with respect to extracapsular extension, seminal vesical invasion, positive margins, final pathological stage, Gleason score, percentage Gleason grade 4/5, serum PSA and patient age between first and second biopsy., Conclusions: With an octant biopsy regime, biochemical and pathological features of cancers detected on initial and repeat biopsy in the PSA range 2.0 to 4 ng/ml are comparable in terms of PSA, grade, stage and cancer volume suggesting identical cancer characteristics, thus advocating for a repeat prostate biopsy in case of a negative finding on initial biopsy.

Objective: To determine the utility of Power Doppler enhanced transrectal ultrasound (PD-TRUS) and its guided prostate biopsies in men with prostate specific antigen (PSA) levels between 2.5 and 10 ng/ml and to evaluate its impact on prostate cancer (PCa) detection in men undergoing first and repeat biopsies., Methods: A total of 136 consecutive referred men with serum total PSA (Abbott Laboratories, Abbott Park, IL, USA) levels between 2.5 and 10 ng/ml (mean age 64 +/- 9 years, range 45-82) and a normal digital rectal examination were included. 101 underwent a first biopsy whereas 35 had repeat biopsy. Gray-scale transrectal ultrasound (TRUS), and PD-TRUS (B&K Medical, Denmark) were performed in lithotomy position before and during the biopsy procedure. Vascularity accumulation and perfusion characteristics were recorded and graded as normal or abnormal in the peripheral zone of the prostate. A Vienna-nomogram based biopsy regime was performed in all patients on first biopsy and a special biopsy regime on repeat biopsy plus additional biopsies from abnormal sites on PD-TRUS., Results: Overall PCa detection rate was 34.7% and 25.7% and abnormal accumulation on PD-TRUS was identified in 42.3% and 48.6% on first and repeat biopsy, respectively. The PCa detection rate, on first and repeat biopsy in patients with and without PD-TRUS accumulation were 67.4% versus 10.3% (p < 0.001) and 47.05% versus 5.6% (p = 0.0049), respectively. PD-TRUS directed biopsies were positive in 5.7% and 11.1% on first and repeat biopsy whereas PCa detection using the routine prostate biopsy regime was 94.3% and 88.9% on first and repeat biopsy. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of PD-TRUS signal alone for PCa detection on first biopsy was 82.8%, 78.8%, 87.9% and 89.7%, respectively, and 88.8%, 68.0%, 47.0% and 94.4% on repeat biopsy, respectively. In comparison, the results PD-TRUS guided biopsies were 53.8%, 59.1%, 16.7%, and 89.5%, on first biopsy, respectively, and 20.0%, 13.3%, 23.5%, 11.1% on repeat biopsy, respectively., Conclusion: Negative PD-TRUS signal is able to exclude most of the patients without PCa in the PSA range of 2.5-10 ng/ml. As an additional tool at TRUS biopsy PD-TRUS has a high negative predictive value and may help to reduce the number of unnecessary biopsies.

Objective: With a shift in prostate cancer stage and a majority of patients operated nowadays with PSA levels <10 ng/ml, rates of seminal vesicle (SV) invasion found on radical prostatectomy specimens have decreased as compared to historical data. Since SV-sparing surgery may possibly have an influence on post-operative erectile dysfunction and urinary recovery, we tried to determine which patients could be safely spared SV excision during radical prostatectomy., Material and Methods: We used preoperative data from 1283 patients operated by radical retropubic prostatectomy--777 with serum PSA <10.0 ng/ml--to predict SV invasion on final pathological examination. Variables analyzed included age, digital rectal examination, serum PSA, biopsy Gleason score and percentage of biopsy cores invaded by prostate cancer. Statistical analysis included univariate, multivariate logistic regression analysis and receiver operating characteristic (ROC) curves., Results: Out of 1283 patients, 137 (10.6%) had SV involvement, 41/777 (5.2%) with PSA <10.0 ng/ml, 16.1% in the 10-20 ng/ml range and 26.2% when PSA was >20 ng/ml. Percentage of biopsies affected by prostate cancer and biopsy Gleason score were significant predictors of SV invasion in multivariate analysis, both in the entire population and in the subset of patients with PSA <10.0 ng/ml (p < 0.0001). Probability graphs created for patients with PSA <10 ng/ml indicate a risk of seminal invasion <5% when Gleason score on biopsy is <7 or when the percentage of biopsies affected by cancer is <50%., Conclusions: Resection of SV might not be "oncologically" necessary in all patients undergoing RP when PSA levels are below 10 ng/ml except when biopsy Gleason score is > or =7 or when more than 50% of prostate biopsy cores show cancer involvement. SV-sparing surgery could be prospectively compared to standard retropubic prostatectomy in selected individuals analyzing potential benefits on erectile function and urinary continence., (Copyright 2004 Elsevier B.V.)

Objectives: To develop an advanced artificial neural network (ANN) to predict the presence of prostate cancer (PCa) and to predict the outcome of repeat prostate biopsies. The predictive accuracy was compared with the accuracy obtained using standard cutoffs for the free/total (f/t) prostate-specific antigen (PSA) ratio, PSA density (PSAD), PSA density of the transition zone (PSA-TZ), and the total and transition zone volumes. Clinical and biochemical diagnostic tests have been shown to improve PCa detection. When these tests are combined using an ANN, significant increases in specificity at high sensitivity are observed., Methods: The Vienna-based multicenter European referral database for early PCa detection of 820 men with a PSA level between 4 and 10 ng/mL was used. The presence of PCa was determined using transrectal ultrasound-guided octant needle repeat biopsy. Variables in the database consisted of age, PSA, f/t PSA ratio, digital rectal examination findings, PSA velocity, and the transrectal ultrasound-guided variables of prostate volume, transition zone volume, PSAD, and PSA-TZ. The ANN used in the analysis was an advanced multilayer perceptron selected for accuracy by a genetic algorithm., Results: The repeat biopsy PCa detection rate was 10% (n = 83). At 95% sensitivity, the specificity for ANN was 68% compared with 54%, 33.5%, 21.4%, 14.7%, and 8.3% for multivariate logistic regression analysis, f/t PSA ratio, PSA-TZ, PSAD, and total PSA, respectively. The ANN reduced unnecessary repeat biopsies by 68% in this study. The area under the curve was 83% for the ANN versus 79%, 74.5%, 69.1%, 61.8%, and 60.5% for multivariate analysis, f/t PSA ratio, PSA-TZ, PSAD, and total PSA, respectively., Conclusions: The current ANN found a strong pattern predictive of PCa in patients with a negative initial biopsy. By combining the individual clinical and biochemical markers into the ANN, 68% specificity at 95% sensitivity was achieved. The ANN allows more accurate and individual counseling of patients with a negative initial biopsy.

Single modality bladder sparing therapy for muscle-invasive bladder cancer, including transurethral resection, systemic chemotherapy or radiotherapy have been demonstrated to result in insufficient local control of the primary tumor as well as decreased long-term survival of the patients when compared to radical cystectomy. Therefore, multimodality treatment protocols that aim at bladder preservation and involve all of the aforementioned approaches have been established. Arguments for combining systemic chemotherapy with radiation are to sensitize tumor tissue to radiotherapy and to eradicate occult metastases that have already developed in as many as 50% of patients at the time of first diagnosis. It has been shown that the clinical outcome observed with this approach approximates that after radical cystectomy. Additionally, a substantial number of patients survive with an intact bladder. However, bladder preserving approaches are costly, and require close co-operation between different clinical specialists as well as very close follow-up. The good long-term results obtained after cystectomy and creation of an orthotopic neobladder make the possible advantage of a bladder preservation strategy questionable in consideration of quality of life issues. Additionally, side effects related to bladder sparing therapy may result in an increased morbidity and mortality in those patients who in fact need to undergo surgery due to recurrent or progressive disease. Multimodality bladder sparing treatment is a therapeutic option that can be offered to the patient at centres that have a dedicated multidisciplinary team at their disposal. However, radical cystectomy remains the standard of care for muscle-invasive bladder tumors.

Prostate-specific antigen (PSA) progression following radical treatments of clinically localized prostate cancer is a common problem facing both the patient and the urologist. Not all patients with relapsing disease have an equal risk of death due to prostate cancer. After surgery, biochemical failure can be defined as persisting detectable levels of PSA after radical prostatectomy or a PSA rise after a period of normalization. On the other hand, definitions of PSA progression after radiation therapy vary and no clear consensus can be found. This review of the recent international literature updates the knowledge about the diagnostic procedures used in relapsing patients. Predictors of progression are precised leading to a better patient selection, based on currently available tables and nomograms. Indeed, identification of high risk patients may allow a more appropriate treatment decision. After radical treatment, the analysis of time to recurrence, PSA doubling time, PSA kinetics combined to modern imaging techniques such as 111In capromab penditide scan may allow a better identification of the recurrence site. Thus, an optimal treatment strategy may be envisaged such as local irradiation, salvage surgery, hormone therapy or combinations for which indications and results are provided. Alternative options such as cryotherapy still need further investigation. At last, the use of artificial neural networks will certainly enhance the selection of patients submitted to radical treatments as well as the selection of relapsing patients to allow a more appropriate adjuvant therapy.

This prospective, multicenter European Prostate Cancer Detection study evaluated the value and performance of the molecular forms of prostate-specific antigen (PSA) and their derivatives in combination with prostate gland and transition zone volumes in early detection of prostate cancer in patients with PSA levels between 4 and 10 ng/mL. Of 750 men enrolled at 7 different European urology centers into the study between November 2001 and March 2002, 340 (45.3%) had a total PSA (tPSA) between 4 and 10 ng/mL (age range, 46 to 87 years). In all patients, the ratio of complexed PSA (cPSA) to tPSA (c/tPSA), cPSA density (cPSAD), cPSAD of the transition zone, PSA, free PSA (fPSA), ratio of fPSA to tPSA (f/tPSA), tPSA density (PSAD), and PSAD of the transition zone were measured and collected 5 to 10 minutes before the sextant biopsy with 2 additional transition zone cores. Measurements of tPSA and fPSA were done with the AxSYM test, whereas cPSA was measured with the ACS 180 cPSA assay. All patients had a transrectal ultrasound-guided sextant prostate biopsy, and 2 additional transition zone biopsies and total and transition zone volumes were measured at the time of biopsy. Histopathologic findings revealed benign histology in 237 patients and prostate cancer in 103 patients (69.7% and 30.3%, respectively). Statistically significant differences included larger total volumes, larger transition zone volumes, and f/tPSA in patients with benign disease (P = 0.0009, P <0.0001, P <0.0001, respectively). At 90% and 95% sensitivity, specificity of cPSA was significantly greater than that for PSA (P <0.0001). At sensitivity levels of 90% and 95%, the specificity of the cPSA assay using cutoff values of 3.06 and 2.52 ng/mL was 20.3% and 9.1%, respectively. A cPSA cutoff value of 6.95 ng/mL and 7.57 ng/mL afforded 90% and 95% specificity for detecting prostate cancer. The area under the curve (AUC) in the receiver operating characteristics curve of cPSA was statistically significantly higher compared with tPSA (60.8 vs 56.9, P = 0.032). AUC for volume-related parameters PSAD, cPSAD, PSAD of the transition zone, and cPSAD of the transition zone were 62.8%, 63.1%, 63.0%, and 63.6%, respectively. cPSA performs better than tPSA in the differentiation between benign disease and prostate cancer and provides similar information to the f/tPSA ratio. In addition, cPSA and cPSA volume-related parameters (cPSAD, cPSAD of the transition zone) further improved the specificity of PSA in early detection of prostate cancer.

Objectives: To evaluate the correlation between the overexpression of mutant protein p53 and disease recurrence and progression in patients treated with bacillus Calmette-Guérin (BCG) intravesical therapy for T1G3 bladder cancer., Methods: We analyzed the outcome of 29 consecutive patients treated for T1G3 bladder tumor with transurethral resection. Patients previously treated for a bladder tumor, those who underwent incomplete resection, and those in whom no assessment of the muscle cell layer was possible were excluded from the study. p53 overexpression was determined using monoclonal p53-DO7 antibody, with a 20% cutoff for definition of positivity. After the initial transurethral resection, all patients were treated with Pasteur BCG (75 mg in 50 mL saline), weekly for 6 weeks. The correlation between p53 overexpression and disease recurrence and progression was assessed by the Fisher exact test., Results: The median follow-up was 36.7 months (range 1 to 108). Of the 29 patients, 18 (62.1%) were p53 positive and 11 (37.9%) were p53 negative. Both groups were similar according to age, tumoral substage (T1a/T1b), association with carcinoma in situ, multifocality, and length of follow-up. The recurrence rate was 54.4% in the p53-negative group versus 38.9% in the p53-positive group (P = 0.47). The progression rate was 18.2% in the p53-negative group versus 33.3% in the p53-positive group (P = 0.67)., Conclusions: These findings suggest that overexpression of p53, as determined immunohistochemically, has no predictive value for recurrence and progression in T1G3 bladder cancers treated with intravesical BCG.

Purpose: To perform a multivariate analysis to investigate the usefulness of eight preoperative variables as predictors of final pathological stage (pT), positive surgical margins (PSM) and biological progression after radical prostatectomy (RP)., Materials and Methods: In 143 patients undergoing RP for T1-T2 prostate cancer, the respective values of age, clinical stage, preoperative prostate-specific antigen (PSA), prostate-specific antigen density (PSAD), number of positive biopsies (NPB), Gleason score, length of tissue core invaded by cancer (LTI) and topography (uni/bilaterality) of positive biopsies for predicting extracapsular extension, PSM and biochemical failure (PSA> or =0.05 ng/ml) were evaluated retrospectively. Univariate and multivariate analyses were applied to define the statistical significance of each variable. Actuarial survival without biological progression was calculated using the Kaplan-Meier method (log-rank test)., Results: In this series, 44.8% of patients had extracapsular extension with 41.3% PSM. The mean PSA was 12.4 ng/ml. In univariate analysis, LTI (p<0.0001), NPB (p = 0.0023), PSA (p = 0.0039) and Gleason score (p = 0.0136) were the most powerful variables to predict pT stage; however, in logistic regression analysis, LTI was the most predictive feature. For prediction of PSM, some variables (LTI, NPB and PSA) were found to be of statistical value in univariate analysis, and LTI in combination with NPB and PSA in multivariate analysis. For biological progression, statistical analysis (log rank test) showed PSAD and LTI to be significant predictors., Conclusion: The pathological report regarding the biopsy contains crucial information influencing the prediction of pT stage, PSM and biological progression after RP. LTI, NPB and PSA are the most useful parameters for this purpose.

Objectives: A multi-institutional study of 280 radical prostatectomy specimens obtained from three independent academic hospitals was undertaken to validate a nomogram developed for the prediction of specimenconfined protstate cancer after prostatectomy., Methods: Three preoperative factors - the Gleason score, prostatespecific antigen (PSA) and apical location of positive biopsies - that were identified with a previous logistic regression formula were collected. Links between margin status and preoperative criteria were confirmed by univariate methods. Subsequently, the predictive indexes of positive margins were calculated and compared to the actual margin status in terms of predictive characteristics., Results: This control series, independent of the initial series that was used to identify the relevant preoperative factors, confirmed that positive apical biopsies(p<0.001), PSA (p<0.005) and the Gleason score (p<0.005) were strongly linked to the occurrence of positive margins. Different cutoff values for the predictive index were compared in a receiver operating characteristic curve. A value of 0.5, similar to the one described in the original series, gave an adequate compromise between sensitivity and specificity with respective values of 68 and 73% and a test accuracy of 72%. In practical terms, it was possible to predict 85% of negative margins, and to delineate two groups with different rates of positive margins (14.5 vs. 50%)., Conclusions: We demonstrated that PSA, the Gleason score and apical biopsy status are cumulative risk factors for positive margins. Risk of positive margins increases when it is not possible to obtain a wide excision of periprostatic fascia, as at the apex. This study substantiates the independent prognostic value of positive preoperative apical biopsies for predicting positive surgical margins.

Objectives: To investigate the prevalence of the microsatellite instability related to mismatch repair (MMR) gene defects using a panel of six microsatellite markers, as recommended by a recent workshop on microsatellite instability in colon cancer, because it is still unclear whether abnormalities in DNA MMR genes are involved in transitional cell carcinoma (TCC) of the bladder., Methods: Three mononucleotide repeats (BAT26, TGFbetaRII, and BAX) were studied in 33 TCC samples and in four bladder cancer cell lines. Three dinucleotide repeats (D2S123, D5S346, and D17S250) were studied in 21 of these 33 TCC samples., Results: No alteration was detected either in the 33 TCC samples analyzed or in the four bladder cancer cell lines (T24, J82, 647V, and 1207) studied. A difference between normal and tumor DNA was observed in only 1 of 21 tumor samples for D17S250., Conclusions: These data indicate that microsatellite instability is very uncommon in TCC of the bladder.

Objective: To evaluate the improvement in the rate of detection of prostate cancer using an extensive protocol involving ten transrectal biopsies., Methods: A total of 162 patients submitted to transrectal ultrasound-guided biopsy for elevated prostate-specific antigen (PSA) and/or abnormality on digital rectal examination were studied consecutively and prospectively. Five biopsies were performed in each lobe: between the three standard biopsies on each side, two additional biopsy specimens were taken in the same plane and at the same 45 degrees angle., Results: The complication rate with the ten-biopsy protocol was 1.85%. Prostate cancer was detected in 40.1% of the patients. In the overall series, the percentage of diagnostic improvement brought about by this ten-biopsy protocol was +3.1%. The percentage improvement was greatest (+4.9%) in patients with PSA

Objective: To compare the BTA stat test (BTA stat), a new one-step immunochromatographic assay that can be performed in the urologist's office or in the laboratory, to voided urine cytology and bladder wash cytology (cytology) in the diagnosis and monitoring of cancer of the bladder (BC)., Methods: BTA stat and cytology were performed in a double-blinded, prospective, clinical study on specimens from 240 subjects (68 females; mean age of subjects: 64 years) suspected of having BC., Results: In 107 subjects with final diagnoses of BC confirmed by cystoscopy or cystoscopy and biopsy, the overall sensitivities of BTA stat and cytology were 65 and 33%, respectively. For tumor grades I, II, and III, the sensitivities of BTA stat were 39, 67 and 83%, respectively. Those of cytology were 4, 20 and 69%. Nine subjects had a diagnosis of 'suspicious for bladder cancer'. The specificities of BTA stat and cytology in the 124 subjects without BC were 64 and 99%, respectively. In the subjects with a history of BC (n = 74), the specificities of BTA stat and cytology were 72 and 99%, respectively. The specificity of BTA stat was lower in subjects with benign or malignant genitourinary disease other than BC (46%) than in subjects without genitourinary disease (71%)., Conclusions: The BTA stat test is considerably more sensitive than cytology in the detection of BC and can replace cytology as an adjunct to cystoscopy in the diagnosis and follow-up of patients with BC. However, due to low specificity, BTA stat should not be used without first ruling out potential interferences such as infections, renal disease and cancer, or genitourinary trauma.

Objective: To evaluate specific urological abnormalities in patients treated with the protease inhibitor indinavir., Methods: A series of 155 consecutive human immunodeficiency virus-positive patients were treated with indinavir 800 mg p.o. three times a day. Of these, 14 (9%) treated for 1-321 (average 110) days experienced severe flank pain and were subjected to clinical and laboratory examinations., Results: Abdominal X-ray was consistently negative for stones. Ultrasonography showed upper-tract dilatation in 12 patients. Intravenous urography showed obstruction above a radiolucent obstacle in 7 patients; in 2 cases, there was a marked delay in urine excretion on the obstructed side. The mean urine pH was 6. Urine culture was negative. Serum uric acid, phosphorus, and calcium levels were normal. In 8 patients there was slight renal insufficiency, and 4 patients required ureteral stenting. In all cases, hyperhydration and oral analgesia led to a favorable outcome. In 3 patients, chemical analysis of the stone demonstrated monohydrate indinavir crystals., Conclusions: In our experience, indinavir therapy is associated with urolithiasis in 9% of the cases. Hydration, analgesia, and acidification of the urine usually lead to a favorable clinical outcome. Prophylactic hydration and acidification of the urine are extremely important.

Introduction: Although the biology and sites of secretion of PSA are well known, its pharmacokinetics are still unclear. This study analyzes the differences between the clearance of total and free serum PSA following open surgery for BPH and radical prostatectomy., Methods: Free and total PSA were measured in 27 patients submitted to radical prostatectomy for clinically localized prostate cancer (group I) and in 27 patients submitted to open surgery for BPH (group II). In both groups, the clearance of free and total PSA was studied., Results: Group I-the mean half-life was 1.416 +/- 0.723 days for free PSA and 2.43 +/- 0.688 days for total PSA. After prostate removal, free PSA showed a marked increase. Group II-the mean half-life of free PSA was 2.157 +/- 1.792 days and 3.391 +/- 2.337 days for total PSA., Conclusions: The increase in free PSA shortly after manipulative procedures of the prostate was higher than the increase in total PSA. Serum clearance of free PSA after eradicative prostatic surgery was related to the indication and type of procedure used.

Prostate-specific antigen (PSA) forms in serum two stable complexes with alpha 1-antichymotrypsin and alpha 2-macroglobulin. PSA complexed to alpha 1-antichymotrypsin is the predominant fraction of PSA. A minor fraction of serum PSA is not associated with proteinase inhibitors. These molecular differences explain the possibility to distinguish free from total PSA (F/T ratio). Free and complexed PSA have different clearances and significant differences between clearance of free PSA after radical prostatectomy (RP) and after open surgery for benign prostatic hyperplasia (BPH) are observed. These differences are explained by the entire removal of prostatic cells responsible for PSA synthesis and storage during RP, i.e. the source of free PSA present in the intravascular pool. The proportion of free PSA is significantly lower in patients with prostate cancer than in patients with BPH. Thus, the mean F/T ratio in prostate cancer is lower than that in BPH and may be helpful to distinguish cancer from BPH especially in the gray zone of total PSA (4-10 ng/ml). The reason why complexed PSA increases in patients with prostate cancer remains unknown but could be explained by the requirement of an enzymatically active PSA released by the malignant prostate tissue to bind to alpha 1-antichymotrypsin. However, a consensual threshold value for L/T ratio is yet to be found to be of widespread clinical use in the differential diagnosis between cancer and BPH.

Objective: To assess the value of the detection of circulating prostate cells [prostate-specific antigen (PSA) positive] by reverse-transcriptase nested polymerase chain reaction (nested RT-PCR) to improve the staging of clinically localized prostate cancer., Methods: Nested PCR was performed on blood samples of 29 patients submitted to radical prostatectomy for clinically localized (T1-T2) prostate cancer. Nine patients with various benign urologic diseases comprised the negative control group. Incubation was for 25 cycles for each PCR, using beta 2-microglobulin to test the integrity of RNA samples. Each sample was tested in quadruplicate and analyzed by agarose gel electrophoresis, blotted and hybridized with specific internal primers. Nested PCR results were compared with the pT stage of the prostate specimen, processed according to the Stanford method., Results: In 6 out of 29 patients (20.7%) with clinically localized prostate cancer, circulating prostate cells were detected by nested PCR. There was no relationship between pathologic stage and RT-PCR results. Eleven out of 14 pT2 patients (78.6%) were PCR negative and only 3 out of 15 pT3 patients (20%) were PCR positive. All control samples were PCR negative., Conclusions: In selected patients with T1-T2 prostate cancer, there was no relationship between pathologic stage and the presence of circulating PSA-positive cells detected by nested PCR. However, in 20.7% of patients with clinically localized prostate cancer, circulating prostate cancer cells were detected. A further follow-up based on PSA is necessary to clarify the clinical relevance of this biologic anomaly.

Objectives: To determine the prevalence of prostate cancer and the diagnostic ability of prostate-specific antigen density (PSAD) in men with lower urinary tract symptoms and intermediate prostate-specific antigen (PSA) levels of 4 to 10 ng/mL (Hybritech assay) and to assess the clinical significance of prostate cancers in men who subsequently underwent radical prostatectomy., Methods: Six systematic transrectal ultrasonography (TRUS)-guided biopsies were performed in 153 symptomatic men (mean age, 66 years) with PSA levels between 4 and 10 ng/mL, irrespective of digital rectal examination (DRE) findings. Prostate volume was also determined by TRUS and PSAD was calculated (serum PSA divided by volume of entire prostate). The rate of positive biopsies was compared with PSAD (more than 0.2 versus less than 0.2), DRE (positive versus negative), and patient's age (more than 70 years versus 61 to 70 versus 60 or less). Eligible patients with cancer underwent radical prostatectomy, and specimens were analyzed with regard to clinical significance of tumors., Results: The overall cancer detection rate was 29.4%. PSAD and DRE, but not age, were both statistically significant in differentiating negative from positive biopsies. Independent of DRE findings, mean PSAD was significantly lower in biopsy-negative cases (0.29 +/- 0.17 and 0.25 +/- 0.16) than it was in positive cases (0.34 +/- 0.17 and 0.35 +/- 0.15). Half of the patients who underwent radical prostatectomy had pathologically nonorgan-confined disease (more than pT3), 34% had positive margins, and 47% had a Gleason score of 8 to 10. PSAD, DRE, and age could not predict outcome, probably owing to the small number of patients. However, the number of positive biopsies (1 or 2 versus 3 to 6) was able to predict pathologic stage., Conclusions: In men with lower urinary tract symptoms and intermediate PSA levels of 4 to 10 ng/mL, PSAD may be useful in the selection of patients for prostate biopsy. Carcinomas found using these criteria are of clinical importance.

Objective: We review the advances in pathology, biology, and radiology which could improve the detection of extracapsular prostate cancer preoperatively., Method: The experiences of others are compared to ours to give a topical overview of advances in the assessment of clinically localized prostate cancer., Results: Despite new technologies, such as colour Doppler and endorectal magnetic resonance imaging, radiology does not enhance the ability to detect small invasion through the prostatic capsule. Biopsy features are one of the new fields of investigation. The number of positive sextant biopsies and the analysis of periprostatic spaces on biopsies appear to be major prognosis factors. In our experience, capsular perforation on biopsy is very powerful with respect to the proportion of positive biopsies ( > 66.7%) and serum PSA ( > 25 ng/ml, polyclonal assay) to predict biological progression after radical prostatectomy. The utility of the proportion of invaded tissue on biopsy is still debated., Conclusions: Despite technical improvements, the staging of clinically confined prostate cancer is still a major issue. The best hope comes from the study of biopsy features in addition to PSA.

Objectives: To determine if methodic analysis of systematic echo-guided biopsies associated with prostatic-specific antigen (PSA) and PSA density can accurately predict the actual pathologic stage of prostate cancer (Ca P)., Methods: One hundred patients with clinically localized (T1, T2) Ca P who underwent radical prostatectomy (RP) were preoperatively staged by digital rectal examination (DRE), measurement of serum PSA (Yang Pros-check) and PSA density (PSAD), and transrectal echo-guided systematic biopsies (three in each lobe aiming to sample prostatic capsule) to evaluate T stage, Gleason grade, number of positive biopsies, and presence of cancer in the periprostatic tissues. Radical prostatectomy specimens were processed following the McNeal method. The PSA levels were measured every month for 2 years., Results: Extracapsular disease was detected on the specimen in 45% of the patients, persistent/recurrent detectable PSA in 47% (mean follow-up 18 months). Clinical stage T2 B, presence of Gleason grade 4, PSA > 25 ng/mL, PSAD > 0.6, number of positive biopsies > 66% of the total number of cores taken had a positive predictive value (PPV), respectively, of 72%, 66%, 80%, and 87%. Periprostatic tissue was evaluable on the core biopsies in 77% of the cases. Presence of cancer in the periprostatic fat on the core biopsies had a PPV of 94% for extracapsular disease/biological recurrence., Conclusions: The presence of extracapsular cancerous tissue on prostatic core biopsies accurately predicts extracapsular extension of Ca P. Therefore, care should be taken when performing prostate biopsies to sample the prostate capsule and surrounding tissues to obtain a more accurate staging of the disease. The second best predictor of extracapsular disease is the percentage of positive biopsies.

Objective: 10-30% of patients with T1/T2 prostate cancer submitted to radical prostatectomy ultimately fail. It may be important to detect failure as early as possible in order to evaluate the extent of recurrent/residual disease and initiate adjuvant therapy., Subjects and Methods: 100 consecutive patients with localized prostate cancer treated by radical prostatectomy have been monitored using the hypersensitive Pros-check prostate-specific antigen (PSA) assay (detection level 0.1 ng/ml). The predictive value of positive surgical margins, involvement of seminal vesicles and perineural spaces as well as Gleason's score for biological failure (persistent or recurrent detectable PSA) has been retrospectively evaluated., Results: Overall 40% of the patients had biological failure (defined as persistence of a detectable or rising PSA after undetectability) and 38% had positive surgical margins. The three main predictive criteria of biological failure were capsular perforation, involvement of seminal vesicles and/or positive margins. All patients in whom these criteria were positive progressed. Seminal vesicle invasion was associated with biological failure in 95% of the cases. 66.7% of the patients with extracapsular disease but no seminal vesicle invasion progressed. 15% of pT2 patients experienced a persistent/recurrent postoperative PSA and were upstaged to pT3 after reevaluation of the specimen., Conclusion: Efforts should be made to increase the preoperative evaluation of seminal vesicle and pericapsular status by a more sophisticated technique of prostate biopsy in order to avoid noncurative surgery.