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Purpose: Biopsy and final pathological Gleason score (GS) are inconstantly correlated with each other. The aim of the current study was to develop and validate a predictive score to screen patients diagnosed with a biopsy GS ≤ 6 prostate cancer (PCa) at risk of GS upgrading., Methods: Clinical and pathological data of 1,179 patients managed with radical prostatectomy for a biopsy GS ≤ 6, clinical stage ≤ T2b and preoperative PSA ≤ 20 ng/ml PCa were collected. The population study was randomly split into a development (n = 822) and a validation (n = 357) cohort. A prognostic score was established using the independent factors related to GS upgrading identified in multivariate analysis. The cutoff value derived from the area under the receiver operating characteristic curve of the score., Results: After RP, the rate of GS upgrading was 56.7%. In multivariate analysis, length of cancer per core > 5 mm (OR 2.938; p < 0.001), PSA level > 15 ng/ml (OR 2.365; p = 0.01), age > 70 (OR 1.746; p = 0.016), number of biopsy cores > 12 (OR 0.696; p = 0.041) and prostate weight > 50 g (OR 0.656; CI; p < 0.007) were independent predictive factors of GS upgrading. A score ranged between -4 and 12 with a cutoff value of 2 was established. In the development cohort, the accuracy of predictive score was 63.7% and the positive predictive value was 71.2%. Results were confirmed in the validation cohort., Conclusion: This predictive tool might be used to screen patients initially diagnosed with low-grade PCa but harboring occult high-grade disease.

Background: The predictive value of the abnormality side during digital rectal examination (DRE) has never been studied, suggesting that physicians examined the left lobe of the gland as well as the right lobe. We aimed to assess the predictive value of the side of DRE abnormality for prostate cancer (PCa) detection and aggressiveness in right-handed urologists., Methods: An analysis of a prospective database was carried out that included all consecutive men undergoing prostate biopsies between 2001 and 2012. The main end point was the predictive value of the abnormality side during DRE for cancer detection in clinically suspicious unilateral T2 disease. The diagnostic performance of left- versus right-sided abnormality was also assessed in terms of sensitivity, specificity and negative/positive predictive values., Results: Overall, 308 patients had a suspicious unilateral clinical disease (detection rate 57.5%). The cancer detection rate was significantly higher in case of left-sided compared with right-sided clinical T2 stage (odds ratio 2.1). In case of left-sided disease, the number of positive cores, the rate of perineural invasion, the rate of primary grade 4 pattern and the percentage of cancer involvement per core were significantly higher compared with those reported for right-sided disease. The predictive value of abnormality laterality for cancer detection and aggressiveness remained statistically independent in multivariate models. The positive predictive value for cancer detection was 64.6 in case of suspicious left-sided disease versus 46.9 in case of right-sided disease., Conclusions: The risks of detecting PCa and aggressive disease on biopsy are significantly higher when DRE reveals a suspicious left-sided clinical disease as compared with right-sided disease. Right-handed physicians should be aware of this variance in diagnostic performance and potential underdetection of left-sided clinical disease, and should improve their examination of the left lobe of the gland by conducting longer exams or changing the patient's position.

Background: The debate on the optimal number of prostate biopsy core samples that should be taken as an initial strategy is open., Objective: To prospectively evaluate the diagnostic yield of a 21-core biopsy protocol as an initial strategy for prostate cancer (PCa) detection., Design, Setting, and Participants: During 10 yr, 2753 consecutive patients underwent a 21-core biopsy scheme for their first set of biopsy specimens., Intervention: All patients underwent a standardized 21-core protocol with cores mapped for location., Outcome Measurements and Statistical Analysis: The PCa detection rate of each biopsy scheme (6, 12, or 21 cores) was compared using a McNemar test. Predictive factors of the diagnostic yield achieved by a 21-core scheme were studied using logistic regression analyses., Results and Limitations: PCa detection rates using 6 sextant biopsies, 12 cores, and 21 cores were 32.5%, 40.4%, and 43.3%, respectively. The 12-core procedure improved the cancer detection rate by 19.4% (p=0.004), and the 21-biopsy scheme improved the rate by 6.7% overall (p<0.001). The six far lateral cores were the most efficient in terms of detection rate. The diagnostic yield of the 21-core protocol was >10% in prostates with volume >70 ml, in men with a prostate-specific antigen level<4 ng/ml, with a prostate-specific antigen density (PSAD) <0.20 ng/ml per gram. A PSAD <0.20 ng/ml per gram was the strongest independent predictive factor of the diagnostic yield offered by the 21-core scheme (p<0.001). The 21-core protocol significantly increased the rate of PCa eligible for active surveillance (62.5% vs 48.4%; p=0.036) than those detected by a 12-core scheme without statistically increasing the rate of insignificant PCa (p=0.503)., Conclusions: A 21-core biopsy scheme improves significantly the PCa detection rate compared with a 12-core protocol. We identified a cut-off PSAD (0.20 ng/ml per gram) below which an extended 21-core scheme might be systematically proposed to significantly improve the overall detection rate without increasing the rate of detected insignificant PCa., (Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: To evaluate the impact of detailed biopsy characteristics such as positive cores location or multifocality on the risk of initial reclassification in prostate cancer (CaP) patients eligible for active surveillance (AS)., Materials and Methods: We reviewed data from 300 consecutive men eligible for AS (PSA ≤ 10 ng/ml, clinical stage T1c, Gleason score ≤ 6, <3 positive cores, extent of cancer in any core < 50%) who have undergone a radical prostatectomy (RP). Reclassification was defined as upstaged disease and/or upgraded disease in RP specimens., Results: Biopsy features showed 36% of CaP involving 2 cores and a mean total tumor length of 2.63 mm. The 2 most frequently positive sites were base and apex. Mean total tumor length was significantly associated with upgraded disease (P = 0.025). In a multivariate model taking into account PSA, PSAD, number of positive cores and total tumor length, a total tumor length > 5 mm were independently predictor for a upgraded disease (OR 1.93, P = 0.046). The number, the multifocality and the bilaterality of positive cores were not associated with reclassification. Upgraded disease was significantly less reported in case of positivity at midline zone compared with positivity at base, apex, or transition zone (P = 0.013)., Conclusions: Detailed biopsy data provide additional information on the initial risk of reclassification in AS patients. Patients having a total tumor length < 5 mm and positive cores at midline zone are more likely to have favorable pathologic characteristics at diagnosis. These variables can be used for selection and monitoring improvement in AS programs., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: To assess the pathological and the oncologic outcomes of the prostate cancer (PCa) missed by 6- and 12-core biopsy protocols by using a reference 21-core scheme., Materials and Methods: Between 2001 and 2009, all patients who had PCa detected in an initial 21-core TRUS biopsy scheme and were treated by a radical prostatectomy (RP) were included. Patients were sorted in 3 groups according to the diagnosis site: sextant (6 first cores; group 1), peripheral zone (12 first cores; group 2) or midline/transitional zone (after 21 cores; group 3). Demographics, pathological features in biopsy and RP specimens and follow-up after RP were analyzed. The 5-year progression-free survival (PFS) was studied in the 3 groups., Results: During the study period, 443 patients were included. Among them, 67, 23.7 and 9.2% were, respectively, diagnosed in groups 1, 2 and 3. Among PCa diagnosed in midline/transition zone cores, 42% were intermediate or high risk. Unfavorable disease was more frequently reported in group 1 in terms of extraprostatic extension (P = 0.001), high Gleason score (P = 0.001) and progression (P = 0.001). No significant difference was observed between groups 2 and 3 in terms of pathological features in RP specimens and oncologic outcome. The 5-year PFS was 89.7% and not significantly different in patients diagnosed with a 12-core scheme compared to those diagnosed only with 21-core scheme (P = 0.332)., Conclusions: Our findings emphasize that PCa diagnosed only in a 21-core protocol is at least as aggressive as PCa detected in a 12-core scheme. This study invalidates the widespread idea sustaining that cancers diagnosed by more than 12 biopsies are less aggressive.

Unlabelled: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Even after a negative set of prostate biopsies, the risk of undetected prostate cancer remains clinically significant. Predictive markers of such a risk are undefined. In addition to PSA and PSAD, low prostate volume and %fPSA are interesting time-varying risk factors and are relevant in biopsy decision-making., Objective: To assess prospectively the time-varying risk of rebiopsy and of prostate cancer (PCa) detection after an initial negative biopsy protocol., Patients and Methods: Over a period of 10 years, 1995 consecutive patients with initially negative biopsies were followed. Rebiopsies were performed in patients who had a persistent suspicion of PCa. Predictive factors for rebiopsy and for PCa detection were tested using univariate, multivariate and time-dependent models., Results: A total of 617 men (31%) underwent at least one rebiopsy after a mean follow-up of 19 months. PCa detection rates during second, third, and fourth sets of biopsies were 16.7, 16.9 and 12.5%, respectively. The overall rate of detected PCa was 7.0%. The 5-year rebiopsy-free and PCa-free survival rates were 65.9 and 92.5%, respectively. Indications for rebiopsy were more frequently reported in patients having a high prostate-specific antigen (PSA) level (P = 0.006) or a high PSA density (PSAD; P < 0.001) and in younger patients (P = 0.008). The risk of PCa on rebiopsies was not correlated with age, but significantly increased more than twofold in cases of PSA >6 ng/mL, PSAD >0.15 ng/mL/g, free-to-total PSA ratio (%fPSA) <15, and/or prostate volume <50 mL. Time-dependent analyses were in line with these findings. The main study limitation was the lack of control of the absence of PCa and PSA kinetics in men not rebiopsied., Conclusions: The overall risk of detected PCa after an initial negative biopsy was low. In addition to PSA and PSAD, which are well-used in rebiopsy indications, low prostate volume and %fPSA are interesting time-varying risk factors for PCa on rebiopsy and could be relevant in biopsy decision-making., (© 2013 BJU International.)

Background: Urinary prostate cancer antigen 3 (PCA3) assay in combination with established clinical risk factors improves the identification of men at risk of harboring prostate cancer (PCa) at initial biopsy (IBX)., Objective: To develop and validate internally the first IBX-specific PCA3-based nomogram that allows an individual assessment of a man's risk of harboring any PCa and high-grade PCa (HGPCa)., Design, Setting, and Participants: Clinical and biopsy data including urinary PCA3 score of 692 referred IBX men at risk of PCa were collected within two prospective multi-institutional studies., Intervention: IBX (≥ 10 biopsy cores) with standard risk factor assessment including prebiopsy urinary PCA3 measurement., Outcome Measurements and Statistical Analysis: PCA3 assay cut-off thresholds were investigated. Regression coefficients of logistic risk factor analyses were used to construct specific sets of PCA3-based nomograms to predict any PCa and HGPCa at IBX. Accuracy estimates for the presence of any PCa and HGPCa were quantified using area under the curve of the receiver operator characteristic analysis and compared with a clinical model. Bootstrap resamples were used for internal validation. Decision curve analyses quantified the clinical net benefit related to the novel PCA3-based IBX nomogram versus the clinical model., Results and Limitations: Any PCa and HGPCa were diagnosed in 46% (n=318) and 20% (n=137), respectively. Age, prostate-specific antigen, digital rectal examination, prostate volume, and PCA3 were independent predictors of PCa at IBX (all p<0.001). The PCA3-based IBX nomograms significantly outperformed the clinical models without PCA3 (all p<0.001). Accuracy was increased by 4.5-7.1% related to PCA3 inclusion. When applying nomogram-derived PCa probability thresholds ≤ 30%, only a few patients with HGPCa (≤ 2%) will be missed while avoiding up to 55% of unnecessary biopsies. External validation of the PCA3-based IBX-specific nomogram is warranted., Conclusions: The internally validated PCA3-based IBX-specific nomogram outperforms a clinical prediction model without PCA3 for the prediction of any PCa, leading to the avoidance of unnecessary biopsies while missing only a few cases of HGPCa. Our findings support the concepts of a combination of novel markers with established clinical risk factors and the superiority of decision tools that are specific to a clinical scenario., (Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: To identify the risk of failure of active surveillance (AS) in men who had the Prostate Cancer Research International: Active Surveillance (PRIAS) criteria and had undergone radical prostatectomy (RP), by studying as primary endpoints the risk of unfavourable disease in RP specimens (stage >T2 and/or Gleason score >6) and of biochemical progression after RP., Patients and Methods: We assessed 626 patients who had the PRIAS criteria for AS defined as T1c/T2, PSA level of ≤10 ng/mL, PSA density (PSAD) of <0.2 ng/mL per mL, Gleason score of <7, and one or two positive biopsies. All patients underwent immediate RP at our department between January 1991 and December 2010. Multivariate logistic regression was used to test factors correlated with the risk of unfavourable prostate cancer. The risk of progression was tested using multivariate Cox regression models. Biochemical recurrence-free survival (BFS) was established using the Kaplan-Meier method., Results: Pathological study of RP specimens showed upstaging (>T2) in 129 patients (20.6%), upgrading (Gleason score >6) in 281 (44.9%) and unfavourable disease in 312 patients (50%). There was a statistically non-significant trend for BFS at P = 0.06. Predictors of favourable tumours were age <65 years (P = 0.005), one vs two positive biopsies (P = 0.01) and a biopsy core number >12 (P = 0.005). Preoperative factors predicting disease progression were a PSAD of >0.15 ng/mL(2) (P = 0.008) and biopsy core number of ≤12 (P = 0.017)., Conclusions: Even with stringent AS criteria, the rate of unfavourable disease remains high. Predictive factors of unfavourable disease and biochemical progression should be considered when including patients in AS protocols., (© 2012 BJU International.)

Unlabelled: Study Type - Diagnostic (case series)., Level of Evidence: 4., Objective: • To investigate the role of magnetic resonance imaging (MRI) in selecting patients for active surveillance (AS)., Patients and Methods: • We identified prostate cancers patients who had undergone a 21-core biopsy scheme and fulfilled the criteria as follows: prostate-specific antigen (PSA) level ≤ 10 ng/mL, T1-T2a disease, a Gleason score ≤ 6, <3 positive cores and tumour length per core <3 mm. • We included 96 patients who underwent a radical prostatectomy (RP) and a prostate MRI before surgery. • The main end point of the study was the unfavourable disease features at RP, with or without the use of MRI as AS inclusion criterion., Results: • Mean age and mean PSA were 62.4 years and 6.1 ng/mL, respectively. Prostate cancer was staged pT3 in 17.7% of cases. • The rate of unfavourable disease (pT3-4 and/or Gleason score ≥ 4 + 3) was 24.0%. A T3 disease on MRI was noted in 28 men (29.2%). MRI was not a significant predictor of pT3 disease in RP specimens (P = 0.980), rate of unfavourable disease (P = 0.604), positive surgical margins (P = 0.750) or Gleason upgrading (P = 0.314). • In a logistic regression model, no preoperative parameter was an independent predictor of unfavourable disease in the RP specimen. • After a mean follow-up of 29 months, the recurrence-free survival (RFS) was statistically equivalent between men with T3 on MRI and those with T1-T2 disease (P = 0.853)., Conclusion: • The results of the present study emphasize that, when the selection of patients for AS is based on an extended 21-core biopsy scheme, and uses the most stringent inclusion criteria, MRI does not improve the prediction of high-risk and/or non organ-confined disease in a RP specimen., (© 2010 THE AUTHORS. BJU INTERNATIONAL © 2010 BJU INTERNATIONAL.)

Objective: To assess transforming growth factor β-receptor II (TGFBRII) protein expression in benign prostatic hyperplasia (BPH) using immunohistochemistry analysis, and to compare the analysis with phenotypic properties., Methods: TGFBRII protein expression was profiled using three clinical outcome tissue microarrays (TMAs), sampled from 231 patients who underwent surgery for BPH. Using these TMAs, five inflammatory cell markers were also assessed, including CD3, CD4, CD8, CD20, and CD163. The surgical procedure was open prostatectomy in 95 patients and transurethral resection of the prostate in 136 patients., Results: TGFBRII protein expression was found in BPH epithelium cells for both basal and secretory cells, as well as in fibromuscular stromal cells. TGFBRII staining was also strong in most of the lymphocytes infiltrating the prostate. TGFBRII stromal staining was found to be significantly associated with prostate volume (P = 0.04), whereas TGFBRII epithelial staining was found to be significantly associated with 5-α-reductase-inhibitor medical therapy received by patients before surgery (P = 0.004). Both stromal and epithelial TGFBRII staining were found to be associated with CD4 T-lymphocyte infiltrate, independently of prostate volume (P < 0.001 and P = 0.002)., Conclusions: TGFBRII protein expression in BPH is associated with prostate gland volume and with CD4 T-lymphocyte prostatitis. TGFBRII might be a promising therapeutic target to prevent prostate enlargement or even to decrease prostate volume., (© 2010 THE AUTHORS. JOURNAL COMPILATION © 2010 BJU INTERNATIONAL.)

Objective: To analyze pathological data of the radical prostatectomy specimen in patients operated for clinically-localized prostate cancer and who meet strict criteria for active surveillance necessary to be included in the French trial SURACAP., Patients and Methods: The data of patients who underwent a radical prostatectomy at our institution between 1998 and 2010 were reviewed. We only included the patients that met the usual criteria for active surveillance: clinical stage T1-2a tumor, PSA ≤ 10 ng/mL, biopsy Gleason sum inferior or equal to 6 with no pattern of grade 4 or 5, cancer involvement inferior or equal to two biopsy cores, inferior to 3 mm of malignant tissue in each positive biopsy core. From them, only those who were diagnosed from a second line biopsies cores were included for further analysis., Results: Overall, 48 patient who met the "SURACAP" criteria had a laparoscopic radical prostatectomy at out institution. Mean age was 65.4 years. The mean preoperative PSA was 6.1 ng/mL. Clinical stage of the tumor was T1c in 95% of patients and T2a in 5%. Biopsy Gleason score was 6 (3+3) in 100%. Pathological analysis of the surgical specimen showed that 19% of patients had a seminal vesicle invasion or an extracapsular extension. The Gleason score of the pathological specimen was 6 (3+3) in 57% of patients, 7 (3+4) in 38% and 8 (4+4) in 5% of patients. The Gleason score upgrading was 43% of patients., Conclusion: In our experience, 19% of patients who meet the criteria for active surveillance show an extracapsular extension or a seminal vesicle invasion on pathological analysis. Active surveillance is still under evaluation., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

Objective: To study the development of stage migration in prostate cancer after controlling for the number of biopsy cores., Patients and Methods: In all, 1826 patients had a first set of 21-core biopsies taken between 2001 and 2008. Among the 801 patients with prostate cancer, 443 had a laparoscopic radical prostatectomy (RP). Patients were divided into three subsets according to the date of biopsy, i.e. period 1 (2001-2003), period 2 (2004-2005), and period 3 (2006-2008). Study end points were the development over time of: (i) clinico-biological characteristics; (ii) biopsy variables; (iii) pathological RP features; and (iv) the biochemical recurrence-free (RFS) rate after surgery., Results: The mean age decreased significantly over time (P = 0.004). The proportion of men with a prostate-specific antigen (PSA) level of 4-10 ng/mL increased significantly over time at the expense of the proportion of men with a PSA level of ≥ 10 ng/mL (P = 0.004). A biopsy Gleason score of ≥ 7 was reported in 53.9% of period 1, compared to 39.6% in period 3 (P = 0.001). RP specimens had a significantly lower proportion of extraprostatic disease (P = 0.013), of high Gleason scores (P = 0.049), and positive margins (P = 0.011) over time. The RFS curves did not vary over time (P = 897)., Conclusion: Current candidates for prostate biopsy are younger and have lower PSA levels than those who had biopsies taken at the beginning of the decade. Cancers are less aggressive in terms of Gleason score, extent of the disease on biopsy cores and rate of extraprostatic disease on RP specimens than those diagnosed at the beginning of the decade., (© 2010 THE AUTHORS. JOURNAL COMPILATION © 2010 BJU INTERNATIONAL.)

Objective: to determine the performance characteristics of the prostate cancer gene 3 (PCA3) score on the outcome of biopsy relative to different ranges of free-to-total prostate-specific antigen (PSA) ratio (f/tPSA) in men with a previous negative biopsy and a PSA level of 2.5-10 ng/mL, as urine tests like PCA3 are currently under investigation in order to improve prostate cancer diagnosis and to decrease the rate of unnecessary rebiopsies., Patients and Methods: data from the previous prospective European multicentre study were reviewed. Only patients with a PSA level of 2.5-10 ng/mL were included in the present study. In all, 301 patients had complete data. The diagnostic accuracy of the PCA3 score for predicting a positive biopsy outcome was studied using sensitivity, specificity, negative and positive predictive values. The PCA3 performance was evaluated relative to three different subgroups of f/tPSA, as follows: >20% (group 1), 10-20% (group 2) and <10% (group 3)., Results: the prostate cancer detection rates were 18.8%, 23.9% and 34.8% in groups 1, 2 and 3, respectively. The area under the receiver operating characteristic curve of the PCA3 score, total PSA and f/tPSA was 0.688, 0.553 and 0.571, respectively. The percentage of men with positive biopsies was 30.6%, 37.0% and 44.4% in those with a PCA3 score of >30, vs 10.3%, 15.5% and 28.6% when the PCA3 score was <30, in groups 1, 2 and 3, respectively. The difference was significant only in groups 1 and 2. In men with a f/tPSA of ≤ 10% the difference in detection rates relative to the PCA3 score was not statistically significant regardless of which PCA3 threshold was used. A high PCA3 score was significantly associated with age, clinical T2 stage and positive biopsy (P < 0.001, 0.013 and <0.001, respectively). In bivariate analysis accounting for the PCA3 score and the f/tPSA, a PCA3 score of >30 was a significant independent predictor of positive biopsies (odds ratio 3.01; 95% confidence interval 1.74-5.23; P < 0.001)., Conclusions: PCA3 remained a better predictor of prostate cancer than f/tPSA. In men with a f/tPSA of >10%, the use of the PCA3 score was highly correlated with the risk of having cancer on re-biopsy, and could prevent unnecessary prostate biopsies if the value is low.

Study Type: Therapy (case series) Level of Evidence 4., Objective: To review the biochemical recurrence-free survival (RFS) rates of laparoscopic radical prostatectomy (LRP) in patients with a high risk of disease progression as defined by preoperative criteria of D'Amico et al., Patients and Methods: Between October 2000 and May 2008, 110 patients had extraperitoneal LRP and bilateral pelvic lymph node sampling for high-risk prostate cancer in our department. High-risk prostate cancer was defined as a prostate-specific antigen (PSA) level of >20 ng/mL, and/or a biopsy Gleason score >or=8, and/or a clinical stage of T2c-T4 stage. The median follow-up was 37.6 months. Risk factors for time to biochemical recurrence were tested using log-rank survivorship analysis and Cox proportional hazards regression., Results: Prostate cancer was organ-confined in 36% of patients; the Overall RFS was 79.4% and 69.8% at 1 and 3 years, respectively. The 3-year RFS rates for organ-confined cancer vs extracapsular extension were 100% and 54.3%, respectively (P < 0.001). The 3-year RFS rates for tumour-free seminal vesicle vs seminal vesicle invasion were 81.8% and 33.6%, respectively (P < 0.001). The 3-year RFS rates for negative surgical margins vs positive were 85.2% and 47.3%, respectively (P = 0.001). Compared with men with any single pathological risk factor or any two risk factors, men with all three risk factors had a significantly shorter time to PSA failure after LRP (log-rank test, P < 0.001)., Conclusion: Among patients at increased risk of disease progression as defined by preoperative criteria, a third of men with organ-confined disease have a favourable prognosis. Men at high risk for early PSA failure could be better identified by pathological assessment of RP specimens, and selected for phase III randomized trials investigating adjuvant systemic treatment.

Objective: We investigated whether an intrafascial approach to prostatectomy would provide significantly improved outcomes compared with retropubic and laparoscopic approaches. We performed 50 radical prostatectomies with an intrafascial, nerve-sparing, laparoscopic, robot-assisted extraperitoneal approach., Methods: From December 2007 to June 2008, 50 consecutive patients underwent nerve sparing surgery using the intrafascial technique with robotic assistance. All surgeries were performed by the same senior urologist. Patient characteristics and perioperative data were collected prospectively. Oncological outcomes were assessed by pathological examination and postoperative prostate-specific antigen levels. Functional outcomes, including continence, potency, and quality of life, were assessed from patient questionnaires., Results: The mean operative time was 127 minutes (range: 80-205), the mean hospital stay was 4.2 days (range: 2-9), and the mean catheterization time was 7.8 days (range: 4-11). No perioperative complications occurred. One patient required a transfusion at the postoperative stage. The overall positive surgical margin rate was 12%; adjusted by tumor, nodes, and metastasis stage, it was 9.5% in pT2 and 17% in pT3 disease. At the 1-month follow-up, 66% of the patients were continent (no pad), 12% presented a minimal stress urinary incontinence (1 pad), and 22% required >1 pad(s) per day. Further, 60% of patients exhibited potency (erection sufficient for intercourse: 30% without the use of phosphodiesterase 5 inhibitors, 30% required a phosphodiesterase 5 inhibitor) and the remaining 40% required prostaglandin injections., Conclusions: An intrafascial approach with robotic assistance provided satisfactory early functional results with respect to postoperative continence and potency. Long-term oncological results remain to be assessed.

The aim of the current study was to analyze gene expression profiles in benign prostatic hyperplasia and to compare them with phenotypic properties. Thirty-seven specimens of benign prostatic hyperplasia were obtained from symptomatic patients undergoing surgery. RNA was extracted and hybridized to Affymetrix Chips containing 54,000 gene expression probes. Gene expression profiles were analyzed using cluster, TreeView, and significance analysis of microarrays softwares. In an initial unsupervised analysis, our 37 samples clustered hierarchically in 2 groups of 18 and 19 samples, respectively. Five clinical parameters were statistically different between the 2 groups: in group 1 compared with group 2, patients had larger prostate glands, had higher prostate specific antigen levels, were more likely to be treated by alpha blockers, to be operated by prostatectomy, and to have major irritative symptoms. The sole independent parameter associated with this dichotome clustering, however, was the prostate gland volume. Therefore, the role of prostate volume was explored in a supervised analysis. Gene expression of prostate glands <60 mL and >60 mL were compared using significance analysis of microarrays and 227 genes were found differentially expressed between the 2 groups (>2 change and false discovery rate of <5%). Several specific pathways including growth factors genes, cell cycle genes, apoptose genes, inflammation genes, and androgen regulated genes, displayed major differences between small and large prostate glands.

Objective: To analyse the outcome of patients undergoing radical prostatectomy (RP) for Gleason 8-10 clinically localized prostate cancer, and to evaluate the prognostic value of well-known predictors of progression., Patients and Methods: In all, 1480 patients had RP between 1988 and 2006, of whom 180 had pathological Gleason score >or=8 and negative lymph nodes. Biochemical progression-free survival was determined using the Kaplan-Meier method. The effect of preoperative prostate-specific antigen (PSA) level, pathological stage and margin status was assessed with univariate and multivariate analyses., Results: Of the 180 patients, the Gleason score in the RP specimen was 8, 9 or 10 in 70%, 27% and 3%, respectively; 24% had stage pT2 disease, 30% stage pT3a, 25% stage pT3b and 20% stage pT4a. The 5- and 7-year biochemical progression-free survival was 73 and 65% for stage pT2, 40% and 27% for stage pT3a, and 30% for stage pT3b (log rank test, P < 0.001). In the univariate model, preoperative PSA level, pathological stage and surgical margins were predictors of survival. In the multivariate analysis, preoperative PSA level and extracapsular extension predicted biochemical progression-free survival., Conclusion: Gleason 8-10 tumours have a poor prognosis. Patients with a PSA level of <10 ng/mL and stage pT2 disease have the greatest likelihood of having a longer progression-free survival after RP.

Objectives: To evaluate prospectively the diagnostic yield of a 21-sample ultrasound-guided needle biopsy procedure for prostate cancer in patients with elevated serum prostate-specific antigen and/or abnormal digital rectal examination findings., Methods: Between December 2000 and May 2002, 303 patients underwent 21-sample needle biopsy under local anesthesia, comprising sextant biopsies at a 45 degrees angle, 3 biopsies in each peripheral zone at an 80 degrees angle, 3 biopsies in each transition zone (TZ), and 3 biopsies in the midline peripheral zone. Morbidity was assessed clinically. A short questionnaire was filled out by 90 consecutive patients., Results: The cancer detection rate using 6 biopsy samples (sextant biopsies only), 12 samples (sextant plus lateral biopsies), 18 samples (sextant plus lateral plus TZ biopsies), and 21 samples (sextant plus lateral plus TZ, plus midline biopsies) was 22.7%, 28.3%, 30.7%, and 31.3%, respectively. The 21-sample procedure statistically improved the cancer detection rate by 37.9% relative to the 6-sample procedure. The improvement was most marked in patients with a prostate volume of more than 40 cm(3) (48.3%), patients with Stage T1c prostate disease (44.9%), patients undergoing repeat biopsy (66.2%), and patients with prostate-specific antigen levels greater than 10 ng/mL (38.5%). Adverse effects were infrequent (3%), consisting of prostatitis in 3 patients, acute urinary retention in 6 patients, and rectal bleeding requiring hospitalization in 1 patient taking aspirin. Using the questionnaire, 84% of patients reported macroscopic hematuria for an average of 3.4 days and hematospermia for 12.8 days, and 45% reported minor rectal bleeding lasting 1.1 days. The mean pain score, with a visual analog scale ranging between 0 (no pain) and 10 (intense pain), was 4.56., Conclusions: A 21-sample needle biopsy procedure increased the prostate cancer detection rate relative to a 6-sample procedure, without increasing morbidity. Patients with elevated prostate-specific antigen values should undergo sextant biopsies and at least 6 additional biopsies in the peripheral zone and 6 in the TZ.

Objectives: To evaluate and compare the location of positive surgical margins after retropubic, perineal, and laparoscopic radical prostatectomy for organ-confined prostate cancer (pT2)., Methods: From 1988 to 2001, 538 patients underwent radical prostatectomy for clinically localized prostate cancer. Patient age at surgery, clinical stage, preoperative prostate-specific antigen, and Gleason score of positive biopsies were noted. Postoperatively, specimen weight, final Gleason score, and capsular, seminal vesicle, and lymph node status, as well as tumor volume, were studied. The incidence and location of positive margins and the pathologic stage were noted according to the surgical approach., Results: A total of 371 patients (69.5%) had organ-confined tumors. Of the 371 patients, 116 underwent the retropubic, 86 the perineal, and 169 the laparoscopic approach, and positive surgical margins were noted in 22 (18.9%), 12 (13.9%), and 32 (18.9%) patients, respectively. Positive surgical margins were reported in 72 specimen locations, 32 (44.4%) at the apex, 17 (23.6%) at the bladder neck, and 29 (31.9%) posterolaterally. The distribution for the retropubic, perineal, and laparoscopic approaches was apex in 50%, 33.3%, and 44.4%, bladder neck in 29.1%, 41.7%, and 13.9%, and posterolaterally in 20.8%, 25%, and 41.6%, respectively., Conclusions: In our series, each approach had a specific high-risk location of positive margins: the apex for the retropubic, the bladder neck for the perineal, and posterolaterally for the laparoscopic approach. Improvements in the surgical techniques should take these specific locations under consideration to decrease the incidence of positive surgical margins.

The diagnosis of prostate cancer is confirmed by histological examination of prostate biopsies. In cases of localized prostate cancer, in which radical prostatectomy can be proposed as curative treatment, these biopsies, directly reflecting the cancer, can provide important prognostic elements, by specifying the tumour staging, allowing better patient selection and guiding surgical techniques in order to improve the postoperative histological results either by decreasing the number of pT3 tumours (extraprostatic) or the positive resection margin rate. Only pejorative elements are a good indicator of extraprostatic spread of the tumour: a Gleason score greater than 7, the presence of extracapsular invasion, perineural invasion, seminal vesicle invasion, 66% of positive biopsies are in favour of extraprostatic tumour. In contrast, the presence of apparently favourable prognostic elements, such as a low Gleason score, one out of six positive biopsies, limited invasion of biopsies cannot confirm the presence of a minimally aggressive, intraprostatic tumour (pT2). Other prognostic criteria may be discovered in the future, which will confirm with greater precision the extraprostatic or intraprostatic nature of localized prostatic tumours.

Objectives: Routine sextant biopsies have proven useful in the diagnosis and local staging of prostate cancer. A single positive biopsy is more frequently associated with a smaller tumor and a low risk of positive margins. Nevertheless, the risk of positive margins in patients with 1 positive sextant biopsy remains high (20%). A better assessment of local invasion is therefore needed. In addition to standard sextant biopsies, we routinely obtain 3 additional mid biopsies from the apex to the base of the prostate. The aim of this study is to analyze the contribution of these 3 additional mid biopsies to local staging., Methods: From 1988 to 1996, 177 men underwent sextant biopsies plus 3 additional mid biopsies prior to radical prostatectomy; 59 men had 1 positive sextant biopsy, and 13 also had 1-3 positive mid biopsies. The pathological results of the prostatectomy specimens from these 13 men (group A) were compared with those of the 46 men with only 1 positive sextant biopsy (group B), by means of the Fisher and Mann-Whitney tests., Results: The two groups were similar in terms of age, preoperative prostate-specific antigen, the Gleason score of positive biopsies, the weight of the specimen, the Gleason specimen score, tumor volume and pathological stage. Positive surgical margins were found in 53.8% of group A and 19.4% of group B patients (p = 0.002). The location of the positive additional biopsies matched that of the positive surgical margins., Conclusions: Additional mid biopsies improve the local assessment of prostate cancer in patients with a single positive sextant biopsy, identifying significantly more positive margins when these additional mid biopsies are positive and indicating the location of the positive surgical margins. These informations could be helpful to avoid positive surgical margins during radical prostatectomy.

Objectives: Prostatic biopsies, a diagnostic tool, are also used as prognostic elements before radical prostatectomy. Their sites within the prostatic gland constitute one of these prognostic criteria. The authors compared the site of positive prostatic biopsies with that of the tumour after radical prostatectomy in order to study the value of this prognostic factor and the way in which it can be improved., Material and Methods: From 1988 to 1996, 166 localized prostatic tumours treated by radical prostatectomy were diagnosed by 6 systematized ultrasound-guided transrectal biopsies and 3 supplementary median biopsies performed from the base to the prostatic apex. The site of positive biopsies was compared to that of the tumour within the prostatic gland., Results: Of the 996 sextant biopsies performed, 331 (33%) were positive, i.e. 1.99 biopsies per prostate. 92 (19%) median biopsies were positive. 331 positive sextant biopsies corresponded to a tumour within the prostate with a specificity of 81.5%, a sensitivity of 39.4%, a positive predictive value (PPV) of 83.3%, a negative predictive value (NPV) of 36.4% and an accuracy of 52%. For 3 median biopsies, the sensitivity was 70.3%, the specificity was 91.6%, the PPV was 61.9%, the NPV was 94%, and the accuracy was 82%. The weight of the prostate (prostates less than and greater than 45 g), influenced these results, as PPV decreased from 90.8% to 76.1% while NPV increased from 32.9% to 37.8%., Conclusion: Negative biopsies in a prostatic zone after 6 randomized biopsies do not exclude the presence of tumour in this zone and cannot be used as a prognostic element before radical prostatectomy for the therapeutic management. The presence of negative biopsies in a prostatic zone must be interpreted by taking the prostatic weight into account. 3 median biopsies are more accurate and less influenced by prostatic weight.

Objectives: To describe a method of calculation of prostatic tumour volume allowing spatial representation of the tumour within the prostate gland., Methods: 60 radical prostatectomy specimens were studied. Each specimen was processed according to the Stanford technique, and each prostatic section was also divided into two parts, anterior and posterior, according to a sagittal plane through the urethra. 5 microns thick serial sections were performed every 3 mm. The tumour surface area was calculated under light microscopy on each slide. The tumour volume between two consecutive slides was considered to be the volume of a truncated cone. The overall volume obtained was then equal to the sum of these various partial volumes. Spatial representation was performed according to two axes for each of the anterior and posterior parts of the prostatic sections: x-axis represented the prostate from the base to the apex, and the y-axis represented the tumour surface area in each prostatic section., Results: The tumour volume ranged from 0.01 cm3, from 0.21 cm3 for pT2A to 1.98 cm3 for pT3C. pT3 tumours corresponded to the largest volumes, but some pT3 had a small volume. pT3 tumours were preferentially located close to Denonvilliers fascia : 40% of posterior tumours were pT3 versus 9% of anterior tumours (p = 0.01)., Conclusion: The tumour volume on prostatectomy specimens can be evaluated by routine preparations and represents an additional element allowing better assessment of the TNM classification, as well as the predictive value of the information provided by prostatic biopsies.

Introduction: The prostate cancer, which is the second cause of cancer, is in constant increase. This is linked to the ageing of population which is in fact a medical and socioeconomic problem. The curative therapeutic attitude of the localized prostate cancer are either wath-full waiting, radiotherapy or radical prostatectomy. With the actual clinical and radiological techniques of stadification, 40% of the localized prostate cancer are extraglandular on the prostatectomy specimen. Recently, the RT-PCR seems to be a more specific and sensitive technique to detect circulating epithelial cells compared to others techniques (immunocytochemistry or flow cytometry). The detection of these circulating cells, would be correlated to the anatomopathologic stage. The use of RT-PCR as a tool of molecular stadification should be considered., Methods: This study evaluates and compares with in vitro pattern, the different techniques of separation (ficoll, gradient, osmotic shock) and detection (immunocytochemistry, flow cytometry and RT-PCR)., Results: The ficoll gradient is the best technique of cellular separation preserving cellular morphology and RNA. The detection level are 1 cell LnCap per 40,000 lymphocytes cell by immunocytochemistry, 1/1000 by flow cytometry, 1/10,000 to 1/1,000,000 by RT-PCR., Conclusion: The RT-PCR with its low detection level and its high specificity, is the best technique of detection of epithelial circulating cells in localized stage. The advantage of immunocytochemistry is its simplicity. Its use for circulating cells caracterization can be considered for metastatic stage.