Microarray gene expression profiling and analysis of bladder cancer supports the sub-classification of T1 tumours into T1a and T1b stages.

OBJECTIVE: To try and identify a molecular signature for pathological staging and/or grading. through microarray analysis. PATIENTS AND METHODS: We performed a prospective multicentre study between September 2007 and May 2008 that included 108 bladder tumours (45 pTa, 35 pT1 and 28>pT1). Microarray analysis was performed using Agilent Technologies Human Whole Genome 4 × 44K oligonucleotide microarrays (Agilent, Santa Clara, CA, USA). A 'dual colour' method was used vs a reference pool of tumours. From the lists of genes provided by the Biometric Research Branch class comparison analyses, we validated the microarray results of 38 selected differentially expressed genes using reverse transcriptase quantitative PCR in another bladder tumour cohort (n = 95). RESULTS: The cluster 'superficial vs invasive stage' correctly classified 92.9% of invasive stages and 66.3% of superficial stages. Among the superficial tumours, the cluster analysis showed that pT1b tumours were closer to invasive stages than pT1a tumours. We also found molecular differences between low and high grade superficial tumours, but these differences were less well defined than the difference observed for staging. CONCLUSIONS: We confirmed that the histopathological classification into subgroups pTa, pT1a and pT1b can be translated into a molecular signature with a continuous progression of deregulation (overexpression or repression of these genes) from superficial (pTa) to more invasive (pT1a then b) stages.

Comparative evaluation of urinary PCA3 and TMPRSS2: ERG scores and serum PHI in predicting prostate cancer aggressiveness.

It has been suggested that urinary PCA3 and TMPRSS2:ERG fusion tests and serum PHI correlate to cancer aggressiveness-related pathological criteria at prostatectomy. To evaluate and compare their ability in predicting prostate cancer aggressiveness, PHI and urinary PCA3 and TMPRSS2:ERG (T2) scores were assessed in 154 patients who underwent radical prostatectomy for biopsy-proven prostate cancer. Univariate and multivariate analyses using logistic regression and decision curve analyses were performed. All three markers were predictors of a tumor volume≥0.5 mL. Only PHI predicted Gleason score≥7. T2 score and PHI were both independent predictors of extracapsular extension(≥pT3), while multifocality was only predicted by PCA3 score. Moreover, when compared to a base model (age, digital rectal examination, serum PSA, and Gleason sum at biopsy), the addition of both PCA3 score and PHI to the base model induced a significant increase (+12%) when predicting tumor volume>0.5 mL. PHI and urinary PCA3 and T2 scores can be considered as complementary predictors of cancer aggressiveness at prostatectomy.

PCA3 and PCA3-based nomograms improve diagnostic accuracy in patients undergoing first prostate biopsy.

While now recognized as an aid to predict repeat prostate biopsy outcome, the urinary PCA3 (prostate cancer gene 3) test has also been recently advocated to predict initial biopsy results. The objective is to evaluate the performance of the PCA3 test in predicting results of initial prostate biopsies and to determine whether its incorporation into specific nomograms reinforces its diagnostic value. A prospective study included 601 consecutive patients addressed for initial prostate biopsy. The PCA3 test was performed before ≥12-core initial prostate biopsy, along with standard risk factor assessment. Diagnostic performance of the PCA3 test was evaluated. The three available nomograms (Hansen's and Chun's nomograms, as well as the updated Prostate Cancer Prevention Trial risk calculator; PCPT) were applied to the cohort, and their predictive accuracies were assessed in terms of biopsy outcome: the presence of any prostate cancer (PCa) and high-grade prostate cancer (HGPCa). The PCA3 score provided significant predictive accuracy. While the PCPT risk calculator appeared less accurate; both Chun's and Hansen's nomograms provided good calibration and high net benefit on decision curve analyses. When applying nomogram-derived PCa probability thresholds ≤30%, ≤6% of HGPCa would have been missed, while avoiding up to 48% of unnecessary biopsies. The urinary PCA3 test and PCA3-incorporating nomograms can be considered as reliable tools to aid in the initial biopsy decision.

Transurethral plasma vaporization of the prostate: 3-month functional outcome and complications.

UNLABELLED: Study Type - Therapy (multi-centre cohort). Level of Evidence 2b. OBJECTIVE: To evaluate the early functional outcomes of transurethral plasma vaporization of the prostate (TUVis) in a multicentre study. PATIENTS AND METHODS: A prospective multicentre observational study was conducted in eight urology departments. The inclusion criterion was benign prostatic hyperplasia (BPH) requiring surgical treatment. Patients on anti-coagulant therapy were not excluded. The TUVis procedure was performed according to a classic transurethral resection of the prostate (TURP) scheme following the manufacturer's recommendations. We evaluated subjective functional outcome using self-questionnaires (International Prostate Symptom Score [IPSS] and five-item International Index of Erectile Function [IIEF-5]) and objective criteria (prostate volume, prostate-specific antigen [PSA], uroflowmetry, post residual volume) at baseline and at 1- and 3-month follow-ups. All types of complications were systematically recorded. RESULTS: Despite 52% of patients receiving anticoagulant therapy before surgery, we reported only 3% with haemorrhagic complications, no blood transfusion, a mean catheterization time of 44 h and a mean postoperative stay of 2.9 nights. No significant change in irrigation time, catheter time or hospital stay was observed in patients with or without anticoagulant therapy. The IPSS and bother scores significantly decreased after the 3-month follow-up (57% and 59%, respectively), but the average remaining prostate volume was 29 cc and the tissue ablation rate was only 0.5 cc/min. Three major complications occurred, consisting of two urinary fistulas and one partial bladder coagulation. CONCLUSIONS: The TUVis procedure has a proven fast postoperative recovery time, good short-term functional outcome and good haemostatic efficiency. However, the tissue ablation rate was lower than expected and we encountered three major complications, the mechanisms of which remain unclear. Considering the high energy level required to create the plasma effect, the generator, cable and resectoscope must be carefully checked before each procedure.

Urinary PCA3 score predicts prostate cancer multifocality.

PURPOSE: The urinary PCA3 gene test has proved helpful for deciding whether to (re)biopsy to diagnose prostate cancer. We searched for pathological features that influence the shedding of PCA3 producing prostate cancer cells in urine after digital rectal examination. MATERIALS AND METHODS: Included in our study were 102 patients with an informative PCA3 score on the Progensa® PCA3 assay who underwent radical prostatectomy. Correlations were evaluated between PCA3 score and histopathological factors on prostatectomy, including tumor site in the prostate and the number of cancer foci. RESULTS: PCA3 score significantly correlated with total tumor volume in prostatectomy specimens (p <0.001) but not with prostatectomy Gleason score or pathological stage. PCA3 score positively correlated with apical and basal invasion, and with bilaterality and multifocality. On multivariate analysis multifocality was an independent factor influencing PCA3 score (p = 0.012). CONCLUSIONS: Site in the prostate gland and the number of cancer foci may explain the observed PCA3 score variation in patients operated on for prostate cancer. The PCA3 test could be helpful in preoperatively selecting patients with unifocal and unilateral cancer who could benefit from active surveillance or focal therapy.

Down-regulation of DcR2 sensitizes androgen-dependent prostate cancer LNCaP cells to TRAIL-induced apoptosis.

BACKGROUND: Dysregulation of many apoptotic related genes and androgens are critical in the development, progression, and treatment of prostate cancer. The differential sensitivity of tumour cells to TRAIL-induced apoptosis can be mediated by the modulation of surface TRAIL receptor expression related to androgen concentration. Our previous results led to the hypothesis that downregulation of TRAIL-decoy receptor DcR2 expression following androgen deprivation would leave hormone sensitive normal prostate cells vulnerable to the cell death signal generated by TRAIL via its pro-apoptotic receptors. We tested this hypothesis under pathological conditions by exploring the regulation of TRAIL-induced apoptosis related to their death and decoy receptor expression, as also to hormonal concentrations in androgen-sensitive human prostate cancer, LNCaP, cells. RESULTS: In contrast to androgen-insensitive PC3 cells, decoy (DcR2) and death (DR5) receptor protein expression was correlated with hormone concentrations and TRAIL-induced apoptosis in LNCaP cells. Silencing of androgen-sensitive DcR2 protein expression by siRNA led to a significant increase in TRAIL-mediated apoptosis related to androgen concentration in LNCaP cells. CONCLUSIONS: The data support the hypothesis that hormone modulation of DcR2 expression regulates TRAIL-induced apoptosis in LNCaP cells, giving insight into cell death induction in apoptosis-resistant hormone-sensitive tumour cells from prostate cancer. TRAIL action and DcR2 expression modulation are potentially of clinical value in advanced tumour treatment.

Impact of oral anticoagulation on morbidity of transurethral resection of the prostate.

AIM: To assess the impact of oral anticoagulation (OA) on morbidity of transurethral resection of the prostate (TURP). OA included warfarin and platelet aggregation inhibitors (PAI). PATIENTS AND METHOD: Multicenter analysis of patients operated for symptomatic benign prostatic hyperplasia (BPH) by TURP. Patients under OA were compared to those with no OA. RESULTS: Out of 612 patients included in the analysis, 206 (33%) were on OA prior surgery (55 warfarin, 142 PAI, and 9 warfarin and PAI). No patient continued warfarin and clopidogrel during the operating period. Patients under OA were significantly older (75 vs. 71 yo, P < 0.001), had larger prostate volume (56 vs. 49 ml, P = 0.05), and had higher rate of bladder catheter prior surgery (26 vs. 17%, P = 0.02). At 3 months follow-up, patients in the OA group had a higher weight of resected tissue (24 vs. 21.7 g, P < 0.001), a longer duration of hospitalization (6.4 vs. 4.7 days P < 0.001), a higher rate of bladder clots (13 vs. 4.7%, P < 0.001), red cell transfusion (1.9 vs. 1.0%, P = 0.026), late hematuria (15.0 vs. 8.4%, P = 0.004), and thromboembolic events (2.4 vs. 0.7, P = 0.02). In multivariable analysis, OA status was the sole independent parameter associated with bladder clots (P = 0.004) and with late hematuria (P = 0.03). CONCLUSION: OA had a significant and independent impact on TURP outcome in terms of bleeding complications. This data could be used for treatment decision and for patient's information prior BPH surgery.

Surgical management of BPH in patients on oral anticoagulation: transurethral bipolar plasma vaporization in saline versus transurethral monopolar resection of the prostate.

INTRODUCTION: To compare postoperative outcomes of patients on oral anticoagulation (OA) treated with transurethral plasma vaporization of the prostate in saline water (TUVis) and transurethral resection of the prostate (TURP). MATERIALS AND METHODS: Between January and December 2009, 111 patients on OA therapy were treated with either TURP or TUVis in eight centers. Types of OA and perioperative management were collected. Postoperative outcomes were statistically compared between the two groups. RESULTS: A total of 57 (51%) and 54 (49%) patients were treated with TURP and TUVis, respectively. Types of OA were not significantly different between the two groups, but bladder catheterization prior to surgery was more frequently observed in the TUVis group. Before surgery, 28 patients were treated with warfarin alone, 74 with a platelet aggregation inhibitor (PAI) alone, and 9 with a combination of both. PAI was withdrawn preoperatively in 50 patients. All treatments with warfarin were switched for heparin. Comparison of the two groups showed significantly less hemorrhagic complications after TUVis. Patients treated with TUVis experienced less bladder washouts (2% versus 18%, p = 0.008), less late hematuria (4% versus 19%, p = 0.02), and lower decrease of serum hemoglobin (mean decrease of 0.66 versus 1.47 g/dL, p = 0.02). Postoperative bladder catheterization and hospital stay were significantly shorter, whereas the rate of urinary retention was significantly higher. Three months after surgery, functional results were not significantly different between the two groups. CONCLUSIONS: In patients on OA, TUVis led to significantly less bleeding, as well as shorter bladder catheterization and hospital stay than TURP.

[Value of PCA3 urinary test for prostate biopsy decision: the Lyon-Sud University Hospital experience]. / Intérêt du test urinaire PCA3 dans la décision de biopsie prostatique : l'expérience du Centre hospitalier Lyon-Sud.

The poor specificity of diagnostic strategy for prostate cancer (digital rectal examination and seric PSA) induces both a great number of useless prostate biopsies and diagnosis of non evolutive cancers. A urinary test (Progensa PCA3(®), Gen-Probe) measuring the expression of PCA3, a prostate cancer-specific gene, has recently be proposed to indicate re-biopsy. The aim of this prospective study was to evaluate diagnostic value of urinary PCA3 test for prostate cancer. In the urines of 245 patients submitted to prostate biopsy, expression of the PCA3 gene was measured and reported to that of PSA to calculate PCA3 score using a method amplifying and detecting RNA. Patients with informative samples (98%) were classified depending of the presence (n = 126) or absence (n = 114) of cancer tissue on biopsies. The median PCA3 score was significantly higher in the group with positive biopsies (p < 0.0001). Area under ROC curve was 0.70 for PCA3 as compared to that of PSA (0.53) and free/total PSA ratio (0.65). At the best threshold of 38, PCA3 test had a 59%-sensitivity and a 72%-specificity, as compared to 66% and 32% for total PSA (threshold 4 ng/mL) and 81% and 28% for free/total PSA ratio (threshold 25%). These performances were maintained in patients with seric PSA within the grey zone (4-10 ng/mL) and those with previous prostate biopsies. This study confirms the clinical value of PCA3 urinary test in helping decision for biopsies in patients with suspected prostate cancer.

Impact of lower urinary tract symptoms on discomfort in men aged between 50 and 80 years.

BACKGROUND/AIMS: There are only a few surveys on the prevalence of lower urinary tract symptoms (LUTS) among the general population. The aim of this survey was to assess the prevalence of LUTS and their impact on discomfort in men. METHODS: A questionnaire was mailed to 3,877 men aged 50-80 years, which included questions on their medical history, demographic and sociological status, and also the International Prostate Symptom Score (IPSS) with additional questions on discomfort related to urinary symptoms. RESULTS: The response rate was 81.5%. Prevalence of mild and severe IPSS was 89.2%. Specific bother for each urinary symptom depended on symptom frequency: urgency, frequency, weak stream, nocturia, incomplete emptying, intermittency and straining 1 time out of 5 were responsible for discomfort in respectively 4.9, 6.1, 7.1, 7.5, 8.7 and 9.9%; the same symptoms more than half of the time were responsible for discomfort in respectively 32.8, 38, 45.3, 45.6, 53.2 and 58.7%. Urgency was much more deeply implicated in discomfort than frequency of nocturia. CONCLUSIONS: Urinary symptoms in men are very common. Nocturia is the most frequent but has a low impact on discomfort. Urgency has a higher impact on discomfort and should therefore be considered in treatment decision-making.