Combining urinary detection of TMPRSS2:ERG and PCA3 with serum PSA to predict diagnosis of prostate cancer.

OBJECTIVES: We sought to develop a clinical algorithm combining serum PSA with detection of TMPRSS2:ERG fusion and PCA3 in urine collected after digital rectal exam (post-DRE urine) to predict prostate cancer on subsequent biopsy. MATERIALS AND METHODS: Post-DRE urine was collected in 48 consecutive patients before prostate biopsy at 2 centers; quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to detect PCA3 and TMPRSS2:ERG fusion transcript expression. Serum PSA was measured by clinical assay. The performance of TMPRSS2:ERG fusion, PCA3, and serum PSA as biomarkers predicting prostate cancer at biopsy was measured; a clinically practical algorithm combining serum PSA with TMPRSS2:ERG and PCA3 in post-DRE urine to predict prostate cancer was developed. RESULTS: Post-DRE urine sediment provided informative RNA in 45 patients; prostate cancer was present on subsequent biopsy in 15. TMPRSS2:ERG in post-DRE urine was associated with prostate cancer (OR = 12.02; P < 0.001). PCA3 had the highest sensitivity in predicting prostate cancer diagnosis (93%), whereas TMPRSS2:ERG had the highest specificity (87%). TMPRSS2:ERG had the greatest discriminatory value in predicting prostate cancer (AUC = 0.77 compared with 0.65 for PCA3 and 0.72 for serum PSA alone). Combining serum PSA, PCA3, and TMPRSS2:ERG in a multivariable algorithm optimized for clinical utility improved cancer prediction (AUC = 0.88; specificity = 90% at 80% sensitivity). CONCLUSIONS: A clinical algorithm specifying biopsy for all patients with PSA ≥ 10 ng/ml, while restricting biopsy among those with PSA <10 ng/ml to only those with detectable PCA3 or TMPRSS2:ERG in post-DRE urine, performed better than the individual biomarkers alone in predicting prostate cancer.

Single center comparison of anastomotic strictures after radical perineal and radical retropubic prostatectomy.

OBJECTIVES: To analyze the incidence and management of anastomotic strictures (ASs) after radical perineal prostatectomy (RPP) and retropubic prostatectomy (RRP) and to identify possible predisposing factors. METHODS: Between 1997 and 2007, we performed 866 RPP and 2052 RRP for localized prostate cancer. Median follow-up was 52 months (12-136). We analyzed preoperative serum prostate-specific antigen, prostate size, clinical and pathologic tumor stage, neoadjuvant hormone deprivation, previous transurethral resection of the prostate, transfusion requirement, anastomotic insufficiency, and acute urinary retention (AUR) and its subsequent management to identify possible predisposing factors for AS formation. RESULTS: The rate of AS after RPP and RRP was 3.8% (33/863) and 5.5% (113/2048), respectively (P = .067). In multivariate analysis, RRP was a statistically significant risk factor for AS (P = .0002). On survival analysis, the incidence of AS was lower for RPP as compared with RRP at median follow-up (P = .0229). Primary response to endoscopic AS incision or resection was 94% (31/33) and 72.6% (82/113) after RPP and RRP, respectively. On multivariate logistic regression analysis biopsy Gleason score, previous transurethral resection of the prostate, prostate volume, pathologic tumor stage and grade, transfusion requirement, AUR, and surgical technique were independent risk factors for the development of AS. An AS developed in 45.4% (20/44) and 10.9% (5/46) of the postoperative AUR cases treated with a suprapubic cystostomy tube and a transurethral Foley catheter, respectively (P <.05). CONCLUSIONS: ASs occur more frequently after RRP in comparison with RPP. Primary endoscopic AS incision or resection are both highly successful. Treating postoperative AUR with a suprapubic cystostomy poses a high risk for AS formation and should be avoided.

Urokinase-plasminogen-activator receptor expression in disseminated tumour cells in the bone marrow and peripheral blood of patients with clinically localized prostate cancer.

OBJECTIVE To evaluate the expression of urokinase-plasminogen-activator receptor (uPA-R) in disseminated tumour cells (DTC) in bone marrow (BM) and peripheral blood (PB) of patients with clinically localized prostate cancer before radical prostatectomy (RP), and to assess the associations with pathological variables and prognosis. PATIENTS AND METHODS In all, 52 patients (47 with clinically localized cancer and five with benign prostatic hyperplasia, BPH, as controls) were prospectively enrolled. BM and PB samples were drawn before surgery. DTC were enriched using a commercial system, cytokeratin (CK) 8/18 was used to detect DTC, and uPA-R expression was detected by dual-immunostaining of the DTC. The final pathology of the RP specimen was compared with the results of immunostaining. Follow-up was initiated to detect tumour relapse (defined as a prostate-specific antigen (PSA) level of > or =0.2 ng/mL). RESULTS Overall, there was expression of 'CK + uPA-R' in 60% of the BM and in 19% of the PB specimens. Expression of this marker in BM was most significantly increased in those with unfavourable Gleason scores (P = 0.004), followed by high-risk cancer (P = 0.005). The relative risk for CK + uPA-R expression in the BM was 3.1 times higher in high-risk than in low-risk prostate cancer. No relevant expression rates were detected for PB. In the control group, no patient showed CK or uPA-R expression in BM or PB. The PSA-recurrence free survival was significantly lower in patients with CK + uPA-R-positive BM cells (P = 0.01). CONCLUSION In this pilot study, the preoperative detection rate of CK + uPAR expression in BM of patients with prostate cancer increased with Gleason score and in those with high-risk disease. All patients with a later PSA relapse had had uPA-R expression in their DTC from the BM. DTC with uPA-R expression was an adverse prognostic factor for prostate cancer.

Indications for preoperative prostate biopsy in patients undergoing radical cystoprostatectomy for bladder cancer.

PURPOSE: We determined indications for preoperative prostate biopsy in patients undergoing radical cystoprostatectomy for bladder cancer. MATERIALS AND METHODS: Of 316 cystoprostatectomy specimens concomitant prostate cancer was diagnosed in 21.5%. Prostate cancer was diagnosed preoperatively in 24% of cases (evident prostate cancer), 32% were suspicious for prostate cancer but no biopsy was done (suspected prostate cancer) and in 44% prostate cancer was incidental. Patients were stratified into probability groups of intermediate/high risk prostate cancer by digital rectal examination and prostate specific antigen. The incidence of unfavorable histopathology was determined in each group. RESULTS: Of prostate cancers 85% were organ confined and the Gleason score was favorable (2-6) in 74%. Of cases of incidental prostate cancer tumors were organ confined in 97%. There were no unfavorable Gleason scores (8-10). In the low probability group 83% of patients had organ confined prostate cancer and only 17% had an unfavorable Gleason score. In the intermediate probability group prostate cancer was organ confined in 73% of patients, 45% had a favorable Gleason score (2-6) and 55% had an intermediate Gleason score (7). In the high probability group 29% of patients had high risk prostate cancer. CONCLUSIONS: Most concomitant prostate cancers were organ confined and had a favorable or intermediate Gleason score when digital rectal examination was not suspicious and prostate specific antigen was less than 10 ng/ml. As a consequence, patients with a low/intermediate probability of detecting intermediate/high risk prostate cancer do not require preoperative prostate biopsy unless nerve sparing surgery is planned. In contrast, all patients should undergo preoperative biopsy for prostate cancer when digital rectal examination is suspicious or prostate specific antigen is more than 10 ng/ml because the rate of high risk prostate cancer was 29% in this group.

TMPRSS2:ERG fusion-associated deletions provide insight into the heterogeneity of prostate cancer.

Prostate cancer is a common and clinically heterogeneous disease with marked variability in progression. The recent identification of gene fusions of the 5'-untranslated region of TMPRSS2 (21q22.3) with the ETS transcription factor family members, either ERG (21q22.2), ETV1 (7p21.2), or ETV4 (17q21), suggests a mechanism for overexpression of the ETS genes in the majority of prostate cancers. In the current study using fluorescence in situ hybridization (FISH), we identified the TMPRSS2:ERG rearrangements in 49.2% of 118 primary prostate cancers and 41.2% of 18 hormone-naive lymph node metastases. The FISH assay detected intronic deletions between ERG and TMPRSS2 resulting in TMPRSS2:ERG fusion in 60.3% (35 of 58) of the primary TMPRSS2:ERG prostate cancers and 42.9% (3 of 7) of the TMPRSS2:ERG hormone-naive lymph node metastases. A significant association was observed between TMPRSS2:ERG rearranged tumors through deletions and higher tumor stage and the presence of metastatic disease involving pelvic lymph nodes. Using 100K oligonucleotide single nucleotide polymorphism arrays, a homogeneous deletion site between ERG and TMPRSS2 on chromosome 21q22.2-3 was identified with two distinct subclasses distinguished by the start point of the deletion at either 38.765 or 38.911 Mb. This study confirms that TMPRSS2:ERG is fused in approximately half of the prostate cancers through deletion of genomic DNA between ERG and TMPRSS2. The deletion as cause of TMPRSS2:ERG fusion is associated with clinical features for prostate cancer progression compared with tumors that lack the TMPRSS2:ERG rearrangement.