In this study, which was terminated for efficacy at the prespecified interim analysis, radium-223 improved overall survival. (Funded by Algeta and Bayer HealthCare Pharmaceuticals; ALSYMPCA ClinicalTrials.gov number, NCT00699751.).

Background Oncologic outcomes in men with radiation-recurrent prostate cancer (PCa) treated with salvage radical prostatectomy (SRP) are poorly defined. Objective To identify predictors of biochemical recurrence (BCR), metastasis, and death following SRP to help select patients who may benefit from SRP. Design, setting, and participants This is a retrospective, international, multi-institutional cohort analysis. There was a median follow-up of 4.4 yr following SRP performed on 404 men with radiation-recurrent PCa from 1985 to 2009 in tertiary centers. Intervention Open SRP. Measurements BCR after SRP was defined as a serum prostate-specific antigen (PSA) ≥0.1 or ≥0.2 ng/ml (depending on the institution). Secondary end points included progression to metastasis and cancer-specific death. Results and limitations Median age at SRP was 65 yr of age, and median pre-SRP PSA was 4.5 ng/ml. Following SRP, 195 patients experienced BCR, 64 developed metastases, and 40 died from PCa. At 10 yr after SRP, BCR-free survival, metastasis-free survival, and cancer-specific survival (CSS) probabilities were 37% (95% confidence interval [CI], 31–43), 77% (95% CI, 71–82), and 83% (95% CI, 76–88), respectively. On preoperative multivariable analysis, pre-SRP PSA and Gleason score at postradiation prostate biopsy predicted BCR (p = 0.022; global p < 0.001) and metastasis (p = 0.022; global p < 0.001). On postoperative multivariable analysis, pre-SRP PSA and pathologic Gleason score at SRP predicted BCR (p = 0.014; global p < 0.001) and metastasis (p < 0.001; global p < 0.001). Lymph node involvement (LNI) also predicted metastasis (p = 0.017). The main limitations of this study are its retrospective design and the follow-up period. Conclusions In a select group of patients who underwent SRP for radiation-recurrent PCa, freedom from clinical metastasis was observed in >75% of patients 10 yr after surgery. Patients with lower pre-SRP PSA levels and lower postradiation prostate biopsy Gleason score have the highest probability of cure from SRP.

Early biofeedback-pelvic floor muscle training not only hastens the recovery of urinary continence after radical prostatectomy but allows for significant improvements in the severity of incontinence, voiding symptoms and pelvic floor muscle strength 12 months postoperatively.

BackgroundPrognosis of prostate cancer (PCa) is based mainly in histological aspects together with PSA serum levels that not always reflect the real aggressive potential of the neoplasia. The micro RNA (miRNA) mir-21 has been shown to regulate invasiveness in cancer through translational repression of the Metaloproteinase (MMP) inhibitor RECK. Our aim is to investigate the levels of expression of RECK and miR-21 in PCa comparing with classical prognostic factors and disease outcome and also test if RECK is a target of miR-21 in in vitro study using PCa cell line.Materials and methodsTo determine if RECK is a target of miR-21 in prostate cancer we performed an in vitro assay with PCa cell line DU-145 transfected with pre-miR-21 and anti-miR-21. To determine miR-21 and RECK expression levels in PCa samples we performed quantitative real-time polymerase chain reaction (qRT-PCR).ResultsThe in vitro assays showed a decrease in expression levels of RECK after transfection with pre-miR-21, and an increase of MMP9 that is regulated by RECK compared to PCa cells treated with anti-miR-21. We defined three profiles to compare the prognostic factors. The first was characterized by miR-21 and RECK underexpression (N = 25) the second was characterized by miR-21 overexpression and RECK underexpression (N = 12), and the third was characterized by miR-21 underexpression and RECK overexpression (N = 16). From men who presented the second profile (miR-21 overexpression and RECK underexpression) 91.7% were staged pT3. For the other two groups 48.0%, and 46.7% of patients were staged pT3 (p = 0.025).ConclusionsOur results demonstrate RECK as a target of miR-21. We believe that miR-21 may be important in PCa progression through its regulation of RECK, a known regulator of tumor cell invasion.

A liberal erythrocyte transfusion strategy with a hemoglobin trigger of 9 g/dl was associated with fewer major postoperative complications in patients having major cancer surgery compared with a restrictive strategy.

Objective: We aim at determining the prognostic value of squamous differentiation in patients with transitional cell carcinoma (TCC) of the bladder that were treated with radical cystectomy. Materials and Methods: From January 1993 to January 2005, we retrospectively selected 113 patients. Correlations among squamous differentiation with other clinical and pathological features were assessed by both chi-square and Fisher tests. The Kaplan-Meier method was used to evaluate survival curves and statistical significance was determined by the log-rank test. Multivariate analysis was performed through a Cox proportional hazards regression model. Results: Squamous differentiation was observed in 25 (22.1%) of the 113 patients. This finding was significantly related only to the pathological stage. Mean follow-up after cystectomy was 31.7 ± 28.5 months. Disease recurrence occurred in 16 (64%) and 30 (34%) patients with and without squamous differentiation (log-rank test, p = 0.001), and mortality occurred in 10 (40%) and 14 (16%) of the patients with and without squamous differentiation respectively. Univariate analysis revealed that pathological stage, squamous differentiation, tumor size and lymph node involvement were significant predictors of cancer-specific survival. However, only squamous differentiation and tumor size were independent prognostic variables on multivariate analysis. Conclusions: Squamous differentiation was an independent prognostic factor for cancer specific survival in patients with bladder cancer treated with radical cystectomy. Further studies with a larger number of patients are necessary to confirm these results.

BackgroundExtracellular matrix homeostasis is strictly maintained by a coordinated balance between the expression of metalloproteinases (MMPs) and their inhibitors. The purpose of this study was to investigate whether the expression of MMP-9, MMP-2 and its specific inhibitors, are expressed in a reproducible, specific pattern and if the profiles are related to prognosis in Bladder Cancer (BC).MethodsMMP-9, MMP-2 and its specific inhibitors expression levels were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) in fresh-frozen malignant tissue collected from 40 patients with BC submitted to transurethral resection of bladder. The control group consisted of normal bladder tissue from five patients who had undergone retropubic prostatectomy to treat benign prostatic hyperplasia.ResultsMMP-9 was overexpressed in 59.0 % of patients, and MMP-2, TIMP-1, TIMP-2, MMP-14, RECK and IL-8 was underexpressed in most of the patients. Regarding prognostic parameters we observed that high-grade tumors exhibited significantly higher levels of MMP-9 and IL-8 (p = 0.012, p = 0.003). Invasive tumors (pT1-pT2) had higher expression levels of MMP-9 than superficial tumors (pTa) (p = 0.026). The same was noted for IL-8 that was more expressed by invasive tumors (p = 0.015, p = 0.048). Most importantly tumor recurrence was related with higher levels of both MMP-9 (p = 0.003) and IL-8 (p = 0.005).ConclusionWe have demonstrated that the overexpression of MMP-9 and higher expression of IL-8 are related to unfavorable prognostic factors of urothelial bladder cancer and tumor recurrence and may be useful in the follow up of the patients.

A high level of miR-100 is related to biochemical recurrence of localized prostate cancer in patients treated with radical prostatectomy. The role of miR-100 during carcinogenesis must be resolved in future studies to better understand the molecular pathways in which miR-100 is involved. This may open the possibility of using it as a prognostic marker and inspire the development of a target drug.