Purpose We evaluated predictors of progression after starting active surveillance, especially the role of prostate specific antigen and immediate confirmatory prostate biopsy. Materials and Methods A total of 238 men with prostate cancer met active surveillance eligibility criteria and were analyzed for progression with time. Cox proportional hazards regression was used to evaluate predictors of progression. Progression was evaluated using 2 definitions, including no longer meeting 1) full and 2) modified criteria, excluding prostate specific antigen greater than 10 ng/ml as a criterion. Results Using full criteria 61 patients progressed during followup. The 2 and 5-year progression-free probability was 80% and 60%, respectively. With prostate specific antigen included in progression criteria prostate specific antigen at confirmatory biopsy (HR 1.29, 95% CI 1.14–1.46, p <0.0005) and positive confir-matory biopsy (HR 1.75, 95% CI 1.01–3.04, p = 0.047) were independent predictors of progression. Of the 61 cases 34 failed due to increased prostate specific antigen, including only 5 with subsequent progression by biopsy criteria. When prostate specific antigen was excluded from progression criteria, only 32 cases progressed, and 2 and 5-year progression-free probability was 91% and 76%, respectively. Using modified criteria as an end point positive confirmatory biopsy was the only independent predictor of progression (HR 3.16, 95% CI 1.41–7.09, p = 0.005). Conclusions Active surveillance is feasible in patients with low risk prostate cancer and most patients show little evidence of progression within 5 years. There is no clear justification for treating patients in whom prostate specific antigen increases above 10 ng/ml in the absence of other indications of tumor progression. Patients considering active surveillance should undergo confirma-tory biopsy to better assess the risk of progression.

BackgroundAberrations in the Wnt pathway have been reported to be involved in the metastasis of prostate cancer (PCa) to bone. We investigated the effect and underlying mechanism of a naturally-occurring Wnt inhibitor, WIF1, on the growth and cellular invasiveness of a bone metastatic PCa cell line, PC3.ResultsThe WIF1 gene promoter was hypermethylated and its expression down-regulated in the majority (7 of 8) of PCa cell lines. Restoration of WIF1 expression in PC-3 cells resulted in a decreased cell motility and invasiveness via up-regulation of epithelial markers (E-cadherin, Keratin-8 and-18), down-regulation of mesenchymal markers (N-cadherin, Fibronectin and Vimentin) and decreased activity of MMP-2 and -9. PC3 cells transfected with WIF1 consistently demonstrated reduced expression of Epithelial-to-Mesenchymal Transition (EMT) transcription factors, Slug and Twist, and a change in morphology from mesenchymal to epithelial. Moreover, WIF1 expression significantly reduced tumor growth by approximately 63% in a xenograft mouse model. This was accompanied by an increased expression of E-cadherin and Keratin-18 and a decreased expression of vimentin in tumor tissues.ConclusionThese data suggest that WIF1 regulates tumor invasion through EMT process and thus, may play an important role in controlling metastatic disease in PCa patients. Blocking Wnt signaling in PCa by WIF1 may represent a novel strategy in the future to reduce metastatic disease burden in PCa patients.

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Introducing a robotic interface for laparoscopic partial/wedge resection allowed a fellowship-trained urologic oncologist with limited reconstructive laparoscopic experience to achieve results comparable to those for laparoscopic partial/wedge resection performed by experienced laparoscopic surgeons. In this regard, the learning curve appears truncated, similar to that with robot-assisted laparoscopic prostatectomy.

Objectives Racial disparities in bladder cancer outcomes have been documented with poorer survival observed among blacks. Bladder cancer outcomes in other ethnic minority groups are less well described. We examined trends in bladder cancer survival among whites, blacks, Hispanics, and Asian/Pacific Islanders in the US over a 30-year period. Methods From the Surveillance, Epidemiology and End Results cancer registry data, we identified patients diagnosed with transitional cell carcinoma of the bladder between 1975 and 2005. This cohort included 163,973 white, 7,731 black, 7,364 Hispanic and 5,934 Asian/Pacific Islander patients. We assessed the relationship between ethnicity and patient characteristics. Disease-specific 5-year survival was estimated for each ethnic group and for subgroups of stage and grade. Results Blacks presented with higher stage disease than whites, Hispanics and Asian/Pacific Islanders, although a trend toward earlier stage presentation was observed in all groups over time. Five-year disease-specific survival was consistently worse for blacks than for other ethnic groups, even when stratified by stage and grade. Five-year disease-specific survival was 82.8% in whites compared with 70.2% in blacks, 80.7% in Hispanics and 81.9% in Asian/Pacific Islanders. There was a persistent disease-specific survival disadvantage in black patients over time which was not seen in the other ethnic groups. Conclusions Ethnic disparities in bladder cancer survival persist between whites and blacks, while survival in other ethnic minority groups appears similar to that of whites. Further study of access to care, quality of care and treatment decision making among black patients is needed to better understand these disparities.

Background-Enthusiasm for laparoscopic surgical approaches to prostate cancer treatment has grown, despite limited evidence of improved outcomes compared with open radical prostatectomy. We compared laparoscopic (with or without robotic assistance) versus open radical prostatectomy in terms of postoperative outcomes and subsequent cancer-directed therapy.

Several groups, including ours, have reported that annexin A2 (ANXA2) expression is reduced in most prostate cancer (CaP). More recently, however, we reported that ANXA2 is expressed in some high-grade tumors, but the biologic consequence of this is currently unknown. To elucidate the function of ANXA2 in CaP, we reduced its expression in DU145 cells using shRNA and tested the impact on characteristics of malignancy. Reduction of ANXA2 suppressed anchorage-dependent and -independent cell growth without affecting invasiveness. Interestingly, interleukin-6 (IL-6) secretion was reduced concomitantly with the reduction of ANXA2 but independently of S100A10. IL-6 expression was restored when wild type but not mutant ANXA2 was reexpressed in these cells. In a retrospective study of radical prostatectomy specimens from patients with nonmetastatic CaP, 100% of patients with ANXA2-positive tumors (n 5 4) had a biochemical relapse while only 50% of patients with ANXA2 negative tumors (n 5 20) relapsed, suggesting that ANXA2 expression in prostate tumors may be predictive of biochemical relapse. Significant cytoplasmic staining of ANXA2 was detected in 3 of 4 ANXA2-positive tumors, whereas ANXA2 is localized to the plasma membrane in benign prostatic glands. These finding, taken together, suggests a possible mechanism whereby ANXA2 expression positively contributes to an aggressive phenotype in a subset of CaP and suggest that ANXA2 has markedly different functions depending on its cellular context. Finally, this is the first description of a role for ANXA2 in IL-6 expression, and ANXA2 represents a new therapeutic target for reducing IL-6 in high-grade prostate cancer.

BACKGROUND: Pelvic lymph node dissection (PLND) is an important component of prostate cancer staging and treatment, especially for surgical patients who have high-risk tumor features. It is not clear how the shift from open radical prostatectomy (ORP) to minimally invasive radical prostatectomy (MIRP) has affected the use of PLND. The objectives of this study were to identify predictors of PLND and to assess the impact of surgical technique in a contemporary, population-based cohort. METHODS: In Surveillance, Epidemiology, and End Results (SEER) cancer registry data linked with Medicare claims, the authors identified men who underwent ORP or MIRP for prostate cancer during 2003 to 2007. The impact of surgical approach on PLND was evaluated, and interactions were examined between surgical procedure, prostate-specific antigen (PSA), and Gleason score with the analysis controlled for patient and tumor characteristics. RESULTS: Of 6608 men who underwent ORP or MIRP, 70% (n ¼ 4600) underwent PLND. The use of PLND declined over time both overall and within subgroups defined by procedure type. PLND was 5 times more likely in men who underwent ORP than in men who underwent MIRP when the analysis was controlled for patient and tumor characteristics. Elevated PSA and biopsy Gleason score, but not clinical stage, were associated with a greater odds of PLND in both the ORP group and the MIRP group. However, the magnitude of the association between these factors and PLND was significantly greater for patients in the ORP group. CONCLUSIONS: PLND was less common among men who underwent MIRP, independent of tumor risk factors. A decline in PLND rates was not fully explained by an increase in MIRP. The authors concluded that these trends may signal a surgical approach-dependent disparity in prostate cancer staging and therapy. Cancer 2011;117:3933-