Purpose-Radical nephrectomy (RN), compared with partial nephrectomy (PN), increases the risk of chronic kidney disease, a significant risk factor for cardiovascular (CV) events and death. Given equivalent oncologic efficacy in patients with small renal tumors (RTs), RN may result in overtreatment. We analyzed a population-based cohort of patients to determine if RN is associated with an increase in CV events and mortality compared with PN.Materials and Methods-Using Surveillance, Epidemiology, and End Results (SEER) cancer registry data linked with Medicare claims, we identified 2991 patients older than 65 years of age treated with RN or PN for RTs 4 cm or smaller between 1995 and 2002. Primary end points of CV events and overall survival were assessed using Kaplan-Meier survival estimation, Cox proportional hazards regression, and negative binomial regression.Results-A total of 2547 (81%) patients underwent RN and 556 (19%) underwent PN. During a median follow-up of 4 years, 609 patients had a CV event and 892 patients died. Adjusting for preoperative demographic and comorbid variables, RN was associated with an increased risk of overall mortality (hazard ratio [HR] 1.38, P<0.01) and a 1.4 times greater number of CV events after surgery (P<0.05). RN, however, was not associated with an increased risk of time to first CV event (HR 1.21, P=0.10) or CV death (HR 0.95, P=0.84).Conclusion-RN, currently the most common treatment for small RTs, may be associated with significant, adverse treatment effects compared with PN. PN should be considered for most patients with small RTs.

CD4+CD25+ T regulatory (Treg) cells were initially described for their ability to suppress autoimmune diseases in animal models. An emerging interest is the potential role of Treg cells in cancer development and progression because they have been shown to suppress antitumor immunity. In this study, CD4+CD25− T cells cultured in conditioned medium (CM) derived from tumor cells, RENCA or TRAMP-C2, possess similar characteristics as those of naturally occurring Treg cells, including expression of Foxp3, a crucial transcription factor of Treg cells, production of low levels of IL-2, high levels of IL-10 and TGF-β, and the ability to suppress CD4+CD25− T cell proliferation. Further investigation revealed a critical role of tumor-derived TGF-β in converting CD4+CD25− T cells into Treg cells because a neutralizing Ab against TGF-β, 1D11, completely abrogated the induction of Treg cells. CM from a nontumorigenic cell line, NRP-152, or irradiated tumor cells did not convert CD4+CD25− T cells to Treg cells because they produce low levels of TGF-β in CM. Finally, we observed a reduced tumor burden in animals receiving 1D11. The reduction in tumor burden correlated with a decrease in tumor-derived TGF-β. Treatment of 1D11 also reduced the conversion of CD4+ T cells into Treg cells and subsequent Treg cell-mediated suppression of antitumor immunity. In summary, we have demonstrated that tumor cells directly convert CD4+CD25− T cells to Treg cells through production of high levels of TGF-β, suggesting a possible mechanism through which tumor cells evade the immune system.

Purpose: Transforming growth factor-β (TGF-β)-mediated epithelial-to-mesenchymal transition (EMT) has been shown to occur in some cancers; however, the pathway remains controversial and varies with different cancers. In addition, the mechanisms by which TGF-β and the EMT contribute to prostate cancer recurrence are largely unknown. In this study, we elucidated TGF-β-mediated EMT as a predictor of disease recurrence after therapy for prostate cancer, which has not been reported before. Experimental Design: We analyzed TGF-β-induced EMT using nuclear factor-κB (NF-κB) as an intermediate mediator in prostate cancer cell lines. A total of 287 radical prostatectomy specimens were evaluated using immunohistochemistry in a high-throughput tissue microarray analysis. Levels of TGF-β signaling components and EMT-related factors were analyzed using specific antibodies. Results were expressed as the percentage of cancer cells that stained positive for a given antibody and were correlated with disease recurrence rates at a mean of 7 years following radical prostatectomy. Results: In prostate cancer cell lines, TGF-β-induced EMT was mediated by NF-κB signaling. Blockade of NF-κB or TGF-β signaling resulted in abrogation of vimentin expression and inhibition of the invasive capability of these cells. There was high risk of biochemical recurrence associated with tumors that displayed high levels of expression of TGF-β1, vimentin, and NF-κB and low level of cytokeratin 18. This was particularly true for vimentin, which is independent of patients' Gleason score. Conclusions: The detection of NF-κB-mediated TGF-β-induced EMT in primary tumors predicts disease recurrence in prostate cancer patients following radical prostatectomy. The changes in TGF-β signaling and EMT-related factors provide novel molecular markers that may predict prostate cancer outcomes following treatment.Prostate cancer is the most common malignancy in American males and is second only to lung cancer as the leading cause of cancer-specific mortality (1). Metastases are responsible for mortality in prostate cancer patients. Post-treatment serum prostate-specific antigen (PSA) values have been used to identify patients at risk for metastases. In fact, depending on the definition used, the 5-year PSA recurrence rates following either radical prostatectomy or radiation therapy were reported to be up to 31%, and the 10-year clinical recurrence rates in these patients were reported to be ∼75% (2-4). A short time interval to biochemical recurrence, rapid PSA doubling times, and high Gleason scores are all considered high-risk factors for prostate cancer-specific mortality (5, 6). However, these clinical characteristics have not been proven to be useful predictors of clinical outcome in patients with low-grade disease (Gleason score ≤6; refs. 7-9). Therefore,

Background The two primary therapeutic interventions for localized prostate cancer are delivered by different types of physicians, urologists and radiation oncologists. We evaluate how visits to specialists and primary care physicians (PCPs) by men with localized prostate cancer relate to treatment choice. Methods Using the Surveillance, Epidemiology and End Results (SEER)-Medicare linked database, we identified 85,088 men with clinically localized prostate cancer diagnosed at age ≥65 years between 1994 and 2002. Men were categorized by primary treatment received within 9 months of diagnosis: radical prostatectomy (n=18,201, 21%), radiotherapy (n=35,925, 42%), androgen deprivation (n=14,021, 17%), or expectant management (n=16,941, 20%). Office visits to urologists, radiation oncologists, medical oncologists, and PCPs were analyzed by patient characteristics and primary therapy received, and were identified using Medicare claims and the AMA Physician Masterfile. Results Overall, 42,309 men (50%) were seen exclusively by urologists, 37,540 (44%) by urologists and radiation oncologists, 2,329 (3%) by urologists and medical oncologists, and 2,910 (3%) by all 3 specialists. There was a strong association between the type of specialist seen and primary therapy received. PCP visits were infrequent between diagnosis and receipt of therapy (22% of patients visited any PCP and 17% visited an established PCP provider) and were not associated with a greater likelihood of specialist visits. Irrespective of age, comorbidity status, or specialist visits, men seen by PCPs were more likely to be managed expectantly. Conclusion Specialist visits relate strongly to prostate cancer treatment choices. In light of these findings, prior evidence that specialists prefer the modality they themselves deliver, the lack of conclusive comparative studies demonstrating superiority of one modality over another, and the differing potential morbidities associated with each treatment, it is essential to ensure that men have access to balanced information before choosing a particular therapy for prostate cancer.

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OBJECTIVETo compare the demographic, behavioural, clinical and medical history characteristics of men with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and asymptomatic controls, to identify characteristics that might be associated with this syndrome. PATIENTS AND METHODSSelf-administered epidemiological questionnaires were completed by 463 men with CP/CPPS and 121 asymptomatic agematched controls. We compared the prevalence of possible risk factors between men with CP/CPPS and controls, using generalized Mantel-Haenszel tests, and developed multivariate predictive models using logistic regression methods, adjusting for clustering by clinical centre within both methods. RESULTSCompared to controls, men with CP/CPPS reported a significantly greater lifetime prevalence of nonspecific urethritis (12% vs 4%, P = 0.008), cardiovascular disease (11% vs 2%, P = 0.004), neurological disease (41% vs 14%, P < 0.001), psychiatric conditions (29% vs 11%, P < 0.001), and haematopoietic, lymphatic or infectious disease (41% vs 20%, P < 0.001). CONCLUSION

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.

Objectives • To quantify the impact of androgen deprivation therapy (ADT) in men with a high baseline risk of skeletal complications and evaluate the risk of mortality after a fracture. Patients and methods • We studied 75 994 men, aged ≥ 66 years, with localized prostate cancer from the Surveillance, Epidemiology and End Results–Medicare linked data. • Cox proportional hazard models were employed to evaluate the risk. Results • Men with a high baseline risk of skeletal complications have a higher probability of receiving ADT than those with a low risk (52.1% vs 38.2%, P < 0.001). • During the 12-year follow-up, more than 58% of men with a high risk and 38% of men with a low risk developed at least one fracture after ADT. • The dose effect of ADT is stronger among men who received ADT only compared to those who received ADT with other treatments. • In the high-risk group, the fracture rate increased by 19.9 per 1000 person-years (from 52.9 to 73.0 person-years) for men who did not receive ADT compared to those who received 18 or more doses of gonadotropin-releasing hormone agonist among men who received ADT only, and by 14.2 per 1000 person-years (from 45.2 to 59.4 person-years) among men who received ADT and other treatments. • Men experiencing a fracture had a 1.38-fold higher overall mortality risk than those who did not (95% CI, 1.34–1.43). Conclusions • Men with a high baseline risk of skeletal complications developed more fractures after ADT. • The mortality risk is 40% higher after experiencing a fracture. • Consideration of patient risk before prescribing ADT for long-term use may reduce both fracture risk and fracture-associated mortality.