Mischel G. Neill

An update on chemoprevention strategies in prostate cancer for 2006.

Purpose of review An increasing volume of research has been directed at the prevention of prostate cancer. This review proposes to summarize the large trials, novel approaches and molecular mechanisms of effect published in 2004 and 2005. Recent findings The impact of the Prostate Cancer Prevention Trial continues and subsequent articles have addressed the increase of high-grade prostate cancers detected in the finasteride arm of the trial, as well as the potential costs and benefits of extrapolating the findings to a public health campaign. Studies of risk have been published warning of excessive vitamin E and cyclooxygenase-2 inhibitor use in chemoprevention. Growing evidence supports the concept of chemopreventative agent combinations and further data on the roles of selenium, lycopene, soy, green tea, anti-inflammatories and statins in prostate-cancer prevention are presented. Summary Level one evidence exists for the preventative effects of finasteride in prostate cancer. The evidence for other agents is less conclusive but a number of large-scale, appropriately designed trials will hopefully address some of the relevant issues in prostate-cancer prevention over the next decade.

Long-term prognostic value of the combination of EORTC risk group calculator and molecular markers in non-muscle-invasive bladder cancer patients treated with intravesical Bacille Calmette-Guérin

Background and Objectives: To evaluate the long-term prognostic value of the combination of the EORTC risk calculator and proapoptotic, antiapoptotic, proliferation, and invasiveness molecular markers in predicting the outcome of intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC) treated with intravesical Bacille Calmette-Guérin (BCG) therapy. Materials and Methods: This study included 42 patients accrued prospectively presenting with intermediate- to high-risk NMIBC (high-grade T1 tumors or multiple rapidly recurrent tumors refractory to intravesical chemotherapy) treated with transurethral resection (TUR) and BCG. TUR samples were analyzed for the molecular markers p53, p21 waf1/cip, Bcl-2, CyclinD1, and metallothionein 9 (MMP9) using immunohistochemistry. Frequency of positivity, measured as a percentage, was assessed alone or in combination with EORTC risk calculator, for interaction with outcome in terms of recurrence and progression using univariate analysis and Kaplan-Meier survival curves. Results: Median follow-up was 88 months (mean, 99; range, 14-212 months). The overall recurrence rate was 61.9% and progression rate was 21.4%. In univariate analysis, CyclinD1 and EORTC risk groups were significantly associated with recurrence (P value 0.03 and 0.02, respectively), although none of the markers showed a correlation to progression. In combining EORTC risk groups to markers expression status, high-risk group associated with positive MMP9, Bcl-2, CyclinD1, or p21 was significantly correlated to tumor recurrence (log rank P values <0.001, 0.03, 0.02, and 0.006, respectively) and when associated with positive MMP9 or p21, it was significantly correlated to progression (log rank P values 0.01 and 0.04, respectively). Conclusion: Molecular markers have a long-term prognostic value when combined with EORTC scoring system and they may be used to improve the predictive accuracy of currently existing scoring system. Larger series are needed to confirm these findings.

Preoperative evaluation of the 'hostile pelvis' in radical prostatectomy with computed tomographic pelvimetry

To determine whether preoperative pelvimetry based on computed tomography (CT) can be used to predict technical difficulties during open radical prostatectomy (RP).

The once and future role of cytoreductive nephrectomy

The role of nephrectomy in the setting of metastatic renal cell carcinoma has long been controversial and has continued to evolve over the last two decades. The practice of cytoreductive nephrectomy has only recently been widely accepted following the publication of 2 large multi-center randomized controlled trials that established a survival benefit for those patients undergoing nephrectomy followed by interferon treatment. Half a decade later, the new paradigm looks set to be questioned with the rapid emergence of tyrosine kinase inhibitors (TKIs). This article reviews the evolution of cytoreductive nephrectomy and speculates on its role in the new frontier of molecular targeting for metastatic renal cell carcinoma.

Tamsulosin oral controlled absorption system (OCAS) in the treatment of benign prostatic hypertrophy.

The efficacy of tamsulosin at the cost of a relatively benign side effect profile has been attributed to receptor selectivity directed at the α1a and α1d adrenergic receptor subtypes. The oral-controlled absorption system (OCAS®) represents a drug delivery refinement that incorporates a matrix of gel-forming and gel-enhancing agents to promote a constant drug release independent of environmental food or fluid. There are clinical data to support the concept that drug peaks are lessened and that drug release continues throughout the alimentary tract due to the OCAS formulation. Furthermore this equates with less adverse effects on physiologic parameters. To date however improvements in cardiovascular symptoms such as dizziness, headache and syncope have not been demonstrated in healthy men. Ejaculatory dysfunction appears less problematic with the OCAS preparation. Tamsulosin OCAS may be of greatest benefit to men with cardiovascular co-morbidities taking anti-hypertensive medications that might predispose them to symptomatic hypotensive episodes. It will be necessary to evaluate this group of men more closely in further trials to determine what they stand to gain from changing medications, and then relate this to drug costs to draw a final conclusion as to the place of tamsulosin OCAS in contemporary urological practice.