Survival Differences in Clinical T4, Nodal and Metastatic Prostate Cancer
Although rare, clinical stage T4 disease has often been thought not to be amenable to surgery because of a poor prognosis. This view was challenged by Hsiao et al (page 512) from Atlanta, Georgia who studied the benefit of radical prostatectomy in 615 patients with clinical T4 disease but no evidence of nodal or metastatic disease compared to patients with known metastasis. Surgery improved survival of patients younger than 50 years with T4 disease compared to those with N1M1 disease. Factors associated with poor survival and clinical T4 disease were higher Gleason score, unknown tumor grade and the absence of a spouse. Based on clinical staging, the authors suggest that the difference in survival between locally advanced T4, node positive (N1) and metastatic (M1) disease appears to be dependent on patient age. In contrast, in patients older than 70 years the difference between M1 disease and clinical T4 disease was less pronounced. The beneficial effect of young age at diagnosis also disappears when patients with nodal or metastatic disease are analyzed using the SEER (Surveillance, Epidemiology and End Results) database.
Feasibility of Radical Transurethral Resection as Monotherapy for Muscle Invasive Bladder Cancer
In a phase II nonrandomized trial patients with muscle invasive disease and negative biopsies of the tumor bed were followed after complete transurethral resection of the bladder. Those with positive biopsies, residual tumor, hydronephrosis or metastasis were excluded from the study, leaving 133 patients who met these criteria. With a minimum followup of more than 15 years, cancer specific survival was 77%. Patient age had a negative impact on overall survival in univariate and multivariate analyses but did not have a negative effect on cancer specific survival. Progression and recurrence usually developed within the first 3 years postoperatively. Solsona et al (page 475) from Valencia, Spain conclude that radical transurethral resection in highly selected patients could be a viable treatment option. However, a prospective randomized trial is needed to support this claim.
NK-1 Receptor Agonist for Overactive Bladder
Neurokinin (NK) receptors in the bladder, pelvic ganglia and spinal cord are thought to influence bladder function. In this randomized, double-blind study undertaken at 69 centers (page 616) 476 patients completed a trial comparing the NK-1 antagonist, serlopitant, to tolterodine or placebo. Reduction in micturitions was significant with serlopitant and tolterodine over placebo. However, the magnitude of these reductions was greater with tolterodine. Although serlopitant possessed a different side effect profile, its efficacy appears to be somewhat less in this comparative study. NK-1 receptor antagonists may represent another treatment option for overactive bladder.
Statin Use and Prostate Cancer Diagnosis
Mounting studies suggest that statin medications, presumably on the basis of their antiproliferation and apoptosis inducing effects, may be beneficial for prostate cancer. In a randomly selected subset of men undergoing biennial urological evaluations including prostate specific antigen Breau et al (page 494) from Rochester, Minnesota report that 38 of 643 statin users (6%) were diagnosed with prostate cancer compared to 186 of 1,813 nonstatin users (10%). Statin use was associated with reduced risk of prostate cancer diagnosis (HR 0.36, 95% CI 0.25–0.53) or high grade prostate cancer diagnosis (HR 0.25, 95% CI 0.11–0.58). Statin use was also associated with a reduced risk of a prostate specific antigen greater than 4 ng/ml. Thus this study is consistent with previous results suggesting that statin use reduces the risk of prostate cancer. The authors note that this association may also be explained by decreased detection rather than an effect on cancer cells.
Combined Therapy Versus Individualized Therapy Alone for Urge Urinary Incontinence
Behavioral intervention is thought to be beneficial for the treatment of stress and urge incontinence. Many clinicians also advocate the use of behavioral intervention with antimuscarinic therapy for urge urinary incontinence. In this prospective randomized trial women were randomized to 8 weeks of drug therapy alone vs 8 weeks of combined drug and behavioral therapy. In an intent to treat analysis Burgio et al (page 598) from Birmingham, Alabama indicate that frequency of incontinence was reduced by 88.5% in the drug only group and 78.3% in the combination therapy group. The study failed to reveal any difference between groups when the analysis was completed. Thus, it does not appear that initiating behavioral therapy enhances outcomes for women with urge urinary incontinence.
Family History and Risk of Recurrent Cystitis and Pyelonephritis
Most experts agree that a family history of cystitis reflects a possible genetic risk for lower urinary tract infections. Whether this risk extends to pyelonephritis is unclear. In a population based, case control study of 1,261 women 18 to 49 years old enrolled in a health plan Scholes et al (page 564) from Seattle, Washington solicited a history of cystitis and pyelonephritis in first-degree female relatives by questionnaire. They found 1 or more female relatives with a history of recurrent urinary tract infection (UTI) in 70.9% of cystitis cases and 75.2% of pyelonephritis cases vs 42.4% of controls. Odds ratios were significantly increased in patients with cystitis and pyelonephritis reporting a UTI history in a mother, sister or daughter. The risk of UTIs increased with a greater number of affected relatives. Thus, in this study a family history of UTI was strongly and consistently associated with recurrent cystitis and pyelonephritis. The causal genetic factors remain uncertain.
Preoperative Prediction of Nonorgan Confined Urothelial Carcinoma of the Upper Urinary Tract
To create a prognostic tool for accurate preoperative prediction of nonorgan confined upper tract urothelial carcinoma, Margulis et al (page 453) gathered comprehensive data on 1,453 patients from 13 institutions who underwent radical nephroureterectomy. A subset of 659 patients had all of the necessary preoperative prognostic variables for statistical analysis. A multivariable logistic regression model containing the relevant clinicopathological variables such as stage, grade and location of the tumor was used to address prediction of nonorgan confined disease at nephroureterectomy. A nomogram using grade, architecture and location of the tumor achieved 76.6% accuracy in predicting nonorgan confined upper tract urothelial cancer. This preoperative predictive model can potentially be used for trial design for the preoperative selection of patients who may benefit from adjuvant chemotherapy or pelvic lymphadenectomy at the time of surgery.
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