This Month in Adult Urology

Article Outline

• Bladder Cancer Screening Using a Urine Protein Tumor Marker
• Predictive Value of Combined Immunohistochemical Markers for Urothelial Carcinoma
• Single Nucleotide Polymorphisms and the Likelihood of Prostate Cancer
• Urinary Incontinence and Overactive Bladder in Patients With Heart Failure
• Holmium Laser Ablation Versus Photoselective Vaporization of the Prostate
• Impact of Obesity on Overall and Cancer Specific Survival of Men With Prostate Cancer
• Clinical Phenotyping and the Interstitial Cystitis/Painful Bladder Syndrome
• Length of Positive Surgical Margin After Radical Prostatectomy Predicts Recurrence
• Copyright

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Bladder Cancer Screening Using a Urine Protein Tumor Marker 

In previous studies only 4.8% of tumors in an asymptomatic screening group older than 50 years were muscle invasive compared to 24% in an unscreened population using a urine dipstick test. However, the positive predictive value of the dipstick was only 5% to 8%. Urine based bladder cancer markers such as NMP22® have superior sensitivity and specificity as possible screening tests. Lotan et al (page 52) from Dallas, Texas screened for bladder cancer in a high risk population (defined by age, smoking and occupational status) of 1,500 patients using the BladderChek® test. Positive tests were observed in 5.7% of the participants of whom 81% agreed to cystoscopy. Only 3 bladder lesions were found, including 1 high grade Ta, 1 low grade Ta and 1 with atypia. The positive rate of 5.7% in the current study is much lower than the rate reported in previous studies. One of the reasons for the yield for bladder tumors in this group may be that urinalysis was performed in 73% of the patients 3 years before screening. Also not all patients agreed to cystoscopy and some tumors may have been missed. While NMP22 BladderChek may be of use for screening an asymptomatic population for noninvasive tumors, the present study was not powered to demonstrate its effectiveness as a screening test for bladder cancer.

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Predictive Value of Combined Immunohistochemical Markers for Urothelial Carcinoma 

Biomarkers hold the promise to improve clinical decision making, especially for the use of neoadjuvant chemotherapy in patients undergoing cystectomy for bladder cancer. Shariat et al (page 78) from New York, New York examined the expression of p53, p21, pRB, p27, survivin and Ki-67 in stage pT1 specimens from 80 patients who also underwent bilateral pelvic lymphadenectomy. The expression of p53 was altered in 25% of patients, p21 in 46%, pRB in 39%, p27 in 35%, survivin in 49% and Ki-67 in 34%. On multivariate analysis p53, p27 and Ki-67 were independently associated with tumor recurrence, and the combination of these markers stratified patients into statistically significant risk groups for disease recurrence after cystectomy and cancer specific mortality. The authors suggest these 3 biomarkers may help stratify the heterogeneous population of patients with pT1 disease into risk groups to guide decision making regarding observation vs adjuvant therapy.

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Single Nucleotide Polymorphisms and the Likelihood of Prostate Cancer 

Single nucleotide polymorphisms at chromosome 19 have been associated with high serum prostate specific antigen (PSA) concentrations and provide insight into the risk of prostate cancer. Especially strong correlations have been found for rs2735839 and rs 2659056 in chromosome 19, and rs10993994 in chromosome 10. Loeb et al (page 101) from Baltimore, Maryland propose that the relationship between genotype and PSA may improve the specificity of PSA screening for prostate cancer. Of 1,806 male participants from the Baltimore Longitudinal Study of Aging with PSA measurements and a DNA sample 61 men with prostate cancer and 444 with no known diagnosis of prostate cancer were included in the study. A proportional hazards model was examined individually for each genotype by PSA with and without age and date adjustment. In men without prostate cancer the increment in PSA with age was independent of genotype. In men with prostate cancer an interaction was found between genotype and time. Men with a minor allele had a risk of prostate cancer that varied by PSA level. In the final subset analysis only rs10993994 and rs2659056 showed a significant difference in the risk ratio for prostate cancer per unit increase in PSA, with lower risk less than 6 ng/ml and higher risk greater than 6 ng/ml. Thus men with a minor allele may still have a low risk of prostate cancer even at PSA levels that might normally trigger a biopsy. The authors propose that examining these genetic markers may help stratify patients for prostate cancer risk.

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Urinary Incontinence and Overactive Bladder in Patients With Heart Failure 

Reports in the literature suggest that heart failure may affect urinary function through a variety of factors including increased nocturnal urine production, effect of pharmacological therapies for heart failure and endogenous release of natural diuretics such as atrial natriuretic factor. Furthermore, urinary incontinence and heart failure share risk factors such as older age, increased body mass index (BMI), diabetes and depression. Palmer et al (page 196) from Chapel Hill, North Carolina evaluated 296 patients of whom 45% had urinary incontinence and 57% reported overactive bladder. The adjusted odds ratio for having overactive bladder over no symptoms for New York Heart Association class III or IV heart failure was 2.9, 95% CI 1.344 to 6.250. Late stage heart disease, higher body mass index and higher fatigue-depression composite were associated with overactive bladder. Patients were assessed using an International Consultation on Incontinence Questionnaire Short Form item. Adjusting for other variables, patients in late stages of heart failure (class II or IV) were 2.9 times more likely to have overactive bladder than no urinary symptoms compared to those in early heart failure. The authors postulate that heart failure and depression share increases in urinary symptoms and suggest a common mechanism. Also, changes in the nervous system may underlie overactive bladder and heart failure.

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Holmium Laser Ablation Versus Photoselective Vaporization of the Prostate 

Surgical management of lower urinary tract symptoms secondary to benign prostatic hyperplasia has increasingly shifted to laser therapy. Currently the holmium (HoLAP) and photoselective vaporization of the prostate (PVP) lasers have gained in popularity for treating benign prostatic hyperplasia. Elzayat et al (page 133) from Egypt and Canada report on a prospective trial of 109 patients with prostate volumes 60 cc or less who were randomized to either PVP or HoLAP laser therapy. With a power of 80% and a significance level of α=0.05, a sample size of 50 patients per group was calculated. While HoLAP required more operating time, International Prostate Symptom Score improved from 20 ± 6.8 to 6.2 ± 3.9, and maximum flow rate increased from 6.7 ± 3.9 to 17.2 ± 8. In the PVP group the symptom score improved from 18.4 ± 6.6 to 8.2 ± 6.2, and maximum flow rate increased from 6.4 ± 3.9 to 18.4 ± 8.4. In the HoLap and PVP groups urethral stricture rate was 1.7% vs 5.7%, bladder neck contracture 3.5% vs 7.7% and revaporization 3.5% vs 1.9%, respectively. The outcomes were not statistically significant using either modality, and the authors had no explanation for the trend toward higher stricture rates with PVP treatment.

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Impact of Obesity on Overall and Cancer Specific Survival of Men With Prostate Cancer 

An increasing body of evidence suggests that a BMI greater than 40 kg/m² is associated with a greater than 50% increase in cancer mortality from a number of malignancies, including prostate cancer. Other studies also suggest that a high BMI is also a risk factor for prostate cancer related death. Davies et al (page 112) from Pennsylvania and California identified 7,274 men from the CapSURE™ database with localized prostate cancer, known BMI and pathological disease characteristics. Patients were classified as normal, overweight, obese and very obese. On multivariate analysis there was no relationship between BMI and prostate cancer specific survival or overall survival in this large community based cohort. Thus, the relationship between obesity and prostate cancer remains elusive.

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Clinical Phenotyping and the Interstitial Cystitis/Painful Bladder Syndrome 

Nickel et al (page 155) from Kingston, Ontario, Canada recently described a clinical phenotype system called UPOINT, which is a 6-point classification system that characterizes the phenotype of interstitial cystitis/painful bladder syndrome into the 6 clinical domains of urinary, psychosocial, organ specific, infection, neurologic/systemic and muscle tenderness. The potential usefulness of this system is that it could help identify individual characteristics for patient groups to individualize therapy. The absence of generalized therapy for this patient population and inference that there may be multiple etiologies of this constellation of symptoms led to this novel scheme. A better system of stratifying cases could be beneficial in regard to treatment as well as provide a framework for future investigations.

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Length of Positive Surgical Margin After Radical Prostatectomy Predicts Recurrence 

Shikanov et al (page 139) from Chicago, Illinois evaluated 1,398 robotic radical cystectomy cases and found positive margins in 17%, of which 11% were pathological stage T2 and 41% were stage T3 disease. Preoperative PSA, pathological stage, Gleason score, margin status and margin length were independent predictors of future biochemical recurrence. Patients with positive margins shorter than 1 mm appeared to have similar recurrence rates as those with negative margins. Thus, not just margin status but margin length are independent predictors of biochemical recurrence after radical prostatectomy. It is tempting to speculate that the short positive margins may be due to technical artifact from the methodology such as grasping prostates during prostatectomy causing capsular penetration. The authors were not able to validate the notion that multiple positive margin locations conferred a less favorable prognosis than a single location.