Faculty Bibliography

PURPOSE: While a clear heritable component underlies lower urinary tract symptoms and benign prostatic hyperplasia, few studies have identified specific genetic factors. In contrast, recent genome-wide association studies identified single nucleotide polymorphisms that increase prostate cancer risk. Some of these single nucleotide polymorphisms may also predispose to surgical intervention for benign prostatic hyperplasia. We determined whether these single nucleotide polymorphisms are also associated with lower urinary tract symptom severity and benign prostatic hyperplasia medication use. MATERIALS AND METHODS: The genotypes of 38 single nucleotide polymorphisms previously associated with prostate cancer risk were determined for 1,168 healthy white male volunteers. American Urological Association symptom index score and medication for benign prostatic hyperplasia were documented prospectively. Statistical analyses were done to compare the frequency of the single nucleotide polymorphisms with American Urological Association symptom index and benign prostatic hyperplasia medication use. RESULTS: Several single nucleotide polymorphisms, including rs2736098 on chromosome 5p15, showed a significant relationship with benign prostatic hyperplasia medication. After adjusting for the other genetic variants, patient age and medication use, rs1571801 on chromosome 9q33.2 (OR 1.31, 95% CI 1.0-1.74) and rs5945572 on chromosome Xp11 (OR 1.28, 95% CI 1.04-1.59) were significantly associated with increased urinary symptoms. In contrast, rs445114 on chromosome 8q24 was marginally associated with decreased urinary symptoms (OR 0.83, 95% CI 0.66-1.01). CONCLUSIONS: Of 38 single nucleotide polymorphisms that predispose to prostate cancer we identified 3 that are also associated with a well characterized lower urinary tract symptom phenotype. These single nucleotide polymorphisms may aid in the improved characterization of men with lower urinary tract symptoms/benign prostatic hyperplasia.

PURPOSE: We recently reported an increasing risk over time of hospitalization among Medicare participants after undergoing an initial prostate biopsy. Less is known about the relative risks of repeat prostate biopsies, which are frequently performed in prostate cancer screening and in active surveillance programs. We determined whether repeat biopsies are associated with an increased risk of hospitalization compared to the initial biopsy. MATERIALS AND METHODS: Using SEER (Surveillance, Epidemiology and End Results)-Medicare linked data from 1991 to 2007 we identified 13,883 men who underwent a single prostate biopsy and 3,640 who had multiple biopsies. The 30-day hospitalization rates were compared between these groups, and with a randomly selected control population of 134,977. ICD-9 codes were then used to examine the frequency of serious infectious and noninfectious urological complications as the primary diagnosis for hospital admissions. RESULTS: Initial and repeat biopsies were associated with a significantly increased risk of hospitalization within a 30-day period compared to randomly selected controls (p <0.0001). However, the repeat biopsy session was not associated with a greater risk of infectious (OR 0.81, 95% 0.49-1.32, p = 0.39) or serious noninfectious urological complications (OR 0.94, 95% CI 0.54-1.62, p = 0.82) compared to the initial biopsy. CONCLUSIONS: Each biopsy was associated with a significant risk of complications compared to randomly selected controls. However, the repeat biopsy procedure itself was not associated with a greater risk of serious complications requiring hospital admission compared to the initial biopsy.

PURPOSE: Prostate cancer (PCa) incidence and prognosis vary geographically. We examined possible differences in PCa risk by clinical risk category between native-born and immigrant populations in Sweden. Our hypothesis was that lower PSA-testing uptake among foreign-born men would result in lower rates of localized disease, and similar or higher risk of metastatic disease. METHODS: Using the Prostate Cancer database Sweden, we identified 117,328 men with PCa diagnosed from 1991 to 2008, of which 8,332 were foreign born. For each case, 5 cancer-free matched controls were randomly selected from the population register. Conditional logistic regression was used to compare low risk, intermediate risk, high risk, regionally metastatic, and distant metastatic PCa based upon region of origin. RESULTS: Across all risk categories, immigrants had significantly lower PCa risk than native-born Swedish men, except North Americans and Northern Europeans. The lowest PCa risk was observed in men from the Middle East, Southern Europe, and Asia. Multivariable adjustment for socioeconomic factors and comorbidities did not materially change risk estimates. Older age at immigration and more recent arrival in Sweden were associated with lower PCa risk. Non-native men were less likely to be diagnosed with PCa through PSA testing during a health checkup. CONCLUSIONS: The risk for all stages of PCa was lower among first-generation immigrants to Sweden compared with native-born men. Older age at immigration and more recent immigration were associated with particularly low risks. Patterns of PSA testing appeared to only partly explain the differences in PCa risk, since immigrant men also had a lower risk of metastatic disease.

PURPOSE OF REVIEW: To determine whether alpha-blockers, commonly used for the treatment of benign prostatic hyperplasia, are associated with prostate cancer risk. RECENT FINDINGS: Alpha-blockers have been associated with a reduced risk of prostate cancer aggressiveness in some observational studies and an increased risk in other studies. However, this relationship is complex as different alpha-blockers have divergent effects in laboratory studies and there are many confounders in daily practice such as differential screening practices. SUMMARY: Both benign prostatic hyperplasia and prostate cancer are common conditions in the aging male population, such that an interaction between alpha-blockers and prostate cancer risk is clinically relevant. Prospective evidence is necessary to establish a definitive link.

Screening and treatment of prostate cancer remain controversial, particularly for elderly men. Since the previous United States Preventive Services Task Force recommendation in 2008 against prostate-specific antigen (PSA) screening after age 75 years, there has not been a substantial reduction in the frequency of PSA testing in this age group. A substantial proportion of elderly men are overdiagnosed and overtreated. On the other hand, men aged >75 years have more aggressive disease. Although screening has questionable benefit for elderly men with significant comorbidities, healthy men >75 years may benefit from definitive therapy. This review discusses prostate cancer screening and management decisions for elderly men, including the use of nomograms and predictive tools for life expectancy. 2013 Springer Science+Business Media New York (outside the USA)