Faculty Bibliography

OBJECTIVE: To evaluate whether genetic correction using the genetic variants prostate-specific antigen (PSA)-single nucleotide polymorphisms (SNPs) could reduce potentially unnecessary and/or delayed biopsies in African-American men. SUBJECTS AND METHODS: We compared the genotypes of four PSA-SNPs between 964 Caucasian and 363 African-American men without known prostate cancer (PCa). We adjusted the PSA values based on an individual's PSA-SNP carrier status, and calculated the percentage of men that would meet commonly used PSA thresholds for biopsy (>/=2.5 or >/=4.0 ng/mL) before and after genetic correction. Potentially unnecessary and delayed biopsies were defined as those men who were below and above the biopsy threshold after genetic correction, respectively. RESULTS: Overall, 349 (96.1%) and 354 (97.5%) African-American men had measured PSA levels <2.5 and <4.0 ng/mL. Genetic correction in African-American men did not avoid any potentially unnecessary biopsies, but resulted in a significant (P < 0.001) reduction in potentially delayed biopsies by 2.5% and 3.9%, based on the biopsy threshold level. CONCLUSIONS: There are significant differences in the influence of the PSA-SNPs between African-American and Caucasian men without known PCa, as genetic correction resulted in an increased proportion of African-American men crossing the threshold for biopsy. These results raise the question of whether genetic differences in PSA might contribute to delayed PCa diagnosis in African-American men.

PURPOSE: Transrectal ultrasound guided biopsy is the gold standard for detecting prostate cancer but international reports suggest that increasing risks are associated with the procedure. We estimated incidence and risk factors for infection after prostate biopsy as well as 90-day mortality using a nationwide Swedish sample. MATERIAL AND METHODS: We performed a population based study of 51,321 men from PCBaSe between 2006 and 2011. Primary outcome measures were dispensed prescriptions of antibiotics for urinary tract infection and hospitalization with a discharge diagnosis of urinary tract infection. Multivariable logistic regression was used to examine risk factors for infection in men who underwent prostate biopsy. RESULTS: During the 6 months before biopsy the background incidence of urinary tract infection was approximately 2%. Within 30 days after biopsy 6% of the men had a dispensed prescription for urinary tract antibiotics and 1% were hospitalized with infection. The strongest risk factors for an antibiotic prescription were prior infection (OR 1.59, 95% CI 1.45-1.73), high Charlson comorbidity index (OR 1.25, 95% CI 1.11-1.41) and diabetes (OR 1.32, 95% CI 1.17-1.49). Risk of an antibiotic prescription after biopsy decreased from 2006 to 2011 (OR 0.79, 95% CI 0.70-0.90) but the risk of hospital admission increased (OR 2.14, 95% CI 1.58-2.94). No significant increase was observed in 90-day mortality. CONCLUSIONS: Severe infections with hospitalization after prostate biopsy are increasing in Sweden. The risk of post-biopsy infection is highest in men with a history of urinary tract infection and those with significant comorbidities.

OBJECTIVE:In countries with widespread prostate cancer screening there has been strong stage migration, but little is known about changes within clinical risk categories. Such data are important for the proper interpretation of studies that recruited cases in an earlier era. The purpose of this study was to examine stage migration between and within clinical risk categories. MATERIAL AND METHODS/METHODS:Using the population-based National Prostate Cancer Register (NPCR) of Sweden, changes in the distribution of prostate-specific antigen (PSA), Gleason score, tumor stage and volume overall between and within clinical risk categories were examined in 120 228 prostate cancer cases diagnosed from 1998 to 2011. RESULTS:Between 1998 and 2011, there was a two-fold increase in the proportion of low-risk prostate cancer (stage T1/T2, Gleason score 2-6 and PSA <10 ng/ml), from 14% to 28%, and more than a two-fold decrease in the proportion of metastatic disease, from 25% to 11%. The proportion of men in the low-risk category with T1c tumors increased two-fold, from 36% to 71%, and PSA levels between 4 and 6 ng/ml increased from 24% to 38%; T2 tumors decreased from 39% to 20% and PSA between 8 and 10 ng/ml decreased from 24% to 15%. The proportion of men with less than 25% of cores involved with cancer increased from 41% to 52% between 2003-2006 and 2007-2011. CONCLUSIONS:Low-risk cases today have substantially lower tumor volume and PSA levels than low-risk cases diagnosed in 1998, indicating that outcomes in studies that recruited cases in previous decades represent worst case scenarios.