Faculty Bibliography

BACKGROUND:Phosphodiesterase type 5 inhibitor (PDE5i) use is common for management of erectile dysfunction. Single-institution studies have reported conflicting data on the relationship between PDE5i use and biochemical recurrence of prostate cancer (BCR) after radical prostatectomy. OBJECTIVE:To evaluate the association between PDE5i use and BCR after radical prostatectomy and radiation therapy in a nationwide population-based cohort. DESIGN, SETTING, AND PARTICIPANTS:This was a nested case-control study using the National Prostate Cancer Register of Sweden linked to the Prescribed Drug Register. Among men with localized prostate cancer who underwent primary radical prostatectomy or radiation therapy during 2006-2007 with 5 yr of follow-up, 293 had BCR after treatment (cases). For each case we identified 20 BCR-free controls (n=5767) using incidence density sampling. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:Multivariable conditional logistic regression was used to examine the association between PDE5i use and BCR risk. Separate multivariable models including clinical variables for men undergoing prostatectomy or radiotherapy and including surgical pathology after prostatectomy were also analyzed. RESULTS AND LIMITATIONS:PDE5i use was not associated with BCR after radical prostatectomy (odds ratio [OR] 0.78, 95% confidence interval [CI] 0.59-1.03) or radiation therapy (OR 0.98, 95% CI 0.49-1.97) after adjusting for marital status, education, income, prostate-specific antigen, clinical stage, Gleason score, and proportion of positive biopsies. Results were similar after additional adjustment for surgical pathology (OR 0.86, 95% CI 0.64-1.16). Men whose cumulative number of PDE5i pills was above the median had a slightly lower BCR risk after prostatectomy in the clinical model, and no difference in BCR risk after adjustment for pathologic tumor features. CONCLUSIONS:Our results from a population-based cohort suggest that BCR risk is not higher among men using PDE5i after prostate cancer treatment. PATIENT SUMMARY:Erectile dysfunction medications are not associated with a higher risk of disease recurrence after prostate cancer treatment.

PURPOSE OF REVIEW:The purpose of this article is to review blood and urine tests that are currently available and under investigation for a role in prostate cancer screening and detection. RECENT FINDINGS:Compared with total prostate-specific antigen (PSA) alone, its combination with percentage free-to-total PSA contributes greater specificity for prostate cancer, and is a component of two newer blood tests called the 4kScore and Prostate Health Index. All three tests improve the prediction of high-grade disease and are commercially available options to aid in initial or repeat prostate biopsy decisions. PCA3 is a urinary marker that is currently available for repeat prostate biopsy decisions. Although PCA3 alone has inferior prediction of clinically significant disease and requires collection of urine after digital rectal examination, it may be combined with other clinical variables or other urine markers like TMPRSS2:ERG to improve performance. Little data are available to support a role for single nucleotide polymorphisms or other investigational markers in early detection. SUMMARY:Several commercially available blood and urine tests have been shown to improve specificity of PSA for high-grade prostate cancer. Use of such tests would decrease unnecessary biopsy and overdiagnosis of indolent disease. Biopsy of men with moderately elevated PSA without use of such a reflex test should be discouraged.

OBJECTIVES: To analyse the activity, content, contributors, and influencers of the Twitter discussion on urologic oncology. MATERIALS AND METHODS: We performed a comprehensive quantitative and qualitative Twitter analysis for the hashtags #prostatecancer, #bladdercancer, #kidneycancer, and #testicularcancer. Symplur was used to analyse activity over different time periods and the top influencers of the Twitter discussion. Tweet Archivist and Twitonomy analysis tools were used to assess characteristics of content and contributors. RESULTS: Twitter discussion on urologic oncology in 2014 contained 100,987 tweets created by 39,326 participants. Mean monthly tweet activity was 6,603+/-2,183 for #prostatecancer, 866+/-923 for #testicularcancer, 457+/-477 for #bladdercancer and 401+/-504 for #kidneycancer. Twitter activity increased by 41% in 2013 and by 122% in 2014. The content analysis detected awareness, cancer, and risk as frequently mentioned words in urologic oncology tweets. Prevalently used related hashtags were the general hashtag #cancer, awareness hashtags, and the respective cancer/urology tag ontology hashtags. Contributors originated from 41 countries on 6 continents and had a mean of 5,864+/-4,747 followers. They tweeted from platforms on exclusively mobile devices (39%) more frequently than from desktop devices (29%). Health care organizations accounted for 58% of the top influencers in all cancers. The largest proportion of physicians were among the #prostatecancer and #kidneycancer (each 9%) influencers and individual contributors were most frequent in the discussion on #kidneycancer (57%) and #testicularcancer (50%). CONCLUSION: There is a significant and growing activity in the Twitter discussion on urologic oncology, particularly on #prostatecancer. The Twitter discussion is global, social, and mobile, and merits attention of stakeholders in health care as a promising communication tool.

PURPOSE: While major prostate cancer active surveillance (AS) programs recommend repeat testing such as PSA and prostate biopsy, compliance with such testing is unknown. Our objective was to determine whether men in the community receive the same intensity of AS testing as in prospective AS protocols. MATERIALS AND METHODS: We performed a retrospective cohort study of men aged >/=66 in the SEER-Medicare database diagnosed with prostate cancer from 2001-2009 who did not receive curative therapy in the year after diagnosis with >/=1 post-diagnosis prostate biopsy. We used multivariable-adjusted Poisson regression to determine the association between frequency of AS testing with patient demographics and clinical features. Among 1349 men with /=14 PSA and >/=2 biopsy), and at Johns Hopkins (>/=10 PSA and >/=4 biopsy). RESULTS: Among 5192 patients undergoing AS, >80% had >/=1 PSA test per year but <13% received biopsy beyond the first 2 years. MRI was rarely used during the study period. On multivariable analysis, recent diagnosis and higher income were associated with higher frequency of surveillance biopsy, while older age and greater comorbidity were associated with fewer biopsies. African American men underwent fewer PSAs but similar numbers of biopsies. During 5 years of AS, only 11.1% and 5.0% met the testing standards of the Sunnybrook/PRIAS and Johns Hopkins programs. CONCLUSIONS: In the community, very few elderly men receive the intensity of AS testing recommended by major prospective AS programs.; Key of Definition for Abbreviations: AS=active surveillance, PCa=prostate cancer, PSA=prostate specific antigen, MRI=magnetic resonance imaging, NCCN=National Comprehensive Cancer Network, PRIAS=Prostate Cancer Research International Active Surveillance, WW=watchful waiting.

OBJECTIVE:To assess 90-day postoperative mortality after robot-assisted laparoscopic radical prostatectomy (RARP) and retropubic radical prostatectomy (RRP) using nationwide population-based registry data. PATIENTS AND METHODS:We conducted a cohort study using the National Prostate Cancer Register of Sweden, including 22 344 men with localized prostate cancer of clinical stage T1-T3, whose prostate-specific antigen levels were <50 μg/mL and who had undergone primary radical prostatectomy in the period 1998-2012. Vital status was ascertained through the Total Population Register. The rates for 90-day postoperative mortality were analysed using logistic regression analysis, and comparisons of 90-day mortality with the background population were made using standardized mortality ratios (SMRs). RESULTS:Of the 14 820 men who underwent RRP, 29 (0.20%) died, and of the 7 524 men who underwent RARP, 10 (0.13%) died. Mortality in the cohort during the 90-day postoperative period was lower than in an age-matched background population: SMR 0.57 (95% confidence interval [CI] 0.39-0.75). There was no statistically significant difference in 90-day mortality according to surgical method: RARP vs RRP odds ratio (OR) 1.14; 95% CI 0.46-2.81. Postoperative 90-day mortality decreased over time: 2008-2012 vs 1998-2007 OR 0.44; 95% CI 0.21-0.95, mainly because of lower mortality after RARP. CONCLUSION:The 90-day postoperative mortality rates were low after RARP and RRP and there was no statistically significant difference between the methods. Given the long life expectancy among men with low- and intermediate-risk prostate cancer, very low postoperative mortality is a prerequisite for RP, which was fulfilled by both RRP and RARP. The selection of healthy men for RP is highlighted by the lower 90-day mortality after RP compared with the background population.

OBJECTIVE: The aim of this study was to compare the outcome of immediate versus delayed radical prostatectomy (RP) in men with low-grade prostate cancer. MATERIALS AND METHODS: The study included a nationwide population-based cohort in the National Prostate Cancer Register of Sweden, of 7608 men with clinically localized, biopsy Gleason score 6 prostate cancer who underwent immediate or delayed RP in 1997-2007. Multivariable models compared RP pathology, use of salvage radiotherapy and prostate cancer mortality based on timing of RP (< 1, 1-2 or >2 years after diagnosis). Median follow-up was 8.1 years. RESULTS: Men undergoing RP more than 2 years after diagnosis had a higher risk of Gleason upgrading [odds ratio 2.93, 95% confidence interval (CI) 2.34-3.68] and an increased risk of salvage radiotherapy [hazard ratio (HR) 1.90, 95% CI 1.41-2.55], but no significant increase in prostate cancer-specific mortality (HR 1.85, 95% CI 0.57-5.99). In competing risk analysis, 7 year prostate cancer-specific cumulative mortality was similar, at less than 1%, for immediate RP and active surveillance regardless of later intervention. Limitations of this study include the lack of data on follow-up biopsies and the limited follow-up time. CONCLUSION: Men undergoing RP more than 2 years after diagnosis had more adverse pathological features and second line therapy, highlighting the trade-off in deferring immediate curative therapy. However, men with delayed RP constitute a minority with higher risk cancer among the much larger group of low-risk men initially surveilled, and the overall risk of prostate cancer mortality at 7 years was similarly low with immediate RP or active surveillance.

Prostate cancer (PC) has the highest degree of genetic transmission of any form of malignancy. In some families, the hereditary pattern is so strong as to mimic an autosomal dominance trait. We reviewed the known predisposing genetic markers to assess possible strategies for screening of families at risk. We carried out a systematic literature search using the Pubmed service of the National Center for Biotechnology Information (NCBI) and several gene libraries, including the NCBI SNP Library, the Online Mendelian Inheritance in Man® Catalog of Human Genes and Genetic Disorders (OMIM) and SNPedia to obtain known gene loci, SNPs and satellite markers associated with PC. We further cross referenced information on identified loci comparing data from different articles and gene reference sites. Whenever possible, we recorded the odds ratio (OR) for the allele associated with PC. In multiple different linkage studies, many independent PC associated loci have been identified on separate chromosomes. Genome-wide association studies have added many more markers to the set derived from linkage investigations. A subset of the alleles is associated with early onset and aggressive cancer. Due to the great heterogeneity, the OR for any one allele predicting future development of this malignancy is low. The strongest predictors are the BRCA2 mutations, and the highly penetrant G84E mutation in HOXB13. The presence of multiple risk alleles is more highly predictive than a single allele. Technical limitations on screening large panels of alleles are being overcome. It is appropriate to begin supplementing prostate specific antigen testing with alleles, such as BRCA2 and HOXB13, disclosed by targeted genomic analysis in families with an unfavorable family cancer history. Future population studies of PC should include genomic sequencing protocols, particularly in families with a history of PC and other malignancies.

BACKGROUND: New five-tiered Gleason grade groups (GGGs) were recently proposed, in which Gleason 6 is GGG 1, Gleason 3+4 is GGG 2, Gleason 4+3 is GGG 3, Gleason 8 is GGG 4, and Gleason 9-10 is GGG 5. OBJECTIVE: To examine the performance of the new GGGs in men with prostate cancer from a nationwide population-based cohort. DESIGN, SETTING, AND PARTICIPANTS: From the National Prostate Cancer Register of Sweden, we identified 5880 men diagnosed with prostate cancer from 2005 to 2007, including 4325 who had radical prostatectomy and 1555 treated with radiation therapy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Kaplan-Meier survival analysis, Cox proportional hazards models, and concordance indices were used to examine the relationship between the GGGs and biochemical recurrence after radical prostatectomy and radiation therapy. RESULTS AND LIMITATIONS: Among men treated with surgery, the 4-yr biochemical recurrence-free survival rates were 89%, 82%, 74%, 77%, and 49% for GGG 1-5 on biopsy, and 92%, 85%, 73%, 63%, and 51% based on prostatectomy GGG, respectively. For men treated by radiation therapy, men with biopsy GGG of 1-5 had 4-yr biochemical recurrence-free survival rates of 95%, 91%, 85%, 78%, and 70%. Adjusting for preoperative serum prostate-specific antigen and clinical stage, biopsy GGGs were significant independent predictors of biochemical recurrence after radical prostatectomy and radiation therapy. The new 5-tier system resulted in virtually no change in predictive accuracy compared with the current 3- and 4-tier classifications. Limitations include a median follow-up of 4.6 yr, precluding the ability to examine long-term oncologic outcomes. CONCLUSIONS: The newly proposed GGGs offer a simplified, user-friendly nomenclature to aid in patient counseling, with similar predictive accuracy in a population-based setting to previous classifications. PATIENT SUMMARY: The new Gleason grade groups, ranging from 1-5, provide a simplified, user-friendly classification system to predict the risk of recurrence after prostatectomy and radiation therapy.