Faculty Bibliography

Active surveillance (AS) has emerged as a standard management option for men with very low-risk and low-risk prostate cancer, and contemporary data indicate that use of AS is increasing in the United States and abroad. In the favorable-risk population, reports from multiple prospective cohorts indicate a less than 1% likelihood of metastatic disease and prostate cancer-specific mortality over intermediate-term follow-up (median 5-6 years). Higher-risk men participating in AS appear to be at increased risk of adverse outcomes, but these populations have not been adequately studied to this point. Although monitoring on AS largely relies on serial prostate biopsy, a procedure associated with considerable morbidity, there is a need for improved diagnostic tools for patient selection and monitoring. Revisions from the 2014 International Society of Urologic Pathology consensus conference have yielded a more intuitive reporting system and detailed reporting of low-intermediate grade tumors, which should facilitate the practice of AS. Meanwhile, emerging modalities such as multiparametric magnetic resonance imaging and tissue-based molecular testing have shown prognostic value in some populations. At this time, however, these instruments have not been sufficiently studied to consider their routine, standardized use in the AS setting. Future studies should seek to identify those platforms most informative in the AS population and propose a strategy by which promising diagnostic tools can be safely and efficiently incorporated into clinical practice.

The Prostate Health Index is a Food and Drug Administration-approved blood test combining total, free, and [-2]pro prostate-specific antigen with greater specificity than free and total prostate-specific antigen for clinically significant prostate cancer. This article reviews the evidence on the performance of the Prostate Health Index to predict prostate biopsy outcome, its incorporation into multivariable risk-assessment tools, and its ability to predict prognosis after conservative management or 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.

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.

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 AND PURPOSE:Whereas open radical prostatectomy is performed extraperitoneally, minimally invasive radical prostatectomy is typically performed within the peritoneal cavity. Our objective was to determine whether minimally invasive radical prostatectomy is associated with an increased risk of small bowel obstruction compared with open radical prostatectomy. PATIENTS AND METHODS:In the U.S. Surveillance, Epidemiology and End Results (SEER)-Medicare database, we identified 14,147 men found to have prostate cancer from 2000 to 2008 treated by open (n = 10,954) or minimally invasive (n = 3193) radical prostatectomy. Multivariable Cox proportional hazard models were used to examine the impact of surgical approach on the diagnosis of small bowel obstruction, as well as the need for lysis of adhesions and exploratory laparotomy. RESULTS:During a median follow-up of 45 and 76 months, respectively, the cumulative incidence of small bowel obstruction was 3.7% for minimally invasive and 5.3% for open radical prostatectomy (p = 0.0005). Lysis of adhesions occurred in 1.1% of minimally invasive and 2.0% of open prostatectomy patients (p = 0.0003). On multivariable analysis, there was no significant difference between minimally invasive and open prostatectomy with respect to small bowel obstruction (HR 1.17, 95% CI 0.90, 1.52, p = 0.25) or lysis of adhesions (HR 0.87, 95% CI 0.50, 1.40, p = 0.57). Limitations of the study include the retrospective design and use of administrative claims data. CONCLUSIONS:Relative to open radical prostatectomy, minimally invasive radical prostatectomy is not associated with an increased risk of postoperative small bowel obstruction and lysis of adhesions.