Faculty Bibliography

OBJECTIVE: To examine the use of the Prostate Health Index (phi)* as a continuous variable in multivariable risk assessment for aggressive prostate cancer in a large multicenter US study. MATERIALS AND METHODS: The study population included 728 men with PSA levels of 2-10 ng/mL and negative digital rectal examination enrolled in a prospective, multi-site early detection trial. The primary endpoint was aggressive prostate cancer, defined as biopsy Gleason score >/=7. First, we evaluated whether the addition of phi improves the performance of currently available risk calculators (PCPT and ERSPC). We also designed and internally validated a new phi-based multivariable predictive model, and created a nomogram. RESULTS: Of 728 men undergoing biopsy, 118 (16.2%) had aggressive prostate cancer. Phi predicted the risk of aggressive prostate cancer across the spectrum of values. Adding phi significantly improved the predictive accuracy of the PCPT and ERSPC risk calculators for aggressive disease. A new model was created using age, prior biopsy, prostate volume, PSA, and phi with an AUC of 0.746. The bootstrap-corrected model showed good calibration with observed risk for aggressive prostate cancer and had net benefit on decision curve analysis. CONCLUSION: Using phi as part of multivariable risk assessment leads to a significant improvement in the detection of aggressive prostate cancer, potentially reducing harms from unnecessary prostate biopsy and overdiagnosis

OBJECTIVE: To explore and identify factors that influence physicians' decisions while monitoring patients with prostate cancer on active surveillance (AS). SUBJECTS AND METHODS: A purposive sampling strategy was used to identify physicians treating prostate cancer from diverse clinical backgrounds and geographic areas across the USA. We conducted 24 in-depth interviews from July to December 2015, until thematic saturation was reached. The Applied Thematic Analysis framework was used to guide data collection and analysis. Interview transcripts were reviewed and coded independently by two researchers. Matrix analysis and NVivo software were used for organization and further analysis. RESULTS: Eight key themes emerged to explain variation in AS monitoring: (i) physician comfort with AS; (ii) protocol selection; (iii) beliefs about the utility and quality of testing; (iv) years of experience and exposure to AS during training; (v) concerns about inflicting 'harm'; (vi) patient characteristics; (vii) patient preferences; and (viii) financial incentives. CONCLUSION: These qualitative data reveal which factors influence physicians who manage patients on AS. There is tension between providing standardized care while also considering individual patients' needs and health status. Additional education on AS is needed during urology training and continuing medical education. Future research is needed to empirically understand whether any specific protocol is superior to tailored, individualized care.

Introduction: Many new markers are now available as an aid for decisions about prostate biopsy for men without prostate cancer, and/or to improve risk stratification for men with newly diagnosed prostate cancer. Methods: A literature review was performed on currently available markers for use in decisions about prostate biopsy and initial prostate cancer treatment. Results: Although total prostate-specific antigen cutoffs were traditionally used for biopsy decisions, PSA elevations are not specific. Repeating the PSA test, and adjusting for factors like age, prostate volume and changes over time can increase specificity for biopsy decisions. The Prostate Health Index (phi) and 4K Score are new PSA-based markers that can be offered as second-line tests to decide on initial or repeat prostate biopsy. The PCA3 urine test and ConfirmMDx tissue test are additional options for repeat biopsy decisions. For men with newly diagnosed prostate cancer, genomic tests are available to refine risk classification and may influence treatment decisions. Conclusions: Numerous secondary testing options are now available that can be offered to patients deciding whether to undergo prostate biopsy and those with newly diagnosed prostate cancer.

Purpose The association between exposure to testosterone replacement therapy (TRT) and prostate cancer risk is controversial. The objective was to examine this association through nationwide, population-based registry data. Methods We performed a nested case-control study in the National Prostate Cancer Register of Sweden, which includes all 38,570 prostate cancer cases diagnosed from 2009 to 2012, and 192,838 age-matched men free of prostate cancer. Multivariable conditional logistic regression was used to examine associations between TRT and risk of prostate cancer (overall, favorable, and aggressive). Results Two hundred eighty-four patients with prostate cancer (1%) and 1,378 control cases (1%) filled prescriptions for TRT. In multivariable analysis, no association was found between TRT and overall prostate cancer risk (odds ratio [OR], 1.03; 95% CI, 0.90 to 1.17). However, patients who received TRT had more favorable-risk prostate cancer (OR, 1.35; 95% CI, 1.16 to 1.56) and a lower risk of aggressive prostate cancer (OR, 0.50; 95% CI, 0.37 to 0.67). The increase in favorable-risk prostate cancer was already observed within the first year of TRT (OR, 1.61; 95% CI, 1.10 to 2.34), whereas the lower risk of aggressive disease was observed after > 1 year of TRT (OR, 0.44; 95% CI, 0.32 to 0.61). After adjusting for previous biopsy findings as an indicator of diagnostic activity, TRT remained significantly associated with more favorable-risk prostate cancer and lower risk of aggressive prostate cancer. Conclusion The early increase in favorable-risk prostate cancer among patients who received TRT suggests a detection bias, whereas the decrease in risk of aggressive prostate cancer is a novel finding that warrants further investigation.

PURPOSE OF REVIEW/OBJECTIVE:This article intends to review biomarkers derived from blood, urine, and tissue that can aid in the diagnosis of prostate cancer (PCa). RECENT FINDINGS/RESULTS:PCa screening requires tools that complement prostate-specific antigen (PSA) with a higher specificity for clinically significant disease. Novel blood biomarkers, such as the Prostate Health Index (phi) and 4Kscore, utilize isoforms of PSA to more accurately predict high-grade PCa than traditional tools such as PSA and the percentage free-to-total PSA. Several gene products associated with PCa can be detected in the urine through commercially available assays. PCa antigen 3 (PCA3), though approved for repeat biopsy decisions, appears inferior to other biomarkers such as phi for identifying aggressive disease. However, combinations of PCA3 with other urine assays have shown promising results. One tissue-based hypermethylation test, named ConfirmMDx, can also be used to determine the need for repeat biopsy in men with a prior negative biopsy. SUMMARY/CONCLUSIONS:Several biomarkers have been developed to aid in the screening and diagnosis of PCa. Such tests are often indicated in men with moderately elevated PSA or history of a prior negative biopsy. Their use facilitates reduction of unnecessary biopsies without sacrificing the early diagnosis of clinically significant PCa.

CONTEXT: Prostate biopsy (PB) represents the gold standard method to confirm the presence of cancer. In addition to traditional random or systematic approaches, a magnetic resonance imaging (MRI)-guided technique has been introduced recently. OBJECTIVE: To perform a systematic review of complications after transrectal ultrasound (TRUS)-guided, transperineal, and MRI-guided PB. EVIDENCE ACQUISITION: We performed a systematic literature search of Web of Science, Embase, and Scopus databases up to October 2015, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Complications and mortality following random, systematic, and image-guided PBs were reviewed. Eighty-five references were included. EVIDENCE SYNTHESIS: The most frequent complication after PB was minor and self-limiting bleeding (hematuria and hematospermia), regardless of the biopsy approach. Occurrence of rectal bleeding was comparable for traditional TRUS-guided and image-guided PBs. Almost 25% of patients experienced lower urinary tract symptoms, but only a few had urinary retention, with higher rates after a transperineal approach. Temporary erectile dysfunction was not negligible, with a return to baseline after 1-6 mo. The incidence of infective complications is increasing, with higher rates among men with medical comorbidities and older age. Transperineal and in-bore MRI-targeted biopsy may reduce the risk of severe infectious complications. Mortality after PB is uncommon, regardless of biopsy technique. CONCLUSIONS: Complications after PB are frequent but often self-limiting. The incidence of hospitalization due to severe infections is continuously increasing. The patient's general health status, risk factors, and likelihood of antimicrobial resistance should be carefully appraised before scheduling a PB. PATIENT SUMMARY: We reviewed the variety and incidence of complications after prostate biopsy. Even if frequent, complications seldom represent a problem for the patient. The most troublesome complications are infections. To minimize this risk, the patient's medical condition should be carefully evaluated before biopsy.

Many patients diagnosed with cancer search for health information on the Web. We aimed to assess the quality and reliability of online health information on prostate cancer. Google, Yahoo, and Bing were searched for the term "prostate cancer." After selecting the most frequented websites, quality was measured by DISCERN score, JAMA benchmark criteria, and presence of HONcode certification. Popularity was assessed by Alexa tool, while accessibility, usability, and reliability were investigated by LIDA tool. Readability was analyzed by Flesch-Kincaid Reading Grade Level and Automated Readability Index. All 13 selected websites were rated as being of high quality according to the DISCERN instrument (76.5 +/- 2.6 out of 80 points). JAMA benchmark criteria were fulfilled by 87 % of websites, whereas only 37 % were certified by the HONcode. Median Alexa Traffic Rank was 2718 ranging from 7 to 679,038. Websites received 2.3 +/- 0.5 daily pageviews per visitor and users spent an average of 2 min 58 s +/- 39 sec on the website. Accessibility (92 +/- 5 %) and usability (92 +/- 3 %) scores were high and reliability (88 +/- 8 %) moderate according to the LIDA tool. Flesch-Kincaid Grade Level was 7.9 +/- 2.2, and Automated Readability Index was 7.5 +/- 2.4, rating the websites as fairly difficult to read. In conclusion, quality, accessibility, and usability of websites on prostate cancer provided a high rating in the current analysis. These findings are encouraging in view of the growing frequency of patients' access of health information online.