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

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.

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.

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.

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.