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.

CONTEXT: Given the highly variable behavior and clinical course of prostate cancer (PCa) and the multiple available treatment options, a personalized approach to oncologic risk stratification is important. Novel genetic approaches offer additional information to improve clinical decision making. OBJECTIVE: To review the use of genomic biomarkers in the prognostication of PCa outcome and prediction of therapeutic response. EVIDENCE ACQUISITION: Systematic literature review focused on human clinical studies reporting outcome measures with external validation. The literature search included all Medline, Embase, and Scopus articles from inception through July 2014. EVIDENCE SYNTHESIS: An improved understanding of the genetic basis of prostate carcinogenesis has produced an increasing number of potential prognostic and predictive tools, such as transmembrane protease, serine2:v-ets avian erythroblastosis virus E26 oncogene homolog (TMPRSS2:ERG) gene fusion status, loss of the phosphatase and tensin homolog (PTEN) gene, and gene expression signatures utilizing messenger RNA from tumor tissue. Several commercially available gene panels with external validation are now available, although most have yet to be widely used. The most studied commercially available gene panels, Prolaris, Oncotype DX Genomic Prostate Score, and Decipher, may be used to estimate disease outcome in addition to clinical parameters or clinical nomograms. ConfirmMDx is an epigenetic test used to predict the results of repeat prostate biopsy after an initial negative biopsy. Additional future strategies include using genetic information from circulating tumor cells in the peripheral blood to guide treatment decisions at the initial diagnosis and at subsequent decision points. CONCLUSIONS: Major advances have been made in our understanding of PCa biology in recent years. Our field is currently exploring the early stages of a personalized approach to augment traditional clinical decision making using commercially available genomic tools. A more comprehensive appreciation of value, limitations, and cost is important. PATIENT SUMMARY: We summarized current advances in genomic testing in prostate cancer with a special focus on the estimation of disease outcome. Several commercial tests are currently available, but further understanding is needed to appreciate the potential benefits and limitations of these novel tests.

CONTEXT/BACKGROUND:The relationship between early detection of prostate cancer (PCa) and disease-specific mortality is still the subject of much debate. OBJECTIVE:This review describes developments in PCa mortality rates and disease-stage shift on a population level. The main findings from the randomised screening trials are also discussed. Finally, we consider the expected consequences for the individual man interested in screening. EVIDENCE ACQUISITION/METHODS:The PubMed database was searched for trials of screening for PCa from inception through October 11, 2014. Supplementary information was collected by cross-referencing the reference lists. EVIDENCE SYNTHESIS/RESULTS:Since the introduction of prostate-specific antigen testing, PCa incidence has risen, and a stage shift towards more favourable disease at diagnosis has been observed. PCa mortality rates are gradually decreasing. Although screening trials show conflicting results, the largest randomised trial of screening for PCa shows a 21% decrease in PCa-specific mortality. After correction for noncompliance and contamination, a risk reduction in PCa-specific mortality of up to 49% has been reported. The main side effect of screening is that some studies have estimated that approximately 50% of detected cases may represent overdiagnosis, which may be reduced by stopping screening in older men and using an individual risk-based approach. CONCLUSIONS:To maximise the benefits while minimising the risk of overdiagnosis, future screening should follow an individual risk-based approach. PATIENT SUMMARY/UNASSIGNED:On a population level, the introduction of screening for prostate cancer (PCa) is associated with more men diagnosed but with more favourable disease. The largest screening study confirmed the reduction in death due to PCa. Individual risk estimation is important to best balance the benefits and potential harms of early detection.

OBJECTIVE: To investigate how much Gleason pattern 3 cancer prostate biopsy specimens may contain without an increased risk of undetected more aggressive cancer, compared with the risk for cancers fulfilling the National Comprehensive Cancer Network (NCCN) criteria for very low-risk prostate cancer. PATIENTS AND METHODS: We identified 1286 men aged <70 years in the National Prostate Cancer Register of Sweden who underwent primary radical prostatectomy (RP) for stage T1c or T2 prostate cancer with Gleason pattern