Kirsten L. Greene

Early Detection of Prostate Cancer: AUA Guideline

PURPOSE The guideline purpose is to provide the urologist with a framework for the early detection of prostate cancer in asymptomatic average risk men. MATERIALS AND METHODS A systematic review was conducted and summarized evidence derived from over 300 studies that addressed the predefined outcomes of interest (prostate cancer incidence/mortality, quality of life, diagnostic accuracy and harms of testing). In addition to the quality of evidence, the panel considered values and preferences expressed in a clinical setting (patient-physician dyad) rather than having a public health perspective. Guideline statements were organized by age group in years (age <40; 40 to 54; 55 to 69; ≥ 70). RESULTS Except prostate specific antigen-based prostate cancer screening, there was minimal evidence to assess the outcomes of interest for other tests. The quality of evidence for the benefits of screening was moderate, and evidence for harm was high for men age 55 to 69 years. For men outside this age range, evidence was lacking for benefit, but the harms of screening, including over diagnosis and overtreatment, remained. Modeled data suggested that a screening interval of two years or more may be preferred to reduce the harms of screening. CONCLUSIONS The Panel recommended shared decision-making for men age 55 to 69 years considering PSA-based screening, a target age group for whom benefits may outweigh harms. Outside this age range, PSA-based screening as a routine could not be recommended based on the available evidence.

Prostate Specific Antigen Best Practice Statement: 2009 Update

PURPOSE We provide current information on the use of PSA testing for the evaluation of men at risk for prostate cancer, and the risks and benefits of early detection. MATERIALS AND METHODS The report is a summary of the American Urological Association PSA Best Practice Policy 2009. The summary statement is based on a review of the current professional literature, clinical experience and the expert opinions of a multispecialty panel. It is intended to serve as a resource for physicians, other health care professionals, and patients. It does not establish a fixed set of guidelines, define the legal standard of care or pre-empt physician judgment in individual cases. RESULTS There are two notable differences in the current policy. First, the age for obtaining a baseline PSA has been lowered to 40 years. Secondly, the current policy no longer recommends a single, threshold value of PSA, which should prompt prostate biopsy. Rather, the decision to proceed to prostate biopsy should be based primarily on PSA and DRE results, but should take into account multiple factors including free and total PSA, patient age, PSA velocity, PSA density, family history, ethnicity, prior biopsy history and comorbidities. CONCLUSIONS Although recently published trials show different results regarding the impact of prostate cancer screening on mortality, both suggest that prostate cancer screening leads to overdetection and overtreatment of some patients. Therefore, men should be informed of the risks and benefits of prostate cancer screening before biopsy and the option of active surveillance in lieu of immediate treatment for certain men diagnosed with prostate cancer.

Outcomes of Active Surveillance for Men With Intermediate-Risk Prostate Cancer

PURPOSE Active surveillance (AS) is an option for the initial management of early-stage prostate cancer. Current risk stratification schema identify patients with low-risk disease who are presumed to be most suitable for AS. However, some men with higher risk disease also elect AS; outcomes for such men have not been widely reported. PATIENTS AND METHODS Men managed with AS at University of California, San Francisco, were classified as low- or intermediate-risk based on serum prostate-specific antigen (PSA), Gleason grade, extent of biopsy involvement, and T stage. Clinical and demographic characteristics, and progression in terms of Gleason score, PSA kinetics, and active treatment were compared between men with low- and intermediate-risk tumors. RESULTS Compared to men with low-risk tumors, those with intermediate-risk tumors were older (mean, 64.9 v 62.3 years) with higher mean PSA values (10.9 v 5.1 ng/mL), and more tumor involvement (mean, 20.4% v 15.3% positive biopsy cores; all P < .01). Within 4 years of the first positive biopsy, the clinical risk group did not differ in terms of the proportions experiencing progression-free survival, (low [54%] v intermediate [61%]; log-rank P = .22) or the proportions who underwent active treatment (low [30%] v intermediate [35%]; log-rank P = .88). Among men undergoing surgery, none were node positive and none had biochemical recurrence within 3 years. CONCLUSION Selected men with intermediate-risk features be appropriate candidates for AS, and are not necessarily more likely to progress. AS for these men may provide an opportunity to further reduce overtreatment of disease that is unlikely to progress to advanced cancer.

Changes in Prostate Cancer Grade on Serial Biopsy in Men Undergoing Active Surveillance

PURPOSE Active surveillance is now considered a viable treatment option for men with low-risk prostate cancer. However, little is known regarding changes in Gleason grade on serial biopsies over an extended period of time. PATIENTS AND METHODS Men diagnosed with prostate cancer between 1998 and 2009 who elected active surveillance as initial treatment, with 6 or more months of follow-up and a minimum of six cores at biopsy, were included in analysis. Upgrading and downgrading were defined as an increase or decrease in primary or secondary Gleason score. Means and frequency tables were used to describe patient characteristics, and treatment-free survival rates were determined by life-table product limit estimates. RESULTS Three hundred seventy-seven men met inclusion criteria. Mean age at diagnosis was 61.9 years. Fifty-three percent of men had prostate-specific antigen of 6 ng/mL or less, and 94% had Gleason score of 6 or less. A majority of men were cT1 (62%), had less than 33% of biopsy cores involved (80%), and were low risk (77%) at diagnosis. Median number of cores taken at diagnostic biopsy was 13, mean time to follow-up was 18.5 months, and 29% of men had three or more repeat biopsies. Overall, 34% (129 men) were found to have an increase in Gleason grade. The majority of men who experienced an upgrade (81%) did so by their second repeat biopsy. CONCLUSION A proportion of men experience an upgrade in Gleason score while undergoing active surveillance. Men who experience early upgrading likely represent initial sampling error, whereas later upgrading may reflect tumor dedifferentiation.

The Relationship Between Prostate Specific Antigen Change and Biopsy Progression in Patients on Active Surveillance for Prostate Cancer

PURPOSE We assessed whether an association exists between a change in prostate specific antigen and biopsy progression in men on active surveillance. MATERIALS AND METHODS A cohort of patients undergoing active surveillance for prostate cancer was identified from the urological oncology database at our institution. Multivariate logistic regression was performed to determine whether prostate specific antigen velocity, defined as the change in ln(prostate specific antigen) per year, is associated with biopsy progression, defined as a Gleason upgrade or volume progression on repeat biopsy within 24 months of diagnosis. RESULTS A total of 241 men with a mean ± SD age of 61 ± 7 years and mean prostate specific antigen 4.9 ± 2.2 ng/ml met study inclusion criteria. Median time to repeat biopsy was 10 months (IQR 6-13). Biopsy progression developed in 55 men (23%), including a Gleason score upgrade in 46 (19%), greater than 33% positive cores in 11 (5%) and greater than 50% maximum single core positive in 12 (5%). The median prostate specific antigen ratio per year was 1.0 (IQR 0.95-1.03), although 1 man had a ratio of greater than 1.26 (doubled over 3 years) and 7 had a ratio of less than 1/1.26 (halved over 3 years). On multivariate analysis prostate specific antigen doubling within 3 years was associated with a 1.4-fold increase in the odds of biopsy progression (OR 1.4, 95% CI 0.6-3.4, p = 0.46). CONCLUSIONS There is little change in prostate specific antigen during the first 24 months of surveillance in men with well staged, low risk prostate cancer. We believe that these findings highlight the importance of repeat biopsy during surveillance.

Extended Followup and Risk Factors for Disease Reclassification in a Large Active Surveillance Cohort for Localized Prostate Cancer

PURPOSE Active surveillance to manage prostate cancer provides an alternative to immediate treatment in men with low risk prostate cancer. We report updated outcomes from a long-standing active surveillance cohort and factors associated with reclassification. MATERIALS AND METHODS We retrospectively reviewed data on all men enrolled in the active surveillance cohort at our institution with at least 6 months of followup between 1990 and 2013. Surveillance consisted of quarterly prostate specific antigen testing, repeat imaging with transrectal ultrasound at provider discretion and periodic repeat prostate biopsies. Factors associated with repeat biopsy reclassification and local treatment were determined by multivariate Cox proportional hazards regression. We also analyzed the association of prostate specific antigen density and outcomes stratified by prostate size. RESULTS A total of 810 men who consented to participate in the research cohort were followed on active surveillance for a median of 60 months. Of these men 556 (69%) met strict criteria for active surveillance. Five-year overall survival was 98%, treatment-free survival was 60% and biopsy reclassification-free survival was 40%. There were no prostate cancer related deaths. On multivariate analysis prostate specific antigen density was positively associated with the risk of biopsy reclassification and treatment while the number of biopsies and time between biopsies were inversely associated with the 2 outcomes (each p <0.01). When stratified by prostate volume, prostate specific antigen density remained significantly associated with biopsy reclassification for all strata but prostate specific antigen density was only significantly associated with treatment in men with a smaller prostate. CONCLUSIONS Significant prostate cancer related morbidity and mortality remained rare at intermediate followup. Prostate specific antigen density was independently associated with biopsy reclassification and treatment while on active surveillance.

Surgical management after active surveillance for low‐risk prostate cancer: pathological outcomes compared with men undergoing immediate treatment

Study Type – Therapy (case control)
Level of Evidence 3b

MicroRNA-23b Functions as a Tumor Suppressor by Regulating Zeb1 in Bladder Cancer

MicroRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression by targeted repression of transcription and translation. In this study we show that miRNA-23b (miR-23b) acts as a tumor suppressor in bladder cancer. Quantitative real-time PCR analysis showed that miR-23b is significantly down-regulated in bladder cancer cell lines and tumor tissues compared to non-malignant cells and normal tissue samples. We also demonstrate that miR-23b expression has a potential to be diagnostic and prognostic biomarker in bladder cancer. High miR-23b expression is positively correlated with higher overall survival of bladder cancer patients as revealed by Kaplan-Meier analysis. ROC analysis showed that miR-23b expression can distinguish between normal and bladder cancer tissues. Further we elucidated the biological significance of miR-23b in bladder cancer. Over-expression of miR-23b in bladder cancer cells inhibited cell proliferation and impaired colony formation. Fluorescence activated cell sorting (FACS) analysis revealed that re-expression of miR-23b in bladder cancer cells induced G0/G1 cell cycle arrest and apoptosis while inhibiting cell migration and invasion. Luciferase reporter assays demonstrated that Zeb1, a crucial regulator of epithelial-to-mesenchymal transition (EMT), is a direct target of miR-23b in bladder cancer. These results show that loss of miR-23b confers a proliferative advantage and promotes bladder cancer cell migration and invasion. Furthermore, re-expression of miR-23b may be a beneficial therapeutic strategy for the treatment of human bladder cancer.

Clinically Localized Prostate Cancer: AUA/ASTRO/SUO Guideline. Part I: Risk Stratification, Shared Decision Making, and Care Options

Purpose This guideline is structured to provide a clinical framework stratified by cancer severity to facilitate care decisions and guide the specifics of implementing the selected management options. The summary presented represents Part I of the two‐part series dedicated to Clinically Localized Prostate Cancer: AUA/ASTRO/SUO Guideline discussing risk stratification and care options by cancer severity. Materials and Methods The systematic review utilized in the creation of this guideline was completed by the Agency for Healthcare Research and Quality and through additional supplementation by ECRI Institute. This review included articles published between January 2007 and March 2014 with an update search conducted through August 2016. When sufficient evidence existed, the body of evidence for a particular treatment was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. Additional information is provided as Clinical Principles and Expert Opinions (table 2 in supplementary unabridged guideline, http://jurology.com/). Results The AUA (American Urological Association), ASTRO, and SUO (Society of Urologic Oncology) formulated an evidence‐based guideline based on a risk stratified clinical framework for the management of localized prostate cancer. Conclusions This guideline attempts to improve a clinician’s ability to treat patients diagnosed with localized prostate cancer, but higher quality evidence in future trials will be essential to improve the level of care for these patients. In all cases, patient preferences should be considered when choosing a management strategy.

How does robot-assisted radical prostatectomy (RARP) compare with open surgery in men with high-risk prostate cancer?

Previous studies have shown that robot‐assisted radical prostatectomy (RARP) can be performed in men with high‐risk prostate cancer with similar outcomes to that of open surgery. However, most of the literature consists of small case series and compares RARP outcomes to open outcomes from the literature. This study compared a cohort of high‐risk patients undergoing open RP and RARP at a single institution with good follow up. We found no difference in positive margin rates or likelihood of prostate cancer recurrence. This adds to the growing evidence that RARP is a safe option for men with high‐risk disease.