A 17-gene Panel for Prediction of Adverse Prostate Cancer Pathologic Features: Prospective Clinical Validation and Utility.

OBJECTIVE: To validate the 17-gene Oncotype DX Genomic Prostate Score (GPS) biopsy-based gene expression assay as a predictor of adverse pathology (AP, Gleason score [pGS] ≥4+3and/or ≥pT3) in a prospectively enrolled cohort. METHODS: Between July 2014 and September 2015, 1200 men with very low-, low-, and favorable intermediate-risk prostate cancer enrolled in a multi-institutional prospective study of the GPS assay (NCT03502213). The subset who proceeded to immediate radical prostatectomy (RP) after GPS testing was included in a prespecified subanalysis of GPS on biopsy and its association with surgical AP on RP using logistic regression and receiver operating characteristic curves. The effect of GPS testing on physicians' and patients' attitudes about decision making was assessed with the Decisional Conflict Scale. RESULTS: One hundred fourteen patients (treated by 59 physicians from 19 sites) elected RP and 40 (35%) had AP. GPS result was a significant predictor of AP (odds ratio per 20 GPS units [OR/20 units]: 2.2; 95% CI 1.2-4.1; P = .008) in univariable analysis and remained significant after adjustment for biopsy Gleason score, clinical T-stage, and logPSA (OR/20 units: 1.9; 95% CI 1.0-3.8; P = .04), or NCCN risk group (OR/20 units: 2.0; 95% CI 1.1-3.7; P = .02). Mean pre-GPS Decisional Conflict Scale score was 27 (95% CI 24-31), which improved significantly after GPS testing to 14 (95% CI 11-17) (P < .001). CONCLUSION: In this real-world multi-institutional study, the GPS assay was prospectively confirmed as an independent predictor of AP at surgery. GPS testing was associated with reduced patient decisional conflict.

Use of a 17-Gene Prognostic Assay in Contemporary Urologic Practice: Results of an Interim Analysis in an Observational Cohort.

OBJECTIVE: To study the impact of genomic testing in shared decision making for men with clinically low-risk prostate cancer (PCa). MATERIALS AND METHODS: Patients with clinically low-risk PCa were enrolled in a prospective, multi-institutional study of a validated 17-gene tissue-based reverse transcription polymerase chain reaction assay (Genomic Prostate Score [GPS]). In this paper we report on outcomes in the first 297 patients enrolled in the study with valid 17-gene assay results and decision-change data. The primary end points were shared decision on initial management and persistence on active surveillance (AS) at 1 year post diagnosis. AS utilization and persistence were compared with similar end points in a group of patients who did not have genomic testing (baseline cohort). Secondary end points included perceived utility of the assay and patient decisional conflict before and after testing. RESULTS: One-year results were available on 258 patients. Shift between initial recommendation and shared decision occurred in 23% of patients. Utilization of AS was higher in the GPS-tested cohort than in the untested baseline cohort (62% vs 40%). The proportion of men who selected and persisted on AS at 1 year was 55% and 34% in the GPS and baseline cohorts, respectively. Physicians reported that GPS was useful in 90% of cases. Mean decisional conflict scores declined in patients after GPS testing. CONCLUSION: Patients who received GPS testing were more likely to select and persist on AS for initial management compared with a matched baseline group. These data indicate that GPS help guide shared decisions in clinically low-risk PCa.

Mesothelial Inclusions in Pelvic Lymph Nodes Initially Diagnosed as Metastatic Prostate Cancer; the Utility of Second Opinions and Genomic Testing in the Setting of Unexpected Results.

Benign mesothelial inclusions in pelvic lymph nodes may be mistaken for metastatic disease in the setting of pelvic malignancy. In this case-report a patient with Low-Risk prostate cancer (confirmed by biopsy and genomic testing) underwent radical prostatectomy with pelvic lymph node dissection. The initial pathological diagnosis was organ-confined Gleason 3 + 3 = 6 cancer with metastasis to a pelvic lymph node. Upon review of the pathological specimen and immunohistochemical staining the lymph node tissue concerning for metastatic disease was recharacterized as mesothelial in origin. This case illustrates the importance of second opinions and immunohistochemistry for unexpected or unusual pathological findings.

The Impact of a Biopsy Based 17-Gene Genomic Prostate Score on Treatment Recommendations in Men with Newly Diagnosed Clinically Prostate Cancer Who are Candidates for Active Surveillance.

INTRODUCTION: The biopsy based 17-gene GPS was clinically validated to predict the likelihood of adverse surgical pathology in men with NCCN® very low, low or low-intermediate risk prostate cancer. We performed a prospective study to assess the impact of incorporating GPS into treatment recommendations in 3 high volume urology practices. METHODS: Men with newly diagnosed prostate cancer meeting specific NCCN criteria were prospectively enrolled in the trial. Biopsy tissue was analyzed. Urologists indicated treatment recommendations on questionnaires administered before and after GPS. The primary study objectives were to assess all changes in treatment modality and/or treatment intensity after GPS. RESULTS: A total of 158 men were included in analysis, including 35, 71 and 52 at NCCN very low, low and low-intermediate risk. Biological risk predicted by GPS differed from NCCN clinical risk alone in 61 men (39%). Overall 18% of recommendations between active surveillance and immediate treatment changed after GPS. The relative increase in recommendations for active surveillance was 24% (absolute change 41% to 51%). In 41 of 158 men (26%) modality and/or intensity recommendations changed after GPS, including 25, 14 and 2 in whom recommendation intensity decreased, increased and were equivocal, respectively. All changes were directionally consistent with GPS. The NCCN low risk group showed the greatest absolute recommendation change after GPS (37%). In 17 of 57 men (30%) the initial recommendation of radical prostatectomy was changed to active surveillance after GPS. Urologists indicated greater confidence and found that incorporating GPS was useful in 85% and 79% of cases, respectively, including when biological risk confirmed the clinical risk category. CONCLUSIONS: This study demonstrates that the 17-gene GPS influenced treatment recommendations among urologists and provided increased confidence in these recommendations in patients at NCCN very low to low-intermediate risk.

Utility of the Oncotype DX® Prostate Cancer Assay in Clinical Practice for Treatment Selection in Men Newly Diagnosed with Prostate Cancer: A Retrospective Chart Review Analysis.

INTRODUCTION: The 17-gene Oncotype DX® prostate cancer assay (Genomic Health Inc., Redwood City, California) is a validated, biopsy based gene expression assay that reports the Genomic Prostate Score. Combined with clinical risk features, Genomic Prostate Score provides an individualized estimation of disease aggressiveness at diagnosis. With this retrospective chart review we assessed the impact of incorporating the Oncotype DX Genomic Prostate Score on treatment recommendations and decisions for men with newly diagnosed low risk prostate cancer in community urology practices. METHODS: A total of 24 urologists who ordered the Oncotype DX prostate cancer assay soon after launch (May 2013) were invited to participate in the study. Clinicopathological data, Genomic Prostate Score results and treatment related information were retrieved from medical records. Data also were collected for a pre-Genomic Prostate Score baseline group diagnosed from May 2012 to April 2013. Descriptive analyses were performed to evaluate the proportion of men for whom active surveillance was recommended and used before and after the availability of Genomic Prostate Score. RESULTS: Overall 15 physicians contributing 211 patients (Genomic Prostate Score group 124, baseline group 87) participated in the chart review. Patients in the Genomic Prostate Score and baseline groups had comparable risk based on traditional clinical pathological features, with 82% with NCCN® very low or low risk disease. With Genomic Prostate Score the relative increase in active surveillance recommended was 22% (baseline 50% and Genomic Prostate Score 61%, absolute increase of 11%) and the relative increase in use of active surveillance was 56% (baseline 43% and Genomic Prostate Score 67%, absolute increase of 24%). Treatment recommendations for active surveillance were directionally consistent with assay reported risk. CONCLUSIONS: Genomic Prostate Score testing was associated with greater physician recommendation of and use of active surveillance in community clinical practices.

Factors influencing prostate-specific antigen response among men treated with testosterone therapy for 6 months.

INTRODUCTION: Factors influencing prostate-specific antigen (PSA) changes in men undergoing testosterone (T) therapy have not been well studied. AIM: The aim of this study was to assess the influence of selected variables on PSA changes in hypogonadal men administered with 1.62% testosterone gel (T-gel) for 6 months. METHODS: A double-blind, placebo-controlled study of 274 (234 T-gel, 40 placebo) hypogonadal men >18 years of age, with baseline T concentrations <300 ng/dL, PSA ≤2.5 ng/mL, and negative digital rectal examination. Subjects received once-daily T-gel for T therapy. MAIN OUTCOME MEASURES: Changes in mean serum PSA, percentage of free PSA (%fPSA), and T from baseline to 6 months (182 days). RESULTS: Mean age was 53.5 years and baseline mean values were total T 247 ng/dL, PSA 0.9 ng/mL, and %fPSA 24.6%. Among men treated with T-gel, T increased to 499 ng/dL and PSA increased by 0.1 ng/mL (P = 0.0012). PSA increased ≥0.3 ng/mL in 26.3%, <0.3 ng/mL in 73.7%, including a decline from baseline in 33.0%. In the placebo group, T increased 29 ng/dL to 274 ng/dL, and PSA decreased 0.1 ng/mL, compared with baseline. A greater increase in PSA was noted in men ≥60 years old than in men <60 years old (0.4 vs. 0.05 ng/mL, respectively; P = 0.0006). Mean PSA did not change in men with baseline serum T >250 ng/dL, whereas it increased by 0.2 ng/mL in men with T ≤250 ng/dL (P = 0.0031). PSA increased 0.3 ng/mL in men with baseline %fPSA <20% and 0.1 ng/mL in men with %fPSA ≥20%. CONCLUSIONS: Overall, T-gel treatment was associated with a minor increase in PSA, of questionable clinical significance. Factors predicting greater PSA increases included age ≥60 years, baseline T ≤250 ng/dL, and %fPSA <20%. Men with T >250 ng/dL and age <60 years demonstrated minimal or no PSA change.

11 techniques to attract patients to your clinical research studies.

Many physicians are searching for the "Holy Grail", i.e., the ability to earn passive medical income without having to see patients. Unfortunately, that rarely exists in most medical practices. However, conducting clinical research studies is an opportunity to approach the objective of passive income. This article discusses tested techniques to increase the number of patients participating in clinical research studies.

Tadalafil relieves lower urinary tract symptoms secondary to benign prostatic hyperplasia.

PURPOSE: We assessed the efficacy and safety of tadalafil dosed once daily for lower urinary tract symptoms secondary to benign prostatic hyperplasia. MATERIALS AND METHODS: Following a 4-week, single-blind, placebo run-in 281 men were randomly assigned (1:1) to 5 mg tadalafil for 6 weeks, followed by dose escalation to 20 mg for 6 weeks or 12 weeks of placebo. RESULTS: Tadalafil significantly improved the mean change from baseline in International Prostate Symptom Score at 6 weeks (5 mg tadalafil -2.8 vs placebo -1.2) and at 12 weeks (5/20 mg tadalafil -3.8 vs placebo -1.7). Larger changes were observed with inclusion of the placebo run-in at 12 weeks (5/20 mg tadalafil -7.1 vs placebo -4.5). Significant improvements were also seen in the International Prostate Symptom Score irritative and obstructive domains, the International Prostate Symptom Score quality of life index, a question about urinary symptom improvement and the Benign Prostatic Hyperplasia Impact Index (significant at 12 weeks) vs placebo. International Prostate Symptom Score and International Index of Erectile Function erectile function domain scores significantly improved in the 56% of men with lower urinary tract symptoms/benign prostatic hyperplasia who were sexually active and had erectile dysfunction. Changes in uroflowmetry parameters were similar in the placebo and tadalafil groups. Commonly reported (2% or greater) treatment emergent adverse events were "erection increased," dyspepsia, back pain, headache, nasopharyngitis and upper respiratory tract infection (each 5.1% or less). No change in post-void residual volume was seen with tadalafil treatment. CONCLUSIONS: Tadalafil once daily was well tolerated and demonstrated clinically meaningful and statistically significant symptomatic improvement for lower urinary tract symptoms/benign prostatic hyperplasia. Tadalafil also improved erectile function in men with lower urinary tract symptoms and erectile dysfunction.