Conventional ultrasound systems operate at 6 to 9 MHz and serve as the standard of care to guide prostate biopsies. We present a protocol using a novel high resolution (29 MHz) transrectal prostate micro-ultrasound system. This protocol includes a scoring system to assess the risk of prostatic carcinoma and enable real-time targeted biopsies. The ExactVu™ system is currently being used in a multisite, 2,000-patient, randomized clinical trial. Cine loops of 400 biopsies from this trial were used to create the PRI-MUS™ (prostate risk identification using micro-ultrasound) protocol and risk scale. Validation was performed in an independent, pathology blinded set of 100 cines. Three of the 5 investigators performing this validation were familiar with micro-ultrasound but naïve to the PRI-MUS protocol and they received only 1 hour of training. Each increase in risk score demonstrated a 10.1% increase (95% CI 9.3-10.8) in the probability of clinically significant cancer. The risk score also increased with Gleason sum and cancer length with a slope of 0.15 (95% CI 0.09-0.21) and 0.58 (95% CI 0.43-0.73), respectively. Sensitivity and specificity were 80% and 37%, respectively, and the mean ± SD ROC AUC was 60% ± 2%. The protocol was more accurate for detecting high grade disease (Gleason sum greater than 7) with a peak AUC of 74% (mean 66%). The new resolution of the micro-ultrasound platform paired with the PRI-MUS protocol shows promise for real-time visualization of suspicious lesions and targeting of biopsies. The improved performance of the protocol in more significant disease is consistent with the focus of the field on decreasing insignificant diagnoses and detecting high risk disease early.

Active surveillance of prostate cancer has emerged as a viable treatment option for men with features of low risk disease. Five prospective studies have enrolled patients for active surveillance with varying inclusion criteria. We evaluated the pathological outcomes of men meeting published criteria for active surveillance who elected immediate radical prostatectomy to assess the risk of under grading and under staging in candidates for active surveillance. Data were extracted from our institutional urological oncology database for all men who underwent radical prostatectomy between 1996 and 2007. The primary outcome was pathological up staging, defined as the occurrence of extracapsular extension or seminal vesicle involvement. Pathological upgrading was identified as a secondary outcome. We determined the proportion of men who would have qualified for each published active surveillance study and the respective rates of upgrading and up staging in each group. We identified 1,097 men who underwent radical prostatectomy with a mean age of 59 years. Overall 28% of the men experienced a Gleason upgrade, 21% had extracapsular extension and 11% had seminal vesicle involvement. In men qualifying based on published active surveillance inclusion criteria, rates of upgrading varied between 23% and 35%, the incidence of extracapsular extension ranged from 7% to 19% and seminal vesicle involvement ranged from 2% to 9%. Varying entry criteria for active surveillance show different rates of adverse pathological features at radical prostatectomy. Predictably fewer men met the more stringent criteria but these men had a lower incidence of seminal vesicle involvement and extracapsular extension. Such data can be used to advise men of the risks of active surveillance.

Purpose: Dietary intake of long-chain ω-3 (LC n-3) polyunsaturated fatty acids may reduce inflammation and in turn decrease risk of prostate cancer development and progression. This potential effect may be modified by genetic variation in cyclooxygenase-2 (COX-2), a key enzyme in fatty acid metabolism and inflammation. Experimental Design: We used a case-control study of 466 men diagnosed with aggressive prostate cancer and 478 age- and ethnicity-matched controls. Diet was assessed with a semiquantitative food frequency questionnaire, and nine COX-2 tag single nucleotide polymorphisms (SNP) were genotyped. We used logistic regression models to estimate odds ratios (OR) for association and interaction. Results: Increasing intake of LC n-3 was strongly associated with a decreased risk of aggressive prostate cancer (P_trend ≤ 0.0001). The OR (95% confidence interval) for prostate cancer comparing the highest with the lowest quartile of n-3 intake was of 0.37 (0.25-0.54). The LC n-3 association was modified by SNP rs4648310 (+8897 A/G), flanking the 3′ region of COX-2 (P_interaction = 0.02). In particular, the inverse association was even stronger among men with this variant SNP. This reflected the observation that men with low LC n-3 intake and the variant rs4648310 SNP had an increased risk of disease (OR, 5.49; 95% confidence interval, 1.80-16.7), which was reversed by increasing intake of LC n-3. Conclusions: Dietary LC n-3 polyunsaturated fatty acids appear protective for aggressive prostate cancer, and this effect is modified by the COX-2 SNP rs4648310. Our findings support the hypothesis that LC n-3 may impact prostate inflammation and carcinogenesis through the COX-2 enzymatic pathway.

Purpose: Radical prostatectomy (RP) patients with positive surgical margins are at increased risk for recurrence, emphasizing the need for prognostic markers to stratify probable outcome for optimal patient management decisions. We tested the hypothesis that nuclear localization of nuclear factor (NF)-κB, a transcription factor involved in the regulation of cell growth, angiogenesis, invasion, and apoptosis, is associated with an increased risk of biochemical recurrence after RP. Experimental Design: Analyses addressed data from 42 patients (age range, 52–72 years; mean age, 63.7 years) who exhibited positive surgical margins after RP. Immunohistochemical analysis of NF-κB (p65) was performed on the positive margin tissue. A nuclear staining cutoff of >5% was considered positive. The relation between nuclear NF-κB expression and biochemical recurrence (prostate-specific antigen >0.3 ng/mL and rising) after RP was tested in univariate and multivariate Cox regression models. Results: Biochemical recurrence was recorded in 23 patients (54.8%; median follow-up, 3.2 years). Univariate Cox regression demonstrated a 4.9-fold (95% confidence interval, 1.5–16.7; P = 0.01) higher rate of recurrence in men with NF-κB > 5%. In the multivariate model, after controlling for primary (P = 0.004) and secondary (P = 0.7) Gleason patterns, lymph node (P = 0.06) and seminal vesicle invasion (P = 0.2), and preoperative prostate-specific antigen (P = 0.009), NF-κB > 5% was associated with a 6.2-fold higher risk of biochemical recurrence (95% confidence interval, 1.7–23.5; P = 0.007). Conclusions: In univariate and multivariate analysis, NF-κB nuclear expression was strongly predictive of biochemical recurrence in patients with positive surgical margins after RP. We propose that nuclear NF-κB may serve as a useful independent molecular marker for stratifying patients at risk for recurrence.

Prostate cancer is the second most common cancer and the fifth leading cause of death from cancer in men worldwide, with an estimated 1 112 000 new diagnoses and 307 000 deaths in 2012.¹ For patients with advanced or recurrent prostate cancer, androgen deprivation is the standard initial therapeutic approach,² but it carries many life-altering adverse effects including fatigue, sexual dysfunction, and cognitive changes.^3-6 Despite initial response rates of 80% to 90%, almost all men eventually develop castration-resistant disease. At this stage, although multiple new agents have become available in the past few years, survival remains limited.⁷

Adjusted multivariate models used to evaluate anatomic MR imaging indicated that the presence of a lesion that was suggestive of cancer conferred a greater risk (hazard ratio, 4.0; 95% confidence interval: 1.1, 14.9) of Gleason score upgrade at subsequent biopsy. PurposeTo determine the role that magnetic resonance (MR) imaging and MR spectroscopic imaging findings obtained at the time of diagnosis play in the progression of disease in patients whose prostate cancer is being managed with active surveillance and to compare the role of these findings with the role of transrectal ultrasonography (US) findings.Materials and MethodsThe institutional review board approved this HIPAA-compliant retrospective study, and informed consent was obtained from all patients whose records were to be entered into the research database. All patients who had prostate cancer managed with active surveillance and who had undergone both MR imaging and MR spectroscopic imaging of the prostate and transrectal US at time of diagnosis were identified. Two urologists blinded to the clinical outcome in these patients independently reviewed and dichotomized the MR imaging report and the MR spectroscopic imaging report as normal or suggestive of malignancy. One experienced urologist performed al...