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Background ETS-related gene (ERG) oncogenic activation is the most common genomic alteration in prostate cancer (CaP) although it occurs less frequently in African American (AA) versus Caucasian (CA) patients, and the potential role of ERG as a prognostic marker has not been confirmed. Objective This study was conducted to confirm strong racial variation in the prevalence of ERG oncoprotein expression and to examine ERG oncoprotein expression, race, and body mass index as independent and joint predictors of CaP biochemical recurrence (BCR) following radical prostatectomy (RP). Design, setting, and participants A retrospective cohort study of CA and AA CaP patients enrolled at Walter Reed National Military Medical Center, who donated clinically annotated, whole-mounted, prostatectomy specimens between 1994 and 2014 following RP, was conducted. Outcome measurements and statistical analysis Kaplan–Meier (KM) estimation curves and multivariable Cox proportional hazards models were used to examine time to BCR as a function of ERG status, patient race, and obesity. Results and limitations Among 930 eligible patients (36.1% AA and 63.9% CA), with 155 (16.7%) BCR events and a median follow-up time of 5.1 yr, ERG oncoprotein expression was significantly less prevalent in index tumors of AA versus CA patients (23.2% vs 49.3%; p 0.0001). KM curves showed significantly poorer BCR-free survival for CA patients with ERG-negative index tumors but not for AA patients. Race-stratified multivariable analyses revealed a significant association between ERG-negative index tumors and poorer BCR-free survival among CA patients (hazards ratio=1.67, confidence interval=1.07, 2.61; p =0.024). Less heterogeneity in ERG expression among AA patients may reduce the ability to show its association with BCR. Conclusions Striking racial variation in ERG oncoprotein expression was confirmed. A novel observation was the importance of index tumor ERG-negative status in predicting CaP progression for CA patients. Patient summary ETS-related gene (ERG) typing of tumors may be useful in prognosticating prostate cancer aggressiveness.

Within the text we describe a 66-year-old male with a history of prostate cancer (PCa), incidentally found to have left-sided hydronephrosis and a left ureteral lesion. Ureteroscopy was employed to visualize the lesion, a biopsy was taken, and a double J stent was placed. The lesion was of prostatic origin and the patient was subsequently started on androgen deprivation therapy (ADT). 6 months following the procedure, the patient's PSA had decreased and his hydronephrosis had resolved. We are the first to report treating a ureteral metastasis from PCa and its associated hydronephrosis solely with ADT and double J stenting, respectively.

Introduction Patients with low-risk prostate cancer (PCa) often have excellent oncologic outcomes. However, treatment with curative intent can lead to decrements in health-related quality of life (HRQoL). Patients treated with radical prostatectomy have been shown to suffer declines in urinary and sexual HRQoL as compared to those managed with active surveillance (AS). Similarly, patients treated with external-beam radiation therapy (EBRT) are hypothesized to experience greater declines in bowel HRQoL. As health-related quality-of-life (HRQoL) concerns are paramount when selecting among treatment options for low-risk PCa, this study examined HRQoL outcomes in men undergoing EBRT as compared to AS in a prospective, racially diverse cohort. Methods A prospective study of HRQoL in patients with PCa enrolled in the Center for Prostate Disease Research (CPDR) Multicenter National Database was initiated in 2007. The current study included patients diagnosed through April 2014. HRQoL was assessed with the Expanded Prostate Cancer Index Composite (EPIC) and the Medical Outcomes Study Short Form (SF-36). Temporal changes in HRQoL were compared for patients with low-risk PCa managed on AS vs. EBRT at baseline, 1-, 2-, and 3 years post-PCa diagnosis. Longitudinal patterns were modeled using linear regression models fitted with generalized estimating equations (GEE), adjusting for baseline HRQoL, demographic, and clinical patient characteristics. Results Of the 499 eligible patients with low-risk PCa, 103 (21%) selected AS and 60 (12%) were treated with EBRT. Demographic characteristics of the treatment groups were similar, though a greater proportion of patients in the EBRT group were African American ( P = 0.0003). At baseline, both treatment groups reported comparable HRQoL. EBRT patients experienced significantly worse bowel function and bother at 1 year (adjusted mean score: 87 vs. 95, P = 0.001 and 89 vs. 95, P = 0.008, respectively) and 2 years (87 vs. 93, P = 0.007 and 87 vs. 96, P = 0.002, respectively) compared to patients managed on AS. In contrast to those on AS, more than half the number of patients who received EBRT experienced a decline in bowel function (52% vs. 17%, p =0.003) and bother (52% vs. 15%, P = 0.002) from baseline to 1 year. Patients who received EBRT were significantly more likely to experience a decrease in more than one functional domain (urinary, sexual, bowel, or hormonal) at 1 year when compared with those on AS (60% vs. 28%, P = 0.004). Conclusions Patients receiving EBRT for low-risk prostate cancer suffer declines in bowel HRQoL. These declines are not experienced by patients on AS, suggesting that management of low-risk prostate cancer with AS may offer a means for preserving HRQoL following prostate cancer diagnosis.

Objectives In patients with a rising prostate-specific antigen (PSA) level during treatment with androgen deprivation therapy, identification of men who progress to bone metastasis and death remains problematic. Accurate risk stratification models are needed to better predict risk for bone metastasis and death among patients with castration-resistant prostate cancer (CRPC). This study evaluates whether alkaline phosphatase (AP) kinetics predicts bone metastasis and death in patients with CRPC. Methods and materials A retrospective cohort study of 9,547 patients who underwent treatment for prostate cancer was conducted using the Center for Prostate Disease Research Multi-center National Database. From the entire cohort, 347 were found to have CRPC and, of those, 165 had 2 or more AP measurements during follow-up. To determine the AP velocity (APV), the slope of the linear regression line of all AP values was plotted over time. Rapid APV was defined as the uppermost quartile of APV values, which was found to be ≥6.3 IU/l/y. CRPC was defined as 2 consecutive rising PSA values after achieving a PSA nadir Results Rapid APV and PSA doubling time (PSADT) less than 10 months were strong predictors of both BMFS and OS in a multivariable analysis. Faster PSADT was a stronger predictor for BMFS (odds ratio [OR] = 12.1, P Conclusion APV is an independent predictor of OS and BMFS in patients with CRPC. APV, in conjunction with PSA-based clinical parameters, may be used to better identify patients with CRPC who are at the highest risk of metastasis and death. These findings need validation in prospective studies.

Over the last several decades, the advances in molecular genetics have elucidated kidney cancer gene pathways. Kidney cancer is a heterogeneous disorder. Each specific type of kidney cancer has its own histologic features, gene, and clinical course. Insight into the genetic basis of kidney cancer has been learned largely from the study of the familial or hereditary forms of kidney cancer. Extirpative surgery is currently the treatment of choice for kidney cancer that is confined to the kidney. Treatment for advanced or metastatic kidney cancer is a formidable challenge with the traditional therapies currently available. However, investigation of the mendelian single-gene syndromes, like von Hippel Lindau (VHL: VHL gene), hereditary papillary renal carcinoma (HPRC: c-Met gene), Birt-Hogg-Dubé (BHD: BHD gene), and hereditary leiomyomatosis renal cell cancer (HLRCC: fumarate hydratase gene) provides an opportunity to develop pathway specific therapies. Advances in molecular therapeutics offer novel treatment options for patients with advanced disease.

OBJECTIVES Alterations of androgen receptor (AR) functions caused by overexpression, amplification, or mutation have been described in a significant subset of advanced prostate cancer (CaP). Because AR mutations or amplification are rare in early stage CaP, we hypothesized that altered AR expression in prostate tumor cells may provide a prognostic indicator of disease progression. METHODS RNA from laser capture microdissected (LCM) tumor and benign epithelial cells from radical prostatectomy specimens of 115 hormone-naive patients were studied. Expression of AR and GAPDH genes were measured by duplex quantitative real-time polymerase chain reaction (RT-PCR) in 230 specimens. A ratio of the expression of AR gene, normalized to GAPDH gene expression in the same specimens, was compared in tumor and benign epithelial cells (tumor-to-benign ratio) and correlated with clinicopathologic features. RESULTS Paired t test analysis revealed a 62% lower AR expression in tumor tissue compared with benign tissue (P = 0.0005). However, multivariate Cox proportional hazards regression analysis of time to PSA recurrence revealed that higher tumor cell associated AR expression (continuous, log-transformed), significantly increases odds of prostate-specific antigen (PSA) recurrence (P = 0.0139) when controlling for age at surgery, race, time from diagnosis to surgery, risk stratification, pathologic T stage, Gleason sum, and margin status. CONCLUSIONS Quantitative determination of AR gene expression levels in prostate epithelial cells may be useful for predicting PSA recurrence. This study supports the accumulating data suggesting that gain of AR function may contribute to CaP progression.

Aim: Molecular markers of tumor aggressiveness can improve risk assessment for men with PCa. A large, racially diverse cohort of men (21% African-American -AA) with PCa in the Center for Prostate Disease Research multi-center national database was used to determine the association of the Oncotype DX® Genomic Prostate Score (GPS) with recurrence following radical prostatectomy (RP) for localized PCa. Methods: Archival biopsy specimens from 431 eligible men treated with RP for NCCN very low, low or intermediate risk PCa from 1990-2011 at 2 U.S. military medical centers were tested to validate the association between GPS and recurrence following RP, and adverse pathology (AP) at RP. Biochemical recurrence (BCR) was defined as 2 successive PSA levels > 0.2 ng/mL or initiation of salvage therapy for a rising PSA. AP was defined as high-grade (primary Gleason pattern 4 or any pattern 5) and/or pT3 disease. RPs were centrally reviewed by a uropathologist (IAS). Cox proportional hazards and logistic regression models were used. Results: GPS (scale 0-100) was successfully obtained in 402 cases (93%). 62 men (15%) experienced BCR, 5 developed metastases (MR) and 163 had AP at RP. In univariate analysis, PSA, biopsy GS and NCCN risk group were associated with BCR, but race was not. GPS was predictive of time to BCR by univariate analysis (HR/20 GPS units = 2.9; 95% CI: 2.0-4.2; p < 0.001), and after adjusting for age, NCCN risk group, and race ((HR/20 units = 2.7; p < 0.001). The gene groups in GPS most strongly associated with BCR included androgen signaling and stromal response genes. GPS was predictive of time to MR (HR/20 units = 3.8; p = 0.032). GPS was strongly associated with AP - OR/ 20 units = 3.3 (95% CI: 2.1–5.1; p < .001) and high-grade disease - OR/20 units = 2.5 (95% CI: 1.6–4.0; p < .001), adjusted for NCCN risk group. GPS values were similar between AA and Caucasians, and similarly predictive of disease outcome. Conclusions: GPS is a significant independent predictor of BCR, MR and AP in men treated with RP for localized PCa. Tumor aggressiveness, as measured by GPS, and clinical outcomes were similar in AA and Caucasians in this patient population with equal healthcare access.