Stephen A. Brassell

Long-term overall survival and metastasis-free survival for men with prostate-specific antigen-recurrent prostate cancer after prostatectomy: analysis of the Center for Prostate Disease Research National Database.

Study Type – Prognosis (retrospective cohort)

Evaluation of the ETS-Related Gene mRNA in Urine for the Detection of Prostate Cancer

Purpose: Prevalent gene fusions in prostate cancer involve androgen-regulated promoters (primarily TMPRSS2) and ETS transcription factors (predominantly ETS-regulated gene (ERG)], which result in tumor selective overexpression of ERG in two thirds of patients. Because diverse genomic fusion events lead to ERG overexpression in prostate cancer, we reasoned that it may be more practical to capture such alterations using an assay targeting ERG sequences retained in such gene fusions. This study evaluates the potential of an assay quantitating ERG mRNA in post–digital rectal exam (DRE) urine for improving prostate cancer detection. Experimental Design: Patients scheduled to undergo transrectal ultrasound-guided needle biopsy of the prostate were prospectively enrolled. On the day of biopsy, patients provided a urine sample immediately following a DRE. Urine ERG mRNA was measured and normalized to urine prostate-specific antigen (PSA) mRNA using the DTS 400 system. Demographic traits, clinical characteristics and biopsy results were analyzed for association with urine ERG score. Results: The study was conducted on 237 patients. Prostate cancer was shown on biopsy in 40.9% of study subjects. A higher urine ERG score associated significantly with malignancy on biopsy (P = 0.0145), but not with clinical stage or Gleason score. Urine ERG score performed best in Caucasians and in men with a PSA of ≤4 ng/mL (area under the curve = 0.8). Conclusions: A higher urine ERG score in post-DRE urine is associated with the diagnosis of prostate cancer on biopsy. Urine ERG score performed particularly well in men with a PSA of ≤4.0 ng/mL, a segment of the screening population in which further diagnostic markers are needed to determine in whom biopsy should be done. Clin Cancer Res; 16(5); 1572–6

Prostate cancer in men 70 years old or older, indolent or aggressive: clinicopathological analysis and outcomes.

PURPOSE Currently there is a lack of consensus on screening recommendations for prostate cancer with minimal guidance on the cessation of screening in older men. We defined the clinicopathological features and outcomes for men 70 years old or older who were diagnosed with prostate cancer. MATERIALS AND METHODS The Center for Prostate Disease Research database was queried for all men diagnosed with prostate cancer from 1989 to 2009. The patients were stratified into age quartiles and by race. Cox proportional hazard models were used to compare clinicopathological features across patient stratifications. Kaplan-Meier analysis was used to compare biochemical recurrence-free, prostate cancer specific and overall survival. RESULTS Of the 12,081 men evaluated 3,650 (30.2%) were 70 years old or older. These men had a statistically significant higher clinical stage, biopsy grade and prediagnosis prostate specific antigen velocity (p < 0.0001). For those patients who underwent prostatectomy, pathological stage, grade and surgical margin status were all significantly higher in men 70 years old or older. Biochemical recurrence and secondary treatment were also more common in this age group (p < 0.0001). Multivariate analysis revealed age 70 years or older as a significant predictor of biochemical recurrence after prostatectomy (HR 1.45, p = 0.0054). Overall survival was lowest in men age 70 years or older who had surgery, but interestingly the mean time to death was comparable regardless of age. CONCLUSIONS Our findings indicate that as men age, parameters consistent with more aggressive disease become more prevalent. The etiology of this trend is unknown. However, these data may have implications for current screening and treatment recommendations.

Update on magnetic resonance imaging, ProstaScint, and novel imaging in prostate cancer.

Purpose of review Despite marked stage migration, approximately a third of patients with clinically organ-confined prostate cancer will have extracapsular extension on pathological analysis. To improve outcomes further, alternative modalities of determining extraprostatic disease must be investigated beyond the current clinical parameters of digital rectal examination, prostate-specific antigen, and Gleason score. In addition, discerning the location of tumor in patients with biochemical recurrence directly affects treatment choice. This review highlights developments in prostate cancer imaging that may improve staging and treatment planning for prostate cancer patients. Recent findings Magnetic resonance imaging is most useful in the initial evaluation of men with prostate cancer. Its high specificity for the diagnosis of extracapsular extension is tempered by its low sensitivity. Positron emission tomography is used to assess regional and distant metastasis in many malignancies. Investigation into the most appropriate radiotracer for prostate cancer is paramount in any future applicability. The unique role of ProstaScint has been in evaluating patients with biochemical failure and in trying to discern metastasis before definitive therapy. The addition of spectroscopic imaging and nanoparticle infusion may lead to further improvements. Therefore, in differentiating local versus distant recurrence, appropriate interventions with radiotherapy or hormonal manipulation may be instituted. Summary Magnetic resonance imaging, ProstaScint, and to some extent positron emission tomography are all relevant imaging modalities for the evaluation of patients with prostate cancer. Current technological advances in each arena are improving the accuracy of diagnosis. Despite their specific limitations, use in the proper clinical setting may provide essential information to improve management decisions and disease outcomes.

Prostate Cancer in Men Less Than the Age of 50: A Comparison of Race and Outcomes

OBJECTIVE To compare clinicopathologic features and survival outcomes for men 50 years of age in relation to other age groups stratified by race to further define prostate cancer (CaP) in young men. Controversy exists regarding the appropriate age to undergo CaP screening, outcomes for early intervention, and whether there is unique age-associated tumor biology. We compared clinicopathologic features and survival outcomes for men <50 years of age in relation to other age groups stratified by race to further define CaP in young men. METHODS A multi-institutional review of 12,081 records of patients diagnosed with CaP from 1989-2009 was conducted. Patients were stratified by age group, race, and decade of treatment. Demographic and clinicopathologic characteristics were compared across age groups using chi-square tests and analysis of variance. The primary study endpoints, time to biochemical recurrence and all-cause mortality, were compared across age groups using Kaplan-Meier estimation and univariable and multivariable Cox proportional hazards analysis. RESULTS Only 4.5% of the study sample was <50 years of age. A higher percentage of African Americans diagnosed were <50 compared with Caucasians (8.3% vs 3.3%, P<.0001). Positive family history was more prevalent in the <50 cohort (36.1% vs 22.0%, P<.0001). Despite these findings, both racial subgroups for men<50 years of age demonstrated improved clinicopathologic features than other age quartiles. Furthermore, both Kaplan-Meier and Cox proportional hazard analysis demonstrated that the <50 cohort had a lower incidence of biochemical recurrence and greater overall survival. CONCLUSIONS Race and family history appear to play a significant role in the incidence of CaP in younger men. Younger age at diagnosis is associated with more favorable outcomes and indicates that population-based screening at younger ages could potentially lead to improved survival for high-risk groups.

Comprehensive quality-of-life outcomes in the setting of a multidisciplinary, equal access prostate cancer clinic.

OBJECTIVES To identify racial and demographic factors that influence treatment choice and its resulting impact on health-related quality of life (HRQoL) for prostate cancer patients. METHODS Patients presenting to an equal access, military, multidisciplinary prostate cancer clinic composed the study group. The Expanded Prostate Cancer Index Composite (EPIC), EPIC Demographic, and Medical Outcomes Study Short Form 36 were the instruments used. Evaluation was performed before treatment and every 3 months after treatment. RESULTS The study group comprised 665 patients. Caucasians were 3-fold more likely to choose surgery (radical prostatectomy [RP]) over external beam radiation therapy (EBRT). Patients who earned more than

Clinicopathological Behavior of Single Focus Prostate Adenocarcinoma

100,000 annually disproportionately chose RP (P < .0001). Similarly, those having a graduate school degree disproportionally chose RP (P < .0001). Patients undergoing RP had the greatest risk of urinary function decline (P < .0001) and sexual bother (P = .0003). African Americans (AA) had a greater risk of urinary function decline irrespective of treatment choice. Patients undergoing EBRT had equivalent urinary function to expectant management (EM) at 12 months (P < .0001). Brachytherapy was the only treatment that posed an increased risk of urinary bother decline when compared with EM (P = .0217). EBRT alone did not show significant decrement in sexual function when compared with EM. CONCLUSIONS RP was chosen by patients of Caucasian ethnicity and patients with higher income and education level, despite providing the greatest risk of HRQoL decline. EBRT had no significant impact on urinary function, sexual function, or sexual bother scores at 12 months. EBRT may be offered to older patients with minimal HRQoL impact. Pretreatment counseling of HRQoL outcomes is essential to overall prostate cancer management.

Prostate cancer in Asian Americans: incidence, management and outcomes in an equal access healthcare system

PURPOSE With the increasing use of focal therapy for prostate adenocarcinoma a pathological basis for its appropriate application must be established. We determined the clinicopathological characteristics and natural history of single focus prostate cancer since this entity seems to be the ideal target for focal therapy. MATERIALS AND METHODS We queried the Center for Prostate Disease Research database for all patients who underwent radical prostatectomy at Walter Reed Army Medical Center from 1993 through 2008. Patients with single focus prostate adenocarcinoma were compared with those who had multifocal disease. Primary outcomes were surgical margin status, pathological stage and biochemical recurrence. Secondary outcomes were Gleason score and total tumor volume. RESULTS A total of 1,159 men were included in the study. Multifocal disease was present in 1,056 patients (99.1%) and 103 (8.9%) had single focus disease. There were statistically higher rates of positive surgical margins (41.0% vs 29.9%, p = 0.0012), Gleason score 8-10 disease (18.7% vs 10.1%, p = 0.0362) and biochemical recurrence (38.5% vs 24.2%, p = 0.0021) in the single focus and multifocal groups, respectively. The single focus group had significantly worse biochemical recurrence-free survival compared to the multifocal group (p = 0.0017). CONCLUSIONS Single focus prostate cancer appears to have more aggressive behavior than multifocal disease. These findings support an aggressive, disciplined pretreatment evaluation to define disease site, extent and grade before focal therapy.

The Center for Prostate Disease Research (CPDR): a multidisciplinary approach to translational research.

Study Type – Therapy (outcomes research)
Level of Evidence 2c

Elevated alkaline phosphatase velocity strongly predicts overall survival and the risk of bone metastases in castrate-resistant prostate cancer.

This article describes the history, structure, and contributions of the Center for Prostate Disease Research. It divides the organization into the clinical program at Walter Reed Army Medical Center, the basic science program in Rockville, MD, and the multi-center national database. The emphasis of this article is not the achievements of the individual programs but their synergy, establishing a comprehensive multidisciplinary prostate center.