Allison H. Feibus

A Whole Blood Assay for AR-V7 and ARv567es in Patients with Prostate Cancer

PURPOSE Most prostate cancer mortality can be attributed to metastatic castration resistant prostate cancer, an advanced stage that remains incurable despite recent advances. The AR (androgen receptor) signaling axis remains active in castration resistant prostate cancer. Recent studies suggest that expression of the AR-V (AR splice variant) AR-V7 may underlie resistance to abiraterone and enzalutamide. However, controversy exists over the optimal assay. Our objective was to develop a fast and sensitive assay for AR-Vs in patients. MATERIALS AND METHODS Two approaches were assessed in this study. The first approach was based on depletion of leukocytes and the second one used RNA purified directly from whole blood preserved in PAXgene® tubes. Transcript expression was analyzed by quantitative reverse transcription-polymerase chain reaction. RESULTS Through a side-by-side comparison we found that the whole blood approach was suitable to detect AR-Vs. The specificity of the assay was corroborated in a cancer-free cohort. Using the PAXgene assay samples from a cohort of 46 patients with castration resistant prostate cancer were analyzed. Overall, AR-V7 and ARv567es were detected in 67.53% and 29.87% of samples, respectively. Statistical analysis revealed a strong association of AR-V positivity with a history of second line hormonal therapies. CONCLUSIONS To our knowledge this is the first study to demonstrate that PAXgene preserved whole blood can be used to obtain clinically relevant information regarding the expression of 2 AR-Vs. These data on a castration resistant prostate cancer cohort support a role for AR-Vs in resistance to therapies targeting the AR ligand-binding domain.

Testosterone and cardiovascular disease – the controversy and the facts

Abstract Since November 2013, there has been a flurry of articles written in the media touting the risk of cardiovascular (CV) disease in men treated with testosterone, based on two recent reports. Since first synthesized in 1935, testosterone therapy has demonstrated substantial benefits for men with testosterone deficiency (also called hypogonadism). Testosterone has an acceptable safety profile and literature spanning more than 30 years, suggesting a decreased CV risk with low levels of testosterone and benefits associated with testosterone therapy. However, nonmedical media outlets have seized on reports of increased CV risk, and published scathing editorials impugning testosterone therapy as a dangerous and overprescribed treatment. Here, we review these recent studies, and find no scientific basis for assertions of increased CV risk. This article is intended to provide the clinician with the facts needed for an informed discussion with men who suffer from testosterone deficiency and who desire treatment for their symptoms.

Active surveillance of prostate cancer in African American men.

Active surveillance (AS) is a treatment strategy for prostate cancer (PCa) whereby patients diagnosed with PCa undergo ongoing characterization of their disease with the intent of avoiding radical treatment. Previously, AS has been demonstrated to be a reasonable option for men with low-risk PCa, but existing cohorts largely consist of Caucasian Americans. Because African Americans have a greater incidence, more aggressive, and potentially more lethal PCa than Caucasian Americans, it is unclear if AS is appropriate for African Americans. We performed a review of the available literature on AS with a focus on African Americans.

Erectile dysfunction and cardiovascular disease

Abstract Erectile dysfunction (ED) is often a comorbid condition commonly associated with cardiovascular disease (CVD). It is important for physicians to understand that the relationship between ED and CVD is not a coincidence but rather a warning signal. The fact that the symptoms of ED normally arise before the symptoms of a cardiovascular event gives physicians the unique opportunity to see the possible future of their patients’ cardiovascular health. Vascular disease is the most common cause of ED. This article reviews the incidence of CVD and ED, the pathophysiology of ED, the risk factors associated with ED and CVD, and the evaluation and treatment options for men with ED, and discusses how ED may serve as an early warning for cardiovascular disease.

Benign prostatic hyperplasia and urinary symptoms: Evaluation and treatment

Abstract Benign prostatic hyperplasia (BPH) is one of the most common conditions affecting middle-aged men. This condition can be microscopic, macroscopic, symptomatic, or asymptomatic. Up to 15% to 25% of men aged 50–65 years have lower urinary tract symptoms (LUTS) consisting of nocturia, urgency, frequency, a sensation of not completely emptying the bladder, stop-start urination, straining to urinate, a need to urinate soon after voiding, and weak urinary stream. These symptoms usually are associated with benign enlargement of the prostate gland that is of sufficient severity to interfere with a man’s quality of life. Although LUTS is often associated with BPH, LUTS can also be due to various unrelated syndromes such as heart failure, urinary tract infections, and diabetes. Most men will have benign hyperplasia of the prostate gland and this benign growth compresses the urethra resulting in LUTS. This article will discuss the evaluation, pharmacological management, minimally invasive treatment, and surgical therapy of this common condition affecting millions of American men.

Racial variation in prostate needle biopsy templates directed anterior to the peripheral zone

OBJECTIVES African Americans (AA) have been reported to have both increased incidence and increased aggressiveness of prostate cancer (PCa) located anterior to the peripheral zone (APZ). We sought to evaluate the utility of prostate biopsies directed toward the APZ in a predominantly AA cohort. METHODS AND MATERIALS We reviewed all patients with PCa found on biopsy schema that included needle biopsies directed at both the peripheral zone (PZ) and APZ from 2010 to 2014. Self-identified race was recorded for all patients. To evaluate the reliability of APZ-directed prostate biopsies, we performed pathologic secondary review of 25 radical prostatectomy specimens. A series of the Mann-Whitney U and Chi-square tests were used to compare variables. RESULTS We identified 398 men, of which 277 (70%) were AA. Compared with non-AA, AA had more National Comprehensive Cancer Network-defined intermediate or high-risk (50% vs. 39%, P = 0.25) PCa. Most patients had PCa limited to the PZ only (n = 190) or in both the PZ and APZ (n = 191). For 17 patients (4%), PCa was limited only to the APZ core(s), 14 (5%) AA vs. 3 (2%) non-AA (P = 0.24). Most of these 17 patients (n = 14, 82%) had Gleason 6 disease. Patients with PCa in both the PZ and APZ had higher serum prostate-specific antigen, prostate-specific antigen density, volume of disease, and increased grade and National Comprehensive Cancer Network category (all P<0.01). Of these patients, there were no differences in race (AA = 135, 71% vs. non-AA = 56, 29%; P = 0.48). In only 21 men (11%), without racial variation, APZ tumor grade was greater than PZ. Radical prostatectomy and APZ-directed biopsies demonstrated a concordance rate of 80% (20/25), false positive rate of 8% (2/25), and false negative rate of 12% (3/25). CONCLUSIONS APZ-directed prostate biopsies are rarely the sole location of PCa and do not show a clear racial predilection. In those men with PCa identified in both regions, the APZ biopsy did not frequently change treatment recommendations. Biopsies directed at the APZ are not of greater benefit to AA than non-AA.

Characterizations of Clinical and Therapeutic Histories for Men With Prostate Cancer-Specific Mortality

BACKGROUND Careful descriptions of men with prostate cancer (PCa)-specific mortality are scant in nontrial settings. The present retrospective review describes the clinical characteristics, timelines, and treatment histories from initial presentation to death in a cohort of men with metastatic, castrate-resistant PCa (mCRPC). Unique to the present study is the unequivocal attribution of PCa death by a single experienced clinician. PATIENTS AND METHODS A total of 119 patients who had been treated at Tulane Cancer Center and had died of mCRPC from 2008 to 2015 were studied through a retrospective review of the medical records. RESULTS The median age at diagnosis was 65 years (range, 40-85 years), and 34.4% of the patients presented with metastatic disease (stage M1). Of these patients, 56% had received definitive primary therapy, all had received androgen-deprivation therapy, and 52% had received docetaxel. The patients had received a median of 7 (1-14) systemic therapies before death. Most were secondary hormonal manipulations after the diagnosis of mCRPC (median, 4; range, 0-9). The median survival was 69 months (range, 5-270 months) after diagnosis, and the median age at death was 73 years (range, 47-95 years). The presence of metastases at diagnosis was a significant predictor of early death (hazard ratio, 4.33; P < .001), and definitive primary therapy was a significant predictor of longer survival (P < .001). The median survival for patients presenting with metastases was 39 months (range, 5-235 months) compared with 100 months (range, 6-270 months) for those with localized disease (P < .001). The median age at diagnosis between the docetaxel- and non-docetaxel-treated patients was significantly different at 62 and 71 years, respectively (P = .002). CONCLUSION The present retrospective analysis provides initial views clarifying the clinical characteristics of men dying of mCRPC and the therapies they received before death. Additional data are needed in multi-institutional settings to confirm these findings.

Racial Variation in the Outcome of Subsequent Prostate Biopsies in Men With an Initial Diagnosis of Atypical Small Acinar Proliferation

Micro‐Abstract African American (AA) men often have more aggressive prostate cancer (PCa) than Caucasian American men. We sought to determine predictive factors for subsequent PCa detection after an initial biopsy showing atypical small acinar proliferation (ASAP). Retrospective analysis of data from 106 men with ASAP showed no racial variation in subsequent PCa detection; therefore, AA and non‐AA with ASAP should be managed similarly. Background: African American (AA) men are known to have more aggressive prostate cancer (PCa) compared with Caucasian American men. We sought to determine predictors of subsequent detection and risk stratification of PCa in a racially diverse group of men with atypical small acinar proliferation (ASAP) on initial prostate biopsy. Materials and Methods: A retrospective analysis was conducted on data from men with ASAP on initial prostate biopsy who subsequently received confirmatory biopsies between September 2000 and July 2015. Biopsies with more than 3 years between initial and confirmatory biopsies were excluded. Race, age, body mass index, transrectal ultrasound volume, serum prostate‐specific antigen (PSA), PSA velocity, PSA density, and elapsed time between biopsies were assessed for predictive value in subsequent PCa diagnosis after an initial finding of ASAP. Results: Of 106 men analyzed, 75 (71%) were AA and 31 (29%) were non‐AA. Baseline variables revealed AA men had higher PSA levels, PSA velocity, and PSA density (all P < .05). PCa was diagnosed in subsequent biopsy in 42 (40%) patients without significant racial variation; 30 (40%) AA versus 12 (39%) non‐AA. Of the 42 PCa patients, 25 (24%) met Epstein criteria for significant disease without racial variation; 18 (24%) AA versus 7 (23%) non‐AA. Only 10 (9%) patients had any component of Gleason 4; 7 (9%) AA versus 3 (10%) non‐AA. In multivariate analysis, increasing age, PSA level, and PSA density were significant predictors of PCa. Conclusion: AA men diagnosed with ASAP on initial prostate biopsy do not have increased risk of PCa on confirmatory biopsy compared with non‐AA men.

Sequencing of treatments in metastatic CRPC for patients who have completed all therapeutic interventions.

339 Background: The current treatment paradigm for metastatic, castrate-resistant prostate cancer (mCRPC) has rapidly changed and six therapies [abiraterone (Abi), enzalutamide (Enza), docetaxel (Doc), cabazitaxel (Cab), radium-223 (Ra-223), and sipuleucel-T (Sip-T)] have now been proven to prolong overall survival. Though sequential therapy is the norm, few studies have reported on the variety and prevalence of these agents over the course of patients lifetime. Herein, we sought to describe the temporal frequencies of mCRPC therapies in patients who completed all of their therapies. Methods: Retrospective chart reviews were conducted on 119 patients who died from mCRPC at Tulane Cancer Center from 2008-2015 (thus completing all possible therapies). Many patients were not treated with multiple life-prolonging therapies given the timing of their death. Post-mCRPC therapies were longitudinally sequenced and a frequency table was generated for first, second, third, etc. line of therapies. Results: Median du...

Racial variation in the outcome of subsequent prostate biopsies in men with an initial diagnosis of atypical small acinar proliferation (ASAP).

141 Background: African Americans (AA) are known to have more aggressive prostate cancer (PCa) and a greater probability of death from PCa. We sought to determine predictors of subsequent detection and risk stratification of PCa in a racially diverse group of men who presented with atypical small acinar proliferation (ASAP) on initial prostate biopsy. Methods: Upon receiving IRB approval, a retrospective analysis was performed on men from the Southeast Louisiana Veterans Health Care System and Tulane University Medical Center who presented with ASAP on initial prostate biopsy and subsequently received confirmatory prostate biopsies from September 2000 through July 2015. Confirmatory biopsy with a greater than 3-year interval from the initial were excluded. Self-identified race, age, body mass index (BMI), transrectal ultrasound (TRUS) volume, serum prostate-specific antigen (PSA), PSA velocity (PSAV), PSA density (PSAD), and elapsed time between biopsies were evaluated to determine if they were predictors...