An update on TroVax® for the treatment of progressive castration-resistant prostate cancer

Prostate cancer is a common human malignancy with few effective therapeutic options for treating advanced castration-resistant disease. The potential therapeutic effectiveness of immunotherapy and vaccines, in particular, has gained popularity based on the identification of prostate-associated antigens, potent expression vectors for vaccination, and data from recent clinical trials. A modified vaccinia Ankara (MVA) virus expressing 5T4, a tumor-associated glycoprotein, has shown promise in preclinical studies and clinical trials in patients with colorectal and renal cell carcinoma. This review will discuss the rationale for immunotherapy in prostate cancer and describe preclinical and limited clinical data in prostate cancer for the MVA-5T4 (TroVax®) vaccine

Prostate cancer assessment using MR elastography of fresh prostatectomy specimens at 9.4 T

Purpose: Despite its success in the assessment of prostate cancer (PCa), in vivo multiparametric MRI has limitations such as interobserver variability and low specificity. Several MRI methods, among them MR elastography, are currently being discussed as candidates for supplementing conventional multiparametric MRI. This study aims to investigate the detection of PCa in fresh ex vivo human prostatectomy specimens using MR elastography. Methods: Fourteen fresh prostate specimens from men with clinically significant PCa without formalin fixation or prior radiation therapy were examined by MR elastography at 500 Hz immediately after radical prostatectomy in a 9.4T preclinical scanner. Specimens were divided into 12 segments for both calculation of storage modulus (G ' in kilopascals) and pathology (Gleason score) as reference standard. Sensitivity, specificity, and area under the receiver operating characteristic curve were calculated to assess PCa detection. Results: The mean G ' and SD were as follows: all segments, 8.74 ± 5.26 kPa; healthy segments, 5.44 ± 4.40 kPa; and cancerous segments, 10.84 ± 4.65 kPa. The difference between healthy and cancerous segments was significant with P ≤ .001. Diagnostic performance assessed with the Youden index was as follows: sensitivity, 69%; specificity, 79%; area under the curve, 0.81; and cutoff, 10.67 kPa. Conclusion: Our results suggest that prostate MR elastography has the potential to improve diagnostic performance of multiparametric MRI, especially regarding its 2 major limitations: interobserver variability and low specificity. Particularly the high value for specificity in PCa detection is a stimulating result and encourages further investigation of this method

Agent Orange and long-term outcomes after radical prostatectomy

PurposeTo investigate the association between Agent Orange (AO) exposure and long-term prostate cancer (PC) outcomes.Material and methodsData from 1,882 men undergoing radical prostatectomy for PC between 1988 and 2011 at Veterans Affairs Health Care Facilities were analyzed from the Shared Equal Access Regional Cancer Hospital database. Men were stratified by AO exposure (binary). Associations between AO exposure and biopsy and pathologic Gleason sum (GS) and pathologic stage were determined by logistic regression models adjusted for preoperative characteristics. Hazard ratios for biochemical recurrence (BCR), secondary treatment, metastases, and PC-specific mortality were determined by Cox models adjusted for preoperative characteristics.ResultsThere were 333 (17.7%) men with AO exposure. AO-exposed men were younger (median 59 vs. 62 y), had lower preoperative prostate-specific antigen levels (5.8 vs. 6.7 ng/ml), lower clinical category (25% vs. 38% palpable), and higher body mass index (28.2 vs. 27.6 kg/m(2)), all P<0.01. Biopsy GS, pathologic GS, positive surgical margins, lymph node positivity, and extracapsular extension did not differ with AO exposure. At a median follow-up of 85 months, 702 (37.4%) patients had BCR, 603 (32.2%) patients received secondary treatment, 78 (4.1%) had metastases, and 39 (2.1%) died of PC. On multivariable analysis, AO exposure was not associated with BCR, secondary treatment, metastases, or PC mortality.ConclusionsAO exposure was not associated with worse preoperative characteristics such as elevated prostate-specific antigen levels or biopsy GS nor with BCR, secondary treatment, metastases, or PC death. Thus, as data on AO-exposed men mature, possible differences in PC outcomes observed previously are no longer apparent

Peyronie's Disease: Evaluation and Review of Nonsurgical Therapy

The purpose of our study was to outline the evaluation of the Peyronie's disease (PD) patient and review the available nonsurgical treatments. A review of the literature on oral, intralesional, external energy, iontophoresis, and mechanical therapies for PD was performed. PubMed was utilized to find all published articles, and several meeting abstracts were reviewed for data ahead of publication. Our medical evaluation of the PD patient is described. The published results of available treatment options are reviewed, with recommendation by the authors for appropriate nonsurgical management of PD. There are no available validated questionnaires for PD, but a thorough history and focused physical examination, including measurement of erect penile deformity, will help the clinician make the diagnosis and guide treatment options. Although there are many published reports that show efficacy of nonsurgical therapies for PD, there is a lack of large-scale, multicenter, controlled clinical trials, which makes treatment recommendations difficult. Careful review of the literature does suggest that there are treatment options that make scientific sense and appear to stabilize the disease process, reduce deformity, and improve function. Offering no treatment at all will encourage our patients to pursue alternative treatments that may do harm, and misses the opportunity to do some good. Clearly, further work is necessary to develop safe and effective nonsurgical treatments for PD

Hyperthermia as Adjunct to Intravesical Chemotherapy for Bladder Cancer

Nonmuscle invasive bladder cancer remains a very costly cancer to manage because of high recurrence rates requiring long-term surveillance and treatment. Emerging evidence suggests that adjunct and concurrent use of hyperthermia with intravesical chemotherapy after transurethral resection of bladder tumor further reduces recurrence risk and progression to advanced disease. Hyperthermia has both direct and immune-mediated cytotoxic effect on tumor cells including tumor growth arrest and activation of antitumor immune system cells and pathways. Concurrent heat application also acts as a sensitizer to intravesical chemotherapy agents. As such the ability to deliver hyperthermia to the focus of tumor while minimizing damage to surrounding benign tissue is of utmost importance to optimize the benefit of hyperthermia treatment. Existing chemohyperthermia devices that allow for more localized heat delivery continue to pave the way in this effort. Current investigational methods involving heat-activated drug delivery selectively to tumor cells using temperature-sensitive liposomes also offer promising ways to improve chemohyperthermia efficacy in bladder cancer while minimizing toxicity to benign tissue. This will hopefully allow more widespread use of chemohyperthermia to all bladder cancer patients, including metastatic bladder cancer

Observational Study of the Association between Air Cadmium Exposure and Prostate Cancer Aggressiveness at Diagnosis among a Nationwide Retrospective Cohort of 230,540 Patients in the United States

Although studies have investigated cadmium and prostate cancer (PC) incidence and mortality, the role of cadmium in PC progression might be more clinically relevant. In this observational study, we assessed the association between air cadmium exposure and PC aggressiveness, with PC stage defined as metastatic or localized and Gleason grade defined as high (Gleason score ≥ 8) or low (Gleason score ≤ 6) among PC patients from the 2010–2014 US Surveillance, Epidemiology, and End Results database. The 2005 and 2011 National Air Toxics Assessment provided county-level air cadmium concentrations. Results were presented as odds ratios (OR) with 95% confidence intervals (CI) and were calculated using random intercept mixed effects logistic regression, comparing the 80th to 20th percentile of exposure. We adjusted for age, sociodemographic status, smoking prevalence, and overall air quality at the county level, and stratified by race, age, and degree of urbanization. The cohort consisted of 230,540 cases from 493 counties. Strong associations were observed in nonmetropolitan, urban areas: (OR 1.26, CI 1.14–1.39) for metastatic vs. localized and (OR 1.41, CI 1.27–1.57) for high- vs. low-grade PC where 40 million Americans reside. This study may be hypothesis-generating to inform future studies and public health measures

Is prostate cancer stage migration continuing for black men in the PSA era?

BACKGROUND: In the United States, disease-specific mortality from prostate cancer (PC) is highest among black men. While the introduction of widespread PSA testing has been associated with a downward stage migration, whether this trend continues in the late PSA era and for black men is unknown. The objective of our study was to evaluate current PC stage migration patterns in the United States by race. METHODS: The Surveillance, Epidemiology and End Results (SEER) registry was queried to obtain all cases of PC reported between 2000 and 2013. Year of diagnosis was categorized into 2000–2003, 2004–2007, 2008–2010 and 2011–2013. Predictors of distant stage PC at diagnosis were determined using logistic regression adjusted for year of diagnosis, age at diagnosis, SEER region and race. RESULTS: A total of 791 184 PC cases were identified. The cohort comprised 78.9% (n = 594 920) white and 14.1% (n = 106 133) black men. The stage at diagnosis was 83.3% localized, 12.0% regional and 4.7% distant. Age-adjusted incidence demonstrated a steady decline for black men in all time groups while white men had a stable incidence of distant disease between 2000 and 2013. In univariate analysis, black men in the 2004–2007 (OR 0.86 (0.81–0.93)) and 2008–2010 cohorts (OR 0.85 (0.79–0.91)) were less likely to be diagnosed with metastatic PC as compared with the 2000–2003 baseline cohort. In multivariate analysis, the 2004–2007 black cohort was less likely to be diagnosed with distant PC (OR 0.90 (0.84–0.97)). This trend was not observed in white men who in multivariate analysis had an increased risk of distant PC in the 2004–2007 (OR 1.08 (1.04–1.11)), 2008–2010 (OR 1.22 (1.18–1.27)) and 2011–2013 (OR 1.65 (1.59–1.71)) groups. CONCLUSIONS: PC downward stage migration continues in black men but not in white men. Discontinuation of PSA-based screening for PC could disproportionately affect black men