Author Interviews, Biomarkers, Cancer, Prostate Cancer, UT Southwestern / 08.10.2016 Interview with: Dr Ryan Hutchinson MD and Yair Lotan MD Department of Urology University of Texas Southwestern Medical Center What is the background for this study? What are the main findings? Response: The United States Preventative Services Task Force recommendation against PSA screening generated significant controversy. Research since then has relied heavily on survey data to examine the impact of the recommendation on PSA screening practices. In a hotly charged issue such as this, such data can carry significant bias. We examined a large, whole-institution data in the years before and after the USPSTF recommendations reflecting actual practice and found that the changes in PSA use at our institution, if any, were small. This is more consistent with behavior seen after the vast majority of practice recommendations. (more…)
Author Interviews, Journal Clinical Oncology, Prostate Cancer, Surgical Research, Urology / 30.09.2016 Interview with: Eric Jacobs, PHD Strategic Director, Pharmacoepidemiology American Cancer Society, Inc. 250 Williams St. Atlanta, GA 30303 What is the background for this study? What are the main findings? Response: Vasectomy is a common, inexpensive, and very effective method of long-term birth control. However, in 2014, an analysis from a large epidemiologic cohort study, the Health Professionals Follow-Up Study, found that vasectomy was associated with about 10% higher overall risk of prostate cancer and about 20% higher risk of fatal prostate cancer. Together with other researchers at the American Cancer Society, I analyzed the association between vasectomy and fatal prostate cancer among more than 363,000 men in the Cancer Prevention Study II (CPS-II) cohort, age 40 and older, who were followed for up to 30 years. This is the largest prospective analysis of vasectomy and fatal prostate cancer to date. We also examined vasectomy and prostate cancer in a subset of about 66,000 CPS-II study participants who were followed for new diagnoses of prostate cancer. We found no link between having had a vasectomy and risk of either developing or dying from prostate cancer. (more…)
Author Interviews, Biomarkers, Cancer Research, Prostate Cancer, Science / 27.09.2016 Interview with: Iryna Saranchova MD PhD candidate Michael Smith Laboratories Vancouver, BC What is the background for this study? • The immune system is efficient at identifying and halting the tumour emergence at early stages. However, when metastatic (sufficient to cause death) tumour appears, the immune system is no longer able to recognize the cancer cells and control their growth and spread. • Recent studies of solid cancers have shown considerable heterogeneity between different tumour types and several lines of evidence suggest that tumours are not only heterogeneous, but they constantly evolve during the disease progression and this often hampers the existing treatment methods. • It means that it is important to consider each patient’s mutational changes accumulated over time in antecedent primary, metastatic lesions and/or local recurrences. This approach will help to understand the mechanism of tumour development, create a background for specific treatment modality and prevent therapeutic failure with consequent systemic relapse of the disease • Therefore, in our project we were aiming to find possible immune markers of tumour transition from the primary stage to its metastatic form. For this purpose, we selected a special study model: two pairs of separate mouse tumour cell lines, where metastatic cells arose from the initial primary tumour. (more…)
Author Interviews, Endocrinology, Prostate, Prostate Cancer, Testosterone, Urology / 19.09.2016 Interview with: Dr. Jesse Ory Department of Urology, Faculty of Medicine Dalhousie University, Halifax Nova Scotia, Canada What is the background for this study? What are the main findings? Response: The use of Testosterone Therapy (TT) in men diagnosed with and treated for prostate cancer (CaP) has been highly controversial for several decades. Unfortunately, this controversy is largely founded on the results of a single patient in a study by Huggins and Hodges in the 1940s [1]. This wasn't challenged until recently, when Morgentaler reviewed the literature on the topic and found no scientific basis for the assumption that TT will act like fuel on the fire of prostate cancer [2]. He also proposed a mechanism, the "saturation hypothesis" that helps account for why TT may in fact be safe for men with prostate cancer. [3]. Over the past decade, retrospective evidence has been accumulating that supports the safety of Testosterone Therapy in hypogonadal men with CaP on Active Surveillance, or in those who have been definitively treated for prostate cancer.. (more…)
Author Interviews, NEJM, Prostate Cancer / 15.09.2016 Interview with: Professor Jenny Donovan  PhD OBE FMedSci NIHR-SI AcSS FFPHM Director, NIHR CLAHRC West (National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care West) at University Hospitals Bristol NHS Trust Bristol, UK What is the background for this study? What are the main findings? Response: PSA testing identifies many men with prostate cancer, but they do not all benefit from treatment. Surgery, radiation therapy and various programs of active monitoring/surveillance can be given as treatments for fit men with clinically localized prostate cancer. Previous studies have not compared the most commonly used treatments in terms of mortality, disease progression and patient-reported outcomes. In the ProtecT study, we used a comprehensive set of validated measures, completed by the men at baseline (before diagnosis), at six and 12 months and then annually for six years. The main finding is that each treatment has a particular pattern of side-effects and recovery which needs to be balanced against the findings from the paper reporting the clinical outcomes (Hamdy et al). (more…)
AACR, Author Interviews, Cancer Research, Prostate Cancer / 04.09.2016 Interview with:  

Ilaria Stura PhD

Università degli Studi di Torino Turin, Piedmont, Italy What is the background for this study? What are the main findings?

Response: Man has always tried to predict the future, especially to prevent catastrophes, diseases and death. In this case, we want to prevent the ‘personal catastrophe’, i.e. the spread of the disease (recurrence of prostate cancer) in the patient. Our work therefore belongs to the so-called ‘personalized medicine’, a very important and innovative clinical approach.

In particular this study may potentially improve the quality of life of the patients and help the clinicians, since it could give valuable information to the urologist, for example reporting that the growth velocity of the tumor is increasing and that a relapse is expected within few months. With this information, the clinician could chose the best therapy for the patient (e.g. hormone or radio therapy) in order to stop the spread of the disease or, conversely, the use of drugs can be delayed if not necessary. Obviously clinicians already try to do this, based on their experience, but our method provides further confidence in their 'investigation' work, since the algorithm is validated on data coming from a database much larger than his/her personal experience. (more…)
Author Interviews, Prostate, Prostate Cancer, Urology / 01.09.2016 Interview with: Jim C. Hu, MD Ronald Lynch Professor of Urologic Oncology Weill Cornell Medicine New York, NY 10065 What is the background for this study? Response: Initial results from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO), a large-scale randomized controlled trial of prostate cancer screening in the United States, radically changed the landscape of prostate cancer screening insofar as it led the United States Preventative Services Task Force (USPSTF) to recommend against routine screening with prostate-specific antigen (PSA). Though many subsequent studies have continued to investigate the role of PSA in screening, there is a paucity of data examining the use of digital rectal examination (DRE) for screening in the PSA era. Indeed, the USPSTF recommendation did not explicitly address DRE, calling for further research to evaluate the role of periodic DRE in prostate cancer screening. Likewise, while recent guidelines from the National Comprehensive Cancer Network (NCCN) recommend use of PSA in all men who elect screening, the role of digital rectal examination is equivocal. We sought to evaluate the value of  digital rectal examination and PSA for detection of clinically significant prostate cancer and prostate cancer-specific (PCSM) and overall mortality in a secondary analysis of the PLCO. (more…)
Author Interviews, Chemotherapy, Prostate Cancer / 30.08.2016 Interview with: Prof. Ronald de Wit, MD, PhD Medical Oncologist Medical Oncology Erasmus MC University Medical Center, Rotterdam What is the background for this study? What are the main findings? Response: Mainsail is one of the largest phase 3 trials in the setting of  Metastatic Castration-Resistant Prostate Cancer (mCRPC)  in the past decade that investigated the addition of a second active biological drug to standard docetaxel every 3 weeks plus prednisone. In Mainsail the greater myelotoxicity caused by the addition of lenalidomide to docetaxel resulted in a reduction of the number of cycles of docetaxel that patients were able to tolerate – median of 6 cycles in the DPL arm vs. 8 in the DP arm. Median overall survival (OS) was shorter in patients receiving lenalidomide, which could have attributed to either a direct adverse effect of lenalidomide on OS, or, alternatively because of the reduction in the number of docetaxel treatment cycles. In this study we investigated the impact of the cumulative dose of docetaxel as reflected by the total number of cycles of docetaxel on median OS, in Univariate and Multivariate analyses on the ITT Population, both dependent upon the treatment arm, as well as irrespective of the treatment arm. In subsequent sensitivity analyses we addressed potential confounding factors on the eventual survival outcome. (more…)
Author Interviews, JAMA, Prostate Cancer / 18.08.2016 Interview with: Dr. Ahmedin Jemal, DVM, PhD Vice President, Surveillance and Health Services Research American Cancer Society What is the background for this study? What are the main findings? Response: We previously showed large decrease in early stage prostate cancer incidence rates from 2011 to 2012 in men 50 years and older following the US Preventive services Task Force recommendation against routine prostate-specific antigen testing in 2011. In this paper, we examined whether the decrease in early stage incidence persisted through 2013. We found that early stage prostate cancer incidence rates in men age 50 and older decreased from 2012 to 2013, although the decrease (6%) was lower compared to the decrease from 2011-2012 (19%). In contrast, rates for distant stage disease between 2012 and 2013 remained unchanged. (more…)
Author Interviews, Prostate Cancer, Urology / 17.08.2016 Interview with: Jennifer Cullen Meyer, PhD, MPH Director of Epidemiologic Research, Center for Prostate Disease Research Assistant Professor, Norman M. Rich Dept. of Surgery, Uniformed Services University Rockville, MD 20852 What is the background for this study? Response: Men diagnosed with prostate cancer who are at low risk for cancer progression may choose to defer immediate treatment with curative intent and, instead, monitor their cancer. This strategy is referred to as “active surveillance.” The primary benefit of active surveillance is that it allows men to temporarily defer definitive cancer treatments that are known to cause decrements in health-related quality of life (HRQoL). Studies have shown that HRQoL is better in men choosing active surveillance as compared to other treatment modalities. However, prior to our study, it was not known whether men on active surveillance experience worse HRQoL than men without prostate cancer. (more…)
Author Interviews, Erectile Dysfunction, Prostate Cancer, Urology / 05.08.2016 Interview with: Juzar Jamnagerwalla, MD Division of Urology, Department of Surgery Cedars-Sinai Medical Center Los Angeles, California What is the background for this study? What are the main findings? Response: In mouse models phosphodiesterase type-5 inhibitors (PDE-5i) have been shown to have anti-neoplastic activity, and given the routine use of PDE-5i for treatment of erectile dysfunction after prostatectomy several studies have examined the association between PDE-5i use and biochemical recurrence after treatment for prostate cancer with mixed findings. Only one previous study has explored the association between risk of prostate cancer, finding that men on PDE-5i had a lower chance of being diagnosed with prostate cancer. Given this, we tested the relationship between PDE-5i use and risk of prostate cancer in 6,501 men in the REDUCE study finding that PDE-5i use was not associated with prostate cancer diagnosis. On secondary analysis, among North American men who had a much higher baseline use of PDE-5i use, there was an inverse association between PDE-5i use and prostate cancer diagnosis, which approached, but did not reach statistical significance. (more…)
Author Interviews, Genetic Research, Prostate Cancer, Race/Ethnic Diversity, Vitamin D / 02.08.2016 Interview with: Gerard (Gary) Hardiman, Ph.D Professor, Department of Medicine Professor Department of Public Health Sciences Bioinformatics Director Center for Genomic Medicine Medical University of South Carolina Charleston, SC 29425 What is the background for this study? What are the main findings? Response: There are significant racial disparities in prostate cancer outcomes. The disease disproportionately affects African American men in terms of incidence, morbidity, and mortality, even after adjustment for stage. African American men have a 2- to 3-times increased risk of developing prostate cancer and have a greater mortality rate compared to European American men. We carried out a prospective clinical study aimed at examining the effects of vitamin D3 supplementation at 4,000 IU per day for two months in male subjects who selected surgical removal of the prostate (prostatectomy) as a definitive treatment for their prostate cancer. The primary goal of this study was to examine molecular differences in gene expression patterns relevant to prostate cancer disparities between African American and European American men, and investigate the global effects of vitamin D3 supplementation on the prostate transcriptome. We carried out genome wide expression profiling experiments using high throughput (HT) RNA sequencing. Transcriptional profiles of each of the patient’s tissue samples were generated and systems level analyses were performed. (more…)
Author Interviews, Outcomes & Safety, Prostate Cancer, Surgical Research / 27.07.2016 Interview with: Prof Robert A Gardiner AM The University of Queensland Centre for Clinical Research Royal Brisbane & Women’s Hospital, Herston Brisbane,Australia What is the background for this study? What are the main findings? Response: We wanted to determine whether one approach gave better results than the other at 12 weeks and 24 months after surgery with respect to the quality of life outcomes of urinary, sexual and bowel function and return to usual activities as well as oncological outcomes. There was no significant statistical difference between the robotic and open surgical approach for these parameters at the early time-point of 12 weeks follow-up. (more…)
Author Interviews, Biomarkers, Prostate Cancer / 20.07.2016 Interview with: Dr. Adam Weiner MD Urology Resident Feinberg School of Medicine Northwestern University What is the background for this study?  Response: There has been a lot of controversy over the past decade regarding whether PSA screening for prostate cancer prevents death from prostate cancer. Accordingly, the US preventive services task force (USPSTF) recommended against PSA screening for older men in 2008 and for all men in 2012. This was mainly based on information from a large clinical trial in the US. Recently it was discovered that men in the non-screening part of this trial received even more PSA screens than men in the screening part of the trial, suggesting the results were likely diluted. In a large European trial, PSA screening was shown to reduce both death from prostate cancer and the number of men diagnosed with metastatic prostate cancer, an incurable and deadly form of prostate cancer. (more…)
Author Interviews, Immunotherapy, Prostate Cancer / 16.07.2016 Interview with: Julie Graff, M.D. Oncologist specializing in prostate cancer Knight Cancer Institute Oregon Health & Science University What is the background for this study? What are the main findings? Response: Men with metastatic prostate cancer that is not responding to second-line androgen receptor blockade (such as enzalutamide) have a very limited life expectancy. We found that adding immunotherapy to enzalutamide in men whose prostate cancer is no longer responding to enzalutamide could exert a very strong anti-cancer effect. Previous experience with this type of immunotherapy in prostate cancer patients suggested this type immunotherapy does not work in patients with prostate cancer. What we have found will lead to more studies of this agent. (more…)
Author Interviews, Biomarkers, Cancer Research, Prostate Cancer / 28.06.2016 Interview with: Thomas Kislinger, PhD Senior Scientist at the Princess Margaret Cancer Centre University Health Network Associate Professor Department of Medical Biophysics University of Toronto What is the background for this study? Response: The goal of this study was to develop a non-invasive, prognostic biomarker that can address the worldwide clinical dilemma of over-treating low-risk prostate cancers. To accomplish this we developed highly accurate proteomics assays in urines collected after a digital rectal examination (termed post-DRE urines). (more…)
Author Interviews, BMJ, Brigham & Women's - Harvard, Nutrition, Prostate Cancer / 22.06.2016 Interview with: Dr. Ying Bao Sc.D., M.D Assistant Professor of Medicine Channing Division of Network Medicine Department of Medicine Brigham and Women's Hospital Harvard Medical School, Boston, MA What is the background for this study? What are the main findings? Response: Nuts are rich in bioactive macronutrients, micronutrients, tocopherols and phytochemicals. Current epidemiological evidence has consistently linked increased nut consumption to reduced risk of several chronic conditions including cardiovascular diseases, type 2 diabetes, and inflammation. In contrast, evidence on nut consumption and cancer risk has been insufficient and equivocal. Prostate cancer is the leading cancer among U.S. men, with approximately 220,800 new cases diagnosed in 2015. However, very few studies have investigated the association between nut intake and prostate cancer. Thus, in the current study, we followed 47,299 US men from 1986-2012, and examined (1) whether consuming more nuts prevents getting prostate cancer, and (2) whether consuming more nuts reduces death rates among non-metastatic prostate cancer patients. During 26 years of follow-up, 6,810 men were diagnosed with prostate cancer, and 4,346 of these patients were without metastasis at diagnosis. We found no association between nut intake and being diagnosed with prostate cancer. However, among non-metastatic prostate cancer patients, those who consumed nuts 5 or more times per week after diagnosis had a significant 34% lower rate of overall mortality than those who consumed nuts less than once per month. (more…)
Author Interviews, Prostate, Prostate Cancer, Urology / 04.06.2016 Interview with: Kenneth A. Iczkowski, M.D. Department of Pathology Medical College of Wisconsin Milwaukee, WI 53226 What is the background for this study? Dr. Iczkowski: The International Society of Urological Pathology (ISUP) in 2014 proposed use of a new 5-tier grade grouping system to supplement traditional Gleason grading to facilitate prognosis stratification and treatment1. The 5 categories subsume: Gleason 3+3=6, Gleason 3+4=7, Gleason 4+3=7, Gleason 8, and Gleason 9-10. We desired to determine whether men with a highest Gleason score of 3+5=8 or 5+3=8 in their set of prostate biopsy specimens, would have differing outcomes from those with Gleason 4+4=8. Because Gleason 5 cancer has been demonstrated to have a higher biologic potential than Gleason 4, it was expected that Gleason score 8 pattern with any Gleason 5 pattern would have a worse outcome. (more…)
Author Interviews, Prostate Cancer, Weight Research / 01.06.2016 Interview with: Aurora Perez-Cornago, PhD Cancer Epidemiology Unit Nuffield Department of Population Health University of Oxford What is the background for this study? What are the main findings? Response: Excessive body size and adiposity have been proposed to influence several metabolic and hormonal mechanisms that can promote cancer development. We found that men who have greater adiposity have an elevated risk of high grade prostate cancer, an aggressive form of the disease, and prostate cancer death. (more…)
Author Interviews, Prostate, Prostate Cancer, Testosterone, Urology / 14.05.2016 Interview with: Ryan Flannigan MD FRCSC PGY 5 Urology Resident Department of Urological Sciences University of British Columbia What is the background for this study? Dr. Flannigan: In the aging population the incidence of both prostate cancer and testosterone deficiency (TD) increase and even overlap in many patients. However, since Huggins’ original research in 1940, we have understood that prostate cancer is largely regulated by the androgen receptor (AR). Thus, the thought of treating someone with exogenous testosterone (T) was concerning for fear of further activation of the androgen receptor, and therefore promoting prostate cancer growth. However, further research has continued to add clarity to this complex interaction between androgens and the prostate. The saturation theory describes the observation that prostate specific antigen (PSA) responds to increasing serum testosterone levels only to a value of approximately 8.7nmol/L, with no inflation of PSA beyond these T levels. This is likely not the whole story when it comes to the interaction of T and the prostate, but it does suggest the prostate may not experience changes in cellular function with serum testosterone beyond low levels. It is also understood that prostate cancer requires AR activation to grow but is not caused by AR activation. Thus, we hypothesized that among those with un-treated prostate cancer, ie. patients on active surveillance, would not experience changes in biochemical recurrence (BCR) or changes in disease progression. In addition, we hypothesized that patients with previously treated prostate cancer would not have viable prostate cancer cells and thus, PSA would not increase. (more…)
Author Interviews, Biomarkers, Prostate Cancer, Urology / 12.05.2016 Interview with: Jonathan Shoag MD Urology Resident at Cornell Department of Urology and Dr. Jim C. Hu MD Ronald Lynch Professor of Urologic Oncology Professor of Urology Director, Lefrak Center for Robotic Surgery Attending Urologist, New York-Presbyterian Hospital (Cornell campus) What is the background for this study? Response: Prostate Specific Antigen (PSA) is a blood test that is used to detect prostate cancers and to follow a cancer’s response to treatment. PSA was widely implemented as a screening tool for prostate cancer in the early 1990s, and became a routine test during an annual physical for men over 40. Doctors started using it because values above a “normal” threshold were associated with a greater risk of prostate cancer. Following the adoption of PSA screening in the early 1990s, there has been a large increase in the number of men diagnosed with cancer, and a decrease of approximately 50% in the rate of prostate cancer death. The PLCO trial was a large randomized trial designed and funded by the National Cancer Institute (NCI) to determine the effect of PSA screening on death from prostate cancer. The trial found that men randomized/assigned to prostate cancer screening had the same number of prostate cancer deaths as men in the control group of the trial, arguing that PSA screening does not decrease prostate cancer mortality. This was a major piece of evidence used by the United States Preventative Services Task Force (USPSTF) to form its 2012 recommendation against PSA screening. The argument was that in spite of the other evidence showing a benefit to PSA testing, including US epidemiologic trends, and another large randomized trial showing PSA screening was effective (the ERSPC), we now had good evidence showing no benefit to PSA testing in the US. Since 2012 we have seen dramatic declines in prostate cancer screening in the US as a result. (more…)
Author Interviews, Biomarkers, Prostate Cancer / 11.05.2016 Interview with: Dr. Michael K. Brawer, MD Northwest Prostate Institute Northwest Hospital Seattle, Washington What is the background for this study? What are the main findings? Dr. Brawer: Prolaris (Cell Cycle Progression Test) is a prostate-cancer prognostic genetic tests that determines how aggressive is a patient’s cancer.  The goal is to reduce the over treatment of tumors that are likely to be harmless while still spotting those that are lethal.  Our key study at AUA (American Urological Society) is a meta-analysis of 440 prostate cancer patients with a Gleason score less than or equal to 6 who were tested with Prolaris. (more…)
AACR, Author Interviews, Cancer Research, Exercise - Fitness, Prostate Cancer / 21.04.2016 Interview with: Ying Wang, PHD | Senior Epidemiologist American Cancer Society, Inc. 250 Williams St. Atlanta, GA 30303 What is the background for this study? Dr. Wang: Although evidence is still limited, previous studies suggest that vigorous activity and brisk walking after prostate cancer diagnosis might be associated with lower risk of prostate cancer progression and disease-specific mortality. We still don’t know if physical activity before diagnosis is associated with the risk or not. This is also important because reverse causation is a concern in the analysis of post-diagnosis physical activity, especially for vigorous activity, that men with advanced diseases may reduce their activity level. In contrast, pre-diagnosis physical activity is less subject to reverse causation and may represent a long-term behavior. When walking, the most common type of physical activity, was examined separately in previous studies, it was not evaluated in the absence of other activities. No study has examined sitting time in relation to mortality among prostate cancer survivors, although previous study suggests longer sitting time is associated with higher risk of all-cause mortality in healthy populations. So in our study, we aimed to examine physical activity, walking only, and sitting time both before and after diagnosis in relation to prostate cancer-specific mortality. (more…)
AACR, Author Interviews, Cancer Research, Nutrition, Prostate Cancer / 21.04.2016 Interview with: Emma Helen Allott, PhD University of North Carolina at Chapel Hill Chapel Hill, NC What is the background for this study? Dr. Allott: Prostate cancer incidence rates vary more than 25-fold worldwide, and are highest in Western countries. This large international variation is due in part to differences in screening practices between countries, but dietary factors may also play a role. Unlike other macronutrients, dietary fat intake varies more than fivefold worldwide, and individuals in Western countries are among the highest consumers of saturated fat. High dietary saturated fat content contributes to raised blood cholesterol levels, and evidence from population-based studies supports an adverse role for serum cholesterol and a protective role for cholesterol-lowering statins in prostate cancer. Our hypothesis in this study was that high saturated fat intake would drive prostate tumor aggressiveness via raising serum cholesterol levels. What are the main findings? Dr. Allott: Using the North Carolina-Louisiana Prostate Cancer Project, a study of 1,854 men with newly-diagnosed prostate cancer, we show that high dietary saturated fat content is associated with increased tumor aggressiveness. We found a slightly weaker effect of saturated fat on prostate cancer aggressiveness in men using statins to control serum cholesterol levels, suggesting that that statins may counteract, but do not completely negate, the effects of high saturated fat intake on prostate cancer aggressiveness. We also found an inverse association between high dietary intake of polyunsaturated fatty acids (PUFAs) and prostate cancer aggressiveness. (more…)
AACR, Author Interviews, Cancer Research, Inflammation, Prostate Cancer, Weight Research / 20.04.2016 Interview with: Charnita Zeigler-Johnson, Ph.D., M.P.H. Assistant Professor Division of Population Sciences Department of Medical Oncology Thomas Jefferson University Philadelphia, PA 19107 Medical Research: What is the background for this study? Dr. Zeigler-Johnson: Obesity has been associated with poor prostate cancer outcomes, included advanced disease at diagnosis, increased risk for cancer recurrence, and risk for mortality. One possible link in the relationship between obesity and prostate cancer progression is inflammation. Obesity produces a state of systemic chronic low-grade inflammation which may contribute to the underlying biology of the tumor microenvironment. The presence of immune cells (T-cells and macrophages) in the tumor microenvironment may indicate aggressive tumors that are likely to metastasize. The goal of this study was to examine prostate cancer tissue to characterize differences in immune cells within the tumor microenvironment by obesity status and cancer severity. We studied tumor samples from 63 non-obese and 36 obese prostate cancer patients. Medical Research: What are the main findings? Dr. Zeigler-Johnson: We found that T-cell and macrophage counts in the tumor did not differ by patient obesity status. However, macrophage (CD68) counts were higher among men diagnosed with higher tumor grade (Gleason Score 7-10). We also found that T-cell (CD8) counts were associated with quicker time to prostate cancer recurrence (indicated by detectable prostate specific antigen levels after treatment.) (more…)
Author Interviews, Cost of Health Care, JAMA, Prostate Cancer / 30.03.2016 Interview with: HICOR portraits, Nov. 4, 2014 Joshua A. Roth, PhD, MHA Assistant Member AHRQ Patient-Centered Outcomes Research K12 Scholar Hutchinson Institute for Cancer Outcomes ResearchJoshua A. Roth, PhD, MHA Assistant Member AHRQ Patient-Centered Outcomes Research K12 Scholar Hutchinson Institute for Cancer Outcomes Research What is the background for this study? What are the main findings? Dr. Roth: PSA prostate cancer screening is controversial because of uncertainty about the overall benefit-risk balance of screening and conflicting recommendations from a variety of prominent national panels. For example, there is debate about whether the cancer early-detection benefits of screening outweigh potential harms related to overdiagnosis of prostate cancer and associated overtreatment (for example, surgery and/or radiation therapy). However, this benefit-risk balance largely depends on how screening programs are structured (for example, the age range over which screening occurs, how often screened occurs, and the PSA level that triggers biopsies) and how screening detected prostate cancers are managed. With these factors in mind, we developed a simulation model to estimate the morbidity, mortality, and cost outcomes of many PSA screening approaches that have been proposed by national panels or discussed in the peer-reviewed literature. The model calculates these outcomes using inputs from national databases and major PSA screening clinical trials. The primary outcome of our model was the cost per quality-adjusted life year gained—a measure that reflects the value of medical interventions through impacts on cost, survival, and health-related quality of life. We don’t have explicit rules for willingness to pay per quality-adjusted life year in the United States, but interventions that cost $100,000 to $150,000 per quality-adjusted life year are generally considered to be of at least low to moderate value (whereas, for example, an intervention that costs $400,000 per quality-adjusted life year would be generally considered to be of very poor value). Using the model, we found that more conservative PSA screening strategies (that is, those with less frequent screening and higher PSA level thresholds for biopsy referral) tended to be more cost-effective than less conservative strategies. Importantly, we found that no strategy was likely to be of high value under contemporary treatment patterns where many men with low-risk prostate cancer (that is, those with a Gleason score lower than 7 and clinical T2a stage cancer or lower) receive treatment with surgery or radiation therapy, but several strategies were likely to be of at least moderate value (cost per qualityadjusted life-year=$70 831-$136 332) with increased use of conservative management (that is, treating only after clinical progression) for low-risk, screen-detected cancers. (more…)
Author Interviews, Prostate Cancer, Surgical Research / 11.03.2016 Interview with: Naveen Pokala, MD Division of Urology University of Missouri Columbia, MO 65212 What is the background for this study? What are the main findings? Dr. Pokala: The main purpose of the study was to determine survival outcome following salvage prostatectomy in men that fail radiation therapy. Radiation and surgery are the main modalities utilized to treat localized prostate cancer. When patients fail radiation treatment, traditionally, only hormonal treatment was offered. With refinements in surgical techniques, a select few of these patients that have recurrence after radiation may benefit with salvage surgery. Salvage prostatectomy is a complex procedure because prior radiation makes this procedure tenuous, but this procedure is offered in most major tertiary medical centers. (more…)
Author Interviews, BMJ, Prostate, Prostate Cancer, Urology / 08.03.2016 Interview with: Robert Nam, MD, FRCSC Ajmera Family Chair in Urologic Oncology Professor of Surgery University of Toronto Head, Genitourinary Cancer Site Odette Cancer Centre Sunnybrook Health Sciences Centre Toronto, Ontario What is the background for this study? Response: Prostate cancer treatment is associated with a number of complications including erectile dysfunction and urinary incontinence. Two years ago, we published a paper examining other, previously undescribed complications. The most controversial finding was a significantly increased risk of secondary cancers among men treated with radiotherapy. We therefore wanted to assess this in a meta-analysis, examining all the research currently available on the topic. What are the main findings? Response: We found that, for patients with prostate cancer, radiotherapy treatment was associated with significantly increased rates of bladder cancer, colorectal cancer and rectal cancer. There wasn't an increased risk for other cancers such as lung and blood system cancer. However, the absolute rates of these cancers remained low (1-4% of patients). (more…)
Author Interviews, Biomarkers, Cleveland Clinic, Genetic Research, Personalized Medicine, Prostate, Prostate Cancer, Urology / 07.03.2016 Interview with: Eric A. Klein, MD Chairman, Glickman Urological and Kidney Institute Cleveland Clinic What is the background for this study? What are the main findings? Dr. Klein: Prostate cancer is an enigma. While this tumor is the second leading cause of cancer death among American men, most newly diagnosed disease detected by PSA screening is biologically indolent and does not require immediate therapy. Currently, the main clinical challenge in these men is to distinguish between those who can be managed by active surveillance from those who require curative intervention. Current clinical and pathological tools used for risk stratification are limited in accuracy for distinguishing between these scenarios. An abundance of research in the last decade has provided evidence that genomics can offer meaningful and clinically actionable biological information to help inform decision making, and current National Comprehensive Cancer Network (NCCN) guidelines on prostate cancer endorse the use of commercially available genomic tools for men considering active surveillance.[1] It has been previously shown that the 22-gene genomic classifier, Decipher, accurately predicts the likelihood of metastasis and prostate cancer specific mortality when measured on tissue from radical prostatectomy specimens.[2] In multiple validation studies, it performed with higher accuracy and discrimination compared to clinical risk factors alone. The current study[3] is the first to examine whether the use of Decipher might aid decision making when measured on biopsy tissue at the time of diagnosis. Men with available needle biopsy samples were identified from a study cohort that previously had Decipher performed on their matched radical prostatectomy tissue. In this cohort of mixed low, intermediate and high risk men, Biopsy Decipher predicted the risk of metastasis 10 years post RP with high accuracy, outperforming NCCN clinical risk categorization, biopsy Gleason score and pre-operative PSA. Furthermore, this study showed that Decipher reclassified 46% of patients into lower or higher risk classification compared to NCCN classification alone. The study also showed that Biopsy Decipher can identify men that are at high risk for adverse pathology as defined by the presence of primary Gleason pattern 4 or greater. (more…)
Author Interviews, Genetic Research, MD Anderson, Nature, Prostate Cancer / 01.03.2016 Interview with Dr. Dingxiao Zhang Ph.D Department of Epigenetics and Molecular Carcinogenesis University of Texas MD Anderson Cancer Center Smithville, TX 78957, USA What is the background for this study? What are the main findings? Dr. Zhang: Prostate cancer (PCa) is a heterogeneous malignancy harboring phenotypically and functionally diverse subpopulations of cancer cells. To better understand PCa cell heterogeneity, it is crucial to dissect the biology of normal prostate epithelial lineages. The background for the current study is to annotate the gene expression profiles of normal prostate epithelial cells, through which we hope to gain insight on Prostate cancer subtypes and the cellular heterogeneity in PCa. The prostate gland mainly contains basal and luminal cells constructed as a pseudostratified epithelium. Annotation of prostate epithelial transcriptomes provides a foundation for discoveries that can impact disease understanding and treatment. In this study, we have performed a genome-wide transcriptome analysis of human benign prostatic basal and luminal epithelial populations using deep RNA sequencing. One of our major findings is that the differential gene expression profiles in basal versus luminal prostate epithelial cells account for their distinct functional properties. Specifically, basal cells preferentially express gene categories associated with stem cells, MYC-transcriptional program, neurogenesis, and ribosomal RNA (rRNA) biogenesis regulated by Pol I. Consistent with this profile, basal cells functionally exhibit intrinsic stem-like and neurogenic properties with enhanced rRNA transcription activity. Of clinical relevance, the basal cell gene expression profile is enriched in advanced, anaplastic, castration-resistant, and metastatic prostate cancers. Therefore, we link the cell-type specific gene signatures to aggressive subtypes of prostate cancer and identify gene signatures associated with adverse clinical features. (more…)