Author Interviews, Prostate, Prostate Cancer, Testosterone, Urology / 14.05.2016

MedicalResearch.com Interview with: Ryan Flannigan MD FRCSC PGY 5 Urology Resident Department of Urological Sciences University of British Columbia MedicalResearch.com: 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

MedicalResearch.com 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) MedicalResearch.com: 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, MRI, Prostate Cancer, Urology / 11.05.2016

MedicalResearch.com Interview with: Dr. Vikas Gulani MD, PhD Director, MRI, University Hospitals Case Medical Center Associate Professor, Radiology CWRU School of Medicine Cleveland, OH  MedicalResearch.com: What is the background for this study? Dr. Gulani: For men that have a suspicion for prostate cancer either via the prostate specific antigen (PSA) test or a digital rectal exam, the current standard of care is to perform a transrectal ultrasound (TRUS) guided biopsy to detect cancer. The problem with TRUS biopsy is that most tumors are not visible on ultrasound and hence many significant cancers are missed. At the same time this strategy detects a high number of low risk, indolent cancers, and leads to overtreatment of disease that would be better left untreated. Diagnostic MRI and MRI-guided biopsy (cognitive, ultrasound-MR fusion, or in-gantry) have been shown to be effective in detecting clinically significant prostate cancer. However, despite these advantages there is reluctance to incorporate MRI into standard practice because it is perceived to be expensive. Our goal was to determine if this presumption is true, and evaluate the cost-effectiveness of the MRI-guided techniques most commonly used. MedicalResearch.com: What are the main findings? Dr. Gulani: We found that every MRI strategy we evaluated was cost-effective compared to standard biopsy. Cognitive MRI guided biopsy – where the operator performs an ultrasound biopsy based on knowledge of lesion location from the MRI – was the most cost-effective strategy compared to standard biopsy. In-gantry MRI yielded the highest net health benefits as measured in quality adjusted life years. (more…)
Author Interviews, Biomarkers, Prostate Cancer / 11.05.2016

MedicalResearch.com Interview with: Dr. Michael K. Brawer, MD Northwest Prostate Institute Northwest Hospital Seattle, Washington MedicalResearch.com: 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…)
Author Interviews, Biomarkers, Prostate Cancer / 02.05.2016

MedicalResearch.com Interview with: Stephen J. Freedland, MD Associate Director, Faculty Development Samuel Oschin Comprehensive Cancer Institute Co-Director, Cancer Genetics and Prevention Program Director, Center for Integrated Research in Cancer and Lifestyle Professor, Surgery Warschaw Robertson Law Families Chair in Prostate Cancer Cedars-Sinai, Los Angeles  MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Freedland:   PSA is a marker of prostate pathology.  While often used to screen for prostate cancer, it is not prostate specific and can be elevated due to inflammation or enlarged prostate or other reasons.  Whether it predicts the development of urinary symptoms is not clear.  Among men with minimal to no urinary symptoms, we found that the higher the PSA, the greater the risk of future development of urinary symptoms. MedicalResearch.com: What should clinicians and patients take away from your report? Dr. Freedland: The readers should know that if a man has an elevated PSA and a negative prostate biopsy, the higher the PSA, the greater the risk of future urinary symptoms.  These are men who may need closer follow-up. (more…)
Author Interviews, MRI, Prostate Cancer / 26.04.2016

MedicalResearch.com Interview with: Dr. Nelly Tan MD David Geffen School of Medicine Department of Radiology UCLA MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Tan: Standard of care for prostate cancer diagnosis has been to perform ultrasound guided random (non-targeted) prostate biopsy (TRUS) which is neither sensitive or specific. The main limitation had been our inability to detect and localize prostate cancer through imaging. Over the past 10 years, MRI has taken center stage for detection and localization of prostate cancer and has shown to improve prostate cancer diagnosis, risk stratification, and staging of the disease. Over the past few years, MRI guided biopsy techniques (in the form of Ultrasound-MRI (US-MRI) fusion and in-bore direct MRI guided biopsy) have been reported. We reported our performance of direct in-bore MRI guided biopsy at UCLA. Our study showed a prostate cancer diagnosis of 59% in all patients and 80% of patients with prostate cancer had clinically significant cancer. (more…)
AACR, Author Interviews, Cancer Research, Exercise - Fitness, Prostate Cancer / 21.04.2016

MedicalResearch.com Interview with: Ying Wang, PHD | Senior Epidemiologist American Cancer Society, Inc. 250 Williams St. Atlanta, GA 30303 MedicalResearch.com: 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

MedicalResearch.com Interview with: Emma Helen Allott, PhD University of North Carolina at Chapel Hill Chapel Hill, NC MedicalResearch.com: 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. MedicalResearch.com: 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

MedicalResearch.com 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

MedicalResearch.com 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 MedicalResearch.com: 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

MedicalResearch.com Interview with: Naveen Pokala, MD Division of Urology University of Missouri Columbia, MO 65212 MedicalResearch.com: 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

MedicalResearch.com 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 MedicalResearch.com: 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. MedicalResearch.com: 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

MedicalResearch.com Interview with: Eric A. Klein, MD Chairman, Glickman Urological and Kidney Institute Cleveland Clinic MedicalResearch.com: 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

MedicalResearch.com Interview with Dr. Dingxiao Zhang Ph.D Department of Epigenetics and Molecular Carcinogenesis University of Texas MD Anderson Cancer Center Smithville, TX 78957, USA MedicalResearch.com: 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…)
Author Interviews, Erectile Dysfunction, Prostate, Prostate Cancer, Surgical Research, Urology / 29.02.2016

Medicalresearch.com Interview with: Dr. Pedro Recabal, MD and Memorial Sloan Kettering Cancer Center Department of Surgery, Urology Service New York, NY Urology service, Fundacion Arturo Lopez Perez, Santiago, Chile Dr. Vincent P. Laudone, Memorial Sloan Kettering Cancer Center Department of Surgery Urology Service New York, NY Medicalresearch.com What is the background for this study? Response:  One of the most concerning adverse events that may arise following surgery for prostate cancer (radical prostatectomy) is postoperative erectile dysfunction. The loss of erectile function after surgery is most frequently caused by intraoperative injury to the neurovascular bundles, tiny packages of blood vessels and nerves that conduct the impulses responsible for erection. It is known that if both bundles are removed, patients seldom recover erectile function. Accordingly, neurovascular bundle preservation during Radical prostatectomy has proven benefits in terms of erectile function recovery. However, as these bundles are intimately associated with the posterolateral aspects of the prostate, they must be carefully separated from the surface of the prostate without cutting them, applying excessive traction, or using cautery, all of which could produce irreversible damage and the consequent loss of function. During this dissection, the surgeon risks cutting into the prostatic capsule , which could result in leaving tumor behind. In some cases, the tumor extends beyond the prostate into the neurovascular bundles, and an attempt to preserve these structures could also result in incomplete tumor removal, defeating the purpose of radical prostatectomy. Therefore, many urologists treating patients with “aggressive” tumors (such as the patients in our cohort) would try to avoid leaving cancer behind by removing not only the prostate but also the tissue around it, including the neurovascular bundles. In other words, if you had to chose between removing all the cancer but loosing erectile function, or preserving erectile function but risking an incomplete cancer removal, most patients and surgeons naturally lean towards the first option. Also, in many centers, patients with aggressive prostate cancers are managed with combined treatments (multimodal therapy), by adding hormonal therapy and/or radiotherapy, which could also result in erectile dysfunction. As such, many surgeons believe that there is no rationale for attempting to preserve the neurovascular bundles in these “high-risk” patients because most will end up with erectile dysfunction . However, with the advent of MRI (and integrating other clinical information such as location of the positive biopsies, and intraoperative cues), surgeons can now have a better idea of where the cancer is located, which may aid in surgical planning. For instance, if a tumor is located in the anterior prostate, removing the neurovascular bundles (located on the posterolateral aspects) would provide no oncologic benefit, regardless of the aggressiveness of the tumor. Similarly, if the tumor compromises only the left side, removing the right neurovascular bundle is unlikely to help the patient, but can instead result in harm. Moreover, neurovascular bundle preservation is not an all-or-none procedure; on each side, these bundles can be completely preserved (meaning dissecting exactly along the border between the prostate and the bundle); partially preserved (meaning preserving some of the nerves that are further away from the prostate, and removing the ones that are closer to the prostate); or completely removed along with the prostate (This has been graded in a scale from 1 to 4, where 1 represents complete preservation, and 4 represents complete removal of the neurovascular bundle, with 2 and 3 being partial preservation. This grade is recorded by the surgeon for each side, at the end of the procedure.) As such, sometimes it’s possible to preserve part of the bundle, even if there is a tumor on the same side We designed a retrospective study to look at how high volume surgeons at MSKCC performed radical prostatectomy in high risk patients (how frequently and to what extent where the neurovascular bundles preserved), and what were the outcomes in terms of positive surgical margins (a surrogate for “leaving tumor behind”); use of additional oncologic treatments such as hormone therapy or radiotherapy, and finally, erectile function recovery in patients with functional erections before the operation. The patients in our cohort had at least one NCCN-defined high risk criteria (Gleason score ≥ 8; PSA ≥ 20 ng/ml; Clinical stage ≥ T3). (more…)
Author Interviews, Biomarkers, JAMA, Prostate Cancer / 09.02.2016

MedicalResearch.com Interview with: Dr. Quoc-Dien Trinh MD Assistant Professor, Harvard Medical School Brigham and Williams Hospital  Medical Research:  Please briefly explain the potential benefits and harms of PSA testing, the rationale for screening all men, and the reason U.S. guidelines now recommend against routine screening.  Response: The goal of cancer screening is to detect the disease early, and consequently treat it before it becomes more aggressive and spread to other parts of the body (which ultimately leads to death). However, cancer screening may lead to overdiagnosis (detecting cancers that would not have been a problem for a while) and overtreatment. The latter is a problem for prostate cancer, because surgery and radiation therapy (the currently accepted first-line treatments for localized prostate cancer) have significant long-term adverse effects on sexual and urinary function. I wouldn't say that 'US' guidelines are against screening. Many professional societies continue to recommend some form of joint decision-making with regard to PSA screening. the USPSTF recommends against screening for all - they argue that the harms mentioned above outweigh the benefits. (more…)
Author Interviews, Breast Cancer, Cancer Research, JAMA, Prostate Cancer / 23.01.2016

More on Cancer Research on MedicalResearch.com MedicalResearch.com Interview with: Firas Abdollah, M.D., F.E.B.U. (Fellow of European Board of Urology) Urology Fellow with the Center for Outcomes Research, Analytics and Evaluation Vattikuti Urology Institute at Henry Ford Hospital in Detroit  MedicalResearch: What is the background for this study? What are the main findings? Dr. Abdollah: Cancer screening aims to detect tumors early, before they become symptomatic. Evidence suggests that detection and treatment of early-stage tumors may reduce cancer mortality among screened individuals. Despite this potential benefit, screening programs may also cause harm. Notably, screening may identify low-risk indolent tumors that would never become clinically evident in the absence of screening (overdiagnosis), subjecting patients to the harms of unnecessary treatment. Such considerations are central to screening for prostate and breast cancers, the most prevalent solid tumors in men and women, respectively. These tumors are often slow growing, and guidelines recommend against screening (non-recommended screening) for these tumors in individuals with limited life expectancy, i.e. those with a life expectancy less than 10 years. Unfortunately, our study found that this practice is not uncommon in the US. Using a nationwide representative survey conducted in 2012, we found that among 149,514 individuals 65 years or older, 76,419 (51.1%) received any prostate/breast screening. Among these, 23,532 (30.8%) individuals had a life expectancy of less than 10 years. These numbers imply that among the screened population over 65 years old, almost one in three individuals received a non-recommended screening. This corresponds to an overall rate of non-recommended screening of 15.7% (23,532 of 149,514 individuals). Another important finding of our study was that there were important variations in the rate of non-recommended screening from state to state; i.e. the chance of an individual older than 65 to receive a non-recommended screening varies based on his/her geographical location in United States. Finally, on a state-by-state level, there was a correlation (40%) between non-recommended screening for prostate and breast cancer, i.e. states that are more likely to offer non-recommended screening for prostate cancer are also more likely to offer non-recommended screening for breast cancer, and vice versa. (more…)
Author Interviews, Biomarkers, Mayo Clinic, Prostate, Prostate Cancer, Urology / 12.01.2016

MedicalResearch.com Interview with: R. Jeffrey Karnes MD Department of Urology, Mayo Clinic, Rochester, MN 55905   MedicalResearch: What is the background for this study? What are the main findings? Dr. Karnes: Cancer recurrence following radical prostatectomy is a concern for men undergoing definitive surgical treatment for prostate cancer. Approximately 20-35% of patients develop a rising prostate specific antigen following radical prostatectomy for clinically localized prostate cancer. PSA monitoring is an important tool for cancer surveillance; however, a standard PSA cutpoint to indicate biochemical recurrence has yet to be established. Over 60 different definitions have been described in literature. This variation creates confusion for the patients and clinicians. By studying a large group of patients who underwent radical prostatectomy at Mayo Clinic, we found that a PSA cutpoint of 0.4 ng/mL is the optimal definition for biochemical recurrence. (more…)
Author Interviews, Prostate Cancer, Race/Ethnic Diversity / 04.01.2016

MedicalResearch.com Interview with: Benjamin A. Rybicki, Ph.D Department of Public Health Sciences Henry Ford Health System Detroit, MI  Medical Research: What is the background for this study? What are the main findings? Dr. Rybicki: Inflammation of the prostate gland—prostatitis—is a complex and heterogeneous condition. Two separate meta-analyses have estimated about a 60% increased risk of prostate cancer associated with clinical prostatitis.  Most prostatitis, however, is asymptomatic and not fully captured in prevalence surveys. In fact, over 50% of surgical prostate specimens demonstrate some histological evidence of chronic inflammation, which has been generally shown to decrease risk of prostate cancer. The race of a patient may also be a factor as far as how inflammation influences prostate cancer risk. African American men are at greater risk for prostate cancer and demonstrate higher levels of circulating prostate specific antigen (PSA), which can confound the relationship between inflammation and prostate cancer. In adjusted analyses, African American men with clinical chronic prostatitis had a significant 53% decreased risk of prostate cancer compared with African American men without prostatitis. Clinical prostatitis did not significantly increase prostate cancer risk in white men overall, but it was associated with a significant 3.5-fold increased risk in those who had no evidence of histologic prostatic inflammation. In addition, the investigators found that clinical prostatitis increased prostate cancer risk nearly 3-fold in white men with a low PSA velocity and nearly 2-fold in white men with more frequent PSA testing. PSA level and PSA density did not significantly modify the effect of clinical prostatitis on prostate cancer risk. (more…)
Author Interviews, Brigham & Women's - Harvard, JAMA, Prostate Cancer, Surgical Research, Testosterone / 04.01.2016

MedicalResearch.com Interview with: Quoc-Dien Trinh MD Assistant Professor, Harvard Medical School Brigham and Williams Hospital  Medical Research: What is the background for this study? What are the main findings? Dr. Trinh: Among elderly Medicare beneficiaries with metastatic prostate cancer, surgical castration is associated with lower risks of any fractures, peripheral arterial disease, and cardiac-related complications compared to medical castration using GnRH agonists. (more…)
Author Interviews, Cancer Research, Prostate Cancer, Surgical Research, Transplantation / 23.12.2015

MedicalResearch.com Interview with: Gerardo Vitiello, MD Emory University School of Medicine Emory Transplant Center NYU Langone Medical Center Department of Surgery  Medical Research: What is the background for this study? What are the main findings? Dr. Vitiello:   Screening for prostate cancer with prostate specific antigen (PSA) levels is highly controversial, as it is a non-specific marker for prostate cancer. A PSA level may be elevated in a variety of disease processes (not only prostate cancer), and even in the general population, the benefit of early intervention for prostate cancer is unclear. In contrast, end stage renal disease (ESRD), where patients no longer have renal function and require dialysis, is a major health problem with a huge impact on a patient’s quality of life. The only cure for ESRD is kidney transplantation, which has been shown to have an enormous health and quality of life benefit for transplant recipients. Transplant centers have rigorously screened candidates for potential malignancy prior to transplantation to ensure that there are no contraindications to receiving a transplant. For the first time, we demonstrate that screening for prostate cancer in kidney transplant candidates is not beneficial, and may actually be harmful, since it delays time to transplant and reduces a patient’s chance of receiving a transplant without an apparent benefit on patient survival. (more…)
Alzheimer's - Dementia, Author Interviews, Journal Clinical Oncology, Prostate Cancer, Testosterone, University of Pennsylvania / 10.12.2015

MedicalResearch.com Interview with: Kevin T. Nead, MD, MPhil Dept. of Radiation Oncology Perelman School of Medicine University of Pennsylvania MedicalResearch: What is the background for this study? What are the main findings? Dr. Nead: There are a growing number of studies suggesting that the use of  Androgen Deprivation Therapy (ADT)  may be associated with cognitive changes and some of these changes overlap with characteristic features of Alzheimer’s disease. In addition, low testosterone levels have been associated with Alzheimer’s disease risk and ADT lowers testosterone levels. Despite these findings, we could not identify any studies examining the association between ADT and Alzheimer’s disease risk. We therefore felt this study could make an important contribution in guiding future research to fully understand the relative risks and benefits of ADT. We examined electronic medical record data from Stanford University and Mt. Sinai hospitals to identify a cohort of 16,888 patients with prostate cancer. We found that men with prostate cancer who received Androgen Deprivation Therapy were more likely to develop Alzheimer’s disease than men who did not receive  Androgen Deprivation Therapy. We also found that this risk increased with a longer duration of ADT. These results were consistent using multiple statistical approaches and separately at both Stanford and Mr. Sinai. (more…)
Author Interviews, JAMA, Prostate Cancer, Radiation Therapy / 30.11.2015

MedicalResearch.com Interview with: Prof Nicholas James STAMPEDE Trial Chief Investigator Director of the Cancer Research Centre Warwick Medical School University of Warwick Coventry and Professor of Clinical Oncology Cancer Centre, Queen Elizabeth Hospital Birmingham Medical Research: What is the background for this study? What are the main findings? Dr. James: The STAMPEDE trial is a multi-arm, multi-stage trials platform testing a range of different therapies in addition to standard of care (SOC) for men commencing long term androgen deprivation therapy (ADT) for newly diagnosed locally advanced or metastatic prostate cancer. These data from the control arm form part of a pair of publications detailing outcomes in the control arm of STAMPEDE and help to make sense of the forthcoming paper on the randomised comparisons currently in press at the Lancet. (more…)
Author Interviews, Prostate, Prostate Cancer, Urology / 26.11.2015

MedicalResearch.com Interview with: Isaac Yi Kim, MD, PhD Acting Chief and Associate Professor, Division of Urology Rutgers Robert Wood Johnson Medical School Chief, Section of Urologic Oncology and Young Suk "Joseph" Kwon, MD Post-doctoral fellow  Section of Urologic Oncology Rutgers Cancer Institute of New Jersey Rutgers, The State University of New Jersey New Brunswick, NJ 08903 Medical Research: What is the background for this study? Response: Although PSA < 10 ng/mL is a typically required condition under which many active surveillance (AS) protocols operate, this current guideline may predispose lower risk patients with incongruently elevated PSA to aggressive and potentially unnecessary therapies. Specifically, urologists infrequently encounter patients with PSA > 10 ng/ml but biopsy demonstrating a relatively lower risk prostate cancer (PCa). Therefore, we wanted to test whether active surveillance may be a viable option in some men with a histologically favorable risk prostate cancer and serum PSA between 10 and 20 ng/ml. Medical Research: What are the main findings? Response: We compared oncologic outcomes in men with favorable biopsy histology and varying PSA levels: low, intermediate, and high PSA levels. The rates of upstaging and upgrading were similar between the intermediate PSA (IP) (≥10 and 20) and low PSA (LP) (<10) group. In contrast, the high PSA  (HP) (≥20) group had higher incidences of both upstaging (p=0.02) and upgrading to ≥4+3 (p=0.046) compared to the IP group. BCR-free survival rates revealed no pair-wise inter-group differences, except between low PSA and high PSA . (more…)
Author Interviews, Prostate Cancer, Radiation Therapy / 26.10.2015

MedicalResearch.com Interview with: Luca Incrocci, MD, PhD Department of Radiation Oncology Erasmus MC-Daniel den Hoed Cancer Rotterdam, The Netherlands  Medical Research: What is the background for this study? What are the main findings? Dr.Incrocci: The trial was designed in 2005-2006. The rationale was to reduce the number of fractions and therefore increase patient's comfort. At that moment some preliminary data was available on the sensitivity of prostate cancer cells to a higher does per fraction. Our calculations brought us to choose this new fractionation schedule. The hypofractionation arm (19x3.4 Gy/3 times per week) has shown equivalence in outcome compared to the conventional treatment (39x2 Gy/5 times per week) at a follow-up of 5 yrs. Toxicity is comparable, with a slight increase in bowel complaints at 5yrs. Patients will be followed-up to 10yrs. (more…)
Author Interviews, Brigham & Women's - Harvard, JAMA, Prostate Cancer, Race/Ethnic Diversity, Surgical Research / 23.10.2015

MedicalResearch.com Interview with: Dr. Quoc-Dien Trinh MD Assistant Professor of Surgery Harvard Medical School  Brigham and Women's Hospital Boston, MA 02115 Medical Research: What is the background for this study? What are the main findings? Dr. Trinh:  Blacks who undergo radical prostatectomy, e.g. surgical removal of the prostate for cancer, are more likely to experience complications, emergency room visits, readmissions compared to their non-hispanic White counterparts. As a result, the 1-year costs of care for Blacks is significantly higher than non-hispanic Whites. Interestingly, despite these quality of care concerns, the survival of elderly Blacks and Whites undergoing prostatectomy is the same. Medical Research: What should clinicians and patients take away from your report? Dr. Trinh: A possible interpretation of our findings is that the biological differences in tumor aggressiveness among Blacks  (e.g. Blacks have more aggressive prostate cancer than Whites) may have been exaggerated, and that the perceived gap in survival is a result of lack of access or cultural perceptions with regard to surgical care for prostate cancer or other factors that differentiate who makes it to the operating table. (more…)
Author Interviews, Brigham & Women's - Harvard, Heart Disease, JAMA, Prostate Cancer, Testosterone / 27.09.2015

Anthony V. D'Amico, MD, PhD Chief, Division of Genitourinary Radiation Oncology Professor of Radiation Oncology, Harvard Medical SchoolMedicalResearch.com Interview with: Anthony V. D'Amico, MD, PhD Chief, Division of Genitourinary Radiation Oncology Professor of Radiation Oncology, Harvard Medical School Medical Research: What is the background for this study? What are the main findings? Dr. D'Amico: Controversy exists as to whether androgen deprivation therapy (ADT) used to treat prostate cancer can cause fatal cardiac events. We found that in men with moderate to severe comorbidity based most often on a history of a heart attack that the use of 6 months of androgen deprivation therapy to treat non metastatic but clinically significant prostate cancer was associated with both an increased risk of a fatal heart attack and shortened survival. (more…)
Author Interviews, Endocrinology, JAMA, Prostate Cancer / 18.09.2015

MedicalResearch.com Interview with: Sindy Magnan, MD, MSc, FRCPC Division of Radiation Oncology, Department of Medicine CHU de Québe Université Laval Québec City, Québec, Canada Medical Research: What is the background for this study? What are the main findings? Dr. Magnan : Androgen deprivation is the standard therapy for patients with advanced or recurrent prostate cancer. Intermittent administration of this treatment could offer several advantages over the standard continuous administration by delaying the development of castration-resistant disease and by reducing the drugs’ adverse effects. However, this mode of administration remains controversial. We thus conducted a systematic review with meta-analysis of randomized controlled trials to compare the effectiveness and tolerability of intermittent versus continuous androgen deprivation. Intermittent therapy was non-inferior to continuous therapy with respect to overall survival. No major difference in global quality of life was observed between the two interventions, but some quality-of-life criteria, mainly in relation with physical and sexual functioning, seemed improved with intermittent therapy. (more…)
Author Interviews, Genetic Research, Prostate Cancer / 09.08.2015

Dr Helen Ross-Adams Cancer Research UK, LondonMedicalResearch.com Interview with: Dr Helen Ross-Adams Cancer Research UK, London Medical Research: What is the background for this study? What are the main findings? Dr. Ross-Adams: Prostate cancer is the most common non-skin cancer in men in both the UK and US. At the moment, prostate cancer is diagnosed and monitored mainly on the basis of blood tests for prostate specific antigen (PSA), a protein in the blood. MRI scans and examination of biopsy tissue samples under a microscope are also used to decide on the best course of action for each patient. Despite all this, as a community, we still struggle to reliably predict which men with an initial diagnosis of prostate cancer will go on to have a fast-growing, aggressive form of the disease (a ‘tiger’) from men who will have a much slower-growing form of the disease that won’t really cause problems in the man’s lifetime (a ‘pussycat’). This means some men may get treatment they don’t need, while others could benefit from earlier, more intensive treatment. With this in mind, we studied a total of 250 men with prostate cancer and tested their tumour and healthy tissues at the molecular level. The idea was two-fold:
  • Could we identify different sub-types of prostate cancer using this genetic information, and
  • Could we link any of the sub-types we did find with other patient characteristics that clinicians would normally have, like histological staging information or PSA test results?
We looked at their DNA, to see whether any regions were deleted or repeated (copy number alterations), and we also measured the activity levels of thousands of genes in the tumour and healthy prostate tissues (gene expression). Each of these approaches on their own can be used to stratify patients, but we decided to combine this information and hopefully find genes that had a big impact on prostate cancer. Using this approach, we identified five different subtypes of prostate cancer, each with their own ‘molecular profile’:
  • One group had lots of DNA deletions and only low levels of certain genes
  • Another had lots of repeated DNA with high levels of associated genes
  • Two more groups had very ‘quiet’ genomes, with very few changes at the DNA level, and not much disruption at the gene expression level
  • The fifth and final group had an intermediate amount of copy number changes (DNA level), but no major changes at the gene expression level (mRNA level)
When we correlated these different molecular subtypes with the patients’ standard post-surgery follow-up data (the results of 6-monthly PSA tests), we found that these subtypes predicted how well a patient would do after surgery. We ultimately identified 100 key genes (a gene signature) that were most useful in classifying men into one of the 5 cancer subtypes we identified. This was derived from 150 men in Cambridge, UK. To check our findings, we repeated the same work in a group of 100 men from Stockholm, Sweden who had also had prostate surgery, and found that the 100 gene signature worked just as well – it subdivided the men into 5 different groups, each with different rates of relapse. In both cases, men with the most genetic alterations had the greatest chance of relapsing after surgery.   (more…)
Author Interviews, Cleveland Clinic, JAMA, Prostate Cancer / 30.06.2015

Hui Zhu, MD, ScD Section Chief, Urology Section Louis Stokes Cleveland Veterans Affairs Medical Center and Staff, Glickman Urological and Kidney Institute, Cleveland Clinic Foundation Cleveland, Ohio MedicalResearch.com Interview with: Hui Zhu, MD, ScD Section Chief, Urology Section Louis Stokes Cleveland Veterans Affairs Medical Center and Staff, Glickman Urological and Kidney Institute, Cleveland Clinic Foundation Cleveland, Ohio MedicalResearch: Tell me a little bit about the impetus for this study. What gap in knowledge were you trying to fill?  Dr. Zhu: Prostate cancer is a very challenging disease to understand and manage. For the minority of men, prostate cancer is a lethal disease, and in fact, it is the second leading cause of cancer death in American men, behind only lung cancer. However, for the majority of men, prostate cancer poses little risk of death. In fact, about 1 man in 7 will be diagnosed with prostate cancer during his lifetime, but only 1 man in 38 will die from prostate cancer. In an effort to avoid suffering and death from prostate cancer for those men with the lethal form, the early detection of prostate cancer (before the disease has reached a stage when it is no longer curable) through widespread prostate cancer screening was instituted in the late 1980s and early 1990s. As a result, prostate cancer diagnosis increased substantially, and most prostate cancers were detected at an early, treatable stage. Screening successfully reduced the risk of death from prostate cancer by 20%. Unfortunately, our best available screening tests, i.e. prostate-specific antigen (PSA) testing and the digital rectal exam, do not differentiate well between lethal and nonlethal prostate cancer. Consequently, screening is associated with a high risk of overdiagnosis of nonlethal prostate cancer. As a result, about 800 men must be screened and about 30 men must be diagnosed and treated to avoid one death from the prostate cancer, according to recent results from the largest prostate cancer screening trial. Since the natural history of newly diagnosed screen-detected prostate cancer is difficult to predict (i.e. lethal or nonlethal), most prostate cancers have been treated aggressively, leading to overtreatment of many nonlethal cancers. Aside from receiving unnecessary treatment, these men are exposed to the potential side effects and complications of treatment, including erectile dysfunction and urinary incontinence. In response to the harms associated with screening and treatment, the US Preventative Services Task Force issued a statement in 2011 (formalized in 2012) recommending against prostate cancer screening in all men. Unfortunately, while minimizing the risks of overdiagnosis and overtreatment for men with nonlethal prostate cancer, this solution eliminates any of the potential benefits of screening for those men with the lethal form of the disease. As urologists, our solution is different. Rather than throw the baby out with the bathwater, we prefer to preserve PSA screening and its benefits by addressing and hopefully minimizing its associated risks. To achieve this, our goal is to better distinguish between those men who have lethal vs. nonlethal prostate cancer, limiting treatment only to those men who have the lethal form of the disease at an early stage when it is still curable. The dilemma is that our currently available diagnostic tests are unable to accurately differentiate lethal from nonlethal prostate cancer with 100% certainty at the time of initial diagnosis. The solution, or at least part of the solution, is active surveillance. In men who appear to have nonlethal (“low risk”) cancer at the time of diagnosis, it now appears to be safe to observe these cancers, at least initially. This is the concept behind active surveillance. Active surveillance entails carefully monitoring men with low-risk prostate cancer using serial testing and reserving the option of treatment for those men with prostate cancers that exhibit lethal characteristics. In this way, active surveillance preserves the benefits of screening while minimizing the harms of overdiagnosis and overtreatment. Active surveillance was first introduced in the early 2000s, but its efficacy and safety have only been elucidated recently over the last 5 years. Given that active surveillance may be one solution to the screening dilemma, we wanted to evaluate contemporary active surveillance utilization, which is the impetus for our study. Based on the most recent data available to us, we chose the years 2010-2011, which coincide to the time immediately before and during the release of the US Preventative Services Task Force statement against PSA screening. (more…)