Author Interviews, Biomarkers, Prostate Cancer / 03.06.2018

MedicalResearch.com Interview with: [caption id="attachment_42152" align="alignleft" width="142"]James T. Kearns, MD Clinical Fellow, Department of Urology University of Washington School of Medicine Seattle, WA  Dr. Kearns[/caption] James T. Kearns, MD Clinical Fellow, Department of Urology University of Washington School of Medicine Seattle, WA MedicalResearch.com: What is the background for this study? What are the main findings? Response: The effects of the USPSTF recommendation against prostate cancer screening had not been fully characterized among a younger population, particularly with respect to downstream effects such as prostate biopsy, prostate cancer diagnosis, and treatment for prostate cancer. We found that PSA testing decreased in the years surrounding the USPSTF recommendation, but we also found a larger proportionate decrease in prostate biopsy, prostate cancer diagnosis, and use of surgery or radiation for the treatment of prostate cancer.
Author Interviews, Biomarkers, Prostate Cancer / 07.03.2018

MedicalResearch.com Interview with: [caption id="attachment_40377" align="alignleft" width="150"]Richard Martin Professor of Clinical Epidemiology Head of Section, Clinical Epidemiology & Public Health Population Health Sciences Bristol Medical School  Prof. Martin[/caption] Richard Martin Professor of Clinical Epidemiology Head of Section, Clinical Epidemiology & Public Health Population Health Sciences Bristol Medical School  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Screening for prostate cancer using the PSA test aims to detect prostate cancer at an early stage, before symptoms develop, when treatment can be offered that may avoid the risks of advanced cancer or may extend life. Evidence from a large European trial suggests that PSA screening at 2 to 4 yearly intervals could reduce prostate-cancer deaths by 20%. after 13 years of follow-up. However, there are problems with the accuracy of the PSA test and potential harmful consequences. In particular, using the PSA test to screen for prostate cancer results in some tested men being diagnosed with low-risk, harmless cancers that are unlikely to progress or require treatment.  This problem may be particularly exacerbated when using repeated PSA testing as a screening strategy. The CAP trial offered a one-off PSA test to men aged 50-69 years in the UK. The goal of this low-intensity, one-off PSA testing was to avoid unnecessary screening while still identifying men with high risk, aggressive cancers for whom screening and early detection can reduce morbidity and mortality. However, we found that after an average 10-years of follow-up, the PSA test still detected too many low-risk prostate cancers, while also missing cancers that did need treatment. After an average 10-years of follow-up, the group who had been screened had the same percentage of men dying from prostate cancer as those who had not been screened (0.29%). 
Author Interviews, Biomarkers, CT Scanning, MRI, Prostate Cancer / 07.02.2018

MedicalResearch.com Interview with: Jeremie Calais PhD Ahmanson Translational Imaging Division UCLA Nuclear Medicine Department Los Angeles, CA 90095Jeremie Calais MD Ahmanson Translational Imaging Division UCLA Nuclear Medicine Department Los Angeles, CA 90095  MedicalResearch.com: What is the background for this study? What are the main findings? Response: The only curative treatment for recurrent prostate cancer after radical prostatectomy is salvage radiotherapy. Unfortunately, current standard imaging modalities are too insensitive to visualize the location of the recurrence until it is too late. As a result, salvage radiotherapy is directed to areas only suspected to harbor the recurrence based upon a "best guess" approach according to standard guidelines that define radiotherapy treatment volumes. PSMA PET/CT is a new imaging technique with sensitivity sufficient to detect and localize the recurrent prostate cancer early enough to potentially guide salvage radiotherapy. The first sign of prostate cancer recurrence is a rising PSA. For salvage radiotherapy to be successful, it should be initiated before the PSA rises above 1 ng/mL, and ideally, closer to 0.2 ng/mL or lower. PSMA PET/CT localizes sites of prostate cancer recurrence in up to 70% of patients with low PSA, below < 1.0. In the US it is not yet FDA approved and currently only used for research purposes. In our current study we included 270 patients with early recurrence of prostate cancer after surgery from Germany and UCLA,  we found that 20 % of the patients had at least one lesion detected by  PSMA PET/CT which was NOT covered by the standard radiation fields. Obviously, salvage radiotherapy is only curative if recurrent disease is completely encompassed by the radiotherapy fields and would have failed in these patients.
Author Interviews, Biomarkers, Prostate Cancer / 24.10.2017

MedicalResearch.com Interview with: Zahava Berkowitz, MSPH, MSc Statistician Division of Cancer Prevention and Control Centers for Disease Control and Prevention MedicalResearch.com: What is the background for this study? Response: The US Preventive Services Task Force 2017 draft prostate cancer screening recommendations  suggest that clinicians inform men aged 55–69 years about the potential benefits and harms of PSA-based screening for prostate cancer. The CDC conducted an analysis using the National Health Interview Surveys in 2005, 2008, 2010, 2013, and 2015 to describe trends in the receipt of routine PSA testing in the past year by age group (40–54, 55–69, ≥70 years) and by risk group. We compared routine PSA screening among higher risk men (defined as African American men or men with a family history of prostate cancer) with other men. The analysis was conducted because CDC wanted to examine how the guidelines affect men at higher risk. The 2017 guideline did not include specific guidelines for African American men who have a higher incidence of prostate cancer than white men, more likely to develop prostate cancer at a young age, more likely to have a high-risk diagnosis and die from prostate cancer.
Author Interviews, Biomarkers, Pharmacology, Prostate Cancer / 19.02.2017

MedicalResearch.com Interview with: Teemu J Murtola, MD, PhD, adjunct professor University of Tampere, Faculty of Medicine and Life Sciences Tampere University Hospital, Department of Urology Tampere, Finland MedicalResearch.com: What is the background for this study? Response: A previous study called Prostate Cancer Prevention Trial (PCPT) showed that finasteride, which belongs to a drug group called 5alpha-reductase inhibitors lowers serum PSA and increases sensitivity of PSA to detect high-grade prostate cancer in men who had little or no symptoms of the lower urinary tract. We postulated that this effect would increase the accuracy and benefits of PSA-based prostate cancer screening. Finnish Randomized Study of Screening for Prostate Cancer was a large trial of over 80,000 men randomized either to be screened for prostate cancer with a PSA test at 4-year intervals or to be followed for prostate cancer incidence and mortality via national registries. Three consecutive screening rounds were commenced between 1996-2008. In the current study we compared the effects of PSA-based screening on prostate cancer risk and mortality separately among men who were using 5alpha-reductase inhibitors finasteride or dutasteride and among men who were not.
Author Interviews, Biomarkers, JAMA, Prostate Cancer, Radiation Therapy / 13.01.2017

MedicalResearch.com Interview with: Trevor Royce MD MS Resident, Harvard Radiation Oncology Program MedicalResearch.com: What is the background for this study? What are the main findings? Response: Clinical trials in early prostate cancer take more than a decade to report on. Multiple early reporting endpoints have been proposed, but which one is best, remains unknown, until now. Of all the possible early endpoints examined, to date, how low a PSA blood test falls to, after treatment with radiation and hormonal therapy, appears to be the best, specifically, if the PSA doesn’t get below half a point, that patient is very likely to die of prostate cancer if given standard treatment for recurrence. Those men deserve prompt enrollment on clinical trials in order to properly save their life.
Author Interviews, Cancer Research, JAMA, Prostate Cancer / 03.01.2017

MedicalResearch.com Interview with: [caption id="attachment_30832" align="alignleft" width="131"]Dr. Jim C. Hu MD MPH Professor of Urology Weill Cornell Medicine Dr. Jim Hu[/caption] Dr. Jim C. Hu MD MPH Professor of Urology Weill Cornell Medicine MedicalResearch.com: What is the background for this study? What are the main findings? Response: The most significant finding from our population based study is that after years of decline following the introduction of PSA screening, we see a rise in the incidence of metastatic prostate cancer at diagnosis among men aged 75 years and older. This is concerning in light of recent criticisms and guidelines against PSA testing. For instance, in 2008, the US Preventative Services Task Force recommended against PSA testing in this age group, and in our study, we see the incidence of metastasis at diagnosis rising in 2012 and 2013. This is significant because there is no cure for men with metastatic prostate cancer of their disease. The traditional argument against PSA screening is that it leads to over-diagnosis and over-treatment of prostate cancer. However, we currently do not have a better test for diagnosing prostate cancers before it has spread beyond the prostate and metastasized. Remarkably, when Ben Stiller shared his personal use of PSA testing in his mid to late 40's and how this led to a detection of intermediate risk prostate cancer that led him to surgery and cure, others criticized him for sharing his story.
Author Interviews, JAMA, Prostate, Prostate Cancer, Surgical Research, Urology / 15.11.2016

MedicalResearch.com Interview with: [caption id="attachment_29302" align="alignleft" width="134"]Jim C. Hu, M.D., M.P.H. Ronald P. Lynch Professor of Urologic Oncology Director of the LeFrak Center for Robotic Surgery Weill Cornell Medicine Urology New York Presbyterian/Weill Cornell New York, NY 10065 Dr. Jim Hu[/caption] Jim C. Hu, M.D., M.P.H. Ronald P. Lynch Professor of Urologic Oncology Director of the LeFrak Center for Robotic Surgery Weill Cornell Medicine Urology New York Presbyterian/Weill Cornell New York, NY 10065 MedicalResearch.com: What is the background for this study? What are the main findings? Response: The US Preventative Services Task Force (USPSTF) recommended against PSA testing in men older than 75 years in 2008 and more recently in all US men regardless of age in 2012. This was largely based on a faulty study, the prostate, lung, colo-rectal and ovarian screening study. We demonstrated in May 2016 that this randomized trial did not compare screening to no screening or apples to oranges, as it set out to do. It compared screening to screening. Although controversial, the guidelines were well-intentioned, as recognize that there is over-diagnosis and over-treatment of men with prostate cancer. Given this background, the goal of our study was to explore the downstream consequences of the recommendation against PSA screening. As such, we explored 3 separate databases to characterize national procedure volumes for prostate needle biopsy and radical prostatectomy, or surgery to cure prostate cancer. The main finding was that prostate biopsy numbers decreased by 29% and radical prostatectomy surgeries decreased by 16% when comparing before to after USPSTF recommendations against PSA screening. Therefore practice patterns followed policy. Prostate biopsies are usually performed due to an elevated, abnormal screening PSA. However, it is also performed to monitor low-risk, slow growing prostate cancers. We also found that while the overall number of prostate biopsies decreased, there was a 29% increase in the proportion or percentage of biopsies performed due to active surveillance, or monitoring of low risk prostate cancers which should be done periodically. Therefore we provide the first national study to demonstrate that there is less over-diagnosis and over-treatment of prostate cancer. However, the concern is that we also recently demonstrated that there is more aggressive prostate cancer on surgical pathology for men who go on to radical prostatectomy. They have high grade, higher stage cancers, which have a lower chance of cure. The link is: http://www.prostatecancerreports.org/fulltext/2016/_Hu_JC160708.pdf
Author Interviews, Biomarkers, Cancer, Prostate Cancer, UT Southwestern / 08.10.2016

MedicalResearch.com Interview with: Dr Ryan Hutchinson MD and Yair Lotan MD Department of Urology University of Texas Southwestern Medical Center MedicalResearch.com: 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.
Author Interviews, Endocrinology, Prostate, Prostate Cancer, Testosterone, Urology / 19.09.2016

MedicalResearch.com Interview with: [caption id="attachment_28090" align="alignleft" width="133"]Dr. Jesse Ory Department of Urology, Faculty of Medicine Dalhousie University, Halifax Nova Scotia, Canada Dr. Jesse Ory[/caption] Dr. Jesse Ory Department of Urology, Faculty of Medicine Dalhousie University, Halifax Nova Scotia, Canada  MedicalResearch.com: 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..
Author Interviews, Prostate, Prostate Cancer, Urology / 01.09.2016

MedicalResearch.com Interview with: [caption id="attachment_27566" align="alignleft" width="160"]Jim C. Hu, MD Ronald Lynch Professor of Urologic Oncology Weill Cornell Medicine New York, NY 10065 Dr. Jim Hu[/caption] Jim C. Hu, MD Ronald Lynch Professor of Urologic Oncology Weill Cornell Medicine New York, NY 10065 MedicalResearch.com: 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.
Author Interviews, Biomarkers, JAMA, Prostate Cancer / 09.02.2016

MedicalResearch.com Interview with: [caption id="attachment_20288" align="alignleft" width="120"]Quoc-Dien Trinh MD Assistant Professor, Harvard Medical School Brigham and Williams Hospital Dr. Trinh[/caption] 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.
Author Interviews, Prostate, Urology / 21.05.2015

David F. Penson, MD, MPHHamilton and Howd Chair in Urologic Oncology Professor and Chair, Department of Urologic Surgery Director, Center for Surgical Quality and Outcomes Research Vanderbilt University Medical Center Nashville, TN 37232-2765MedicalResearch.com Interview with: David F. Penson, MD, MPH Hamilton and Howd Chair in Urologic Oncology Professor and Chair, Department of Urologic Surgery Director, Center for Surgical Quality and Outcomes Research Vanderbilt University Medical Center Nashville, TN 37232-2765 Medical Research: What is the background for this editorial? What are the main findings? Response: This editorial discusses the implication of the recent removal of the PSA data from the seer-medicare dataset. It reviews the significance of the action: specifically what it means for prior publications that used this information to address clinical research questions in prostate cancer. It makes the point that, while these datasets are powerful, researchers have stretched the limits of what they can do too far. Simply put, we cant always guarantee that the clinical data collected in administrative datasets will necessarily be accurate so we need to be more selective in how we use these data and not simply run analyses on the data just because it is easy.
Author Interviews, Erasmus, Lancet, Prostate Cancer / 10.08.2014

Professor Fritz H Schröder Department of Urology, Erasmus University Medical Center Rotterdam, NetherlandsMedicalResearch.com Interview with: Professor Fritz H Schröder Department of Urology, Erasmus University Medical Center Rotterdam, Netherlands Medical Research: What are the main findings of the study? Professor Schröder: I consider as the main finding that we could report a continuing effect of PSA driven screening on prostate cancer mortality for men aged 55 – 69 years in the screen arm of our study after 13 years of follow-up. The absolute reduction in the risk of death from prostate cancer amounts to 1.28 per 1000 men randomized to the screening arm. This translated into numbers to be invited to screening and numbers needed to be diagnosed to save one prostate cancer death of 781 and 27. These figures show an increasing effect with increasing time of follow-up. The relative risk reduction related to the control arm has remained unchanged with respect to the 11 year follow-up period. For men who actually participated and were screened the relative risk reduction amounted to 27%, the figure most applicable to men who consider to be tested.
Author Interviews, Duke, Prostate Cancer / 10.10.2013

Susan Halabi, PhD Duke University Medical Center Durham, NC 2771MedicalResearch.com Interview with Susan Halabi, PhD Duke University Medical Center Durham, NC 27710 MedicalResearch.com: What are the main findings of the study? Dr. Halabi: The purpose of assessing surrogate endpoints is to allow for a more rapid and efficient determination of whether a given therapy provides clinical benefit to patients by prolonging their life. We sought to evaluate PSA kinetics as surrogate endpoints for overall survival (OS) in mCRPC patients who were receiving second line chemotherapy (cabazitaxel or mitoxantrone) following progression after docetaxel. Using different analytical approaches, we found that PSA declines within the first three months of treatment are not appropriate as surrogate markers of clinical benefit in men who were receiving second line chemotherapy. This analysis has important clinical care and study design implications:  it has become common to use ≥30% decline in PSA as a clinical trial endpoint for all patients with metastatic CRPC, based on the original front-line docetaxel data. The data presented in this study suggest that this is erroneous. Further we believe these data are important because they demonstrate that there are different disease states within the group of patients with “metastatic CRPC". To make the assumption that the same surrogate endpoint can be used across the board may seem like an obvious mistake, but permeates the literature.