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…)
Author Interviews, Erectile Dysfunction, Prostate, Prostate Cancer, Surgical Research, Urology / 29.02.2016 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 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 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, Biomarkers, Mayo Clinic, Prostate, Prostate Cancer, Urology / 12.01.2016 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, Brigham & Women's - Harvard, JAMA, Prostate Cancer, Surgical Research, Testosterone / 04.01.2016 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 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…)
Author Interviews, JAMA, Prostate Cancer, Radiation Therapy / 30.11.2015 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 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 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 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 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 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…)
Accidents & Violence, Technology / 18.09.2015

Dr. Xiaohu Xia Ph.D. Assistant Professor Department of Chemistry Michigan Technological University Houghton, MI Interview with: Dr. Xiaohu Xia Ph.D. Assistant Professor Department of Chemistry Michigan Technological University Houghton, MI 49931 Medical Research: What is the background for this study? What are the main findings? Xiaohu Xia, Jingtuo Zhang, Ning Lu, Moon J. Kim, Kushal Ghale, Ye Xu, Erin McKenzie, Jiabin Liu, Haihang Ye. Pd–Ir Core–Shell Nanocubes: A Type of Highly Efficient and Versatile Peroxidase Mimic. ACS Nano, 2015; 150910154147007 DOI: 10.1021/acsnano.5b03525Dr. Xia: Peroxidases, a family of enzymes that catalyze the oxidation of certain compounds with peroxides, have found widespread use in areas such as biomedicine and environmental protection. Over the past several years, researchers have found that certain inorganic nanomaterials (such as nanoparticles made of metal, metal oxides, and carbon) possess intrinsic peroxidase-like activities. As the major advantage over their natural counterparts, these peroxidase mimics are much more stable because they are less vulnerable to denaturation and protease digestion. In spite of the superior stability of the mimics, improvement in their catalytic efficiency has been met with limited success. The catalytic efficiencies for most of the previously reported peroxidase mimics with sizes 1-100 nm are limited to the range of 101-104 s-1 in terms of catalytic constant (Kcat, which measures the maximum number of chemical conversions of substrate molecules per second per enzyme/mimic). Our research team have recently developed a new type of peroxidase mimic with a record high efficiency that was engineered by coating ~18 nm palladium (Pd) nanocubes with ultrathin iridium (Ir) skins of a few atomic layers (i.e., Pd-Ir core-shell cubes, see Figure). The catalytic efficiency of our Pd-Ir cubes could reach a level of Kcat = 106 s-1. In view of the substantially enhanced efficiency, we applied our Pd-Ir cubes to the colorimetric enzyme-linked immunosorbent assay (ELISA) of human prostate surface antigen (PSA) by functionalizing their surface with antibodies. The detection limit of the Pd-Ir cubes-based ELISA of PSA was determined to be 0.67 pg/mL, which is over 100-fold lower than that of the conventional horseradish peroxidase(HRP)-based ELISA using the same set of antibodies and the same procedure (see Figure). (more…)
Author Interviews, Genetic Research, Prostate Cancer / 09.08.2015

Dr Helen Ross-Adams Cancer Research UK, 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 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…)
Author Interviews, Education, Prostate Cancer, Urology / 12.06.2015 Interview with: Prajakta Adsul, MBBS, MPH, PhD; Ricardo Wray, PhD, and Sameer Siddiqui, MD Center for Cancer Prevention, Research and Outreach Saint Louis University MedicalResearch: What is the background for this study? What are the main findings? Response: Patient decision aids are interventions designed to help patients engage in shared decision making with their providers when multiple choices with more or less equivalent efficacy are available for a particular medical decision. Several patient decision aids exists for numerous medical conditions and previous research has demonstrated them to be effective in improving the patient's knowledge and understanding of treatment options and their relative efficacy and side-effects and resulting in a higher proportion of decision that are consistent with patient's values and personal preferences. In the context of prostate cancer treatment, the practice of shared decision making is vital as highlighted by recent calls from the American Urological Association and the American Cancer Society. To aid with this process, several patient decision aids exist. However, the content presented, the format and presentation styles of decision aids can be variable and can have an influence on the choice made by the patients. The purpose of this study was to assess the characteristics of the patient decision aids designed for men facing prostate cancer treatment. We used the widely accepted International Patient Decision Aids Standards (IPDAS) for the assessment, supplemented with implementation criteria to strategize successful future improvement and promotion of decision aids in routine urological practice. The main findings of the review were that none of the decision aids reviewed met all standards. The aids had variable content, format and presentation of prostate cancer treatment information. Several decision aids were outdated and critical issues such as the risk of overtreatment and active surveillance as a treatment option for prostate cancer were not always covered in decision aids. (more…)
Author Interviews, Biomarkers, Chemotherapy, JAMA, Johns Hopkins, Prostate Cancer / 08.06.2015

Emmanuel S. Antonarakis, M.B.B.CH   Department of Urology and Oncology Johns Hopkins University School of Medicine Baltimore, Interview with: Emmanuel S. Antonarakis, M.B.B.CH Department of Urology and Oncology Johns Hopkins University School of Medicine Baltimore, Maryland Medical Research: What is the background for this study? What are the main findings? Dr. Antonarakis: In a previous publication, we reported that detection of the androgen receptor splice variant 7 (AR-V7; an abnormal version of the androgen receptor) in circulating tumor cells from patients with advanced prostate cancer was associated with resistance to hormonal therapies such as abiraterone and enzalutamide. Here, we aimed to explore the role of AR-V7 in the context of chemotherapy treatment. We showed that detection of AR-V7 was not associated with resistance to the chemotherapy drugs docetaxel or cabazitaxel, and that AR-V7-positive patients could still derive benefit from these chemotherapies. (more…)
Author Interviews, Nutrition, Prostate Cancer / 01.06.2015

Meng Yang, PhD MPH Research Fellow Harvard T. H. Chan School of Public Interview with: Meng Yang, PhD MPH Research Fellow Harvard T. H. Chan School of Public Health Medical Research: What is the background for this study? What are the main findings? Dr. Yang: There are nearly 3 million American men living with prostate cancer. However, there is very little information for patients and clinicians about how to manage patients’ lifestyles, like diet, after prostate cancer diagnosis to decrease the risk of death due to this disease and improve their survivorship. The most important finding is that men initially diagnosed with prostate cancer without metastases whose diet was more “Westernized”, i.e. higher processed meats, refined grains, potatoes and high-fat dairy, had a significantly higher prostate cancer-related death and all cause mortality. Men whose diet was more “prudent”, i.e. higher intake of vegetables, fruits, fish, whole grains and healthy oils had a lower risk of death. (more…)
Author Interviews, Biomarkers, Nature, Prostate Cancer, Technology / 27.05.2015

Gabriel Popescu PhD Associate Professor Department of Electrical and Computer Engineering & Bioengineering University of Illinois at Urbana-Champaign Beckman Institute for Advanced Science and Technology Urbana, IL Interview with: Gabriel Popescu PhD Associate Professor and Shamira Sridharan, Ph.D. candidate Quantitative Light Imaging Laboratory, Department of Bioengineering, Beckman Institute for Advanced Science and Technology University of Illinois at Urbana Champaign Urbana, IL Medical Research: What is the background for this study? What are the main findings? Dr. Popescu: We developed a new optical tool that can identify patients at high risk for recurrence of prostate cancer after undergoing radical prostatectomy as treatment.  Early identification of risk for recurrence can allow early treatment of disease. Our main finding was that among individuals with worse disease outcomes, the tissue is more disorganized.  This manifests as a decrease in anisotropy, or light scattering angle, which reports on nano-scale differences in tissue architecture. (more…)
Author Interviews, Prostate Cancer / 17.05.2015 Interview with: Michael Fenstermaker MD NYU School of Medicine | MD, MS | Class of 2015 Northwestern University | BA | Biochemistry, Psychology Medical Research: What is the background for this study? What are the main findings? Dr. Fenstermaker: The benefits of using prostate-specific antigen (PSA) testing to screen for prostate cancer are uncertain. In response to this, many medical societies have recently scaled back their recommendations for PSA screening.  One common thread among these groups is that shared decision-making should guide whether or not men get tested. Shared decision-making is a process by which physicians and patients work together to make a medical decision that aligns with the patient’s values and follows the best available medical evidence. Several studies have shown a decline in PSA testing since new guidelines have been published.  While a decrease in screening is not necessarily problematic itself, it could be an issue if this is the result of fewer physicians discussing screening with their patients. Some experts worry that disparities in screening could develop, such that only informed patients go on to speak with their physicians and receive PSA testing.  By analyzing data from a national survey, we had the chance to investigate just how much men know about the controversies leading to these guidelines changes and whether this knowledge influences PSA usage. Our findings show that the majority of U.S. males of screening age report that they were not informed of many key facts important to understanding the risks and controversies surrounding PSA testing.  Of particular concern, certain vulnerable populations, such as those without regular healthcare providers were less likely to be informed of these facts. Surprisingly, those men who had more awareness of the controversies about PSA testing were more likely to undergo testing.   (more…)
Prostate Cancer / 17.05.2015

Ryan P. Terlecki, MD, FACS Director, Men's Health Clinic Director, Fellowship in Urologic Reconstruction, Prosthetic Urology, and Infertility Director, Medical Student Education Associate Professor of Urology Wake Forest Baptist Interview with: Ryan P. Terlecki, MD, FACS Director, Men's Health Clinic Director, Fellowship in Urologic Reconstruction, Prosthetic Urology, and Infertility Director, Medical Student Education Associate Professor of Urology Wake Forest Baptist Health Medical Research: What is the background for this study? What are the main findings? Response: In recent years, the value of generalized screening for prostate cancer (PCa) in adult men has been questioned, with several national associations recommending against the practice in men without recognized risk factors. Screening, when performed, often consists of a blood test for prostate specific antigen (PSA) and a digital rectal exam (DRE). Once PSA was developed as a screening tool, we witnessed a stage migration such that observing a locally advanced cancer that would be initially found via DRE became a rarer event. In practice, we have noticed that some men will actually avoid a clinic visit because of the DRE. Additionally, the digital rectal exam has limitations and is often poorly reproducible among providers. We chose to review a large body of data to shed some light on the utility of the digital rectal exam exam. We analyzed data from the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) Screening trial, to determine the ability of the digital rectal exam to result in a diagnosis of clinically significant PCa in the setting of a normal PSA. We found that if PSA is normal and digital rectal exam is considered abnormal, the chance of detecting a clinically significant cancer is similar to a situation of normal DRE and normal PSA. Also, 1,372 men would need to undergo a digital rectal exam to identify a single case of clinically significant prostate cancer not detected by PSA. (more…)
Author Interviews, Prostate Cancer, Radiology / 06.05.2015

Matthias Eiber, MD Department of Nuclear Medicine Munich, Interview with: Matthias Eiber, MD Department of Nuclear Medicine Munich, Germany Medical Research: What is the background for this study? What are the main findings? Dr. Eiber: The background of the study is the investigation of a novel 68Ga-PSMA ligand using PET/CT in the workup of patients with recurrent prostate cancer after radical prostatectomy. Hereby, we found substantial higher detection rate compared to other methods. In total 222 (89.5%) patients showed pathological findings in 68Ga-PSMA-ligand PET/CT. Stratified by PSA-level the detection rates were 96.8%,93.0%,72.7% and 57.9% of ≥2,1-<2, 0.5-<1 and 0.2-<0.5ng/mL, respectively. (more…)
Author Interviews, Prostate Cancer, Radiation Therapy / 25.03.2015 Interview with: Timothy N. Showalter, MD, MPH Associate Professor & Residency Program Director Department of Radiation Oncology University of Virginia School of Medicine Medical Research: What is the background for this study? What are the main findings? Dr. Showalter: Early radiation therapy has been shown to be an effective curative treatment for prostate cancer patietns with a rising PSA blood test after radical prostatectomy and for men with locally advanced prostate cancer who are at high risk of recurrence after prostatectomy. Despite evidence that radiation therapy is more effective when delivered early (or when the PSA is low), radiation therapy delivery is often delayed to allow more time for patients to recover urinary and sexual function. In order to provide evidence regarding whether delaying radiation therapy does reduce the risks of side effects of treatment, my colleagues and I evaluated outcomes of for a large cohort of patients who received treatment in the Emilia Romagna Region of Italy. We identified a total 0f 9,786 prostate cancer patients who received prostatectomy, including 22% of whom received post-prostatectomy radiation therapy. We found that earlier delivery of radiation therapy was not associated with increased risk of any adverse events, including gastrointestinal, urinary or sexual complications. (more…)
Author Interviews, Prostate Cancer / 24.03.2015 Interview with: Grace Lu-Yao, PhD, MPH, Professor of Medicine Cancer epidemiologist at the Cancer Institute of New Jersey Rutgers Robert Wood Johnson Medical School Medical Research: What is the background for this study? What are the main findings? Response: Prostate cancer is the most common non-skin cancer and the second most common cause of cancer death in the United States. Because of widespread prostate specific antigen (PSA) screening, most contemporary men are diagnosed with localized disease. Data from large well executed trials have shown improvement in overall mortality for men <65 years of age undergoing surgery for localized prostate cancer but no significant benefit for men 65 years of age or older. More than half of prostate cancer patients are diagnosed at age 65 or older. Despite that the majority of elderly patients with low-risk prostate cancer might be over-treated, only a small percentage of men in the United States have their prostate cancer managed conservatively. This study was undertaken to provide crucial long-term outcomes data so that prostate cancer patients can use these data for treatment decision. (more…)
Author Interviews, Cost of Health Care, JAMA, Medical Imaging, NYU / 12.03.2015

Danil Makarov, MD Lead Investigator Assistant Professor, Departments of Urology, Population Health and Health Policy Member, Laura and Isaac Perlmutter Cancer Center NYU Langone Medical Center, New York, Interview with: Danil Makarov, MD Lead Investigator Assistant Professor, Departments of Urology, Population Health and Health Policy Member, Laura and Isaac Perlmutter Cancer Center NYU Langone Medical Center, New York, NY Medical Research: What is the background for this study? Dr. Makarov: The background for this study is that regional variation in patterns of care and healthcare spending is widely known.  The drivers of this regional variation, though, are poorly understood.  Certain policy groups like the IOM have suggested that policy efforts be focused on individual providers and patients. Programs such as Choosing Wisely, which encourage a dialogue between physicians and patients, are a great example of such efforts.  However, some of our prior research suggests that regional variation is not random and that there might be are regional-level factors which drive variation. To test out our hypothesis, we wanted to see whether inappropriate imaging for two unrelated cancers was associated at a regional level (it should not be). Medical Research: What are the main findings? Dr. Makarov: We found that, at a regional level, inappropriate breast cancer imaging was associated with inappropriate prostate cancer imaging. (more…)
Author Interviews, Prostate Cancer / 05.03.2015

M. Minhaj Siddiqui, MD Director of Urologic Robotic Surgery Assistant Professor of Surgery - Urology University of Maryland School of Medicine Baltimore MD Interview with: M. Minhaj Siddiqui, MD Director of Urologic Robotic Surgery Assistant Professor of Surgery - Urology University of Maryland School of Medicine Baltimore MD 21201 Medical Research: What is the background for this study? Response: A history of testicular cancer has been suggested to have an association with an increased risk of developing prostate cancer (PCa) in epidemiologic studies. We hypothesized that there may be an increased risk of developing intermediate to high-risk prostate cancer as well. Medical Research: What are the main findings? Response: 147,044 men with melanoma and 32,435 men with testicular cancer were identified. Prostate cancer was diagnosed in 3,205 men in total. The cumulative incidence of all prostate cancer by age 80 was 2.8% in the control melanoma cohort and 12.6% in the case cohort of men with history of testicular cancer (p<0.0001 for KM survival curves, Figure 1). For intermediate/high-risk disease, the incidence was 1.1% versus 5.8% for each cohort respectively (p<0.0001 for KM survival curves, Figure 2). No association with prostate cancer was seen with non-seminomatous versus seminomatous germ cell tumors. Upon multivariate analysis, testis cancer was associated with an increased risk of all prostate cancer (HR 4.7, p<0.0001) and intermediate/high-risk PCa (HR 5.2, p<0.0001) when controlling for race and radiation history. (more…)
Author Interviews, Hormone Therapy, Lancet, Prostate Cancer, Radiation Therapy / 22.02.2015

Almudena Zapatero MD PhD Senior Consultant Dpt Radiation Oncology Instituto Investigación Sanitaria IIS-IP Hospital Universitario de la Princesa Interview with: Almudena Zapatero MD PhD Senior Consultant Dpt Radiation Oncology Instituto Investigación Sanitaria IIS-IP Hospital Universitario de la Princesa Madrid Medical Research: What is the background for this study? What are the main findings? Dr. Zapatero: There is a significant body of evidence from randomized trials showing a significant improvement in clinical outcome with the combination of androgen deprivation and conventional-dose radiotherapy (≤70 Gy) in patients with high-risk and intermediate-risk prostate cancer. However, the optimal duration the optimum duration of androgen deprivation in the setting of high-dose radiotherapy remained to be determined. The results of our trial (DART01/05) show that 2 years of adjuvant androgen deprivation is superior to 4 months androgen deprivation when combined with plus high-dose radiotherapy  in terms of biochemical control, freedom from metastasis and overall survival, particularly in patients with high-risk prostate cancer. (more…)