Author Interviews, Cancer Research, JAMA, MRI, Prostate Cancer, UCLA / 12.09.2019

MedicalResearch.com Interview with: [caption id="attachment_51263" align="alignleft" width="150"]Rajiv Jayadevan, MD Department of Urology UCLA Dr. Jayadevan[/caption] Rajiv Jayadevan, MD and  Leonard S. Marks, MD Department of Urology UCLA MedicalResearch.com: What is the background for this study? Response: Men with low risk prostate cancer often enter “active surveillance” programs. These programs allow patients to defer definitive treatment (and avoid their associated side effects) until more aggressive disease is detected, if at all. Patients typically undergo a “confirmatory biopsy” 6 to 12 months after diagnosis to verify that their disease is low risk, and then undergo repeat biopsies every 1 to 2 years. These biopsies have traditionally been performed under the guidance of transrectal ultrasonography. Transrectal ultrasonography is unable to accurately visualize tumors within the prostate, necessitating that biopsy cores be obtained systematically from all parts of the prostate. MRI-ultrasonography fusion biopsy is a newer technology that has been shown to characterize biopsy findings more accurately than transrectal ultrasonography, leading to improved disease detection. This technology also allows us to visualize tumors within the prostate, and directly target these tumors during a biopsy session.
Author Interviews, Bayer, FDA, Prostate Cancer / 16.08.2019

MedicalResearch.com Interview with: [caption id="attachment_50898" align="alignleft" width="133"]Neal D. Shore, MD, FACS Director, CPI, Carolina Urologic Research Center Atlantic Urology Clinics Myrtle Beach, South Carolina Dr. Shore[/caption] Neal D. Shore, MD, FACS Director, CPI, Carolina Urologic Research Center Atlantic Urology Clinics Myrtle Beach, South Carolina Neal D. Shore, MD, FACS is the Medical Director for the Carolina Urologic Research Center. He practices with Atlantic Urology Clinics in Myrtle Beach, South Carolina. Dr. Shore discusses the recent announcement that the FDA has approved Nubeqa®(darolutamide),  for the treatment of patients with non-metastatic castration-resistant prostate cancer..  MedicalResearch.com: What is the background for this study? How does NUBEQA®(darolutamide) differ from other treatments for nmCRPC?  Response: In 2017, patients did not have an approved therapy for non-metastatic castration-resistant prostate cancer, or nmCRPC. If untreated, patients with this diagnosis will go on to develop metastases, or progression of the cancer throughout the body. NUBEQA® (darolutamide) became the third and most recently approved treatment for nmCRPC, demonstrating a benefit of metastasis-free survival, or MFS. NUBEQA is different due to its adverse event and safety profile reported in the Phase III ARAMIS trial. In that study, there were no significant findings of falls and fractures as well as other adverse events reported from the earlier Phase III trials. 
Author Interviews, Cancer Research, FDA, Vaccine Studies / 14.08.2019

MedicalResearch.com Interview with: [caption id="attachment_50871" align="alignleft" width="150"]Dr. Graca Dores (left) and Dr. Perez-Vilar (senior author) Dr. Graca Dores (left) and Dr. Perez-Vilar (senior author)[/caption] Dr. Graca Dores MD MPH US Food and Drug Administration Center for Biologics Evaluation and Research Office of Biostatistics and Epidemiology Division of Epidemiology Silver Spring, Maryland Oklahoma City, OK MedicalResearch.com: What is the background for this study? Would you briefly explain what Sipuleucel-T is used for?  Response: Sipuleucel-T was the first therapeutic vaccine approved by the U.S. Food and Drug Administration (FDA) in 2010.  It is indicated for the treatment of asymptomatic or minimally symptomatic, metastatic, castration-resistant prostate cancer (CRPC; prostate cancer that spreads while an individual is on hormone-blocking therapy).  During the preparation of this product, the patient’s cells are collected (leukapheresis), sent for processing to generate a dose of patient-specific vaccine, and then administered intravenously back to the patient.  This process is repeated approximately every two weeks for a total of three doses. Except for the pre-marketing clinical trials that were reviewed during the sipuleucel-T approval process, post-marketing studies that have evaluated the safety profile of sipuleucel-T are scarce. Therefore, we used the FDA’s Adverse Event Reporting System (FAERS) database to summarize the adverse events reported to FDA by industry, medical professionals, and consumers.  We also assessed whether sipuleucel-T and specific adverse events (product-event pairs) were reported more than expected compared to all other drug/biologic-adverse event pairs in the FAERS database.
Author Interviews, Cancer Research, JAMA, MRI, Prostate Cancer / 07.08.2019

MedicalResearch.com Interview with: Dr Martha Elwenspoek PhD Research Associate in Epidemiology and Health Services Research NIHR CLAHRC West, Bristol MedicalResearch.com: What is the background for this study? Response: Prostate cancer is one of the most common cancers in men. Prostate cancer is usually diagnosed by taking 10 to 14 systematic samples from the prostate guided by ultrasound. However, these biopsies are unpleasant for patients, can miss cancer even when it’s present, can misclassify the severity of the cancer, and can cause side effects, such as bleeding and infection. If biopsies could be targeted better, men wouldn’t have to undergo so many and there would be less risk of getting a misleading result. Multiparametric MRI (mpMRI) scans are sometimes used before doing a biopsy to help diagnose prostate cancer, and while this approach is now being recommended by the UK National Institute for Clinical Excellence (NICE) their use isn’t widespread.
Author Interviews, Cancer Research, Hormone Therapy, JAMA, Prostate Cancer, University of Pennsylvania / 15.07.2019

MedicalResearch.com Interview with: [caption id="attachment_50254" align="alignleft" width="180"]Ravi Jayadevappa, PhD, MS Department of Medicine Perelman School of Medicine University of Pennsylvania Philadelphia, PA 19104-2676  Dr. Jayadevappa[/caption] Ravi Jayadevappa, PhD, MS Department of Medicine Perelman School of Medicine University of Pennsylvania Philadelphia, PA 19104-2676  MedicalResearch.com: What is the background for this study? Response: In the US, prostate cancer is the most commonly diagnosed non-skin cancer and the second leading cause of cancer death among men. Research shows that hormone therapy or ADT reduces the levels of male hormones in the body, called androgens, to stop them from stimulating cancer cells to grow., and thus is effective in reducing the spread and progression of prostate cancer. At the same time, some research has suggested that decreasing androgen levels may increase the risk factors for Alzheimer’s and dementia, including loss of lean body mass, diabetes, cardiovascular disease, and depression. The ADT therapy may lead to impaired neuron growth and the regeneration of axons, thus affecting the cognitive function. Thus there is growing interest in the possible association between exposure to ADT and cognitive dysfunction. Our study investigates the association between exposure to ADT and subsequent diagnosis of Alzheimer’s or dementia in elderly, fee-for-service Medicare enrollees using SEER-Medicare linked databases.
Author Interviews, JAMA, Prostate, Prostate Cancer, Urology / 25.06.2019

MedicalResearch.com Interview with: [caption id="attachment_49921" align="alignleft" width="160"]Kari Tikkinen, MD, PhD, Adjunct Professor Departments of Urology and Public Health University of Helsinki and Helsinki University Hospital Helsinki, Finland Dr. Tikkinen[/caption] Kari Tikkinen, MD, PhD, Adjunct Professor Departments of Urology and Public Health University of Helsinki and Helsinki University Hospital Helsinki, Finland MedicalResearch.com: What is the background for this study? What are the main findings?  Response: Men’s choice of whether to undergo screening is value and preference sensitive: fully informed men will make different choices depending on their experience and perspective. For such decisions, shared decision-making represents an ideal approach to decision making. In shared decision-making both the patient and health care provider contribute to the medical decision-making process. The health care provider explains alternatives to patients, informs them of the best evidence regarding the anticipated consequences of a decision for or against the intervention, and helps them choose the option that best aligns with their preferences. All major guidelines of prostate cancer screening acknowledge the importance of informing men about risks and benefits of PSA screening. Shared decision-making is challenging because it requires time, knowledge, and specific skills. Prostate cancer screening decisions aids may, by summarizing the current best evidence and by supporting conversations that address what matters most to men, address these challenges. The impact of decision aids on the decision-making process is, however, uncertain. We therefore undertook a systematic review and meta-analysis of the randomized trials that have addressed the impact of decision aids in the context of prostate cancer screening. 
Author Interviews, Environmental Risks, Genetic Research, Prostate Cancer / 20.06.2019

MedicalResearch.com Interview with: [caption id="attachment_49841" align="alignleft" width="130"]Emanuela Taioli, MD, PhD, Director of the Institute for Translational Epidemiology Icahn School of Medicine at Mount Sinai Asociate director for Population Science Tisch Cancer Institute Dr. Taioli[/caption] Emanuela Taioli, MD, PhD, Director of the Institute for Translational Epidemiology Icahn School of Medicine at Mount Sinai Asociate director for Population Science Tisch Cancer Institute  MedicalResearch.com: What is the background for this study? What are the main findings?  Response: An excess incidence of prostate cancer has been identified among World Trade Center responders. We wanted to study if this excess was associated with exposure to WTC dust The results suggest that respiratory exposure to WTC dust can induce inflammatory and immune responses in prostate tissue. Chronic inflammation could facilitate prostate cancer development Taken together, our results suggest that World Trade Center prostate cancer cases have a distinct gene expression pattern that may be the result of exposure to specific carcinogens during the WTC attacks. WTC dust-exposed rat prostate displayed unique changes in gene expression and immune cell infiltrates after acute dust exposure, suggesting that the effect of exposure may be measured locally in target organs such as prostate. In addition, some of the genes overexpressed in rat normal prostates as a consequence of exposure are also overexpressed in human prostate cancer tissues, suggesting a link between exposure, local immune dysregulation, and prostate cancer development
Author Interviews, Brigham & Women's - Harvard, Prostate Cancer, Weight Research / 10.06.2019

MedicalResearch.com Interview with: [caption id="attachment_49690" align="alignleft" width="200"]Barbra Dickerman, PhD Research Fellow Department of Epidemiology Harvard T.H. Chan School of Public Health Boston, MA Dr. Dickerman[/caption] Barbra Dickerman, PhD Research Fellow Department of Epidemiology Harvard T.H. Chan School of Public Health Boston, MA MedicalResearch.com: What is the background for this study? Response: Obesity is associated with a higher risk of advanced prostate cancer and poorer prognosis after diagnosis. However, emerging evidence suggests that the specific distribution of body fat may be an important prognostic factor for prostate cancer outcomes. In this original investigation, we analyzed body fat distribution on computed tomography imaging and the risk of being diagnosed with, and dying from, prostate cancer. This study was conducted among 1,832 Icelandic men with over a decade of follow-up in the Age, Gene/Environment Susceptibility-Reykjavik Study.
Author Interviews, Cancer Research, Prostate Cancer / 03.06.2019

[caption id="attachment_49560" align="alignleft" width="181"] Dr. Julie Graff[/caption] MedicalResearch.com Interview with: Julie N. Graff, MD Associate Professor of Medicine Knight Cancer Institute Chief of Hematology/Oncology VA Portland Health Care System MedicalResearch.com: What is the background for this study? Response: Androgen deprivation therapy is often deployed in patients with a rising PSA after local therapy (such as radical prostatectomy or radiation therapy). With time, the prostate cancer can develop resistance to ADT, at which point it is called castration resistant prostate cancer (CRPC). There were 6 treatments for metastatic CRPC that have shown improved survival. However, in non-metastatic disease, there was nothing that showed improved survival. The SPARTAN study was designed to determine if a next generation androgen receptor antagonist could delay the time to metastatic disease. Overall survival was a secondary endpoint. 
ASCO, Author Interviews, Cancer Research, J&J-Janssen, NEJM, Prostate Cancer / 01.06.2019

MedicalResearch.com Interview with: [caption id="attachment_49474" align="alignleft" width="142"]Dr. Kim Chi. MDProfessor of MedicineMedical Oncologist and Medical Director at BC Cancer – VancouverUniversity of British Columbia,Principal Investigator of the TITAN Study. Dr. Kim Chi[/caption] Dr. Kim Chi. MD Professor of Medicine Medical Oncologist and Medical Director at BC Cancer – Vancouver University of British Columbia, Principal Investigator of the TITAN Study. MedicalResearch.com: What is the background for this study? Response: For more than 70 years, androgen deprivation therapy (ADT) has been the standard of care therapy for patients with metastatic prostate cancer. The Phase 3 TITAN study looked at adding apalutamide (®®®®) to ADT compared with placebo plus ADT in a broad group of patients with metastatic castration-sensitive prostate cancer (mCSPC), regardless of disease volume or prior docetaxel treatment history. Metastatic castration-sensitive prostate cancer is prostate cancer that still responds to androgen deprivation therapy and has spread to other parts of the body. Patients with mCSPC tend to have a poor prognosis, with a median overall survival (OS) of less than five years, underscoring the need for new treatment options. The dual primary endpoints of this study were overall survival and radiographic progression-free survival (rPFS). 
Author Interviews, Pharmaceutical Companies, Prostate, Urology / 31.05.2019

MedicalResearch.com Interview with: [caption id="attachment_49467" align="alignleft" width="160"]Steven A. Kaplan, M.D., FACS Professor of Urology Director, The Men's Health Program Icahn School of Medicine at Mount Sinai Dr. Kaplan[/caption] Steven A. Kaplan, M.D., FACS Professor of Urology Director, The Men's Health Program Icahn School of Medicine at Mount Sinai MedicalResearch.com: What is the background for this study? Response: PLUS is the first large-scale trial conducted in North America and Europe specifically designed to study the effects of mirabegron in controlling residual symptoms of urinary urgency and frequency in men with benign prostatic hyperplasia (BPH) using common agents such as tamsulosin (Flomax). We explored whether mirabegron (Myrbetriq), an agent approved for the treatment of overactive bladder (OAB), improved patient outcomes when added to tamsulosin. This was a randomized, double-blind, placebo-controlled, multi-center study enrolling 715 male patients 40 years of age and older.
Annals Internal Medicine, Author Interviews, Cancer Research, Prostate Cancer / 05.03.2019

MedicalResearch.com Interview with: Charlotte Skriver, PhD student, MSc Danish Cancer Society Research Center Statistics & Pharmacoepidemiology Danish Cancer Society Copenhagen  MedicalResearch.com: What is the background for this study?   Response: The drug aspirin is widely used due to its established protection against cardiovascular diseases. Increasing evidence also supports an effect of aspirin use on reducing the risk of and mortality from colorectal cancer and possibly other cancer types. Recent studies have suggested that aspirin use after a diagnosis of prostate cancer may improve the prognosis. We examined whether use of low-dose aspirin was associated with survival after prostate cancer in a nationwide study of prostate cancer patients in Denmark.
ASCO, Author Interviews, Cancer Research, NEJM, Prostate Cancer / 25.02.2019

MedicalResearch.com Interview with: [caption id="attachment_47619" align="alignleft" width="180"]Prof. Karim Fizazi, MD, PhD Head of the Department of Cancer Medicine Institute Gustave Roussy Prof. Fizazi[/caption] Prof. Karim Fizazi, MD, PhD Head of the Department of Cancer Medicine Institute Gustave Roussy MedicalResearch.com: What is the background for this study? How does darolutamide differ from other medications for prostate cancer? Response: Despite recent treatment advances, there is still significant unmet need for new therapeutic options for men with non-metastatic castration-resistant prostate cancer (nmCRPC). In laymen’s terms, nmCRPC is cancer that has not spread beyond the prostate region; PSA levels are elevated, despite treatment with hormone therapy, and men with nmCRPC generally feel well and do not have symptoms. The unmet medical need is for treatments that achieve disease control and delay the spread of the cancer without impacting their daily lives or increasing the burden of disease with treatment side effects. While the current treatments in this space are effective in delaying onset of metastases, the side effects can be unpleasant and disruptive to men’s lives; particularly cognitive issues, seizures, impact on balance which may lead to falls and bone fractures, rash and hypertension. Furthermore, new treatment options that have limited interactions with medications typically used in this patient population are also important. 
Author Interviews, Genetic Research, JAMA, Prostate Cancer / 24.02.2019

MedicalResearch.com Interview with: [caption id="attachment_47572" align="alignleft" width="160"]Masaki Shiota MD, PhD Department of Urology, Graduate School of Medical Sciences Kyushu University Fukuoka , Japan Dr. Shiota[/caption] Masaki Shiota MD, PhD Department of Urology Graduate School of Medical Sciences Kyushu University Fukuoka , Japan MedicalResearch.com: What is the background for this study? What are the main findings? Response:  3β-hydroxysteroid dehydrogenase-1 encoded by HSD3B1 is a rate-limiting enzyme required for all pathways of dihydrotestosterone synthesis, as well as converts abiraterone into Δ4-abiraterone (D4A), which blocks multiple steroidogenic enzymes and antagonizes the androgen receptor. A mutation (1245A>C) in HSD3B1 is shown to be resistant to proteasomal degradation, causing substantial accumulation of this enzyme and gain-of-function. Although the HSD3B1 (1245C) allele can be acquired by mutation, germ-line single nucleotide polymorphism (SNP; rs1047303) is also known to exist. Then, in this study, we investigated the significance of missense polymorphism in HSD3B1 gene among men treated with primary ADT or abiraterone. The results showed men carrying variant allele showed higher risk of progression in primary androgen-deprivation therapy, but vulnerable to abiraterone treatment.
ASCO, Author Interviews, Prostate Cancer / 22.02.2019

MedicalResearch.com Interview with: Kim Nguyen Chi, MD FRCPC Professor of Medicine, University of British Columbia Regional Medical Director, BC Cancer - Vancouver MedicalResearch.com: What is the background for this study? What are the main findings? Response: For over 70 years, androgen deprivation therapy (ADT) has been the main treatment therapy for metastatic prostate cancer patients. This Phase 3 final analysis study looked at adding abiraterone acetate and prednisone to ADT for patients with metastatic prostate cancer, with the primary objectives being to assess improvements in overall survival and radiographic progression-free survival. At the first interim analysis reported in 2017, both primary endpoints were met, and the study was unblinded and patients on the ADT and placebos arm crossed over to receive ADT with abiraterone and prednisone. This study is the final analysis reporting on overall survival. The study findings found abiraterone acetate and prednisone plus ADT continued to demonstrate an improvement in overall survival, hazard ratio (HR) = 0.66, meaning a 34% decrease in the risk of death associated with the use of ADT with abiraterone and prednisone. The median overall survival, which had not been reached before in the ADT with abiraterone and prednisone arm, was 53.3 months compared to 36.5 months for ADT plus placebo, prolonging median overall survival by 16.8 months.
Author Interviews, Emory, JAMA, Prostate Cancer, Radiation Therapy / 15.02.2019

MedicalResearch.com Interview with: [caption id="attachment_47492" align="alignleft" width="200"]Deborah Watkins Bruner RN, PhD, FAAN Senior Vice President of Research Emory University Professor and Robert W. Woodruff Chair in Nursing Nell Hodgson Woodruff School of Nursing Professor, Department of Radiation Oncology Emory University School of Medicine Dr. Bruner[/caption] Deborah Watkins Bruner RN, PhD, FAAN Senior Vice President of Research Emory University Professor and Robert W. Woodruff Chair in Nursing Nell Hodgson Woodruff School of Nursing Professor, Department of Radiation Oncology Emory University School of Medicine MedicalResearch.com: What is the background for this study? Response: In a randomized clinical trial entitled, “Quality of Life in Patients With Low-Risk Prostate Cancer Treated With Hypofractionated vs Conventional Radiotherapy” the NRG Oncology Group previously demonstrated that men with low risk prostate cancer had  similar 5-year disease- free survival of about 85%  when treated with either conventional radiotherapy  (C-RT) of 73.8 Gy in 41 fractions over 8.2 weeks, or with  hypofractionated radiotherapy (H-RT) of 70 Gy in 28 fractions over 5.6  weeks. However, late physician reported side effects of mild bowel and bladder symptoms were increased in patients treated  with H-RT and raised questions if the H-RT arm is acceptable to patients. The current study asked the patient’s directly about their bowel, bladder, sexual function, anxiety, depression and general quality of life using valid patient reported questionnaires. These questionnaires have been found to be more accurate for reporting patient symptoms than physician report alone.
Author Interviews, JAMA, Prostate Cancer, Radiation Therapy / 12.02.2019

MedicalResearch.com Interview with: [caption id="attachment_47468" align="alignleft" width="200"]Amar U. Kishan, MD Assistant Professor Department of Radiation Oncology University of California, Los Angeles Dr. Kishan[/caption] Amar U. Kishan, MD Assistant Professor Department of Radiation Oncology University of California, Los Angeles MedicalResearch.com: What is the background for this study? What are the main findings? Response: Typical external beam radiation courses range up to 8-9 weeks in length (39-45 treatments). There are data that shorter courses, delivering a higher dose per day, may be just as effective. Stereotactic body radiotherapy (SBRT) really pushes this concept by condensing the treatment to just four to five treatments, with a high dose per day. Here, we present the pooled results of the outcomes of 2142 men with low and intermediate risk prostate cancer and a median of 6.9 years of followup. We demonstrate a very favorable efficacy and safety profile. Specifically, the rates of recurrences were 4.5% and 10.2% for low and intermediate risk disease at 7 years, and rates of late severe toxicity were 2.4% for urinary toxicity and 0.4% for gastrointestinal toxicity.
Author Interviews, MRI, Prostate Cancer, Technology / 12.02.2019

MedicalResearch.com Interview with: [caption id="attachment_47464" align="alignleft" width="130"]Gaurav Pandey, Ph.D. Assistant Professor Department of Genetics and Genomic Sciences Icahn Institute of Data Science and Genomic Technology Icahn School of Medicine at Mount Sinai, New York  Dr. Pandey[/caption] Gaurav Pandey, Ph.D. Assistant Professor Department of Genetics and Genomic Sciences Icahn Institute of Data Science and Genomic Technology Icahn School of Medicine at Mount Sinai, New York  MedicalResearch.com: What is the background for this study?  Response: Multiparametric magnetic resonance imaging (mpMRI) has become increasingly important for the clinical assessment of prostate cancer (PCa), most routinely through PI-RADS v2, but its interpretation is generally variable due to its relatively subjective nature. Radiomics, a methodology that can analyze a large number of features of images that are difficult to study solely by visual assessment, combined with machine learning methods have shown potential for improving the accuracy and objectivity of mpMRI-based prostate cancer assessment. However, previous studies in this direction are generally limited to a small number of classification methods, evaluation using the AUC score only, and a non-rigorous assessment of all possible combinations of radiomics and machine learning methods.
Author Interviews, Cancer Research, Prostate Cancer, Radiation Therapy / 12.02.2019

MedicalResearch.com Interview with: [caption id="attachment_47453" align="alignleft" width="132"]Graham Kelly, BSc (Vet) (Hons, BVSc (Hons), PhD Managing Director and Chief Executive Officer Noxopharm  Dr. Kelly[/caption] Graham Kelly, BSc (Vet) (Hons, BVSc (Hons), PhD Managing Director and Chief Executive Officer Noxopharm  MedicalResearch.com: What is the background for this announcement? What are the main findings? Response: Veyonda is an experimental drug being developed as a means of enhancing the anti-cancer effect of radiotherapy. The Phase 1b DARRT-1 study is assessing the ability of Veyonda to boost a palliative dose of external beam radiotherapy (EBRT) applied to a single lesion, to result in a systemic response in non-irradiated lesions (known as an abscopal response) in men with metastatic, end-stage prostate cancer. The aim is to provide at the least better palliation, and at best a survival advantage. The reported data concerns the study’s initial dose-finding arm involving three different dosages of Veyonda. This arm involves 12 subjects and the report concerns their clinical status at 12-weeks post-irradiation. The data provide clinical evidence of an abscopal effect in at least half of the eight subjects receiving the two highest Veyonda dosages and demonstrate that the combination of Veyonda and palliative radiotherapy was well-tolerated. The 1200 mg dosage was confirmed as the therapeutic dose.
Author Interviews, Brigham & Women's - Harvard, JAMA, Prostate Cancer, Radiation Therapy, Surgical Research / 16.11.2018

MedicalResearch.com Interview with: [caption id="attachment_45955" align="alignleft" width="200"]Anthony Victor D'Amico, MD, PhD Professor and Chief, Genitourinary Radiation Oncology Harvard Medical School Dr. D'Amico[/caption] Anthony Victor D'Amico, MD, PhD Professor and Chief, Genitourinary Radiation Oncology Harvard Medical School MedicalResearch.com: What is the background for this study? Response: This study investigated whether surgery followed by the use of adjuvant low dose radiation and short course hormonal therapy as compared to high dose radiation and hormonal therapy could provide an equivalent low risk of death from prostate cancer amongst men presenting with aggressive and not infrequently fatal Gleason score 9 or 10 prostate cancer. It has been shown previously (https://jamanetwork.com/journals/jama/fullarticle/2673969) and validated in the current study that surgery alone in such cases leads to a more then 2.5-fold increase in the risk of death from prostate cancer as compared to high dose radiation and hormonal therapy. 
Author Interviews, Biomarkers, Endocrinology, Prostate Cancer / 14.11.2018

MedicalResearch.com Interview with: [caption id="attachment_45946" align="alignleft" width="200"]Diagram_showing_prostate_cancer_that_has_spread_to_the_bones_CRUK_183.svg.png Prostate cancer that has metastasized to the bone: Wikipedia Image[/caption] Vincenza Conteduca, MD, PhD Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) Srl - IRCCS Meldola , Italy MedicalResearch.com: What is the background for this study? What are the main findings? Response: In our previous publications, we showed that the study of plasma cell-free DNA holds promise for improving treatment choice in metastatic castration-resistant prostate cancer (mCRPC). Specifically, we demonstrated that the detection in plasma of aberrations (copy number alterations and/or point somatic mutations) of androgen receptor (AR), using an easy and robust multiplex droplet digital PCR method, predicted an adverse outcome in mCRPC patients treated with second-generation AR-directed therapies (abiraterone or enzalutamide) in both settings: chemotherapy-naïve and post-docetaxel. This current multi-institution work builds on our previous discoveries. We investigated the association of androgen receptor status and survival in men treated with docetaxel. Moreover, we performed an exploratory analysis in patients treated with docetaxel or AR-directed therapies as first-line therapy. Interestingly, we observed that plasma AR-gained patients do not have a worse outcome compared to AR-normal patients when treated with docetaxel as first-line therapy. This introduces the opportunity to use plasma to select for docetaxel in preference to androgen receptor-directed therapies in AR gained mCRPC patients.
Author Interviews, Biomarkers, Cancer Research, Prostate Cancer / 28.10.2018

MedicalResearch.com Interview with: [caption id="attachment_45534" align="alignleft" width="128"]Davide Pellacani Ph.D. Postdoctoral Fellow, Eaves' Lab Terry Fox Laboratory, BC Cancer Research Centre Vancouver, BC Dr. Pellacani[/caption] Davide Pellacani Ph.D. Postdoctoral Fellow, Eaves' Lab Terry Fox Laboratory, BC Cancer Research Centre Vancouver, BC MedicalResearch.com: What is the background for this study? What are the main findings? Response: Prostate cancer is characterized by frequent DNA methylation changes compared to normal tissue. Nevertheless, understanding which of those changes lead to the acquisition of malignant proprieties is complicated by the predominance of cells with luminal features in prostate cancers. In this study we generated DNA methylation maps of two distinct cell populations found within prostate cancer samples (called basal and luminal) and their normal counterparts. These datasets clearly showed that many of the common DNA methylation changes found in prostate cancer are present in luminal cells from both cancer and normal tissues. These changes are not necessarily cancer-specific, and are likely due to the bias associated with analyzing tissues in bulk, where most cancer cells have luminal-like features. We used these datasets to derive two cancer-specific and phenotype-independent DNA methylation signatures: one specific to prostate cancer luminal cells, and one composed of changes measured in both luminal and basal cancer cells. We then validated the potential clinical utility of these signatures by testing their ability to distinguish prostate cancer from normal samples, and tumours that have already escaped the prostate from those that have not, using the publicly available dataset from The Cancer Genome Atlas.
Author Interviews, Endocrinology, JAMA, Prostate Cancer, UCLA / 22.09.2018

MedicalResearch.com Interview with: [caption id="attachment_44624" align="alignleft" width="200"]Amar U. Kishan, MD Assistant Professor Department of Radiation Oncology University of California, Los Angeles Dr. Kishan[/caption] Amar U. Kishan, MD Assistant Professor Department of Radiation Oncology University of California, Los Angeles MedicalResearch.com: What is the background for this study? What are the main findings? Response: Three large randomized trials demonstrated an overall survival (OS) benefit when androgen deprivation therapy (ADT) is combined with radiotherapy (RT) for high-risk prostate cancer (PCa). The duration of ADT in these seminal studies ranged from six months to lifelong. Because ADT has multiple attendant adverse effects--including bone loss, altered metabolism, diminished muscle mass, gynecomastia, hot flashes, and possibly increased cardiovascular events--shortening the duration of ADT without compromising oncologic effectiveness has been an area of active study. Five trials have compared various durations of ADT, reaching conflicting conclusions with respect to overall survival outcomes, with some suggesting an improvement with longer durations of ADT and others failing to show a uniform survival benefit. Most of these trials have amalgamated Gleason grade group 4 (Gleason score 8) PCa with Gleason grade group (GG) 5 (Gleason score 9-10) PCa. Emerging data indicate that GS 9-10 PCa constitutes a distinct subset of high-risk PCa with inferior outcomes and earlier progression than GS 8 disease. With the knowledge that GS 9-10 PCas constitute a distinct, more aggressive form of PCa, one might hypothesize that longer durations of ADT may be more advantageous in both augmenting local control and controlling potential micrometastatic disease. Alternatively, as GS 9-10 lesions by definition contain highly de-differentiated Gleason pattern 5 disease foci and may proceed to a castrate-resistant state more rapidly, one may also hypothesize that GS 9-10 lesions are less responsive to ADT, and longer durations may be counter-productive. In order to identify differences in the impact of ADT duration on clinical outcomes of patients with GG 4 and GG 5 PCa, we performed an individual patient-level meta-analysis of six randomized trials. Our working hypothesis was that longer durations of ADT would offer significant survival benefits in both groups.
Alcohol, Author Interviews, Prostate Cancer / 23.08.2018

MedicalResearch.com Interview with: [caption id="attachment_44104" align="alignleft" width="200"]Emma H. Allott, PhD Research Assistant Professor of Nutrition UNC GILLINGS SCHOOL OF GLOBAL PUBLIC HEALTH  University of North Carolina, Chapel Hill  Dr. Emma Allott[/caption] Emma H. Allott, PhD Research Assistant Professor of Nutrition UNC GILLINGS SCHOOL OF GLOBAL PUBLIC HEALTH University of North Carolina, Chapel Hill  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Prostate cancer development may span decades. In addition, the prostate grows rapidly during puberty and therefore may be particularly susceptible to dietary or lifestyle factors during this time. Our study found that heavier alcohol intake earlier in life, as well as higher cumulative alcohol intake across the lifespan, was associated with an increased odds of being diagnosed with an aggressive (clinically significant) prostate cancer in later life. However, current alcohol intake at the time of prostate cancer diagnosis was unrelated to tumor aggressiveness.
Author Interviews, Cost of Health Care, JAMA, Medicare, NYU, Prostate Cancer / 22.08.2018

MedicalResearch.com Interview with: [caption id="attachment_44063" align="alignleft" width="200"]Danil V. Makarov, MD, MHS Department of Urology and Department of Population Health New York University Langone School of Medicine VA New York Harbor Healthcare System, Robert F. Wagner Graduate School of Public Service Cancer Institute, New York University School of Medicine, New York Dr. Makarov[/caption] Danil V. Makarov, MD, MHS Department of Urology and Department of Population Health New York University Langone School of Medicine VA New York Harbor Healthcare System, Robert F. Wagner Graduate School of Public Service Cancer Institute, New York University School of Medicine, New York MedicalResearch.com: What is the background for this study? What are the main findings?  Response: Reducing prostate cancer staging imaging for men with low-risk disease is an important national priority to improve widespread guideline-concordant practice, as determined by the National Comprehensive Cancer Network guidelines. It appears that prostate cancer imaging rates vary by several factors, including health care setting. Within Veterans Health Administration (VHA), physicians receive no financial incentive to provide more services. Outside VHA, the fee-for-service model used in Medicare may encourage provision of more healthcare services due to direct physician reimbursement. In our study, we compared these health systems by investigating the association between prostate cancer imaging rates and a VA vs fee-for-service health care setting. We used novel methods to directly compare Veterans, Medicare Recipients, and Veterans that chose to receive care from both the VA at private facilities using Medicare insurance through the Choice Act with regard to rates of guideline-discordant imaging for prostate cancer. We found that Medicare beneficiaries were significantly more likely to receive guideline-discordant prostate cancer imaging than men treated only in VA. Moreover, we found that men with low-risk prostate cancer patients in the VA-only group had the lowest likelihood of guideline-discordant imaging, those in the VA and Medicare group had the next highest likelihood of guideline-discordant imaging (in the middle), and those in the Medicare-only group had the highest likelihood of guideline-discordant imaging. 
Author Interviews, Cancer Research, JAMA, Prostate Cancer / 26.07.2018

MedicalResearch.com Interview with: [caption id="attachment_43522" align="alignleft" width="168"]Alison L. Allan, PhD Department of Oncology, Western University London Regional Cancer Program, London Health Sciences Centre London, Ontario, Canada  Dr. Allan[/caption] Alison L. Allan, PhD Department of Oncology, Western University London Regional Cancer Program, London Health Sciences Centre London, Ontario, Canada  MedicalResearch.com: What is the background for this study? What are the main findings?  Response: This was an international collaborative study between Lawson Health Research Institute (London, ON), Memorial Sloan Kettering Cancer Center (New York), the Royal Marsden (London, UK) and molecular diagnostics company Epic Sciences (San Diego, CA). The study used a liquid biopsy test developed by Epic Sciences that examines circulating tumour cells (CTCs) in blood samples from patients with advanced prostate cancer who are deciding whether to switch from hormone-targeting therapy to chemotherapy. CTCs are cancer cells that leave a tumour, enter the blood stream and invade other parts of the body, causing the spread of cancer. The test identifies whether or not a patient’s CTCs contain a protein in the nucleus called AR-V7. The research team set out to determine whether the presence of this protein predicted which treatment would best prolong a patient’s life. They found that patients who tested positive for the protein responded best to taxane-based chemotherapy while those who tested negative for the protein responded best to hormone-targeting therapy with drugs called androgen-receptor signaling (ARS) inhibitors. These are the two most widely used drug classes to treat advanced prostate cancer.
Author Interviews, Biomarkers, Cancer Research, Genetic Research, Prostate Cancer / 23.07.2018

MedicalResearch.com Interview with: [caption id="attachment_43400" align="alignleft" width="189"]Gong-Hong Wei, PhD Professor, Academy Research Fellow Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu University of Oulu, Finland Dr. Gong-Hong Wei,[/caption] Gong-Hong Wei, PhD Professor, Academy Research Fellow Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu University of Oulu, Finland MedicalResearch.com: What is the background for this study? What are the main findings? Response: Prostate cancer is the second most common cancer and the fifth leading cause of cancer-related death in men, with more than 1,100,000 new cases diagnosed and 300,000 deaths yearly around the globe. Among the risk factors for prostate cancer development, the genetic heritability of prostate cancer has been reported near 60%. Over the past decade, genome-wide association studies have identified more than 150 independent single nucleotide polymorphisms (SNPs) associated with prostate cancer risk. However, we know very little mechanisms accounting for these associations. SNP rs11672691 at the chromosome 19q13 locus has been found not only associated with prostate cancer risk but also aggressiveness, a form of prostate cancer often with worse prognosis and eventually progression to incurable stage. However, how this genomic variant accounts for prostate cancer severity remains totally unknown. Here we found the association of rs11672691 with additional clinical features of aggressive prostate cancer in an independent cohort of patients with prostate cancer, and discovered a rs11672691-mediated gene regulatory network including several novel genes, HOXA2, CEACAM21 and PCAT19, likely causing prostate cancer progression to incurable stage. In particular, the risk G (guanine) allele of rs11672691 was associated with higher RNA levels of PCAT19 and CEACAM21, and poor prognosis in prostate cancer patients. Rs11672691 G allele enhances chromatin binding of HOXA2 to regulate the expression of CEACAM21 and PCAT19. Using the CRISPR-Cas9 genome editing method, we revealed that rs11672691 genotype directly influence HOXA2 in regulating PCAT19 and CEACAM21 expression, and prostate cancer cellular phenotype.
Author Interviews, Prostate, Prostate Cancer, Urology / 06.07.2018

MedicalResearch.com Interview with: [caption id="attachment_42965" align="alignleft" width="149"]Prof. Hashim Ahmed Professor and Chair of Urology Imperial College London Prof. Ahmed[/caption] Prof. Hashim Ahmed Professor and Chair of Urology Imperial College London MedicalResearch.com: What is the background for this study? What are the main findings? Response: Men with localised clinically significant prostate cancer currently undergo radical (whole gland) surgery or radiotherapy. These treatments are effective but can cause urine leakage in 5-30% and erectile dysfunction in 30-60%. Radiotherapy can cause rectal problems in 5%. So, although there is benefit in treating the cancer in these men, the side effects significantly affect the quality of life.