Dr. Perez-Cornago[/caption]
Aurora Perez-Cornago, PhD
Cancer Epidemiology Unit
Nuffield Department of Population Health
University of Oxford
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Greater height and adiposity have been suggested as possible prostate cancer risk factors, but these associations are not clear, probably
because most previous studies have not looked separately at different tumour subtypes.
For this reason, we wanted to look at these associations splitting tumours into subtypes according to tumour stage and histological grade, looking as well at death from prostate cancer.
We found a marked difference in risks looking at low and high risk tumours. Taller men and men with greater adiposity had an elevated of high-grade prostate cancer and prostate cancer death.
Dr. Lee[/caption]
Dr. Norman Lee PhD
Professor of Pharmacology and Physiology
School of Medicine and Health Sciences
George Washington University
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: There are health disparities when it comes to prostate cancer. The African American population, in general, has a higher prostate cancer incidence and mortality rate compared to other racial groups such as European Americans. A major reason for this disparity is due to socioeconomic factors such as access to health care. There are also biological influences for the disparities, such as specific gene mutations and genetic polymorphisms that are found at a higher incidence in the African American population.
My lab has been studying other potential contributing biological factors in prostate cancer disparities; namely, RNA splicing. RNA splicing is a cellular program that increases the diversity of expressed proteins by regulating which exons are included in an mRNA transcript, leading to mRNA variants encoding slightly different proteins (or isoforms) in different cells, organs, and individuals. One can think of RNA splicing as a form of genetic diversity. What we have found is that the repertoire of mRNA variants can differ in prostate cancer between African and European Americans. We also find that the mRNA variants in African American prostate cancer encode signal transduction proteins that are more oncogenic and resistant to targeted therapies, compared to the variants found in European American prostate cancer.
Dr. Yong-Jie Lu[/caption]
Dr. Yong-Jie Lu MBBS, MD, PhD
Reader in Medical Oncology
Centre for Molecular Oncology
Barts Cancer Institute - a CR-UK Centre of Excellence
Queen Mary University of London
John Vane Science Centre, Charterhouse Square
London
MedicalResearch.com: What is the background for this study?
Response: Identifying/monitoring the occurrence of metastasis and the prediction of the length that a patient may survive with a prostate cancer is critical for doctors to select the proper treatment, aiming to achieve the best control of the cancer with a balance of quality of life. Currently this is achieved mainly by analysing the cancer tissues acquired through very invasive procedures or by expensive imaging techniques, most of which expose the patient to toxic radioactive materials.
Circulating tumour cells (CTCs), which play a key role in the metastasis process, have been shown for their potential to be used for cancer prognosis by a simple blood sample analysis. However, previous CTC studies mainly detect the epithelial type of CTCs. Using the ParsortixTM (ANGLE plc) cell-size and deformability based CTC isolation system, we analysed not only epithelial CTCs, but also CTCs with epithelial-mesenchymal transition (EMT), a cellular process associated with cancer invasion and metastasis.
Dr. Gulani[/caption]
Vikas Gulani, MD, PhD
Director, MRI, UH Cleveland Medical Center
Associate Professor, Radiology, CWRU School of Medicine
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: We wanted to learn if performing MR before prostate biopsy, followed by MR guided strategies for biopsy, are cost effective for the diagnosis of prostate cancer in men who have not previously undergone a biopsy and who have a suspicion of prostate cancer.
The most significant findings are as follows:
We found that all three MR guided strategies for lesion targeting (cognitive targeting, MR-ultrasound fusion targeting, and in-gantry targeting) are cost effective, as the increase in net health benefits as measured by addition of quality adjusted life years (QALY), outweigh the additional costs according to commonly accepted willingness to pay thresholds in the United States.
Cognitive targeting was the most cost effective. In-gantry biopsy added the most health benefit, and this additional benefit was cost-effective as well.
Dr. Bela S. Denes[/caption]
Bela S. Denes, MD, FACS
Senior Director Medical Affairs
UROLOGY
Genomic Health Inc.
Redwood City, CA. 94063
MedicalResearch.com: What is the background for this study?
Response: This is a prospective community based non-interventional study designed to provide information on the utility of Oncotype GPS in the management of men presenting with a new diagnosis of clinically localized low risk prostate cancer. We sought to understand the impact of incorporating a molecular marker into the shared treatment decision in practices already well versed in Active Surveillance (AS) as measured by persistence on surveillance at 2 years as well as a number of patient reported outcomes. The current publication reports on the results of a one year pre-specified interim analysis.
Dr. Keyan Salari[/caption]
Keyan Salari, MD, PhD
Resident in Urologic Surgery
Keyan Salari is currently completing his residency in the Harvard Program in Urologic Surgery at the Massachusetts General Hospital, and is conducting post-doctoral research in cancer genomics in the
Garraway Lab at the Dana-Farber Cancer Institute
and the Broad Institute of Harvard and MIT
MedicalResearch.com: What is the background for this study?
Response: Active surveillance is an effective strategy addressing the problem of over treatment of clinically indolent prostate cancer, but data on the role of active surveillance in younger men is limited. Younger men diagnosed with prostate cancer are typically counseled to undergo treatment as opposed to surveillance of their prostate cancer.
To potentially expand the role of active surveillance to younger patient populations, we undertook this study evaluating the outcomes of younger men under 60 years of age who elected to pursue active surveillance of their prostate cancer.
Dr. Klein[/caption]
Eric A. Klein, MD
Chairman, Glickman Urological and Kidney Institute
Cleveland Clinic
MedicalResearch.com: Which of these results did you find most interesting or surprising?
Response: What’s most interesting is that the IsoPSA assay redefines how PSA is measured, which links it more closely to the underlying biology of cancer. Current assays measure only the concentration of PSA, which can be affected by conditions other than cancer – BPH most commonly, but also infection and inflammation – which limits its diagnostic accuracy for finding cancer. Its been known for several decades that PSA exists in multiple different forms in the bloodstream in patients with prostate cancer.
These novel molecules arise because cancer cells have deranged cellular metabolism that result in the generation of new species of PSA, making their measurement more tightly linked to the presence or absence of cancer and even the presence of high grade cancer (where cellular metabolism is even more disordered).
The IsoPSA assay is the first assay to measure all of these isoforms and thus has better diagnostic accuracy for cancer.
Dr. Bibbins-Domingo[/caption]
Kirsten Bibbins-Domingo, Ph.D., M.D., M.A.S.
Lee Goldman, MD, endowed chair in medicine and professor of medicine and of epidemiology and biostatistics
University of California, San Francisco
Chair of the U.S. Preventive Services Task Force
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Prostate cancer is one of the most common cancers to affect men, and the Task Force believes all men should be aware of the benefits and harms of screening for prostate cancer. Prostate cancer screening with PSA testing can help men reduce their chance of dying of prostate cancer or of having metastatic cancer. These are important benefits but occur in a small number of men. There are risks associated with screening, specifically overdiagnosis and overtreatment with surgery and radiation that can have important side effects like impotence and incontinence.
Since the release of our 2012 recommendation, new evidence has emerged that increased the Task Force’s confidence in the benefits of screening, which include reducing the risk of metastatic cancer (a cancer that spreads) and reducing the chance of dying from prostate cancer. This draft recommendation also reflects new evidence on the use of active surveillance in men with low-risk prostate cancers that may help mitigate some of the harms in these men by allowing some men with low risk cancer to delay or avoid surgery or radiation. Therefore, in our new 2017 draft recommendation, the Task Force encourages men ages 55 to 69 to make an individual decision about whether to be screened after a conversation with their clinician about the potential benefits and harms. For men age 70 years and older, the potential benefits do not outweigh the harms, and these men should not be screened for prostate cancer.
Dr. Alice Levine[/caption]
Dr. Alice Levine MD
Professor, Medicine, Endocrinology, Diabetes and Bone Disease
Associate Professsor ,Oncological Sciences
Icahn School of Medicine at Mount Sinai
MedicalResearch.com: What is the background for this study?
Response: Prostate cancer (PCa) bone metastases are a major cause of morbidity and mortality. This cancer is unique in its tendency to produce osteoblastic (OB) bone metastases, which affects 90% of men with PCa bone metastases, compared to others that produce osteolytic bone metastases. Currently, there are no existing therapies that specifically target the OB phase and no effective therapies for PCa bone metastases that prolong survival. We have identified a secretory protein that promotes the development PCa osteoblastic bone metastases, Prostatic acid phosphatase (PAP). Prostatic epithelial cells produce PAP. The physiologic function of PAP is unknown. It was the first human tumor marker ever described. Patients with PCa bone metastases demonstrated high levels of PAP. PAP is expressed by PCa cells in OB metastases and increases OB growth, differentiation, and bone mineralization.
Dr. Catton[/caption]
Charles N Catton, MD, FRCPC
Cancer Clinical Research Unit (CCRU)
Princess Margaret Cancer Centre
UHN
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Prostate cancer is a very common malignancy which is frequently treated with external beam radiotherapy. A typical standard treatment course can extend over 7.5-8.5 weeks.
The introduction of high-precision radiotherapy treatment techniques provided the opportunity to compress treatment courses by delivering fewer, but more intensive daily treatments. The concerns with giving fewer and larger daily treatments (hypofractionation) is that toxicity may increase and that cancer control may become worse.
This international randomized trial enrolled 1206 men with intermediate risk prostate cancer and compared a standard 8 week course of external beam radiation treatment with a novel hypofractionated treatment course that was given over 4 weeks. Cancer control as measured by PSA control and clinical evidence of failure, bowel and bladder toxicity and quality of life were compared.
At a median follow-up of 6 years the hypofractionated regimen was found to be non-inferior to the standard regimen for cancer control. There was no difference early or late bladder toxicity between the two treatments. There was slightly worse early bowel toxicity during and immediately after treatment with the hypofractionated regimen, but there was actually slightly less long-term bowel toxicity with this same regimen.
Dr. Stacy Loeb[/caption]
Dr. Stacy Loeb MD Msc
Assistant Professor of Urology and Population Health
New York University Langone Medical Center
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: The association between exposure to testosterone replacement therapy and prostate cancer risk is controversial. The purpose of our study was to examine this issue using national registries from Sweden, with complete records on prescription medications and prostate cancer diagnoses. Overall, we found no association between testosterone use and overall prostate cancer risk. There was an early increase in favorable cancers which is likely due to a detection bias, but long-term users actually had a significantly reduced risk of aggressive disease.
Dr. Caram[/caption]
Megan Elizabeth Veresh Caram MD
Clinical Lecturer
Internal Medicine, Hematology & Oncology
University of Michigan
MedicalResearch.com: What is the background for this study?
Response: Abiraterone and enzalutamide are oral medications that were approved by the Food & Drug Administration in 2011 and 2012 to treat men with metastatic castration-resistant prostate cancer. Most men with advanced prostate cancer are over age 65 and thus eligible for Medicare Part D. We conducted a study to better understand the early dissemination of these drugs across the United States using national Medicare Part D and Dartmouth Atlas data.
Dr. Hamstra[/caption]
Daniel A. Hamstra, MD PhD
Radiation Oncologist
Beaumont Hospital
Dearborn Michigan
MedicalResearch.com: What is the background for the The SpaceOAR phase 3 trial study and the hydrogel spacer?
Response: External beam radiation therapy is commonly used to treat men with prostate cancer. As part of this treatment, side effects can occur involving bowel, urinary, and sexual symptoms.
This study was performed to test if an absorbable hydrogel placed between the prostate and rectum (using a simple outpatient procedure) could move the rectum away from the prostate and thus result in sparing of the rectum and decreased bowel toxicity. The study randomized 222 men and the three-year data were just published (The International Journal of Radiation Oncology Biology and Physics). With three years of follow-up, we saw that the spacer did improve the radiation plans and decreased both rectal toxicity and urinary toxicity.
Dr. Neeraj Agarwal[/caption]
Neeraj Agarwal, MD
Associate Professor, Division of Oncology, Department of Medicine
University of Utah School of Medicine
MedicalResearch.com: What is the background for this study?
Response: Biomarkers predicting response to cancer therapy help guide physicians personalize medicine. Significant advances have been made in the development of therapeutic biomarkers in various malignancies, but not in prostate cancer. Dr. Nima Sharifi’s group at the Cleveland Clinic recently discovered that a germline inherited polymorphic variant (1245A→C) in the HSD3B1 gene correlates with shorter duration of response to androgen deprivation therapy (ADT) in hormone sensitive prostate cancer (HSPC). HSD3B1 gene encodes the enzyme 3β-hydroxysteroid dehydrogenase-1 (3βHSD1), which catalyzes adrenal androgen precursors into dihydrotestosterone, the most potent androgen.
The authors found that the variant allele of HSD3B1 led to decreased progression-free survival in a dose-dependent manner in post-prostatectomy biochemical recurrence and metastatic HSPC (mHSPC). These results needed external validation before application in the clinic. In our study, we sought to provide the first independent validation of these results in patients with mHSPC.
Dr. John Gore[/caption]
Dr. John L. Gore, MD
Associate Professor
Adjunct Associate Professor-Surgery
Department of Urology
University of Washington
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: The rationale for our study derives from the uncertainty that both patients and clinicians confront when trying to make decisions about adjuvant therapy for prostate cancers found to have aggressive pathologic features at the time of radical prostatectomy. There is level 1 evidence in support of adjuvant radiation therapy in this setting, but several factors restrain providers from recommending adjuvant radiation. We found that interjecting a genomic test that predicts the risk of clinical metastases 5 years after surgery impacts the treatment recommended and helps men and clinicians feel more confident in the decision they are making or recommending.
Dr. Nina Klemann[/caption]
Dr. Nina Klemann
MD, PhD-student
Copenhagen Prostate Cancer Center
Copenhagen
MedicalResearch.com: What is the background for this study?
Response: For 30 years, ultrasound-guided biopsies of the prostate have been used in the evaluation of men suspected for prostate cancer. The biopsy needles are employed systematically into the prostate at different sites where prostate cancer is typically present. However, it has been recognized for years, that there is a risk of not hitting the cancer areas, simply by chance. Although cancer diagnosis may be missed in the initial biopsy set by sampling error, it has been a continuous debate whether lethal prostate cancer is missed. Today, we know that prostate cancer is a common finding in men age 50-80, but that the life-time risk of prostate cancer death in this age-group is low. Consequently, we know that there is a considerable risk of diagnosing, and ultimately treating, a disease that will never result in symptoms or death.
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.
Rebecca Siegel[/caption]
Rebecca Siegel, MPH
Strategic Director, Surveillance Information Services
American Cancer Society, Inc.
250 Williams St.
Atlanta, GA 30303
MedicalResearch.com: What is the bottom line for incidence and mortality trends?
Response: The bottom line for cancer mortality is that in contrast to many other major causes of death, cancer death rates continue to decline, dropping by 25% from 1991 to 2014. This translates to about 2 million fewer cancer deaths over this time period than would be expected if cancer death rates had remained at their peak. Death rates are the best measure of progress against disease.
Cancer incidence rates also dropped in men over the past decade of data, whereas in women they are flat. The drop in men is because of large declines for the top 3 cancers (prostate, lung, and colorectum), which account for more than 40% of cancers diagnosed in men. The stable trend in women is largely because declines in lung and colorectal cancers are offset by a flat trend for both breast and uterine corpus (i.e., endometrial) cancers, which combined account for almost 40% of cases in women, as well as rapid increases for thyroid cancer over the past decade -- increasing by almost 5% annually. Importantly, thyroid incidence rates have stabilized in the past few data years because of modifications in diagnostic criteria.
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.
Dr. Lauren P. Wallner[/caption]
Lauren P. Wallner, PhD, MPH
Assistant Professor, Departments of Medicine and Epidemiology, University of Michigan
Adjunct Investigator
Kaiser Permanente Southern California
North Campus Research Complex
Ann Arbor, MI
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: 5 alpha-reductase inhibitors (5ARIs) are often used for the management of lower urinary tract symptoms in men. Two prior clinical trials found 5ARIs also reduced the risk of prostate cancer, but there was an increase in more aggressive (Gleason 7-10) cancers among the men who were diagnosed. Thus, concerns over whether 5ARIs may increase the risk of prostate cancer death have limited their use in the prevention of prostate cancer, which remains controversial. To address the safety of 5ARIs for the primary prevention of prostate cancer, we conducted a large population-based study of over 200,000 men in community practice settings of over a 19 year observation period to assess whether 5ARI use (as compared to alpha-blocker use) was associated with prostate cancer mortality.
Our results suggest that 5ARI use was not associated with an increased risk of prostate cancer mortality when compared to alpha-blocker use.
Prof. Jenny Donovan[/caption]
Professor Jenny Donovan
OBE FMedSci NIHR-SI AcSS FFPHM
Director, NIHR CLAHRC West
(National Institute for Health Research Collaboration for
Leadership in Applied Health Research and Care West)
at University Hospitals Bristol NHS Trust
Lewins Mead, Bristol
Professor of Social Medicine
School of Social and Community Medicine
University of Bristol
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: PSA testing identifies many men with prostate cancer, but they do not all benefit from treatment. Surgery, radiation therapy and various programs of active monitoring/surveillance can be given as treatments for fit men with clinically localized prostate cancer. Previous studies have not compared the most commonly used treatments in terms of mortality, disease progression and patient-reported outcomes. In the ProtecT study, we used a comprehensive set of validated measures, completed by the men at baseline (before diagnosis), at six and 12 months and then annually for six years.
The main finding is that each treatment has a particular pattern of side-effects and recovery which needs to be balanced against the findings from the paper reporting the clinical outcomes (Hamdy et al).