Older Men Continue To Have PSA Screening Despite Benefits Unlikely To Outweigh Risks

MedicalResearch.com Interview with:
Zahava Berkowitz, MSPH, MSc
Statistician
Division of Cancer Prevention and Control
Centers for Disease Control and Prevention

MedicalResearch.com: What is the background for this study?

Response: The US Preventive Services Task Force 2017 draft prostate cancer screening recommendations  suggest that clinicians inform men aged 55–69 years about the potential benefits and harms of PSA-based screening for prostate cancer.

The CDC conducted an analysis using the National Health Interview Surveys in 2005, 2008, 2010, 2013, and 2015 to describe trends in the receipt of routine PSA testing in the past year by age group (40–54, 55–69, ≥70 years) and by risk group. We compared routine PSA screening among higher risk men (defined as African American men or men with a family history of prostate cancer) with other men. The analysis was conducted because CDC wanted to examine how the guidelines affect men at higher risk. The 2017 guideline did not include specific guidelines for African American men who have a higher incidence of prostate cancer than white men, more likely to develop prostate cancer at a young age, more likely to have a high-risk diagnosis and die from prostate cancer.

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Prostate Cancer: Immune Content May Predict Response To Post-Op Radiation

MedicalResearch.com Interview with:

Dr. Shuang George Zhao, MD House Officer, Radiation Oncology University Hospital Ann Arbor, MI 48109-5010

Dr. Zhao

Dr. Shuang George Zhao, MD
House Officer, Radiation Oncology
University Hospital
Ann Arbor, MI 48109

MedicalResearch.com: What is the background for this study?

Response: Targeting cancer through the immune system has been a longstanding goal of cancer research, and with recent advances in immunotherapy, it is now a reality. However, the role of immunotherapy in prostate cancer is still being defined. Sipuleucel-T was the first FDA approved immunotherapy in prostate cancer, and is a personalized cellular therapy that has been shown to prolong survival in patients with metastatic prostate cancer. On the other hand, two recent phase III randomized trials looking at ipilimumab, a CTLA-4 checkpoint inhibitor in metastatic prostate cancer have both been negative for their primary endpoint of OS. Interestingly, there was a PSA response, suggesting that there may be some therapeutic effect in a subset of patients. Therefore, understanding the immune infiltrate is likely critical to selecting patients and therapeutic strategies utilizing the immune system. Unfortunately, it is difficult and laborious to histologically assess immune infiltrate directly. Therefore, we used existing high throughput transcriptomic data with new computational methods in order to more fully characterize the immune landscape of localized prostate cancer.

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20 Year Follow-Up of Surgery vs Active Surveillance for Early Prostate Cancer

MedicalResearch.com Interview with:
Dr. Timothy Wilt, MD MPH

Core Investigator: Minneapolis VA Center for Chronic Disease Outcomes Research
Staff Physician: Section of General Internal Medicine, Minneapolis VA Health Care System
Professor: Medicine, University of Minnesota School of Medicine 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Prostate cancer is common and potentially serious. However, the comparative benefits and harms of surgery versus observation in men with localized prostate cancer are not known.

After nearly 20 years, surgery did not significantly reduce all-cause or prostate cancer mortality compared to observation, particularly in men with low risk disease. Surgery was associated with more harms than observation, causing complications within 30 days in about 20% of men and large long term increases in urinary incontinence, sexual dysfunction and dissatisfaction, as well as treatment related bother and reductions in daily functioning.

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Overweight, Tall Men Have Greater Risk of Aggressive Prostate Cancer

MedicalResearch.com Interview with:

Aurora Perez-Cornago, PhD Cancer Epidemiology Unit Nuffield Department of Population Health University of Oxford

Dr. Perez-Cornago

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.

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RNA Splicing Variants Linked To Aggressive Prostate Cancer in African Americans

MedicalResearch.com Interview with:

Dr. Norman Lee PhD Professor of Pharmacology and Physiology School of Medicine and Health Sciences George Washington University

Dr. Lee

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.

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Photodynamic Therapy Being Developed To Target Prostate Cancer

MedicalResearch.com Interview with:
Dr. Susanne Lütje
Ärztlicher Dienst
Universitätsklinikum Essen (AöR)
Klinik für Nuklearmedizin
Essen Germany

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Prostate cancer (PCa) is the most common cancer in men and accounts for a significant amount of morbidity and mortality. At present, the curative treatment option of choice for localized stages of PCa is radical prostatectomy, which may include extended lymph node dissection. Unfortunately, surgical procedures can be accompanied by complications such as urinary incontinence. Most importantly, small tumor deposits may not be seen by the surgeon during surgery and could ultimately lead to disease recurrence. To overcome these issues, new and innovative treatments are needed. The prostate-specific membrane antigen (PSMA) is a surface protein that is overexpressed in prostate cancer and can be used as a target to guide new therapies.

Photodynamic therapy (PDT) is an ablative procedure in which tumor cells can be destroyed effectively by irradiation of light of a specific wavelength, which activates previously administered photosensitizers. The photosensitizers can respond by emitting fluorescence or emitting oxygen radicals which can cause cellular damage. Coupling the photosensitizer to an agent that targets PSMA on the tumor surface offers the possibility to selectively and effectively destroy prostate tumor remnants and micrometastases, while surrounding healthy tissues remain unaffected.

In our study, the PSMA targeting antibody D2B was coupled to the photosensitizer IRDye700DX and radiolabeled with 111In. In a mouse model, this multi-modality agent was used to preoperatively visualize tumor lesions with SPECT/CT to allow rough localization of the tumors. During surgery, the fluorescent signal originating from the photosensitizer facilitates visualization of tumors and residual tumor tissue, so the surgeon can be guided towards accurate resection of the entire tumors and metastases. In addition, the PSMA-targeted PDT can be applied to destroy small tumor deposits in cases where close proximity of the tumors.

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Circulating Cell Scoring System Identifies High Risk Prostate Cancer

MedicalResearch.com Interview with:

Dr. Yong-Jie Lu 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

Dr. Yong-Jie Lu

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.

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MRI Guided Prostate Biopsies Can Improve Care and Reduce Costs

MedicalResearch.com Interview with:

Vikas Gulani, MD, PhD Director, MRI, UH Cleveland Medical Center Associate Professor, Radiology, CWRU School of Medicine

Dr. Gulani

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.

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Genomic Profile Can Improve Confidence in Active Surveillance of Prostate Cancer

MedicalResearch.com Interview with:

Bela S. Denes, MD, FACS Senior Director Medical Affairs UROLOGY Genomic Health Inc. Redwood City, CA. 94063

Dr. Bela S. Denes

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.

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Active Surveillance Can Be Expanded To Select Group of Younger Men With Prostate Cancer

MedicalResearch.com Interview with:

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 MI

Dr. Keyan Salari

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.

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New Prostate Cancer Specific Assay May Reduce Need For Biopsies

MedicalResearch.com Interview with:

Eric A. Klein, MD</strong> Chairman, Glickman Urological and Kidney Institute Cleveland Clinic

Dr. Klein

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.

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USPSTF Recommends Men 70 or Older Not Be Screened for Prostate Cancer

MedicalResearch.com Interview with:

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

Dr. Bibbins-Domingo

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.

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PAP May Provide New Therapeutic Target For Bone Metastatic Prostate Cancer

MedicalResearch.com Interview with

Dr. Alice Levine MD Professor, Medicine, Endocrinology, Diabetes and Bone Disease Associate Professsor ,Oncological Sciences Icahn School of Medicine at Mount Sinai

Dr. Alice Levine

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.

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Shorter Term Precision Radiation Found Effective For Prostate Cancer

MedicalResearch.com Interview with:

Charles N Catton, MD, FRCPC Cancer Clinical Research Unit (CCRU) Princess Margaret Cancer Centre UHN

Dr. Catton

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.

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Taking Testosterone Doesn’t Increase Prostate Cancer Risk

MedicalResearch.com Interview with:

Dr. Stacy Loeb, MD, MScDepartment of Urology, Population Health, and Laura and Isaac Perlmutter Cancer CenterNew York University, New York

Dr. Stacy Loeb

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.

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Clinical Outcomes Following a Low-Suspicion MRI for Prostate Cancer

MedicalResearch.com Interview with:

Lars Boesen MD PhD Department of Urology Herlev Gentofte University Hospital Herlev

Dr. Boessen

Lars Boesen MD PhD
Department of Urology
Herlev Gentofte University Hospital
Herlev

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Transrectal ultrasound-guided biopsies (TRUS-bx) traditionally used for detecting prostate cancer (PCa) are prone to sampling errors due to difficulties in target identification. Therefore, concerns about the possibility of missing significant prostate cancer result in men with negative biopsy results frequently undergo repeated biopsies, leading to increased medical costs, patient anxiety and morbidity.

Multiparametric MRI (mp-MRI) has become increasingly important in prostate cancer diagnosis. A suspicious lesion can be targeted by MRI-guided biopsies and improve diagnosis. Conversely, a normal mp-MRI may non-invasively exclude the possibility of an aggressive disease, avoiding the need for further biopsies. However, there are no current guidelines for clinicians whether standard repeated biopsies (TRUS-bx) should be performed in men with either a low-suspicion mp-MRI or benign MRI-targeted biopsies of a suspicious lesion and the clinical outcome and future risk of detecting significant prostate cancer following these findings is unknown.

Therefore, we assessed the risk of being diagnosed with prostate cancer after either a low-suspicion mp-MRI or benign targeted biopsies of a suspicious lesion in men with prior negative TRUS-bx, but a persistent clinical suspicion of missed significant cancer over a follow-up period of at least three years. Our results suggest that a low-suspicion MRI in men with prior negative TRUS-bx can be used non-invasively in ruling out longer term significant cancer and immediate repeated biopsies are of limited clinical value and might be avoided even if prostate-specific-antigen levels are persistently elevated.

MedicalResearch.com: What should readers take away from your report?

Response: A low-suspicion mp-MRI in a man with prior negative TRUS-bx has a high accuracy in ruling out a significant aggressive prostate cancer during follow-up of at least three years. Thus, immediate repeated biopsies rarely find significant disease and could be avoided even if the prostate-specific-antigen level is persistently elevated.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response: Our results should be verified in larger prospective studies with a longer follow-up period to assess other clinical endpoints that include disease progression, cancer specific mortality and associated costs with an mp-MRI approach.

There are no disclosures or conflicts of interest

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

Citation:
J Urol. 2017 Feb 21. pii: S0022-5347(17)30297-5. doi: 10.1016/j.juro.2017.02.073. [Epub ahead of print]
Clinical outcome following a low-suspicion multiparametric prostate MRI or benign MRI-guided biopsy to detect prostate cancer: A follow-up study in men with prior negative transrectal ultrasound-guided biopsies.
Boesen L1, Nørgaard N2, Løgager V3, Thomsen HS4.
Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

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Regional Variation in Chemotherapy Prescriptions For Metastatic Prostate Cancer

MedicalResearch.com Interview with:

Megan Elizabeth Veresh Caram MD Clinical Lecturer Internal Medicine, Hematology & Oncology University of Michigan

Dr. Caram

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.

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Using a Spacer During Prostate Radiation May Help Preserve Sexual Function

MedicalResearch.com Interview with:

Daniel A. Hamstra, MD PhD The Texas Center for Proton Therapy Irving, TX

Dr. Hamstra

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.

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Prostate Cancer: No Association Between Androgen Deprivation Therapy and Dementia

MedicalResearch.com Interview with:
Farzin Khosrow-Khavar, M.Sc. Ph.D. Candidate
Department of Epidemiology, Biostatistics and Occupational Health, McGill University
Center for Clinical Epidemiology – Jewish General Hospital
Montreal, QC 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Previous studies have shown an association between androgen deprivation therapy (ADT) and risk of dementia and Alzheimer’s disease. However, these studies had methodological limitations that may account for this positive association. Using appropriate study design and methodology, we found no association between androgen deprivation therapy and risk of dementia (including Alzheimer’s disease) in patients with prostate cancer. These results were consistent by cumulative duration of  androgen deprivation therapy use and by ADT modality.

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Genetic Defect in DNA Repair Enzyme Linked to Prostate Cancer

MedicalResearch.com Interview with:
G. Andrés Cisneros, Ph.D.

Associate Professor
Department of Chemistry Center for Advanced Scientific Computing and Modeling, University of North Texas

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The accurate maintenance of DNA is crucial, if DNA damage is not addressed it can lead to various diseases including cancer. Therefore, the question arises about what happens if enzymes in charge of DNA repair are themselves mutated. We previously developed a method to perform targeted searches for cancer-related SNPs on genes of interest called HyDn-SNP-S. This method was applied to find prostate-cancer SNPs on DNA dealkylases in the ALKB family of enzymes.

Our results uncovered a particular mutation on ALKBH7, R191Q, that is significantly associated with prostate cancer. Subsequent computer simulations and experiments indicate that this cancer mutation results in a decreased ability of ALKBH7 to bind its co-factor, thus impeding its ability to perform its native function.

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Prostate Cancer: Genetic Biomarker Predicts Response To Androgen Deprivation Therapy

MedicalResearch.com Interview with:

Neeraj Agarwal, MD Associate Professor, Division of Oncology, Department of Medicine University of Utah School of Medicine

Dr. Neeraj Agarwal

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.

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Penile Length One Year After Radical Prostatectomy Not Statistically Different Than Pre-Op

MedicalResearch.com Interview with:
Yoshifumi Kadono, MD. PhD.
Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science,
Kanazawa, Ishikawa, Japan 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: I had experienced some patients who underwent radical prostatectomy (RP) complained penile shortening after RP. Once I checked that kind of reports, some reports mentioned the phenomenon of penile shortening (PS) after radical prostatectomy; however, the results were little bit different and the reasons of PS after RP were not well elucidated.

Therefore, we started our study to obtain our data. In our study, the penile length (PL) was measured before, 10 days after, and at 1, 3, 6, 9, 12, 18, and 24 months after RP. And the PL at 10 days after RP was shortest, and it gradually recovered thereafter. Penile length at 12 months after radical prostatectomy was not significantly different from preoperative penile length. Based on MRI investigation, slight vertical repositioning of the membranous urethra after radical prostatectomy caused chronological changes in penile length.

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5-alpha reductase inhibitors For BPH Linked to Higher, Not Lower, PSA Levels

MedicalResearch.com Interview with:
Teemu J Murtola, MD, PhD, adjunct professor
University of Tampere, Faculty of Medicine and Life Sciences
Tampere University Hospital, Department of Urology
Tampere, Finland

MedicalResearch.com: What is the background for this study?

Response: A previous study called Prostate Cancer Prevention Trial
(PCPT) showed that finasteride, which belongs to a drug group called
5alpha-reductase inhibitors lowers serum PSA and increases sensitivity
of PSA to detect high-grade prostate cancer in men who had little or
no symptoms of the lower urinary tract. We postulated that this effect
would increase the accuracy and benefits of PSA-based prostate cancer
screening.

Finnish Randomized Study of Screening for Prostate Cancer was a large
trial of over 80,000 men randomized either to be screened for prostate
cancer with a PSA test at 4-year intervals or to be followed for
prostate cancer incidence and mortality via national registries. Three
consecutive screening rounds were commenced between 1996-2008. In the
current study we compared the effects of PSA-based screening on
prostate cancer risk and mortality separately among men who were using
5alpha-reductase inhibitors finasteride or dutasteride and among men
who were not.

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Genomic Testing Can Improve Confidence in Prostate Cancer Treatment Strategy

MedicalResearch.com Interview with:

Dr. John L. Gore, MD Associate Professor Adjunct Associate Professor-Surgery Department of Urology University of Washington

Dr. John Gore

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.

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Cancer-Related Mortality Low In Men With Benign Prostate Biopsy

MedicalResearch.com Interview with:

Dr. Nina Klemann MD, PhD-student Copenhagen Prostate Cancer Center Copenhagen

Dr. Nina Klemann

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.

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Fall in PSA Best Predictor of Mortality After Prostate Cancer Treatment

MedicalResearch.com Interview with:

Trevor Royce MD MS
Resident, Harvard Radiation Oncology Program

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Clinical trials in early prostate cancer take more than a decade to report on.

Multiple early reporting endpoints have been proposed, but which one is best, remains unknown, until now. Of all the possible early endpoints examined, to date, how low a PSA blood test falls to, after treatment with radiation and hormonal therapy, appears to be the best, specifically, if the PSA doesn’t get below half a point, that patient is very likely to die of prostate cancer if given standard treatment for recurrence.

Those men deserve prompt enrollment on clinical trials in order to properly save their life.

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Breast and Prostate Cancer Screenings Have Similar Potential for OverDiagnosis

MedicalResearch.com Interview with:
Karsten Juhl Jørgensen, MD, Dr. MedSci
The Nordic Cochrane Centre
Rigshospitalet, Copenhagen 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Our systematic Cochrane review of the original randomised breast screening trials showed substantial conflict between their estimates of the benefit. Some trials showed a large benefit, others none or a small benefit. This difference was related to the design of the trials.

The most optimistic trials were those with suboptimal randomisation.

The main findings of our current study support those of the most rigorously performed randomised trials: breast screening does not fulfill its fundamental premise, which is to reduce the occurrence of late stage disease. This means a mortality reduction is unlikely and that use of less invasive surgery due to breast screening is also unlikely.

However, we did find very substantial increases in early stage breast cancer, which persisted over our 17 year observation period. This means that breast screening likely leads to substantial overdiagnosis of breast cancers that would otherwise not have caused health problems during a woman’s lifetime. We estimate that 1 in 3 breast cancers detected in a screened population is likely overdiagnosed.

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Prostate Cancer Treatment Declines Sharply in General Population, But Not Among Diagnosed Men

MedicalResearch.com Interview with:
Tudor Borza, MD, MS
Urologic Oncology and Health Service Research Fellow
Department of Urology, University of Michigan

MedicalResearch.com: What is the background for this study?

Response: Starting in the late 2000’s studies began to identify overdiagnosis and overtreatment in men with prostate cancer. Because of the indolent nature of some prostate cancers many men who ended up diagnosed and treated would have never had any consequences from their prostate cancer. This led national organizations (like the American Urological Association and the National Comprehensive Cancer Network) to call for decreased prostate cancer screening (using the serum PSA test) and eventually led to the US Preventive Services Task Force to recommend against routine PSA screening, citing that the harms from diagnosis and treatment outweighed the harms from the disease. Over the same specialists treating the disease began to report on the safety of surveillance strategies in select men with prostate cancer.

Watchful waiting (delaying any treatment until men become symptomatic from their cancer and then offering palliative treatment) was found to be comparable to initial treatment in men with a limited life expectance, either from advanced age or multiple comorbidities. Similarly, active surveillance (a technique employing intense monitoring with PSA testing, digital rectal exams, repeat biopsies and possible use of MRI or other biomarkers) was introduced with the goal of delaying treatment in some men with low risk cancer until the cancer becomes more aggressive and was shown to have similar outcomes to initial treatment in carefully selected men.

We wanted to study the trends in initial prostate cancer treatment in this context of recommendations for decreased screening and recognition of the feasibility of surveillance in certain patients with prostate cancer.

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Incidence of Metastatic Prostate Cancer at Diagnosis Rises in US

MedicalResearch.com Interview with:

Dr. Jim C. Hu MD MPH Professor of Urology Weill Cornell Medicine

Dr. Jim Hu

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.

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Photodynamic Therapy May Be Useful In Some Low-Risk Prostate Cancer

MedicalResearch.com Interview with:
Prof Mark Emberton
UCL Faculty of Medical Sciences
London

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The key driver was a desire to come up with a treatment for men with localised prostate cancer that was better tolerated that the traditional options. The intervention is a combination of padeliporphin, a short acting photosensitiser which was developed by Drs Shertz and Salomon at the Weismann Institute. This is activated by a laser inserted into the prostate.

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Prostate Biopsies and Prostatectomies Drop After PSA Recommendation Changes

MedicalResearch.com Interview with:

Jim C. Hu, M.D., M.P.H. Ronald P. Lynch Professor of Urologic Oncology Director of the LeFrak Center for Robotic Surgery Weill Cornell Medicine Urology New York Presbyterian/Weill Cornell New York, NY 10065

Dr. Jim Hu

Jim C. Hu, M.D., M.P.H.
Ronald P. Lynch Professor of Urologic Oncology
Director of the LeFrak Center for Robotic Surgery
Weill Cornell Medicine
Urology
New York Presbyterian/Weill Cornell
New York, NY 10065

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The US Preventative Services Task Force (USPSTF) recommended against PSA testing in men older than 75 years in 2008 and more recently in all US men regardless of age in 2012. This was largely based on a faulty study, the prostate, lung, colo-rectal and ovarian screening study. We demonstrated in May 2016 that this randomized trial did not compare screening to no screening or apples to oranges, as it set out to do. It compared screening to screening. Although controversial, the guidelines were well-intentioned, as recognize that there is over-diagnosis and over-treatment of men with prostate cancer. Given this background, the goal of our study was to explore the downstream consequences of the recommendation against PSA screening. As such, we explored 3 separate databases to characterize national procedure volumes for prostate needle biopsy and radical prostatectomy, or surgery to cure prostate cancer.

The main finding was that prostate biopsy numbers decreased by 29% and radical prostatectomy surgeries decreased by 16% when comparing before to after USPSTF recommendations against PSA screening. Therefore practice patterns followed policy. Prostate biopsies are usually performed due to an elevated, abnormal screening PSA. However, it is also performed to monitor low-risk, slow growing prostate cancers. We also found that while the overall number of prostate biopsies decreased, there was a 29% increase in the proportion or percentage of biopsies performed due to active surveillance, or monitoring of low risk prostate cancers which should be done periodically. Therefore we provide the first national study to demonstrate that there is less over-diagnosis and over-treatment of prostate cancer.

However, the concern is that we also recently demonstrated that there is more aggressive prostate cancer on surgical pathology for men who go on to radical prostatectomy. They have high grade, higher stage cancers, which have a lower chance of cure. The link is:

http://www.prostatecancerreports.org/fulltext/2016/_Hu_JC160708.pdf

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5ARIs Found Not Linked To Increased Prostate Cancer Mortality

MedicalResearch.com Interview with:

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

Dr. Lauren P. Wallner

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.

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Patient-Reported Outcomes after Monitoring, Surgery, or Radiotherapy for Localized Prostate Cancer

MedicalResearch.com Interview with:

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

Prof. Jenny Donovan

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).

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Androgen Deprivation For Prostate Cancer Linked to Dementia

MedicalResearch.com Interview with:
Kevin T. Nead, MD, MPhil

Resident, Radiation Oncology
Perelman School of Medicine
Hospital of the University of Pennsylvania.

MedicalResearch.com: What is the background for this study?

Response: Androgen deprivation therapy is a primary treatment for prostate cancer and works by lowering testosterone levels. There is a strong body of research suggesting that low testosterone can negatively impact neurovascular health and function. We were therefore interested in whether androgen deprivation therapy is associated with dementia through an adverse impact on underlying neurovascular function.

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Little Change in PSA Use After Taskforce Recommendation

MedicalResearch.com Interview with:
Dr Ryan Hutchinson MD and
Yair Lotan MD

Department of Urology
University of Texas Southwestern Medical Center

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The United States Preventative Services Task Force recommendation against PSA screening generated significant controversy. Research since then has relied heavily on survey data to examine the impact of the recommendation on PSA screening practices. In a hotly charged issue such as this, such data can carry significant bias.

We examined a large, whole-institution data in the years before and after the USPSTF recommendations reflecting actual practice and found that the changes in PSA use at our institution, if any, were small. This is more consistent with behavior seen after the vast majority of practice recommendations.

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No Link Found Between Vasectomy and Developing or Dying From Prostate Cancer

MedicalResearch.com Interview with:

Eric Jacobs, PHD | Strategic Director, Pharmacoepidemiology American Cancer Society, Inc. 250 Williams St. Atlanta, GA 30303

Dr. Eric Jacobs

Eric Jacobs, PHD
Strategic Director, Pharmacoepidemiology
American Cancer Society, Inc.
250 Williams St.
Atlanta, GA 30303

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Vasectomy is a common, inexpensive, and very effective method of long-term birth control. However, in 2014, an analysis from a large epidemiologic cohort study, the Health Professionals Follow-Up Study, found that vasectomy was associated with about 10% higher overall risk of prostate cancer and about 20% higher risk of fatal prostate cancer. Together with other researchers at the American Cancer Society, I analyzed the association between vasectomy and fatal prostate cancer among more than 363,000 men in the Cancer Prevention Study II (CPS-II) cohort, age 40 and older, who were followed for up to 30 years. This is the largest prospective analysis of vasectomy and fatal prostate cancer to date. We also examined vasectomy and prostate cancer in a subset of about 66,000 CPS-II study participants who were followed for new diagnoses of prostate cancer.

We found no link between having had a vasectomy and risk of either developing or dying from prostate cancer.

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IL-33 May Be First Stand Alone Biomarker of Prostate Cancer Recurrence

MedicalResearch.com Interview with:
Iryna Saranchova MD
PhD candidate
Michael Smith Laboratories
Vancouver, BC

MedicalResearch.com: What is the background for this study?

• The immune system is efficient at identifying and halting the tumour emergence at early stages. However, when metastatic (sufficient to cause death) tumour appears, the immune system is no longer able to recognize the cancer cells and control their growth and spread.
• Recent studies of solid cancers have shown considerable heterogeneity between different tumour types and several lines of evidence suggest that tumours are not only heterogeneous, but they constantly evolve during the disease progression and this often hampers the existing treatment methods.
• It means that it is important to consider each patient’s mutational changes accumulated over time in antecedent primary, metastatic lesions and/or local recurrences. This approach will help to understand the mechanism of tumour development, create a background for specific treatment modality and prevent therapeutic failure with consequent systemic relapse of the disease
• Therefore, in our project we were aiming to find possible immune markers of tumour transition from the primary stage to its metastatic form. For this purpose, we selected a special study model: two pairs of separate mouse tumour cell lines, where metastatic cells arose from the initial primary tumour.

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Is Testosterone Therapy Safe in Patients with Treated and Untreated Prostate Cancer?

MedicalResearch.com Interview with:

Dr. Jesse Ory Department of Urology, Faculty of Medicine Dalhousie University, Halifax Nova Scotia, Canada

Dr. Jesse Ory

Dr. Jesse Ory
Department of Urology, Faculty of Medicine
Dalhousie University, Halifax
Nova Scotia, Canada 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The use of Testosterone Therapy (TT) in men diagnosed with and treated for prostate cancer (CaP) has been highly controversial for several decades. Unfortunately, this controversy is largely founded on the results of a single patient in a study by Huggins and Hodges in the 1940s [1]. This wasn’t challenged until recently, when Morgentaler reviewed the literature on the topic and found no scientific basis for the assumption that TT will act like fuel on the fire of prostate cancer [2]. He also proposed a mechanism, the “saturation hypothesis” that helps account for why TT may in fact be safe for men with prostate cancer. [3]. Over the past decade, retrospective evidence has been accumulating that supports the safety of Testosterone Therapy in hypogonadal men with CaP on Active Surveillance, or in those who have been definitively treated for prostate cancer..

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Localized Prostate Cancer: Patient-Reported Outcomes after Monitoring, Surgery, or Radiotherapy

MedicalResearch.com Interview with:

Professor Jenny Donovan  PhD   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 Bristol, UK

Prof. Jenny Donovan

Professor Jenny Donovan  PhD
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
Bristol, UK

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).

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Math Algorithm Helps Predict Recurrence of Prostate Cancer


MedicalResearch.com Interview with:  

Ilaria Stura PhD

Università degli Studi di Torino
Turin, Piedmont, Italy


MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Man has always tried to predict the future, especially to prevent catastrophes, diseases and death. In this case, we want to prevent the ‘personal catastrophe’, i.e. the spread of the disease (recurrence of prostate cancer) in the patient. Our work therefore belongs to the so-called ‘personalized medicine’, a very important and innovative clinical approach.

In particular this study may potentially improve the quality of life of the patients and help the clinicians, since it could give valuable information to the urologist, for example reporting that the growth velocity of the tumor is increasing and that a relapse is expected within few months. With this information, the clinician could chose the best therapy for the patient (e.g. hormone or radio therapy) in order to stop the spread of the disease or, conversely, the use of drugs can be delayed if not necessary.

Obviously clinicians already try to do this, based on their experience, but our method provides further confidence in their ‘investigation’ work, since the algorithm is validated on data coming from a database much larger than his/her personal experience.

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Digital Rectal Exam and PSA May Detect Distinct Subtypes of Prostate Cancer

MedicalResearch.com Interview with:

Jim C. Hu, MD Ronald Lynch Professor of Urologic Oncology Weill Cornell Medicine New York, NY 10065

Dr. Jim Hu

Jim C. Hu, MD
Ronald Lynch Professor of Urologic Oncology
Weill Cornell Medicine
New York, NY 10065

MedicalResearch.com: What is the background for this study?

Response: Initial results from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO), a large-scale randomized controlled trial of prostate cancer screening in the United States, radically changed the landscape of prostate cancer screening insofar as it led the United States Preventative Services Task Force (USPSTF) to recommend against routine screening with prostate-specific antigen (PSA). Though many subsequent studies have continued to investigate the role of PSA in screening, there is a paucity of data examining the use of digital rectal examination (DRE) for screening in the PSA era. Indeed, the USPSTF recommendation did not explicitly address DRE, calling for further research to evaluate the role of periodic DRE in prostate cancer screening. Likewise, while recent guidelines from the National Comprehensive Cancer Network (NCCN) recommend use of PSA in all men who elect screening, the role of digital rectal examination is equivocal.

We sought to evaluate the value of  digital rectal examination and PSA for detection of clinically significant prostate cancer and prostate cancer-specific (PCSM) and overall mortality in a secondary analysis of the PLCO.

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Docetaxel Adds To Overall Survival in Metastatic Castration-Resistant Prostate Cancer

MedicalResearch.com Interview with:
Prof. Ronald de Wit, MD, PhD
Medical Oncologist
Medical Oncology
Erasmus MC
University Medical Center, Rotterdam

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Mainsail is one of the largest phase 3 trials in the setting of  Metastatic Castration-Resistant Prostate Cancer (mCRPC)  in the past decade that investigated the addition of a second active biological drug to standard docetaxel every 3 weeks plus prednisone. In Mainsail the greater myelotoxicity caused by the addition of lenalidomide to docetaxel resulted in a reduction of the number of cycles of docetaxel that patients were able to tolerate – median of 6 cycles in the DPL arm vs. 8 in the DP arm. Median overall survival (OS) was shorter in patients receiving lenalidomide, which could have attributed to either a direct adverse effect of lenalidomide on OS, or, alternatively because of the reduction in the number of docetaxel treatment cycles. In this study we investigated the impact of the cumulative dose of docetaxel as reflected by the total number of cycles of docetaxel on median OS, in Univariate and Multivariate analyses on the ITT Population, both dependent upon the treatment arm, as well as irrespective of the treatment arm. In subsequent sensitivity analyses we addressed potential confounding factors on the eventual survival outcome.

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Reported Early Stage Prostate Cancer Incidence Again Decreased

MedicalResearch.com Interview with:

Dr. Ahmedin Jemal, DVM, PhD Vice President, Surveillance and Health Services Research American Cancer Societ

Dr. Ahmedin Jemal

Dr. Ahmedin Jemal, DVM, PhD
Vice President, Surveillance and Health Services Research
American Cancer Society

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: We previously showed large decrease in early stage prostate cancer incidence rates from 2011 to 2012 in men 50 years and older following the US Preventive services Task Force recommendation against routine prostate-specific antigen testing in 2011. In this paper, we examined whether the decrease in early stage incidence persisted through 2013.

We found that early stage prostate cancer incidence rates in men age 50 and older decreased from 2012 to 2013, although the decrease (6%) was lower compared to the decrease from 2011-2012 (19%). In contrast, rates for distant stage disease between 2012 and 2013 remained unchanged.

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Quality of Life Similar For Men on Active Surveillance For Prostate Cancer vs Negative Biopsy

MedicalResearch.com Interview with:

Jennifer Cullen Meyer, PhD, MPH Director of Epidemiologic Research, Center for Prostate Disease Research Assistant Professor, Norman M. Rich Dept. of Surgery, Uniformed Services University Rockville, MD 20852

Dr. Jennifer Cullen Meyer

Jennifer Cullen Meyer, PhD, MPH
Director of Epidemiologic Research, Center for Prostate Disease Research
Assistant Professor, Norman M. Rich Dept. of Surgery, Uniformed Services University
Rockville, MD 20852

MedicalResearch.com: What is the background for this study?

Response: Men diagnosed with prostate cancer who are at low risk for cancer progression may choose to defer immediate treatment with curative intent and, instead, monitor their cancer. This strategy is referred to as “active surveillance.” The primary benefit of active surveillance is that it allows men to temporarily defer definitive cancer treatments that are known to cause decrements in health-related quality of life (HRQoL). Studies have shown that HRQoL is better in men choosing active surveillance as compared to other treatment modalities. However, prior to our study, it was not known whether men on active surveillance experience worse HRQoL than men without prostate cancer.

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Data For Risk of Prostate Cancer with Drugs for Erectile Dysfunction Mixed

MedicalResearch.com Interview with:

Juzar Jamnagerwalla, MD Division of Urology, Department of Surgery Cedars-Sinai Medical Center Los Angeles, California

Dr. Juzar Jamnagerwalla

Juzar Jamnagerwalla, MD
Division of Urology, Department of Surgery
Cedars-Sinai Medical Center
Los Angeles, California

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: In mouse models phosphodiesterase type-5 inhibitors (PDE-5i) have been shown to have anti-neoplastic activity, and given the routine use of PDE-5i for treatment of erectile dysfunction after prostatectomy several studies have examined the association between PDE-5i use and biochemical recurrence after treatment for prostate cancer with mixed findings. Only one previous study has explored the association between risk of prostate cancer, finding that men on PDE-5i had a lower chance of being diagnosed with prostate cancer. Given this, we tested the relationship between PDE-5i use and risk of prostate cancer in 6,501 men in the REDUCE study finding that PDE-5i use was not associated with prostate cancer diagnosis. On secondary analysis, among North American men who had a much higher baseline use of PDE-5i use, there was an inverse association between PDE-5i use and prostate cancer diagnosis, which approached, but did not reach statistical significance.

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Prostate Cancer Genes in African American Men May Be Affected by Vitamin D Supplementation

MedicalResearch.com Interview with:

Gerard (Gary) Hardiman, Ph.D Professor, Department of Medicine Professor Department of Public Health Sciences Bioinformatics Director Center for Genomic Medicine Medical University of South Carolina Charleston, SC 29425

Dr. Gerard Hardiman

Gerard (Gary) Hardiman, Ph.D
Professor, Department of Medicine Professor
Department of Public Health Sciences Bioinformatics Director
Center for Genomic Medicine Medical
University of South Carolina
Charleston, SC 29425

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: There are significant racial disparities in prostate cancer outcomes. The disease disproportionately affects African American men in terms of incidence, morbidity, and mortality, even after adjustment for stage. African American men have a 2- to 3-times increased risk of developing prostate cancer and have a greater mortality rate compared to European American men. We carried out a prospective clinical study aimed at examining the effects of vitamin D3 supplementation at 4,000 IU per day for two months in male subjects who selected surgical removal of the prostate (prostatectomy) as a definitive treatment for their prostate cancer. The primary goal of this study was to examine molecular differences in gene expression patterns relevant to prostate cancer disparities between African American and European American men, and investigate the global effects of vitamin D3 supplementation on the prostate transcriptome. We carried out genome wide expression profiling experiments using high throughput (HT) RNA sequencing. Transcriptional profiles of each of the patient’s tissue samples were generated and systems level analyses were performed.

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No Difference in Outcomes at 12 Weeks With Robotic vs Open Prostate Surgery

MedicalResearch.com Interview with:

Prof Robert A Gardiner AM The University of Queensland Centre for Clinical Research Royal Brisbane & Women’s Hospital, Herston Brisbane,Australia

Prof. Robert Gardiner

Prof Robert A Gardiner AM
The University of Queensland Centre for Clinical Research
Royal Brisbane & Women’s Hospital, Herston
Brisbane,Australia

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: We wanted to determine whether one approach gave better results than the other at 12 weeks and 24 months after surgery with respect to the quality of life outcomes of urinary, sexual and bowel function and return to usual activities as well as oncological outcomes.

There was no significant statistical difference between the robotic and open surgical approach for these parameters at the early time-point of 12 weeks follow-up.

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Metastatic Prostate Cancer Surges: Could Reduced PSA Screening Be A Cause?

MedicalResearch.com Interview with:

Dr. Adam Weiner MD Urology Resident Feinberg School of Medicine Northwestern University

Dr. Adam Weiner

Dr. Adam Weiner MD
Urology Resident
Feinberg School of Medicine
Northwestern University

MedicalResearch.com: What is the background for this study? 

Response: There has been a lot of controversy over the past decade regarding whether PSA screening for prostate cancer prevents death from prostate cancer. Accordingly, the US preventive services task force (USPSTF) recommended against PSA screening for older men in 2008 and for all men in 2012. This was mainly based on information from a large clinical trial in the US.

Recently it was discovered that men in the non-screening part of this trial received even more PSA screens than men in the screening part of the trial, suggesting the results were likely diluted.

In a large European trial, PSA screening was shown to reduce both death from prostate cancer and the number of men diagnosed with metastatic prostate cancer, an incurable and deadly form of prostate cancer.

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PD-1 Blocker May Help Some With Metastatic Prostate Cancer

MedicalResearch.com Interview with:

Julie Graff, M.D. Oncologist specializing in prostate cancer Knight Cancer Institute Oregon Health & Science University

Dr. Julie Graff

Julie Graff, M.D.
Oncologist specializing in prostate cancer
Knight Cancer Institute
Oregon Health & Science University

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Men with metastatic prostate cancer that is not responding to second-line androgen receptor blockade (such as enzalutamide) have a very limited life expectancy. We found that adding immunotherapy to enzalutamide in men whose prostate cancer is no longer responding to enzalutamide could exert a very strong anti-cancer effect. Previous experience with this type of immunotherapy in prostate cancer patients suggested this type immunotherapy does not work in patients with prostate cancer. What we have found will lead to more studies of this agent.

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Targeted Proteomics Furthers Goal of Liquid Biopsy To Predict Aggressiveness of Prostate Cancer

MedicalResearch.com Interview with:

Thomas Kislinger, PhD Senior Scientist at the Princess Margaret Cancer Centre University Health Network Associate Professor Department of Medical Biophysics University of Toronto

Dr. Thomas Kislinger

Thomas Kislinger, PhD
Senior Scientist at the Princess Margaret Cancer Centre
University Health Network
Associate Professor
Department of Medical Biophysics
University of Toronto

MedicalResearch.com: What is the background for this study?

Response: The goal of this study was to develop a non-invasive, prognostic biomarker that can address the worldwide clinical dilemma of over-treating low-risk prostate cancers. To accomplish this we developed highly accurate proteomics assays in urines collected after a digital rectal examination (termed post-DRE urines).

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