Is Low-Dose Aspirin Protective After Prostate Cancer Diagnosis?

MedicalResearch.com Interview with:
Charlotte Skriver, PhD student, MSc
Danish Cancer Society Research Center
Statistics & Pharmacoepidemiology
Danish Cancer Society
Copenhagen 

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

Response: The drug aspirin is widely used due to its established protection against cardiovascular diseases. Increasing evidence also supports an effect of aspirin use on reducing the risk of and mortality from colorectal cancer and possibly other cancer types. Recent studies have suggested that aspirin use after a diagnosis of prostate cancer may improve the prognosis.

We examined whether use of low-dose aspirin was associated with survival after prostate cancer in a nationwide study of prostate cancer patients in Denmark.

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Prostate Cancer: Novel Androgen Blocker Darolutamide Has Potential to Delay Mets and Extend Survival

MedicalResearch.com Interview with:

Prof. Karim Fizazi, MD, PhD Head of the Department of Cancer Medicine Institute Gustave Roussy

Prof. Fizazi

Prof. Karim Fizazi, MD, PhD
Head of the Department of Cancer Medicine
Institute Gustave Roussy

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

How does darolutamide differ from other medications for prostate cancer?

Response: Despite recent treatment advances, there is still significant unmet need for new therapeutic options for men with non-metastatic castration-resistant prostate cancer (nmCRPC).

In laymen’s terms, nmCRPC is cancer that has not spread beyond the prostate region; PSA levels are elevated, despite treatment with hormone therapy, and men with nmCRPC generally feel well and do not have symptoms. The unmet medical need is for treatments that achieve disease control and delay the spread of the cancer without impacting their daily lives or increasing the burden of disease with treatment side effects.

While the current treatments in this space are effective in delaying onset of metastases, the side effects can be unpleasant and disruptive to men’s lives; particularly cognitive issues, seizures, impact on balance which may lead to falls and bone fractures, rash and hypertension.

Furthermore, new treatment options that have limited interactions with medications typically used in this patient population are also important.  Continue reading

Genetic Mutation May Predict Outcomes of Prostate Cancer Treated With Androgen-Deprivation Therapy or Abiraterone

MedicalResearch.com Interview with:

Masaki Shiota MD, PhD Department of Urology, Graduate School of Medical Sciences Kyushu University Fukuoka , Japan

Dr. Shiota

Masaki Shiota MD, PhD
Department of Urology
Graduate School of Medical Sciences
Kyushu University
Fukuoka , Japan

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

Response:  3β-hydroxysteroid dehydrogenase-1 encoded by HSD3B1 is a rate-limiting enzyme required for all pathways of dihydrotestosterone synthesis, as well as converts abiraterone into Δ4-abiraterone (D4A), which blocks multiple steroidogenic enzymes and antagonizes the androgen receptor.

A mutation (1245A>C) in HSD3B1 is shown to be resistant to proteasomal degradation, causing substantial accumulation of this enzyme and gain-of-function. Although the HSD3B1 (1245C) allele can be acquired by mutation, germ-line single nucleotide polymorphism (SNP; rs1047303) is also known to exist. Then, in this study, we investigated the significance of missense polymorphism in HSD3B1 gene among men treated with primary ADT or abiraterone.

The results showed men carrying variant allele showed higher risk of progression in primary androgen-deprivation therapy, but vulnerable to abiraterone treatment. Continue reading

Metastatic Prostate Cancer: Final Analysis of Adding Abiraterone Acetate (ZYTIGA® ) and Prednisone to Androgen Deprivation Therapy

MedicalResearch.com Interview with:
Kim Nguyen Chi, MD FRCPC

Professor of Medicine, University of British Columbia
Regional Medical Director, BC Cancer – Vancouver

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

Response: For over 70 years, androgen deprivation therapy (ADT) has been the main treatment therapy for metastatic prostate cancer patients. This Phase 3 final analysis study looked at adding abiraterone acetate and prednisone to ADT for patients with metastatic prostate cancer, with the primary objectives being to assess improvements in overall survival and radiographic progression-free survival. At the first interim analysis reported in 2017, both primary endpoints were met, and the study was unblinded and patients on the ADT and placebos arm crossed over to receive ADT with abiraterone and prednisone.

This study is the final analysis reporting on overall survival. The study findings found abiraterone acetate and prednisone plus ADT continued to demonstrate an improvement in overall survival, hazard ratio (HR) = 0.66, meaning a 34% decrease in the risk of death associated with the use of ADT with abiraterone and prednisone. The median overall survival, which had not been reached before in the ADT with abiraterone and prednisone arm, was 53.3 months compared to 36.5 months for ADT plus placebo, prolonging median overall survival by 16.8 months.

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Hypofractionated Radiation for Low Risk Prostate Cancer Saves Time and Money

MedicalResearch.com Interview with:

Deborah Watkins Bruner RN, PhD, FAAN Senior Vice President of Research Emory University Professor and Robert W. Woodruff Chair in Nursing Nell Hodgson Woodruff School of Nursing Professor, Department of Radiation Oncology Emory University School of Medicine

Dr. Bruner

Deborah Watkins Bruner RN, PhD, FAAN
Senior Vice President of Research
Emory University
Professor and Robert W. Woodruff Chair in Nursing
Nell Hodgson Woodruff School of Nursing
Professor, Department of Radiation Oncology
Emory University School of Medicine

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

Response: In a randomized clinical trial entitled, “Quality of Life in Patients With Low-Risk Prostate Cancer Treated With Hypofractionated vs Conventional Radiotherapy” the NRG Oncology Group previously demonstrated that men with low risk prostate cancer had  similar 5-year disease- free survival of about 85%  when treated with either conventional radiotherapy  (C-RT) of 73.8 Gy in 41 fractions over 8.2 weeks, or with  hypofractionated radiotherapy (H-RT) of 70 Gy in 28 fractions over 5.6  weeks. However, late physician reported side effects of mild bowel and bladder symptoms were increased in patients treated  with H-RT and raised questions if the H-RT arm is acceptable to patients.

The current study asked the patient’s directly about their bowel, bladder, sexual function, anxiety, depression and general quality of life using valid patient reported questionnaires. These questionnaires have been found to be more accurate for reporting patient symptoms than physician report alone.

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Stereotactic Radiation Can Condense Treatment Times For Prostate Cancer

MedicalResearch.com Interview with:

Amar U. Kishan, MD Assistant Professor Department of Radiation Oncology University of California, Los Angeles

Dr. Kishan

Amar U. Kishan, MD
Assistant Professor
Department of Radiation Oncology
University of California, Los Angeles

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

Response: Typical external beam radiation courses range up to 8-9 weeks in length (39-45 treatments). There are data that shorter courses, delivering a higher dose per day, may be just as effective.

Stereotactic body radiotherapy (SBRT) really pushes this concept by condensing the treatment to just four to five treatments, with a high dose per day.

Here, we present the pooled results of the outcomes of 2142 men with low and intermediate risk prostate cancer and a median of 6.9 years of followup.

We demonstrate a very favorable efficacy and safety profile. Specifically, the rates of recurrences were 4.5% and 10.2% for low and intermediate risk disease at 7 years, and rates of late severe toxicity were 2.4% for urinary toxicity and 0.4% for gastrointestinal toxicity.

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Radiomics Plus Machine Learning Can Optimize Prostate Cancer Classification

MedicalResearch.com Interview with:

Gaurav Pandey, Ph.D. Assistant Professor Department of Genetics and Genomic Sciences Icahn Institute of Data Science and Genomic Technology Icahn School of Medicine at Mount Sinai, New York 

Dr. Pandey

Gaurav Pandey, Ph.D.
Assistant Professor
Department of Genetics and Genomic Sciences
Icahn Institute of Data Science and Genomic Technology
Icahn School of Medicine at Mount Sinai, New York 

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

 Response: Multiparametric magnetic resonance imaging (mpMRI) has become increasingly important for the clinical assessment of prostate cancer (PCa), most routinely through PI-RADS v2, but its interpretation is generally variable due to its relatively subjective nature.

Radiomics, a methodology that can analyze a large number of features of images that are difficult to study solely by visual assessment, combined with machine learning methods have shown potential for improving the accuracy and objectivity of mpMRI-based prostate cancer assessment. However, previous studies in this direction are generally limited to a small number of classification methods, evaluation using the AUC score only, and a non-rigorous assessment of all possible combinations of radiomics and machine learning methods. Continue reading

Veyonda Enhanced Benefit of Radiation Therapy in Metastatic Prostate Cancer Trial

MedicalResearch.com Interview with:

Graham Kelly, BSc (Vet) (Hons, BVSc (Hons), PhD Managing Director and Chief Executive Officer Noxopharm 

Dr. Kelly

Graham Kelly, BSc (Vet) (Hons, BVSc (Hons), PhD
Managing Director and Chief Executive Officer
Noxopharm 

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

Response: Veyonda is an experimental drug being developed as a means of enhancing the anti-cancer effect of radiotherapy. The Phase 1b DARRT-1 study is assessing the ability of Veyonda to boost a palliative dose of external beam radiotherapy (EBRT) applied to a single lesion, to result in a systemic response in non-irradiated lesions (known as an abscopal response) in men with metastatic, end-stage prostate cancer. The aim is to provide at the least better palliation, and at best a survival advantage. The reported data concerns the study’s initial dose-finding arm involving three different dosages of Veyonda. This arm involves 12 subjects and the report concerns their clinical status at 12-weeks post-irradiation. The data provide clinical evidence of an abscopal effect in at least half of the eight subjects receiving the two highest Veyonda dosages and demonstrate that the combination of Veyonda and palliative radiotherapy was well-tolerated. The 1200 mg dosage was confirmed as the therapeutic dose.

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Advanced Prostate Cancer: Risk of Mortality with Surgery vs Radiotherapy

MedicalResearch.com Interview with:

Anthony Victor D'Amico, MD, PhD Professor and Chief, Genitourinary Radiation Oncology Harvard Medical School

Dr. D’Amico

Anthony Victor D’Amico, MD, PhD
Professor and Chief,
Genitourinary Radiation Oncology
Harvard Medical School

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

Response: This study investigated whether surgery followed by the use of adjuvant low dose radiation and short course hormonal therapy as compared to high dose radiation and hormonal therapy could provide an equivalent low risk of death from prostate cancer amongst men presenting with aggressive and not infrequently fatal Gleason score 9 or 10 prostate cancer.

It has been shown previously (https://jamanetwork.com/journals/jama/fullarticle/2673969) and validated in the current study that surgery alone in such cases leads to a more then 2.5-fold increase in the risk of death from prostate cancer as compared to high dose radiation and hormonal therapy.  Continue reading

Advanced Prostate Cancer: Androgen-Receptor Testing May Guide Selection of Treatment

MedicalResearch.com Interview with:

Diagram_showing_prostate_cancer_that_has_spread_to_the_bones_CRUK_183.svg.png

Prostate cancer that has metastasized to the bone: Wikipedia Image

Vincenza Conteduca, MD, PhD
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) Srl – IRCCS
Meldola , Italy

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

Response: In our previous publications, we showed that the study of plasma cell-free DNA holds promise for improving treatment choice in metastatic castration-resistant prostate cancer (mCRPC). Specifically, we demonstrated that the detection in plasma of aberrations (copy number alterations and/or point somatic mutations) of androgen receptor (AR), using an easy and robust multiplex droplet digital PCR method, predicted an adverse outcome in mCRPC patients treated with second-generation AR-directed therapies (abiraterone or enzalutamide) in both settings: chemotherapy-naïve and post-docetaxel.

This current multi-institution work builds on our previous discoveries. We investigated the association of androgen receptor status and survival in men treated with docetaxel. Moreover, we performed an exploratory analysis in patients treated with docetaxel or AR-directed therapies as first-line therapy.

Interestingly, we observed that plasma AR-gained patients do not have a worse outcome compared to AR-normal patients when treated with docetaxel as first-line therapy. This introduces the opportunity to use plasma to select for docetaxel in preference to androgen receptor-directed therapies in AR gained mCRPC patients.

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Computer Algorithm Can Distinguish Dangerous From Manageable Prostate Cancer

MedicalResearch.com Interview with:

Davide Pellacani Ph.D. Postdoctoral Fellow, Eaves' Lab Terry Fox Laboratory, BC Cancer Research Centre Vancouver, BC

Dr. Pellacani

Davide Pellacani Ph.D.
Postdoctoral Fellow, Eaves’ Lab
Terry Fox Laboratory,
BC Cancer Research Centre
Vancouver, BC

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

Response: Prostate cancer is characterized by frequent DNA methylation changes compared to normal tissue. Nevertheless, understanding which of those changes lead to the acquisition of malignant proprieties is complicated by the predominance of cells with luminal features in prostate cancers.

In this study we generated DNA methylation maps of two distinct cell populations found within prostate cancer samples (called basal and luminal) and their normal counterparts. These datasets clearly showed that many of the common DNA methylation changes found in prostate cancer are present in luminal cells from both cancer and normal tissues. These changes are not necessarily cancer-specific, and are likely due to the bias associated with analyzing tissues in bulk, where most cancer cells have luminal-like features.

We used these datasets to derive two cancer-specific and phenotype-independent DNA methylation signatures: one specific to prostate cancer luminal cells, and one composed of changes measured in both luminal and basal cancer cells.

We then validated the potential clinical utility of these signatures by testing their ability to distinguish prostate cancer from normal samples, and tumours that have already escaped the prostate from those that have not, using the publicly available dataset from The Cancer Genome Atlas.

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MidLife PSA Can Risk-Stratify Prostate Cancer in African American Men

MedicalResearch.com Interview with:

Mark Preston, MD, MPH Associate Surgeon, Brigham and Women's Hospital Assistant Professor of Surgery, Harvard Medical School Brigham and Women's Hospital Department of Surgery, Urology Boston, MA

Dr. Preston

Mark Preston, MD, MPH
Associate Surgeon, Brigham and Women’s Hospital
Assistant Professor of Surgery, Harvard Medical School
Brigham and Women’s Hospital
Department of Surgery, Urology
Boston, MA
MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Black men are at significantly increased risk of developing and dying from prostate cancer. Unfortunately, there is limited research on screening strategies in this high-risk population. In this original investigation, we studied how baseline PSA levels measured in midlife predict later risk of aggressive prostate cancer in a population of black men. This study used stored blood samples and over a decade of follow-up in the Southern Community Cohort Study, an on-going cohort study with the highest representation of black men in the U.S.

We demonstrated that PSA levels in midlife very strongly predict future aggressive prostate cancer. Our data identify subgroups of black men who have widely divergent long-term risk of aggressive prostate cancer based on baseline PSA during midlife. We suggest that these groups could benefit from screening intervals tailored to their actual magnitude of disease risk.

These important findings build on our previous work on baseline PSA and subsequent risk of lethal prostate cancer in mainly white men, which was published in the Journal of Clinical Oncology in August 2016. 

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

Response: One strategy for improving PSA screening is to do an earlier measurement of PSA during midlife (aged 40-55). PSA levels during midlife have been shown by our group and others to strongly predict long-term risk of prostate cancer, particularly risk of aggressive disease, in now both black and white men.

This baseline PSA level during midlife can be used to risk-stratify PSA screening, targeting higher risk men for screening in order to diagnosis and treat them early while an opportunity exists for cure.  In addition, men at low risk could safely be screened less frequently. As a result, much of the benefit of PSA screening on prostate cancer mortality could be maintained, while overdiagnosis and overtreatment would be reduced.

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

Response: Prospective studies of a risk stratified screening program should be conducted.  We are also studying ways to further improve risk prediction and to explore biologic mechanisms why a midlife PSA is so predictive.

Disclosures. I have no disclosures. Disclosures for other authors are listed in the manuscript.

Citation:

Eur Urol. 2018 Sep 17. pii: S0302-2838(18)30627-4. doi: 10.1016/j.eururo.2018.08.032. [Epub ahead of print]

Baseline Prostate-specific Antigen Level in Midlife and Aggressive Prostate Cancer in Black Men.

Preston MA1, Gerke T2, Carlsson SV3, Signorello L4, Sjoberg DD5, Markt SC6, Kibel AS7, Trinh QD7, Steinwandel M8, Blot W9, Vickers AJ5, Lilja H10, Mucci LA6, Wilson KM11.

Oct 14, 2018 @ 12:36 pm

The information on MedicalResearch.com is provided for educational purposes only, and is in no way intended to diagnose, cure, or treat any medical or other condition. Always seek the advice of your physician or other qualified health and ask your doctor any questions you may have regarding a medical condition. In addition to all other limitations and disclaimers in this agreement, service provider and its third party providers disclaim any liability or loss in connection with the content provided on this website.

 

High-Risk Gleason 5 Prostate Cancers Not Resistant to Androgen Deprivation Therapy

MedicalResearch.com Interview with:

Amar U. Kishan, MD Assistant Professor Department of Radiation Oncology University of California, Los Angeles

Dr. Kishan

Amar U. Kishan, MD
Assistant Professor
Department of Radiation Oncology
University of California, Los Angeles

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

Response: Three large randomized trials demonstrated an overall survival (OS) benefit when androgen deprivation therapy (ADT) is combined with radiotherapy (RT) for high-risk prostate cancer (PCa). The duration of ADT in these seminal studies ranged from six months to lifelong. Because ADT has multiple attendant adverse effects–including bone loss, altered metabolism, diminished muscle mass, gynecomastia, hot flashes, and possibly increased cardiovascular events–shortening the duration of ADT without compromising oncologic effectiveness has been an area of active study. Five trials have compared various durations of ADT, reaching conflicting conclusions with respect to overall survival outcomes, with some suggesting an improvement with longer durations of ADT and others failing to show a uniform survival benefit.

Most of these trials have amalgamated Gleason grade group 4 (Gleason score 8) PCa with Gleason grade group (GG) 5 (Gleason score 9-10) PCa. Emerging data indicate that GS 9-10 PCa constitutes a distinct subset of high-risk PCa with inferior outcomes and earlier progression than GS 8 disease. With the knowledge that GS 9-10 PCas constitute a distinct, more aggressive form of PCa, one might hypothesize that longer durations of ADT may be more advantageous in both augmenting local control and controlling potential micrometastatic disease. Alternatively, as GS 9-10 lesions by definition contain highly de-differentiated Gleason pattern 5 disease foci and may proceed to a castrate-resistant state more rapidly, one may also hypothesize that GS 9-10 lesions are less responsive to ADT, and longer durations may be counter-productive.

In order to identify differences in the impact of ADT duration on clinical outcomes of patients with GG 4 and GG 5 PCa, we performed an individual patient-level meta-analysis of six randomized trials. Our working hypothesis was that longer durations of ADT would offer significant survival benefits in both groups.

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Factor in Quality of Life When Deciding Radiotherapy vs Surgery in Patients With Oropharyngeal Cancer

MedicalResearch.com Interview with:

Dr. David Sher MD MPH Radiation Oncology, Harold C. Simmons Comprehensive Cancer Center UTSouthwestern Medical Center Associate Senior Editor International Journal of Radiation Oncology

Dr. Sher

Dr. David Sher MD MPH
Radiation Oncology,
Harold C. Simmons Comprehensive Cancer Center
UTSouthwestern Medical Center
Associate Senior Editor International Journal of Radiation Oncology

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

Response: The prevalence of oropharyngeal cancer is rising rapidly, and the two primary therapeutic approaches – upfront radiation therapy or surgery resection – have both been improving in terms of acute and late toxicity profiles. There is significant debate as to which therapy is better, and comparative data are necessary to help physicians and patients decide which paradigm is preferred for a given clinical scenario. Although there is a lot of anecdotal experience in comparing the two treatments, there really is a lack of published data on the question, and this is where our study fits in. 

MedicalResearch.com: What is the background for this study? Were there significant quality-of-life differences between the two treatment modalities?

Response: The main findings were comparable outcomes in long-term survival, toxicity and even cost between primary radiation therapy and primary surgery. This equivalence highlights the importance of patient-centered decision-making and engaging patient preferences in their optimal treatment approach. There was clearly an increase in stomach tube use in patients receiving primary chemoradiotherapy, which may be an important consideration in some patients, depending on the expected functional outcome of initial surgery. This difference became non-significant after a short period of time, but it was real and may influence decision-making.

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

Response: Readers should take away that there are no particularly large differences between these treatments. Survival, toxicity and cost are all comparable in the long-run. It was quite clear, though, that primary surgery was associated with a lower risk of gastrostomy tube use. Although the difference in tube use was negligible within a few months, the use of any feeding tube may be a deciding factor for some patients. We showed here this difference was due to concurrent chemotherapy during radiotherapy. This result echoes our clinical experience, but we were able to show this finding quite clearly. On the other hand, we also found that the increased dependence with radiation therapy was clearly short-lived, so patients should absolutely not consider this difference as a long-term problem preferentially associated with radiotherapy.

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

Response: It is critical for future research to consider the functional and quality-of-life outcomes in future comparisons of these different treatment approaches. Claims-based analyses such as this can uniquely show the “big picture” with respect to complications that require a medical treatment. However, more granular and subtle patient-reported outcomes are not included in this study, and they will be essential to help patients and physicians in the decision-making process.   

The study was funded by the Radiation Oncology Institute.

Citation:

Sher DJ, Agiro A, Zhou S, Day AT, DeVries A. Commercial Claims–Based Comparison of Survival and Toxic Effects of Definitive Radiotherapy vs Primary Surgery in Patients With Oropharyngeal Squamous Cell Carcinoma. JAMA Otolaryngol Head Neck Surg. Published online September 20, 2018. doi:10.1001/jamaoto.2018.1929

Sep 21, 2018 @ 3:05 pm 

The information on MedicalResearch.com is provided for educational purposes only, and is in no way intended to diagnose, cure, or treat any medical or other condition. Always seek the advice of your physician or other qualified health and ask your doctor any questions you may have regarding a medical condition. In addition to all other limitations and disclaimers in this agreement, service provider and its third party providers disclaim any liability or loss in connection with the content provided on this website.

 

Heavy Alcohol Use Early in Life Linked to Aggressive Prostate Cancer

MedicalResearch.com Interview with:

Emma H. Allott, PhD Research Assistant Professor of Nutrition UNC GILLINGS SCHOOL OF GLOBAL PUBLIC HEALTH  University of North Carolina, Chapel Hill 

Dr. Emma Allott

Emma H. Allott, PhD
Research Assistant Professor of Nutrition
UNC GILLINGS SCHOOL OF GLOBAL PUBLIC HEALTH
University of North Carolina, Chapel Hill 

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

Response: Prostate cancer development may span decades. In addition, the prostate grows rapidly during puberty and therefore may be particularly susceptible to dietary or lifestyle factors during this time.

Our study found that heavier alcohol intake earlier in life, as well as higher cumulative alcohol intake across the lifespan, was associated with an increased odds of being diagnosed with an aggressive (clinically significant) prostate cancer in later life. However, current alcohol intake at the time of prostate cancer diagnosis was unrelated to tumor aggressiveness.

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Low Risk Prostate Cancer Imaging More Common Outside of VA Hospitals

MedicalResearch.com Interview with:

Danil V. Makarov, MD, MHS Department of Urology and Department of Population Health New York University Langone School of Medicine VA New York Harbor Healthcare System, Robert F. Wagner Graduate School of Public Service Cancer Institute, New York University School of Medicine, New York

Dr. Makarov

Danil V. Makarov, MD, MHS
Department of Urology and
Department of Population Health
New York University Langone School of Medicine
VA New York Harbor Healthcare System,
Robert F. Wagner Graduate School of Public Service
Cancer Institute, New York University School of Medicine, New York

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

Response: Reducing prostate cancer staging imaging for men with low-risk disease is an important national priority to improve widespread guideline-concordant practice, as determined by the National Comprehensive Cancer Network guidelines. It appears that prostate cancer imaging rates vary by several factors, including health care setting. Within Veterans Health Administration (VHA), physicians receive no financial incentive to provide more services. Outside VHA, the fee-for-service model used in Medicare may encourage provision of more healthcare services due to direct physician reimbursement.

In our study, we compared these health systems by investigating the association between prostate cancer imaging rates and a VA vs fee-for-service health care setting. We used novel methods to directly compare Veterans, Medicare Recipients, and Veterans that chose to receive care from both the VA at private facilities using Medicare insurance through the Choice Act with regard to rates of guideline-discordant imaging for prostate cancer.

We found that Medicare beneficiaries were significantly more likely to receive guideline-discordant prostate cancer imaging than men treated only in VA.

Moreover, we found that men with low-risk prostate cancer patients in the VA-only group had the lowest likelihood of guideline-discordant imaging, those in the VA and Medicare group had the next highest likelihood of guideline-discordant imaging (in the middle), and those in the Medicare-only group had the highest likelihood of guideline-discordant imaging.  Continue reading

Liquid Biopsy for CTCs Can Predict Treatment Response in Advanced Prostate Cancer

MedicalResearch.com Interview with:

Alison L. Allan, PhD Department of Oncology, Western University London Regional Cancer Program, London Health Sciences Centre London, Ontario, Canada 

Dr. Allan

Alison L. Allan, PhD
Department of Oncology, Western University
London Regional Cancer Program, London Health Sciences Centre
London, Ontario, Canada 

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

Response: This was an international collaborative study between Lawson Health Research Institute (London, ON), Memorial Sloan Kettering Cancer Center (New York), the Royal Marsden (London, UK) and molecular diagnostics company Epic Sciences (San Diego, CA). The study used a liquid biopsy test developed by Epic Sciences that examines circulating tumour cells (CTCs) in blood samples from patients with advanced prostate cancer who are deciding whether to switch from hormone-targeting therapy to chemotherapy. CTCs are cancer cells that leave a tumour, enter the blood stream and invade other parts of the body, causing the spread of cancer. The test identifies whether or not a patient’s CTCs contain a protein in the nucleus called AR-V7. The research team set out to determine whether the presence of this protein predicted which treatment would best prolong a patient’s life.

They found that patients who tested positive for the protein responded best to taxane-based chemotherapy while those who tested negative for the protein responded best to hormone-targeting therapy with drugs called androgen-receptor signaling (ARS) inhibitors. These are the two most widely used drug classes to treat advanced prostate cancer.

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Novel Mechanisms and Clinical Aspects for an Aggressive Prostate Cancer Risk Locus Uncovered

MedicalResearch.com Interview with:

Gong-Hong Wei, PhD Professor, Academy Research Fellow Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu University of Oulu, Finland

Dr. Gong-Hong Wei,

Gong-Hong Wei, PhD
Professor, Academy Research Fellow
Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu
University of Oulu, Finland

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

Response: Prostate cancer is the second most common cancer and the fifth leading cause of cancer-related death in men, with more than 1,100,000 new cases diagnosed and 300,000 deaths yearly around the globe. Among the risk factors for prostate cancer development, the genetic heritability of prostate cancer has been reported near 60%. Over the past decade, genome-wide association studies have identified more than 150 independent single nucleotide polymorphisms (SNPs) associated with prostate cancer risk. However, we know very little mechanisms accounting for these associations.

SNP rs11672691 at the chromosome 19q13 locus has been found not only associated with prostate cancer risk but also aggressiveness, a form of prostate cancer often with worse prognosis and eventually progression to incurable stage. However, how this genomic variant accounts for prostate cancer severity remains totally unknown. Here we found the association of rs11672691 with additional clinical features of aggressive prostate cancer in an independent cohort of patients with prostate cancer, and discovered a rs11672691-mediated gene regulatory network including several novel genes, HOXA2, CEACAM21 and PCAT19, likely causing prostate cancer progression to incurable stage. In particular, the risk G (guanine) allele of rs11672691 was associated with higher RNA levels of PCAT19 and CEACAM21, and poor prognosis in prostate cancer patients. Rs11672691 G allele enhances chromatin binding of HOXA2 to regulate the expression of CEACAM21 and PCAT19. Using the CRISPR-Cas9 genome editing method, we revealed that rs11672691 genotype directly influence HOXA2 in regulating PCAT19 and CEACAM21 expression, and prostate cancer cellular phenotype.

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Ultrasound Therapy Found To Be Effective Option For Prostate Cancer

MedicalResearch.com Interview with:

Prof. Hashim Ahmed Professor and Chair of Urology Imperial College London

Prof. Ahmed

Prof. Hashim Ahmed
Professor and Chair of Urology
Imperial College London

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

Response: Men with localised clinically significant prostate cancer currently undergo radical (whole gland) surgery or radiotherapy. These treatments are effective but can cause urine leakage in 5-30% and erectile dysfunction in 30-60%. Radiotherapy can cause rectal problems in 5%.

So, although there is benefit in treating the cancer in these men, the side effects significantly affect the quality of life. 

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Enzalutamide (Xtandi) Provides Men with NonMetastatic Castration Resistant Prostate Cancer an Effective Treatment Option

MedicalResearch.com Interview with:

Maha Hussain, MD, FACP, FASCO Genevieve Teuton Professor of Medicine Division of Hematology/Oncology Deputy Director Robert H. Lurie Comprehensive Cancer Center Northwestern University Feinberg School of Medicine

Dr. Hussain

Maha Hussain, MD, FACP, FASCO
Genevieve Teuton Professor of Medicine
Division of Hematology/Oncology
Deputy Director
Robert H. Lurie Comprehensive Cancer Center
Northwestern University Feinberg School of Medicine

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

Response: Until recently patients with non metastatic castration resistant prostate cancer (nmcrpc) had no impactful systemic therapy options.  Progression to metastatic crpc; the deadly phase of the cancer, is a given in the vast majority of patients.

Enzalutamide significantly delayed the time to metastases development by almost 2 years compared to placebo with a 71% reduction in the risk of metastases or death and a median metastases free survival of 36.6 compared to 14.7 months respectively.  This was accomplished without negative impact on quality of life (qol).  Enzalutamide treated patients had a higher rate of PSA declines and delayed time to requiring other anticancer therapies.   

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

Response: Androgen receptor targeting continues to be clinically relevant in this disease and the therapeutic impact is greater in earlier disease settings with lower tumor burden. This data provides men with non metastatic castration resistant prostate cancer an effective treatment option.

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

Response: In this disease setting maximizing the antitumor effect with rational combinations to increase tumor kill with the goal of further reducing the risk of metastasis and prolonging overall survival and potentially hope for “cure”. 

MedicalResearch.com: Is there anything else you would like to add? Any disclosures:

Response: On behalf of all my coauthors and study investigators I wish to thank the patients and their caregivers for participating in this trial.  Their partnership is critical to defeat prostate cancer.

Research funding to our institutions for clinical trials from Pfizer.

Citation:

Enzalutamide in Men with Nonmetastatic, Castration-Resistant Prostate Cancer

Maha Hussain, M.D., Karim Fizazi, M.D., Ph.D., Fred Saad, M.D., Per Rathenborg, M.D., Neal Shore, M.D., Ubirajara Ferreira, M.D., Ph.D., Petro Ivashchenko, M.D., Eren Demirhan, Ph.D., Katharina Modelska, M.D., Ph.D., De Phung, B.S., Andrew Krivoshik, M.D., Ph.D., and Cora N. Sternberg, M.D.
June 28, 2018
N Engl J Med 2018; 378:2465-2474
DOI: 10.1056/NEJMoa1800536

 

 

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Genetic Variants Help Identify Men At Highest Risk of Prostate Cancer

MedicalResearch.com Interview with:

Fredrick R. Schumacher, PhD, MPH. Associate Professor, Department of Population & Quantitative Health Sciences Case Western Reserve University Cleveland

Dr. Schumacher

Fredrick R. Schumacher, PhD, MPH.
Associate Professor, Department of Population & Quantitative Health Sciences
Case Western Reserve University
Cleveland

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

Response: Our study examines the genetic underpinnings of prostate cancer initiation using technology to test variants across the genome. Our study focused on men of European ancestry and included over 80,000 men with prostate cancer and 60,000 men without disease. We discovered 63 novel genetic variants associated with prostate cancer risk, which increases our knowledge of prostate cancer genetic risk factors by more than 60%.

A genetic risk score created from the combination of 163 new and known prostate cancer risk variants revealed men with the highest genetic risk score are nearly seven times more likely to develop disease compared to the average man. Additionally, men with the lowest genetic risk score have a 85% risk reduction of developing prostate cancer compared to the average. Lastly, these new discoveries uncover several biological mechanisms involved in the initiation of prostate cancer.

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bpMRI Can Be Used to Improve Prostate Cancer Risk

MedicalResearch.com Interview with:

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

Dr. Boessen

Dr. Lars Boesen MD PhD
Department of Urology
Herlev Hospital

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

Response: The current standard of care in prostate cancer diagnosis includes untargeted transrectal ultrasound-guided biopsies for all biopsy-naïve men with clinically suspicion of prostate cancer. However, this strategy that practically has remained unchanged for decades has limited diagnostic accuracy as significant cancers are missed or under-graded and insignificant cancers are unintendedly detected by the random sampling leading to possible overtreatment.

Multiparametric MRI in the diagnosis of prostate cancer has been studied extensively in recent years and has improved detection, localization, staging and risk stratification. It has been suggested that if multiparametric MRIs were used as a triage test prior to biopsies, a significant proportion of men might safely avoid prostate biopsies and the diagnostic ratio of significant vs. insignificant cancer could be improved compared to performing standard biopsies in all men. However, multiparametric MRIs are generally time-consuming (~40 min scan time), expensive and include intravenous contrast media. This reduces its feasibility for widespread clinical implementation in larger patient populations in the western community with its high PCa prevalence.

The development of a simpler and faster (~15 min) biparametric MRI protocol using less scan sequences and circumvents intravenous contrast-media seems to preserve adequate diagnostic accuracy in a detection setting and could facilitate dissemination of prostate MRI as a triage test before any biopsy.

Here we present a large prospective study that assesses the diagnostic accuracy of a novel biparametric MRI to rule out significant prostate cancer in N=1020 biopsy-naive men with clinically suspicion of prostate cancer.

We found that a low suspicion biparametric MRI had a very high negative predictive value (97%) for ruling out significant cancer on confirmatory biopsies. Furthermore, bpMRI suspicion scores were strongly associated with prostate cancer detection rates and restricting biopsies (targeted plus standard) to men with suspicious biparametric MRIs meant 30% could avoid prostate biopsies, improved significant prostate cancer diagnosis by 11%, and reduced insignificant prostate cancer diagnosis by 40% compared to our current diagnostic approach – standard biopsies for all men with clinically suspicion of prostate cancer.  Continue reading

What Happened to Prostate Cancer Screening and Treatment After PSA Guidelines Changed?

MedicalResearch.com Interview with:

James T. Kearns, MD Clinical Fellow, Department of Urology University of Washington School of Medicine Seattle, WA 

Dr. Kearns

James T. Kearns, MD
Clinical Fellow, Department of Urology
University of Washington School of Medicine
Seattle, WA

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

Response: The effects of the USPSTF recommendation against prostate cancer screening had not been fully characterized among a younger population, particularly with respect to downstream effects such as prostate biopsy, prostate cancer diagnosis, and treatment for prostate cancer.

We found that PSA testing decreased in the years surrounding the USPSTF recommendation, but we also found a larger proportionate decrease in prostate biopsy, prostate cancer diagnosis, and use of surgery or radiation for the treatment of prostate cancer.

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Prostate Cancer: ERLEADA (apalutamide) Delayed Metastases While Not Reducing Quality of Life

MedicalResearch.com Interview with:

Dr. Fred Saad, MD FRCS Full Professor and Chief of Urologic Oncology, CHUM; Medical Director of Interdisciplinary Urologic Oncology Group, CHUM; Department of Surgery/Faculty of Medicine; Institut du cancer de Montréal/CRCHUM

Dr. Saad

Dr. Fred Saad, MD FRCS
Professor and Chief of Urology
Director of GU Oncology
Raymond Garneau Chair in Prostate Cancer
University of Montreal Hospital Center (CHUM)
Director, Prostate Cancer Research , Montreal Cancer Institute

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

Response: Patient Reported Outcomes (PRO) data from the Phase 3 SPARTAN study showed adding ERLEADA (apalutamide) to androgen deprivation therapy (ADT) for patients with nmCRPC who were asymptomatic and well, did not worsen or cause detriment to HRQoL when compared to the placebo.The percent of patients who felt “quite a bit” or “very much” bothered was low (<2–6 percent of patients in the apalutamide group and 0–6 percent of those in the placebo group), suggesting that ERLEADA treatment was generally well-tolerated. This outcome, coupled with the efficacy results seen in SPARTAN, suggest that apalutamide can be given to patients at risk of metastasis without worry about compounded side effects or negative HRQoL..

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Smokers At Increased Risk of Prostate Cancer Recurrence

MedicalResearch.com Interview with:
“Stop smoking!” by Emil_95 is licensed under CC BY 2.0Shahrokh F. Shariat, M.D.
Professor and Chairman
Department of Urology,
Comprehensive Cancer Center
Medical University Vienna
Adjunct Professor of Urology and Medical Oncology
Weill Medical College of Cornell University, New York, NY, USA
Adjunct Professor of Urology
UT Southwestern, Dallas, TX

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

Response: We know that tobacco smoking produces more than 70 carcinogens and is associated with worse prognosis in many solid cancers.

Although the association between cigarette smoking and prostate cancer death has been demonstrated, such association regarding other end points is still unclear. We evaluated different disease endpoints, such as recurrence, occurrence of metastasis and cancer-specific mortality at an earlier stage of disease. We found that smokers who underwent primary treatment for localized prostate cancer – such as radical prostatectomy and radiotherapy – are at increased risk of recurrence, metastasis and cancer-specific mortality.  Continue reading

Apalutamide (Erleada™) Extended Metastasis-Free Survival in Resistant Prostate Cancer

MedicalResearch.com Interview with:

Dr. Fred Saad, MD FRCS Full Professor and Chief of Urologic Oncology, CHUM; Medical Director of Interdisciplinary Urologic Oncology Group, CHUM; Department of Surgery/Faculty of Medicine; Institut du cancer de Montréal/CRCHUM

Dr. Saad

Dr. Fred Saad, MD FRCS
Full Professor and Chief of Urologic Oncology, CHUM;
Medical Director of Interdisciplinary Urologic Oncology Group, CHUM;
Department of Surgery/Faculty of Medicine;
Institut du cancer de Montréal/CRCHUM

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

Response: The SPARTAN study was a Phase 3, randomized, double-blind, placebo-controlled, multicenter study that evaluated ERLEADA (apalutamide), a next-generation androgen signaling inhibitor, in patients with non-metastatic castration-resistant prostate cancer (nmCRPC) who had a rapidly rising PSA (PSA doubling time ≤10 months). The post-hoc analysis presented at the American Urological Association (AUA) 2018 annual meeting showed in patients who received the treatment apalutamide while receiving continuous androgen deprivation therapy (ADT) significantly decreased the risk of PSA progression by 94 percent compared with the placebo group. Continue reading

Automated Bone Scan Index Correlates with Survival in Metastatic Prostate Cancer

MedicalResearch.com Interview with:

Andrew J. Armstrong, MD ScM FACP Associate Professor of Medicine, Surgery, Pharmacology and Cancer Biology Associate Director for Clinical Research in Genitourinary Oncology Duke Cancer Institute Divisions of Medical Oncology and Urology Duke University

Dr. Armstrong

Andrew J. Armstrong, MD ScM FACP
Associate Professor of Medicine, Surgery, Pharmacology and Cancer Biology
Associate Director for Clinical Research in Genitourinary Oncology
Duke Cancer Institute
Divisions of Medical Oncology and Urology
Duke University

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

Response: Men with prostate cancer commonly develop bone metastases and undergo nuclear medicine bone scans. However, these scans are non-quantitative, and disease burden has been challenging to assess over time and to relate to clinical outcomes.

We developed a software program and measurement called the automated bone scan index that essentially reads a standard of care nuclear bone scan, provides a quantitative metric, and demonstrate in a phase 3 trial that this aBSI is highly associated with clinical outcomes including survival, time to symptomatic progression, and prostate cancer specific survival.

We accomplished this within a prospective phase 3 international trial of men with metastatic hormone resistant prostate cancer who were followed over a long period of time.  All bone scans were read and measured using the aBSI at baseline, and we found that the aBSI was highly prognostic.  This work validates prior smaller phase 2 BSI studies, and demonstrates both the feasibility and clinical utility for incorporating the aBSI into clinical practice to provide this important prognostic information to patients and providers.

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USPSTF: Men 70 and Older Should Not Be Screened for Prostate Cancer

MedicalResearch.com Interview with:

Alex Krist, M.D., M.P.H Professor of family medicine and population health Virginia Commonwealth University and Active clinician and teacher at the Fairfax Family Practice residency

Dr. Krist

Alex Krist, M.D., M.P.H
Professor of family medicine and population health
Virginia Commonwealth University and
Active clinician and teacher at the Fairfax Family Practice residency

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. However, the decision about whether to be screened is complex and personal. The U.S. Preventive Services Task Force reviewed the latest research on the benefits and harms of screening for prostate cancer using PSA-based testing, as well as evidence on treatment.

We found that men who are 55 to 69 years old should discuss the benefits and harms of screening with their doctor, so they can make the best choice for themselves based on their values and individual circumstances. Men age 70 and older should not be screened, as the benefits of screening diminish as men age and the harms are greater.

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MRI-Guided Prostate Biopsy Improves Precision Diagnosis of Cancer

MedicalResearch.com Interview with:

Veeru Kasivisvanathan MBBS BSc MRCS MSc PGCert Lead for CPD, Division of Surgery and Interventional Science, UCL Academic Section Committee, British Association of Urological Surgeons Twitter: @veerukasi PRECISION Study Coordinator https://clinicaltrials.gov/ct2/show/NCT02380027  

Dr. Kasivisvanathan

Veeru Kasivisvanathan MBBS BSc MRCS MSc PGCert
Lead for CPD, Division of Surgery and Interventional Science, UCL
Academic Section Committee, British Association of Urological Surgeons
Twitter: @veerukasi
PRECISION Study Coordinator
https://clinicaltrials.gov/ct2/show/NCT02380027  

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

  • We knew that there were limitations in the standard of care pathway for the diagnosis of prostate cancer, TRUS biopsy which missed harmful cancers and over diagnosed harmless cancers.
  • Emerging reports in the literature showed that using an alternative diagnostic pathway, MRI and MRI-targeted biopsy, showed promising prostate cancer detection rates
  • In 2012 we set out in an international working group to design a study that could change clinical practice and replace the standard of care with a pathway involving MRI 

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YONSA (abiraterone acetate) In Metastatic Castration-Resistant Prostate Cancer

MedicalResearch.com Interview with:

https://www.churchillpharma.com/

Paul Nemeth, Ph.D.
Sr. Vice President, Regulatory Affairs, Clinical Development & Quality Assurance
Churchill Pharmaceuticals LLC
King of Prussia, PA 19406


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

Response: In the STAAR study, 53 patients with metastatic castration-resistant prostate cancer (mCRPC) were randomized to receive YONSA, an abiraterone acetate fine particle formulation 500 mg once daily in combination with 4 mg of methylpresnisolone twice daily or 1,000 mg daily of the originator abiraterone acetate (OAA) in combination with 5 mg of prednisone twice daily for a period of 84 days.  Previous studies in healthy volunteers under fasted conditions had shown that single oral doses of 500 mg of YONSA are bioequivalent to single oral doses of 1,000 mg OAA and that a background of 4 mg of methylprednisolone twice daily on a single oral dose of 500 mg of YONSA results in the same extent of absorption as a background of 5 mg of prednisone twice daily on a single oral dose of 1,000 mg of OAA.  Continue reading