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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