madman
Super Moderator
Prostate Cancer Biomarker Development: National Cancer Institute’s Early Detection Research Network Prostate Cancer Collaborative Group Review
ABSTRACT
Prostate cancer remains the most common non-skin cancer and the second leading cause of death among men in the United States. Although progress has been made in diagnosis and risk assessment, many clinical questions remain regarding early identification of prostate cancer and management. The early detection of aggressive disease continues to provide high curative rates if diagnosed in a localized state. Unfortunately, prostate cancer displays significant heterogeneity within the prostate organ and between individual patients making detection and treatment strategies complex. Although prostate cancer is common among men, the majority will not die from prostate cancer, introducing the issue of over-treatment as a major concern in the clinical management of the disease. The focus of the future is to identify those at the highest risk for aggressive prostate cancer and to develop prevention and screening strategies, as well as, discerning the difference in malignant potential of diagnosed tumors. The Prostate Cancer Research Group of the National Cancer Institute’s Early Detection Research Network has contributed to the progress in addressing these concerns. This summary is an overview of the activities of the group.
INTRODUCTION
Prostate Cancer and Early Detection of Prostate cancer remains the most commonly diagnosed non-cutaneous cancer in the United States and the second most common cause of cancer death in men (1). The 4-year survival rate for the local-regional disease is >99%, but if a man is diagnosed with distant disease his 4-year survival rate drops to 30% (1). Two large randomized controlled trials evaluating the effect of prostate cancer screening on mortality have demonstrated a reduction in the risk of death by 20-40% in those undergoing screening (2,3). Despite the potential benefits, considerable concern remains regarding overdiagnosis and ultimately overtreatment in the screened population (4). The concern for potential harm served as the impetus for the United States Preventive Services Task Force (USPSTF) to recommend against screening in 2012 (5) and later advise on informed decision-making between physicians and patients to decide on screening (6). A focus of the National Cancer Institute’s Early Detection Research Network (NCI-EDRN) is to allow data-driven discussions during the patient-provider interactions that guide individualized, informed decision making. Given the grim statistics of metastatic prostate cancer, the NCIEDRN Prostate Cancer Research Group focuses on actionable biomarkers that can be utilized in early-stage settings to prevent progression by early intervention. Important targets of the group include the identification of aggressive, potentially lethal, cancer at an early stage and providing biomarker-driven decisional support to maximize benefit and minimize harm in prostate cancer treatment. Other targets include the identification of known prostate cancer at risk for progression and metastasis or conversion to castration-resistant prostate cancer.
The EDRN Prostate Cancer Research Group
The EDRN network research activities are leveraged toward specific cancer types through organ-site collaborative teams. The Prostate Cancer Research Group is composed of the investigators that comprise major components and associate member programs, as well as prostate cancer expertise not directly funded through the NCI. In the current cycle, there are three Biomarker Development Laboratories (BDL), two of these programs focus on protein-based biomarkers, and one focuses on nucleic acid-based biomarkers. There are also two Clinical Validation Centers (CVC), three Biomarker Reference Laboratories (BRL), statistical expertise from the Data Management Consulting Center (DMCC), and investigator teams supported through the EDRN Associate Membership program. Critical patient perspective and advocacy are provided through regular participation by the president of the National Association of State Prostate Cancer Coalitions. The collaborative group also includes representation from the industry. All members of the collaborative group participate in monthly video conferences to build shared network expertise, discuss research progress, and evaluate programmatic activities. The group develops core projects to support critical research needs that are then reviewed by the full steering committee of the EDRN. The core projects serve to focus on the research activities across the collaborative group. For the prostate cancer research group, many of the core projects have focused on the development of unique reference sets. These references set are designed to assist in the validation of new biomarkers.
One of the most valuable aspects of the collaborative group is the establishment of biomarker development goals within the collective expertise of the team, which consists of patient advocates, clinicians, epidemiologists, and basic scientists. In developing this focus, the team has considered the current clinical workflow within which decisions are made regarding clinical care and management of disease (Figure 1). Diagnosis of prostate cancer is initiated through screening and confirmed through subsequent biopsy. This is a critical junction for decision-making and an area of considerable focus of the EDRN. A positive diagnosis demands accurate risk stratification between active surveillance and treatment. A negative biopsy leads to more vigilant follow-up involving repeat biopsies and the risk of associated complications. Thus, early and accurate assessment of disease is critical in the clinical care continuum for prostate cancer.
CONCLUSIONS
The research activities of the Prostate Collaborative Group are focused on providing tools to improve the clinical management of men with prostate cancer. The EDRN supported the infrastructure of both resources and expertise are leveraged by the group to facilitate discovery, guide progress through biomarker development, provide an unbiased evaluation of progress and design, and implement appropriate validation studies. State-of-the-art omics technologies provide comprehensive data-driven discovery with an eye toward combined multi-omics assays that can be integrated into current clinical decision making. The strong focus on biomarker application optimizes the development of biomarkers with clinical utility as well as the early adoption of disruptive technologies, such as MRI imaging, into biomarker development workflows. Likewise, efforts to validate findings from laboratories outside of the EDRN, such as polygenic risk scores, and capture of in-depth data from clinical cohorts, provides unique resources to the biomarker community.
ABSTRACT
Prostate cancer remains the most common non-skin cancer and the second leading cause of death among men in the United States. Although progress has been made in diagnosis and risk assessment, many clinical questions remain regarding early identification of prostate cancer and management. The early detection of aggressive disease continues to provide high curative rates if diagnosed in a localized state. Unfortunately, prostate cancer displays significant heterogeneity within the prostate organ and between individual patients making detection and treatment strategies complex. Although prostate cancer is common among men, the majority will not die from prostate cancer, introducing the issue of over-treatment as a major concern in the clinical management of the disease. The focus of the future is to identify those at the highest risk for aggressive prostate cancer and to develop prevention and screening strategies, as well as, discerning the difference in malignant potential of diagnosed tumors. The Prostate Cancer Research Group of the National Cancer Institute’s Early Detection Research Network has contributed to the progress in addressing these concerns. This summary is an overview of the activities of the group.
INTRODUCTION
Prostate Cancer and Early Detection of Prostate cancer remains the most commonly diagnosed non-cutaneous cancer in the United States and the second most common cause of cancer death in men (1). The 4-year survival rate for the local-regional disease is >99%, but if a man is diagnosed with distant disease his 4-year survival rate drops to 30% (1). Two large randomized controlled trials evaluating the effect of prostate cancer screening on mortality have demonstrated a reduction in the risk of death by 20-40% in those undergoing screening (2,3). Despite the potential benefits, considerable concern remains regarding overdiagnosis and ultimately overtreatment in the screened population (4). The concern for potential harm served as the impetus for the United States Preventive Services Task Force (USPSTF) to recommend against screening in 2012 (5) and later advise on informed decision-making between physicians and patients to decide on screening (6). A focus of the National Cancer Institute’s Early Detection Research Network (NCI-EDRN) is to allow data-driven discussions during the patient-provider interactions that guide individualized, informed decision making. Given the grim statistics of metastatic prostate cancer, the NCIEDRN Prostate Cancer Research Group focuses on actionable biomarkers that can be utilized in early-stage settings to prevent progression by early intervention. Important targets of the group include the identification of aggressive, potentially lethal, cancer at an early stage and providing biomarker-driven decisional support to maximize benefit and minimize harm in prostate cancer treatment. Other targets include the identification of known prostate cancer at risk for progression and metastasis or conversion to castration-resistant prostate cancer.
The EDRN Prostate Cancer Research Group
The EDRN network research activities are leveraged toward specific cancer types through organ-site collaborative teams. The Prostate Cancer Research Group is composed of the investigators that comprise major components and associate member programs, as well as prostate cancer expertise not directly funded through the NCI. In the current cycle, there are three Biomarker Development Laboratories (BDL), two of these programs focus on protein-based biomarkers, and one focuses on nucleic acid-based biomarkers. There are also two Clinical Validation Centers (CVC), three Biomarker Reference Laboratories (BRL), statistical expertise from the Data Management Consulting Center (DMCC), and investigator teams supported through the EDRN Associate Membership program. Critical patient perspective and advocacy are provided through regular participation by the president of the National Association of State Prostate Cancer Coalitions. The collaborative group also includes representation from the industry. All members of the collaborative group participate in monthly video conferences to build shared network expertise, discuss research progress, and evaluate programmatic activities. The group develops core projects to support critical research needs that are then reviewed by the full steering committee of the EDRN. The core projects serve to focus on the research activities across the collaborative group. For the prostate cancer research group, many of the core projects have focused on the development of unique reference sets. These references set are designed to assist in the validation of new biomarkers.
One of the most valuable aspects of the collaborative group is the establishment of biomarker development goals within the collective expertise of the team, which consists of patient advocates, clinicians, epidemiologists, and basic scientists. In developing this focus, the team has considered the current clinical workflow within which decisions are made regarding clinical care and management of disease (Figure 1). Diagnosis of prostate cancer is initiated through screening and confirmed through subsequent biopsy. This is a critical junction for decision-making and an area of considerable focus of the EDRN. A positive diagnosis demands accurate risk stratification between active surveillance and treatment. A negative biopsy leads to more vigilant follow-up involving repeat biopsies and the risk of associated complications. Thus, early and accurate assessment of disease is critical in the clinical care continuum for prostate cancer.
CONCLUSIONS
The research activities of the Prostate Collaborative Group are focused on providing tools to improve the clinical management of men with prostate cancer. The EDRN supported the infrastructure of both resources and expertise are leveraged by the group to facilitate discovery, guide progress through biomarker development, provide an unbiased evaluation of progress and design, and implement appropriate validation studies. State-of-the-art omics technologies provide comprehensive data-driven discovery with an eye toward combined multi-omics assays that can be integrated into current clinical decision making. The strong focus on biomarker application optimizes the development of biomarkers with clinical utility as well as the early adoption of disruptive technologies, such as MRI imaging, into biomarker development workflows. Likewise, efforts to validate findings from laboratories outside of the EDRN, such as polygenic risk scores, and capture of in-depth data from clinical cohorts, provides unique resources to the biomarker community.
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