FY99 CDMRP Annual Report
Section VI. Prostate Cancer Research Program
Prostate Cancer Research Program Background
Congressional Appropriation and Funding Execution
PCRP Vision and Mission
Program Accomplishments and Outcomes
FY99 Integration Panel Members
FY99 Ad Hoc Integration Panel Members
Prostate cancer is the most common male malignancy (aside from skin cancer) and the second most common cause of cancer death in the United States. Every 13 minutes, an American life is lost to prostate cancer.1 An estimated 179,300 men will be diagnosed with and approximately 37,000 will die from prostate cancer in 1999.2 These figures are even more daunting among African American men, who have the highest incidence rates in the world and whose mortality rates are more than twice those of Caucasians. In spite of the prevalence of prostate cancer as a public health crisis, there is a relative paucity of information about the cause, prevention, and treatment of this disease.
The Department of Defense (DOD) Prostate Cancer Research Program (PCRP) was established in fiscal year 1997 (FY97) by Joint Appropriations Bill 104-863, to address "the need for both basic and clinical research in prostate cancer in order to reduce the incidence of this life-threatening disease and to develop more specific and less toxic forms of therapy for patients in all stages of the disease." Of the $45M, $7M was directed to the Walter Reed Center for Prostate Disease Research by Congress, leaving $38M for the peer-reviewed effort. The overall goal of the PCRP is to promote innovative ideas and technology through both basic and clinical science in an effort to conquer prostate cancer. The program’s areas of emphasis were developed after consultation with renowned scientists, clinicians, and advocates. Other national prostate cancer research funding agencies (including the National Cancer Institute, the American Cancer Society, the American Foundation for Urological Disease, and CaP CURE) were invited in order to avoid overlap of programs and to target underrepresented avenues of research and novel applications of existing technologies. In FY98, Joint Appropriations Bill 105-265 provided $40M to conduct basic and clinical research studies aimed at combating diseases of the prostate. Of the FY98 appropriation, $2M was directed to the Walter Reed Center for Prostate Disease Research by Congress, leaving $38M for peer-reviewed research. Congress has continued to support the DOD PCRP by appropriating an additional $50M in FY99.
In FY97-99, Congress appropriated $135M for peer-reviewed prostate cancer research. Table B-2 in Appendix B summarizes the directions from Congress for the PCRP appropriations, the program’s withholds and management costs, and the investment strategy executed by the program. Prior to receipt of funds by the office of the Congressionally Directed Medical Research Programs (CDMRP), Congress and the DOD withhold funds for designated initiatives. The CDMRP sets aside funds for program development, scientific peer review, programmatic review, and the administration of grants/contracts through the entire period of performance up to 7 years (see Appendix B). The investment strategy executed is consistent with Congressional language and reflects the program’s vision.
The vision of the PCRP has remained consistent since its conception: to conquer prostate cancer. The program’s mission is to promote innovative, multi-institutional, and multidisciplinary ideas and technology through both clinical and basic science directed toward eliminating prostate cancer. Scientific ventures that represent underinvestigated avenues of research or novel applications of existing technologies are highly sought. In addition, research that addresses the needs of minority, low-income, rural, and special populations are encouraged.
Due to the high scientific quality of proposals received for the FY97 PCRP and the enthusiasm of both the scientific and advocacy communities to quickly distribute funds to scientists, the funds appropriated in FY98 for the continuation of the PCRP were combined with the FY97 appropriation to fund additional investigators with highly meritorious proposals submitted to the FY97 program.
The programmatic strategy for the FY97/98 PCRP embodied the continuing evolution and flexibility of the U.S. Army Medical Research and Materiel Command (USAMRMC) and the CDMRP. The strategy was implemented by a solicitation in the 15 July 1997 announcement for proposals in two subcategories: New Investigator Awards and Idea Development Awards. The intent of New Investigator Awards was to support innovative approaches to prostate cancer that may be untested but are expected to reveal breakthroughs or new avenues of investigation. The intent of Idea Development Awards was to give established prostate cancer investigators and those established investigators who want to move into the prostate cancer field the opportunity to undertake underinvestigated avenues of research using innovative scientific approaches. Forty-three New Investigator and 126 Idea Development awards were funded with the FY97/98 appropriation.
The following tables reflect the funding summaries, in terms of dollars and number of awards, for the FY97-98 PCRP.
Additionally, a military Tri-Service prostate cancer research project was proposed, in part, by the Army, Navy, and Air Force Surgeons General to increase military participation in the PCRP. Subsequently, the PCRP Integration Panel developed an investment strategy to support a military Tri-Service Project. The project was funded by the PCRP to enhance the infrastructure of an existing serum and tissue repository. Samples are collected from active duty, retired, and dependent DOD men with prostate cancer. It is anticipated that this repository will serve as a national resource to the prostate cancer research community.
A unique feature of the CDMRP is its ability to adapt and quickly implement processes that meet the needs of targeted communities. Two important program innovations, dual-phase funding and minority population studies, were developed to address the unique needs of prostate cancer research.
Dual-Phase Funding. After 2 years of research, the USAMRMC will challenge all FY97/98 funded investigators to compete for an additional 2 years of support (with doubled funding level), pending appropriations in FY00. This unique dual-phase strategy was designed to encourage the rapid development of ideas in Phase I and to provide transition support to position investigators for successful competition in traditional funding mechanisms in Phase II. Pending appropriations, Phase II awards will be made to those investigators who (1) demonstrate the most productivity and innovation in Phase I, and (2) submit the most scientifically promising research project for Phase II.
Minority Population Research Initiative. Concerns were raised by the PCRP Integration Panel about the disparity in mortality and morbidity rates of patients with prostate cancer among different ethnic groups. In response to these concerns, a new award mechanism was proposed—the Minority Population Focused Training Awards (MPFTA). These awards were designed to enable investigators to develop a prostate cancer research concept that focuses on the disparity in prostate cancer incidence and mortality. One of the goals of these awards was to establish collaborations between applicants and established investigators. Seventeen MPFTAs were funded.
The FY99 PCRP focused on expanding scientific inquiry in three research areas: (1) cancer biology, (2) prevention, and (3) therapy. The programmatic strategy was to fund proposals in three award categories: Research Awards, Training/Recruitment Awards, and Prostate Cancer Center Initiation Awards. Approximately $18M was made available to fund the Research Award mechanisms that were introduced in the FY97/98 program: New Investigator and Idea Development Awards. The MPFTA category was renamed the Minority Population Focused Collaborative Training (MPFCT) Awards since emphasis was placed on fostering collaborations between applicants and established prostate cancer researchers. Additionally, two new award mechanisms were introduced: Postdoctoral Traineeship Awards and Prostate Cancer Center Initiation Awards. The intent of Traineeship Awards was to enable recent doctoral degree students to conduct research in prostate cancer. Approximately $4M was made available to support the training awards, MPFCT Awards, and Postdoctoral Traineeships. Approximately $18M was made available to fund Cancer Center Initiation Awards with the intent to engage experts from multiple disciplines to establish regional centers for the study and treatment of prostate cancer.
Negotiation of 23 Postdoctoral Traineeships Awards has been completed; 6 were funded from the FY98 appropriation and 17 were funded from FY99. All remaining mechanisms are in various stages of review or negotiation. The FY99 PCRP will be finalized early in FY00.
——FY00 Program Plans
Joint Conference Committee Report 106-371 specifies $75M for peer-reviewed prostate cancer research. Vision setting for the FY00 program will occur in late October 1999. At that time, an investment strategy will be developed, including plans for funding the dual phase awards, taking into account Congressional language, recommendations from scientific and advocacy groups, and gaps in research funding.
A request from the Senate Appropriations Committee-Defense was made to the PCRP to address the speed at which promising prostate cancer research opportunities can be funded. The DOD was directed to develop a business plan that presented specific approaches for expediting FY97-99 funding of prostate cancer research. A Business Plan for Accelerated Prostate Cancer Research Funding was released by the USAMRMC on 30 April 1998 that outlined specific approaches to streamline and accelerate the acquisitions process while maintaining rigorous review standards of regulatory compliance and scientific and technical merit.
The PCRP has increased its efforts to attract grants from investigators at Historically Black Colleges and Universities/Minority Institutions (HBCU/MI) and proposals that study special populations. For instance, due to the disparity in prostate cancer incidence and mortality rates among different ethnic groups, the PCRP designed the MPFCT Awards to initiate and increase research efforts investigating this disparity (see FY97-99 Funding History). Furthermore, a percentage of the PCRP funds is directed to support proposals submitted by HBCU/MI. Investigators of any ethnicity working at HBCU/MI are eligible for funding with this set-aside. Proposals from HBCU/MI are reviewed concurrently with other proposals in the same research categories during scientific peer review but are evaluated separately during programmatic review when award recommendations are determined. Consistent with the PCRP’s goal, the final investment strategy for HBCU/MI funds will be determined based upon scientific excellence and program relevance.
As noted earlier under the FY97/98 program, a unique dual-phase funding strategy was implemented as part of the FY97/98 program. After 2 years of research, the USAMRMC will challenge funded investigators to compete for 2 additional years of support, pending appropriations in FY00.
In an effort to invigorate the PCRP, the FY97/98 PCRP requested that the investigator/institution award recipient cost-share in the research expenses. This request enabled the program to maximize monies spent in the effort to conquer prostate cancer.
To date, 193 proposals have been awarded with FY97/98 funds totaling $62.0M. It is anticipated that the dual-phase mechanism designed in FY97/98 will lead to the development of breakthrough approaches and ideas in FY00.
The FY99 PCRP will support Cancer Center Initiation awards for the establishment of regional centers for the study and treatment of prostate cancer. It is anticipated that these infrastructure awards will invigorate the research community, bring new investigators into the field of prostate cancer, and make strides toward conquering prostate cancer.
The PCRP has consistently welcomed the brightest minds in science to its research programs with the ultimate goal of disease eradication. To achieve this goal, a significant investment has been made to stimulate talented new investigators, as well as superb established investigators currently working in other fields. The FY97/98 PCRP made a significant investment in training by supporting 43 talented new prostate cancer investigators. New investigators were defined as individuals who have their own independent research facilities; were within 6 years of postdoctoral, residency, fellowship or equivalent training; and were holding positions as Assistant Professors or equivalent. The FY99 PCRP continued with the theme of training and offered New Investigator and Postdoctoral Traineeship Awards; to date, 23 Postdoctoral Traineeship Awards have been negotiated.
While the PCRP is relatively young, it is anticipated that funded research will provide the framework/foundation for contemporary and future scientific discoveries. The following examples of FY97/98 research awards highlight the innovative ideas and technology in both clinical and basic science aimed at conquering prostate cancer.
Risk Factors. Researchers funded by the PCRP are studying how environmental, genetic, and lifestyle risk factors lead to the development of prostate cancer in males, with the hope of significantly reducing the incidence of prostate cancer. For example, researchers at Wayne State University are exploring the role of the pesticide DDT [1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane] and its metabolite DDE [1,1-dichloro-2,2-bis(4-chlorophenyl)ethylene] as potential etiologic risk factors for prostate cancer. Data show that DDT persists in the soil for an extended period of time, and once in humans is metabolized to DDE where it remains in adipose tissue for years. Evidence suggests that both DDT and DDE may be associated with cancer. The principal investigator (PI) of this study is measuring DDE levels in blood from men with and without prostate cancer. It is anticipated that work from this funding effort will lead to new insights regarding the etiology of prostate cancer.
Additionally, a study from the Veterans Administration Medical Center is examining risk factors for prostate cancer in African American veterans. Data show that African American men have the highest prostate cancer incidence rate in the world and have mortality rates more than twice those of Caucasians. Using the large cohort of men in the VA health care system, the PI of this study is gathering information about lifestyle and dietary factors from both African American and Caucasian men. It is anticipated that data from this project will provide insights into the racial differences in prostate cancer incidence and mortality rates.
Oxidative Stress. PCRP-funded researchers are determining how oxidants (i.e., damage-inducing chemical species) lead to the development of prostate cancer. A study at the University of Wisconsin Comprehensive Cancer Center has shown that exposure of prostate cancer cells to androgens (i.e., male hormones) results in increased concentration of oxidants in the cells. To determine the mechanism by which androgens increase oxidative stress, the source of the oxidants must be identified. The PI of this study is focusing on mitochondria since they contain enzymes involved in the oxidation. It was shown that mitochondria increase in number in prostate cancer cells after androgen exposure. It was also determined that two inhibitors of the mitochondrial electron transport system (ETS), rotenone and antimycin A, decreased the production of oxidants from the ETS. Ultimately, this study may allow for the development of strategies for blocking the oxidative stress induced by androgens and may validate the use of agents such as antioxidants for the prevention of prostate cancer.
Molecular Markers. Several studies funded by the PCRP are examining proteins, genes, and genetic alterations in prostate cancer with the overall goal of identifying key molecular factors and events that underlie the development, growth, and spread of prostate cancer. For example, a study at the University of Alabama aims to identify oncogenes (i.e., cancer-causing genes) in prostate cancer. The PI is accomplishing this by inserting genes from tumors into host cells that have the properties of non-cancerous cells, and then identifying the cells within the host cell population that have turned into cancer cells. The PI is using standard molecular biological methods to determine the tumor gene responsible for this conversion. Ultimately, he hopes to identify a number of novel oncogenes in prostate cancer using this method.
Additionally, investigators at the Mount Sinai Medical Center are employing novel technology to isolate proteins that may represent targets for the early detection and treatment of androgen-independent prostate tumors. It is expected that work from this project will lead to the identification of markers that may serve for the development of therapies for patients with advanced stages of prostate cancer.
Nutrition. Researchers funded by the PCRP are identifying micronutrients that help slow the growth and inhibit the spread of prostate cancer. For example, a study at the University of Miami is using hepatocyte growth factor in combination with vitamin D in an attempt to limit the growth of advanced prostate cancer. The PI has found that this combination significantly inhibits growth of androgen-unresponsive prostate cancer cells. The PI is also preparing to pursue preclinical studies in mice that have been implanted with human prostate cancer cells to demonstrate the feasibility of using the combination of vitamin D and hepatocyte growth factor in men with advanced prostate cancer.
Additionally, investigators at the University of Arizona are assessing the potential of the nutrient selenium to inhibit the progression of prostate cancer. This trial is based on an earlier study in which the PI observed a 63% decrease in incidence of prostate cancer during the initial 10-year follow-up period in patients who were given 200 micrograms of selenium versus those who received placebos. Patients in the present clinical trial will receive either 200 or 400 micrograms of selenium per day. The PI will examine the rate at which prostate-specific antigen (the main marker for prostate cancer progression) increases in the blood of the various patients. The ultimate goal of this study is to determine if selenium can effectively treat, without any significant side effects, the early stages of prostate cancer.
Chair, Andrew C. von Eschenbach, M.D.: Director, Program Center – Genitourinary Cancers, Special Assistant for External Affairs; Roy M. & Phyllis Gough Huffington Chair in Urologic Oncology; Professor, Department of Urology and Consulting Professor of Cell Biology, The University of Texas, M.D. Anderson Cancer Center; and Director, Prostate Cancer Research Program. Has served on numerous international, national, and local committees of several organizations including the American Cancer Society (ACS). Discipline(s): Urology/Cell Biology.
Brent A. Blumenstein, Ph.D.: Group Statistician, American College of Surgeons Oncology Group. Has been involved in numerous multicenter clinical trials, particularly clinical trials in prostate cancer (formerly with the Southwest Oncology Group). Discipline(s): Biostatistics.
Robert E. Bookstein, M.D.: Research Fellow, CANJI, Inc. Research interests include tumor suppressor genes in several cancers with emphasis on prostate cancer. Discipline(s): Genetics.
Otis W. Brawley, M.D.: Director, Office of Special Populations, Office of the Director of the National Cancer Institute (NCI); Assistant to the Director, Office of Science Policy, NCI; and Commander, Public Health Service. Served as NCI Coordinator and Project Officer of the Prostate Cancer Prevention Trial, and Coordinator of the Minority-based Community Clinical Oncology Program. Discipline(s): Medical Oncology.
Donald S. Coffey, Ph.D.: Catherine Iola and J. Smith Michael Distinguished Professor of Urology, Professor of Oncology, Professor of Pharmacology and Molecular Sciences, and Professor of Pathology, The Johns Hopkins School of Medicine; Director of Research Laboratories, Department of Urology. Recipient of numerous national and international honors including the Eugene Fuller Prostate Award of the American Urological Society. Member of numerous associations and current President of the American Association for Cancer Research. Discipline(s): Urology/Oncology/Pharmacology and Molecular Science.
Ralph W. DeVere White, M.D.: Medical Director of the Cancer Center, and Professor and Chair of Urology, University of California, Davis. Has served on numerous national and local committees. Current research focuses on the molecular biology of prostate cancer. Discipline(s): Molecular Biology.
Reginald Ho, M.D.: Clinical Professor of Medicine, John A. Burns School of Medicine, University of Hawaii and Clinical Science Adjunct Professor, Cancer Research Center of Hawaii. Discipline(s): Medical Oncology.
Stuart Holden, M.D.: Clinical Assistant Professor Surgery (Urology); Chairman, Operating Room Advisory Committee, Cedars-Sinai Medical Center; and Medical Director, CaP Cure. Discipline(s): Urology.
Dick Howe, Ph.D.: Prostate cancer survivor. Retired President of Pennzoil Company. Received American Foundation for Urological Disease’s Presidential Award in 1996. Currently a member of the Prostate Health Council, NCI’s Committee on Prostate Cancer Genetics, NCI’s Chemoprevention Committee, Advisory Board of Baylor’s SPORE and Co-Chair of the National Prostate Cancer Coalition’s Medical/Scientific Committee. Discipline(s): Consumer
Carl Mansfield, M.D., D.Sc.: Professor and Chairman, Department of Radiation Oncology, University of Maryland Medical Center. Has received numerous awards and has been recognized as a top radiation oncologist in the Delaware Valley Region. Discipline(s): Radiation Oncology.
Carl A. Olsson, M.D.: Professor and Chairman, Department of Urology, College of Physicians and Surgeons, Columbia University; Director of Urological Service, The Presbyterian Hospital and the Squier Urological Clinic. Served on numerous committees and associations including President of the Society of Urologic Oncology and President of the American Board of Urology. Has received numerous awards including the John K. Lattimer Award from the National Kidney Foundation. Discipline(s): Molecular Biology/Cell Biology.
William U. Shipley, M.D.: Professor of Radiation Oncology, Harvard Medical School; and Head of Genitourinary Oncology Unit, Department of Radiation Oncology, Massachusetts General Hospital. Discipline(s): Radiation Oncology.
Sandra M. Underwood, Ph.D., R.N., F.A.A.N.: Professor, Health Maintenance Department, University of Wisconsin Milwaukee School of Nursing; and ACS Oncology Nursing Professor; Northwestern Mutual Life Research Scholar. Has served on national and regional committees including the ACS, the Oncology Nursing Society, the National Black Nurses Association, and the National Coalition of Cancer Survivorship. Has received several honors for her efforts relative to cancer prevention and control including awards from the National Office of the ACS and the National Black Leadership Initiative on Cancer. Discipline(s): Nursing.
Nicholas J. Vogelzang, M.D.: Fred C. Buffet Professor of Medicine and Surgery (Urology), University of Chicago; Director, Genitourinary Program; and Director, University of Chicago Cancer Research Center. Has served on numerous national and local committees including the Board of Directors of the American Society of Clinical Oncology and the ACS. Discipline(s): Hematology and Oncology/Experimental Therapeutics.
James E. Williams, Jr., M.S., S.P.H.R.: Prostate cancer survivor. Employment Manager, Human Resources, Penn State Geisinger Health-System Milton S. Hershey Medical Center; retired Colonel, U.S. Army; member, Advisory Council, Intercultural Cancer Council (ICC); and Regional Director and Member, Board of Directors, US TOO International, Inc. Discipline(s): Consumer.
Lucille Campbell-Adams, Ph.D.: Howard University Cancer Center. Discipline(s): Epidemiology.
Thomas Carey, Ph.D.: University of Michigan Cancer Center. Discipline(s): Cellular Biology and Genetics.
Ronald Morton, Jr., M.D.: Baylor College of Medicine. Discipline(s): Urology.
Frederic Waldman, M.D., Ph.D.: University of California, San Francisco. Discipline(s): Pathology.
Table VI-1. Funding Summary for the FY97-98 PCRP Awards
Table VI-2. Number of Proposals Received and Number of Awards Made for the FY97-98 PCRP
1 CapCure website (www.capcure.org).
2 American Cancer Society - Cancer Facts & Figures 1999: Selected Cancers.
3 One Idea Development and six training awards from the FY99 program were funded with the FY98 appropriation and are therefore counted as part of the 1997/1998 program.