Full Text PA-97-019
NIH GUIDE, Volume 25, Number 44, December 20, 1996
PA NUMBER:  PA-97-019


National Institute on Aging
National Cancer Institute
National Institute of Environmental Health Sciences
The National Institute on Aging (NIA), the National Cancer Institute
(NCI) and the National Institute of Environmental Health Sciences
(NIEHS) invite research grant applications to expand the
understanding of biological and clinical factors leading to the
development, progression, and treatment of prostate cancer in aging
men. The increased risk of prostate cancer with advancing age and its
prominence in older-aged men are well known characteristics of this
tumor.  The unusually high incidence and mortality rates of prostate
cancer for older white and black American men and, by contrast, the
much lower rates in men of Hispanic and Asian descent, provide the
need for research that emphasizes the role of race and ethnic
factors, as well as age, in early diagnosis, management, and etiology
of this tumor.  This Program Announcement is intended to stimulate
research that applies the expanding scientific  knowledge gained on
prostate cancer to older men and to extend the knowledge base on
age-related aspects of the etiology of this malignancy.
The Public Health Service (PHS) is committed to achieving the health
promotion and disease prevention objectives of "Healthy People 2000,"
a PHS-led national activity for setting priority areas.  This PA,
Aging, Race, and Ethnicity in Prostate Cancer, is related to the
priority area of cancer.  Potential applicants may obtain a copy of
"Healthy People 2000" (Full Report:  Stock No. 017-001-00474-0 or
Summary Report:  Stock No. 017-001-00473-1) through the
Superintendent of Documents, Government Printing Office, Washington,
DC 20402-9325 (telephone 202-512-1800).
Applications may be submitted by foreign and domestic for-profit and
non-profit organizations, public and private, such as universities,
colleges, hospitals, laboratories, units of State and local
governments, and eligible agencies of the Federal government.
Foreign institutions are not eligible for the research program
project or First Independent Research Support and Transition (FIRST)
awards (R29).  Racial/ethnic minority individuals, women, and persons
with disabilities are encouraged to apply as principal investigators.
The mechanisms of support will be the investigator-initiated research
project grant (R01) and FIRST award (R29).
Though investigators acknowledge aging as a high risk factor for
prostate cancer, current studies are limited by a lack of attention
to the aging process and/or old age in combination with race, and
ethnic factors.  Further, it is also recognized that black Americans
are affected by this tumor to an even greater extent than white
Americans and that men of other race or ethnic origin are affected
far less. Despite these striking age, race, and ethnic differences,
no extensive research focus has been directed toward the role of
aging, race, and ethnicity in prostate cancer.  The magnitude of the
prostate cancer problem for aging men, recent scientific and
technologic advancements made relevant to prostate cancer detection
and management, and the projected expansion of the aged male
population combine to provide the impetus for this research
Summary Data -- Prostate cancer has the highest incidence of any
tumor affecting men in the United States.   In 1996, 317,000 new
prostate cancer cases will be diagnosed according to estimates made
by the American Cancer Society (ACS).  Population-based data from the
NCI Surveillance, Epidemiology, and End Results  (SEER) Program show
that the majority (81 percent) of persons affected by prostate cancer
are 65 years and older.  The median age for this malignancy is 72
years (SEER).
Race and ethnic disparities in prostate cancer are portrayed with
data collected on newly diagnosed cancers between 1988 and 1992 by
the NCI SEER Program showing age-adjusted incidence rates for cancer
for men of all ages.  The summary incidence rate among black men is
180.6 per 100,000 population as compared to a rate of 134.7 for white
men.  Rates for men of other race and ethnic backgrounds are much
lower:  Hispanics, 89.0;  Japanese, 88.0; American Indian, 52.5;
Alaskan Native, 45.1; Chinese, 46.0; Filipino, 69.8; Hawaiian, 57.2;
Vietnamese, 40.0; and Korean,  24.2 (SEER Racial/Ethnic Patterns
Using age 65 years as a breakpoint, age-adjusted rates per 100,000
population for 1988-1992, show that white men under 65 years have a
rate of 32.0 as compared to 48.3 for blacks. For men 65 years and
older, the rates are 1120.3 for whites as compared to 1458.9 for
blacks. Age-adjusted mortality rates are more than twice as high for
blacks as compared to whites for both younger and older age groups.
For men under 65 years, the mortality rate for whites is 2.6 as
compared to 7.3 for blacks.  For men 65 years and older, the rates
are 219.7 for whites as compared to 475.6 for blacks (SEER).
The overall incidence and mortality rates for black Americans are not
only the highest in the United States, they are the highest in the
world.  Cross-national comparisons with selected industrial nations
show that only Sweden has prostate cancer incidence and mortality
rates comparable to U.S. whites.  Netherlands and Italy follow with
rates about half as high as American blacks and whites, respectively.
Japan has the lowest prostate cancer incidence and mortality rates of
all these countries.
Knowledge Development -- Much work has been done to increase the
understanding of prostate cancer and great strides have been made in
recent years to develop information on effective modalities in early
detection and diagnosis of this malignancy.   Investigations have
explored  the relationship between prostatic intraepithelial
neoplasia (PIN), a putative precursor lesion to prostate cancer, and
the serum marker for prostate cancer known as
prostate-specific-antigen (PSA), a screening technique used in
combination with other modalities in evaluating men for prostate
cancer.  Transrectal ultrasound development is another important
advancement made in urology techniques that allows characterization
of the prostate's normal and abnormal tissue, which when complemented
by digital rectal examination (DRE) and PSA, provides valuable
information for the detection and study of prostate cancer.
Though benefits of different forms of therapy for prostate cancer
have not been definitively determined, many investigators continue to
address different treatment options that include radical
prostatectomy, radiation, and expectant management as the most common
therapies. The impact of how aging and concurrent comorbid conditions
of the patient with prostate cancer affect treatment decisions and
outcomes remain an under investigated area.
Demographic Transition -- Unparalleled increases in the aging of the
U.S. population impose a considerable public health challenge.  The
numerical growth of the older-aged male population will increase.
Thus, in the future there will be even more older men vulnerable to
prostate cancer. The proportion of males in the age segment 65 years
and older in the U.S. population currently constitutes 13.9 million.
At the beginning of the 21st century (2000), that number is expected
to increase to 14.6 million.  Fifteen years later, in 2015, 20.0
million of the male population will be in this age group. By 2030,
31.8 million men will be 65 years and older (reflecting the total
effects of the "baby boom" phenomenon). Because of population growth
alone, there will be even greater numbers of males likely to be
affected by prostate cancer. An organized focus to ascertain what
transpires at the aging/prostate cancer interface is needed to deal
with the current and future problems caused by this malignancy.
Research Goals and Scope
This PA encourages the extramural research community to take
advantage of recently acquired scientific knowledge and expertise
developed in biology, gerontology, oncology, urology, and other
disciplines and professions and apply these resources to aging
relevant research questions on prostate cancer for aging males of
different races and minority backgrounds.
Major questions on prostate cancer in the context of an aging host
invite multidisciplinary research in the areas of early diagnosis,
management, and etiology of prostate cancer.  Research efforts,
single or in combination, focusing on diagnosis, management, and
etiology, may be addressed as these areas pertain to aging, race,
and/or ethnic groups.
The targeted areas of research relevant to this PA are identified
below.  These are not exclusive and related issues designated by the
applicant will be considered.
Etiology and Risk Factors
o  Studies on factors that affect the rate of increase with age in
risk for prostate cancer, and/or the rate of development and
progression of premalignant changes in prostate tissue, as well as
their interaction with familial factors, race, and/or ethnicity;
o  Epidemiologic studies of age-related familial, genetic, and
environmental factors that may affect the age of onset, rate of
progression, and duration of survival for prostate cancer;
o  Interactions of aging and age with prostate cancer risk factors
(e.g., relative prominence of various risk factors for onset of
prostate cancer at different ages;
o  Risk factors for occurrence of multiple primary prostate tumors.
Disease Progression
o  Extent to which, and mechanism by which, age-related prostate
growth leads to increased incidence of prostate cancer;
o  Role of other age-related biological factors that lead to the
development and affect the progression rate of prostate cancer;
o  Assessment of protective factors that mitigate against prostate
cancer (allow aging without development of premalignant changes);
o  Metastatic potential of various precursor lesions for prostate
cancer in aging men.
o  Testing of improved methods to identify high risk older white and
black men and low risk men of different race and ethnic origin
through development of new techniques to distinguish premalignant
changes from nonmalignant age-associated changes in prostate tissue;
o  Validation of new and/or current methodologies or application of
current biological, physiological, and clinical techniques to
identify high-risk older white and black men [e.g., prostatic
intraepithelial neoplasia (PIN) and prostate-specific antigen (PSA)];
o  Methods to distinguish older men with "clinically significant"
cancer preoperatively;
o  Verification of diagnostic specificity and predictive value of PSA
parameters for older men;
o  Studies of the causes of racial/ethnic disparities in disease
stage at diagnosis (black men present with advanced disease stage
more frequently);
o  Effects of age-associated changes on sensitivity, specificity,
prognostic value of diagnostic techniques and their predictive value
for response to treatment. Testing new methods and technologies to
reduce age-associated problems in diagnosis and prognosis.
o  Testing new interventions or treatment strategies in older men
with comorbid conditions to reduce age-associated complications or
lessen age-associated reduction in treatment efficacy (as measured by
treatment outcomes such as quality of life, functional status, and/or
survival experience);
o  Clinical determinants of age- and ethnicity-associated differences
in prostate cancer treatment efficacy and effectiveness for such
outcomes as survival, treatment complications, side effects of
treatment, and functional status;
o  Factors responsible for differences among age and ethnic groups in
treatment received and clinical outcomes (e.g., stage at diagnosis,
presence of comorbid conditions, age selection bias by physicians)
and the effects of interactions among such factors.  These may
--  Special features of aging and/or symptoms of illness in old age
that influence the treatment and care of older-aged prostate cancer
patients and relate to treatment differences or modifications made
because of old age;
--  Assessment of the effectiveness of different treatments relative
to the stage of disease and characteristics of old age (e.g., poor
repair mechanisms, functional loss, greater susceptibility to
toxicity of treatment);
--  Evaluation of tolerance and response to standard or experimental
adjuvant radiotherapy regimens or multimodality prostate cancer
treatment interventions, controlling for physiologic parameters and
other factors;
--  Effects of age-associated, cultural, and life-style changes on
sensitivity, specificity, prognostic value, and predictive value for
treatment responsiveness and diagnostic techniques;
--  Effects of previous and/or concurrent illnesses on prostate
cancer treatment recommendations.
Ancillary Studies/Existing Databases
o  Ancillary studies conducted with the NCI Clinical Trials Research
Cooperative Groups, SEER Special Studies, and population-based tumor
registry studies related to aging, race, and ethnicity in prostate
cancer are welcome for this research solicitation.  These may include
studies on barriers to recruitment of older white and black males to
prostate cancer clinical trials (e.g., comorbid conditions, physical
frailty, lack of transportation), quality of life parameters for
cancer patient survival follow-up;
o  Analyses of existing databases applicable and relevant to
addressing treatment of older prostate cancer patients.  Emphasis on
older ethnic populations that may be compared with white and black
populations is encouraged (e.g., longitudinal studies such as the
Baltimore Longitudinal Study on Aging; Normative Aging Study;
Framingham Study; as well as clinical studies).  Research
applications require a thorough and detailed explanation of the data
elements in the studies identified as candidates for this research
solicitation. Special attention should be given to ascertaining
biases in the databases.
This PA focuses in particular on men aged 65 years and older because
the highest cancer incidence and mortality rates are found in this
age group.  Also, men in their mid-seventies and older are generally
those most severely affected by prostate cancer. These men are also
already quite likely to have preexisting chronic conditions which may
be problematic in the diagnosis and management of cancer.  The
definition of "old age" or "elderly," however, is flexible and
dependent on investigator-defined parameters.  Applicants are
expected to identify what is meant by "old" in the context of their
research.  Age comparisons with younger men are appropriate and may
be included.
It is the policy of the NIH that members of minority groups and their
subpopulations must be included in all NIH supported biomedical and
behavioral research projects involving human subjects, unless a clear
and compelling rationale and justification is provided that inclusion
is inappropriate with respect to the health of the subjects or the
purpose of the research.  This new policy results from the NIH
Revitalization Act of 1993 (Section 492B of Public Law 103-43) and
supersedes and strengthens the previous policies (Concerning the
Inclusion of Minorities in Study Populations), which have been in
effect since 1990.  The new policy contains some provisions that are
substantially different from the 1990 policies.
All investigators proposing research involving human subjects should
read the "NIH Guidelines For Inclusion of Women and Minorities as
Subjects in Clinical Research," which have been published in the
Federal Register of March 28, 1994 (FR 59 14508-14513) and reprinted
in the NIH Guide for Grants and Contracts, Volume 23, Number 11,
March 18, 1994.
Investigators also may obtain copies of the policy from the program
staff listed under INQUIRIES.  Program staff may also provide
additional relevant information concerning the policy.
Applications are to be submitted on the grant application form PHS
398 (rev. 5/95) and will be accepted at the standard application
deadlines as indicated in the application kit.  Application kits are
available at most institutional offices of sponsored research and may
be obtained from the Office of Extramural Outreach and Information
Resources, National Institutes of Health, 6701 Rockledge Drive, MSC
7910, Bethesda, MD 20892-7910, telephone 301/710-0267, email:
ASKNIH@odrockm1.od.nih.gov.  The title and number of the program
announcement must be typed in Section 2 on the face page of the
application.  Applications for the FIRST award (R29) must include at
least three sealed letters of reference attached to the face page of
the original application.  FIRST award (R29) applications submitted
without the required number reference letters will be considered
incomplete and will be returned without review.
The completed original application and five legible copies must be
sent or delivered to:
6701 ROCKLEDGE DRIVE, ROOM 1040 - MSC 7710
BETHESDA, MD  20892-7762
BETHESDA, MD  20817 (for express/courier service)
Receipt dates for new Research Project Grants and FIRST Awards
applications are February 1, June 1, and October 1 of each year.
Applications will be assigned on the basis of established Public
Health Service referral guidelines.  Applications will be reviewed
for scientific and technical merit by study sections of the Division
of Research Grants, NIH, in accordance with the standard NIH peer
review procedures.  Following scientific-technical review, the
applications will receive a second-level review by the appropriate
national advisory council.
Review Criteria
o  Scientific, technical, or medical significance and originality of
proposed research;
o  Appropriateness and adequacy of the experimental approach and
methodology proposed to carry out the research;
o  Qualifications and research experience of the Principal
Investigator and staff, particularly, but not exclusively, in the
area of the proposed research;
o  Availability of the resources necessary to perform the research;
o  Appropriateness of the proposed budget and duration in relation to
the proposed research;
o  Adequacy of plans to include minorities and their subgroups as
appropriate for the scientific goals of the research.  Plans for the
recruitment and retention of subjects will also be evaluated.
The initial review group will also examine the provisions for the
protection of human and vertebrate animal subjects, and the safety of
the research environment.
Applications will compete for available funds with all other approved
applications assigned to that IC.  The following will be considered
in making funding decisions:  Quality of the proposed project as
determined by peer review, availability of funds, and program
Inquiries are encouraged.  The opportunity to clarify any issues or
questions from potential applicants is welcome.
Direct inquiries regarding programmatic issues to:
Rosemary Yancik, Ph.D.
Geriatrics Program
National Institute on Aging
Building 31, Room 5C05
Bethesda, MD  20892
Telephone:  (301) 496-5278
FAX:  (301) 496-2793
Email:  YancikR@31.nia.nih.gov
Andrew Chiarodo, Ph.D.
Organs System Coordinating Branch
National Cancer Institute
Executive Plaza North, Room 512
Bethesda, MD  20892
Telephone:  (301) 496-8528
FAX:  (301) 402-0181
Email:  ac53a@nih.gov
Gwen Collman, Ph.D.
Division of Extramural Research and Training
National Institute of Environmental Health Sciences
P.O. Box 12233
Research Triangle Park, NC  27709
Telephone:  (919) 541-4980
FAX:  (919) 541-4937
Email:  collman@niehs.nih.gov
Direct inquiries regarding fiscal matters to:
Joseph Ellis
Grants and Contracts Management Office
National Institute on Aging
7201 Wisconsin Avenue, Suite 2N212, MSC 9205
Bethesda, MD  20892-9205
Telephone:  (301) 496-1472
FAX:  (301) 402-3672
Email:  EllisJ@gw.nia.nih.gov
Robert E. Hawkins, Jr.
Grants Administration Branch
National Cancer Institute
Executive Plaza South, Room 243
Bethesda, MD  20892
Telephone:  (301) 496-7800 Ext. 213
FAX:  (301) 496-8601
Email:  HawkinsR@gab.nci.nih.gov
David L. Mineo
Grants Management Branch
National Institute of Environmental Health Sciences
P.O. Box 12233
Research Triangle Park, NC  27709
Telephone:  (919) 541-1373
FAX:  (919) 541-2860
Email:  mineo@niehs.nih.gov
This program is described in the Catalog of Federal Domestic
Assistance No. 93.866, Aging Research; No. 93.394, Cancer Detection
and Diagnosis Research; No. 93.395, Cancer Treatment Research; No.
93.396, Cancer Biology Research; No. 93.399, Cancer Control Research;
and No. 93.113, Biological Response to Environmental Health Hazards.
Awards are made under authorization of the Public Health Service Act,
Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158,
42 USC 241 and 285) and administered under PHS grants policies and
Federal Regulations 42 CFR 52 and 45 CFR Part 74.  This program is
not subject to the intergovernmental review requirements of Executive
Order 12372 or Health Systems Agency review.
The PHS strongly encourages all grant and contract recipients to
provide a smoke-free workplace and promote the non-use of all tobacco
products.  In addition, Public Law 103-227, the Pro-Children Act of
1994, prohibits smoking in certain facilities (or in some cases, any
portion of a facility) in which regular or routine education,
library, day care, health care or early childhood development
services are provided to children.  This is consistent with the PHS
mission to protect and advance the physical and mental health of the
American people.

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