BETHESDA, Md--Citing "an unprecedented opportunity to make
substantial strides in the treatment of prostate cancer," an
outside panel has urged the National Cancer Institute to increase
funding and broaden efforts to understand and defeat the second
leading cause of cancer deaths among US men.
"An investment in biomedical research at this crucial period
could bring the forces of modern biological and clinical sciences to
the control of prostate cancer," the Prostate Cancer Progress
Review Group reported.
The Institute asked the panel to identify and prioritize the
scientific needs and opportunities critical to quickening progress
against the disease and to develop a national plan for implementing
these priorities. Its report was released at a meeting of the
National Cancer Advisory Board (NCAB). (See below for the report from
the breast cancer panel.)
In its review of the prostate cancer research currently funded by
NCI, the committee identified some 460 individual projects that
received a total of $87 million in support. The panel said this
represents "a substantial commitment" by NCI, but it also
noted key gaps in research that require increased funding.
"There is no better way to spend our money than to bring the
best brain power we can to focus on prostate cancer," said Peter
Scardino, MD, chief of urology, Memorial Sloan-Kettering Cancer
Center, the panels co-chair.
It was a view shared by NCAB member Philip S. Schein, MD, adjunct
professor of medicine and pharmacology at the University of
Pennsylvania. He noted that "$87 million, perhaps supplemented
by the VA and others, just doesnt do justice to the enormous need."
The review groups top priorities for prostate cancer research
Biology, progression, and metastasis. Improving diagnosis,
prevention, and treatment requires a strong focus on the molecular,
cellular, physiological, and pathological events that lead to
uncontrolled growth and metastasis, the report stated.
"We recommend that renewed emphasis be placed on understanding
the genes that are involved in the progression of these cancer cells
and metastasis, and that great emphasis be placed on the
understanding of cell biology, including cell-to-cell interactions,
hormonal regulation, and proliferation, apoptosis, and
angiogenesis," said co-chair Donald J. Tindall, PhD, professor
of urology and biochemical and molecular biology, Mayo Clinic Foundation.
Etiology and primary prevention. The committee also
noted the importance of genetic research in our understanding of the
etiology of prostate cancer and recommended aggressive pursuit of
studies directed at prevention, including determining which
environmental and lifestyle factors influence the risk of developing
prostate cancer and how chemopre-vention may reduce risk.
Citing evidence that some diet components inhibit prostate cancer,
Dr. Tindall said, "we can take advantage of these naturally
occurring substances to prevent the disease as well as treat it."
Early detection, diagnosis, and prognosis. Although PSA
testing has revolutionized the early detection of prostate cancer,
"we dont have the evidence that we need to show that early
detection of prostate cancer really reduces the risk of dying,"
Dr. Scardino said.
The report said: "Progress in early detection requires that
tests used for detection be refined to ensure that, whenever
possible, the cancers detected are clinically important; that is, to
detect only those cancers with the potential to kill their host if
left untreated without missing any clinically important cancers."
The committee also advised the NCI to "place major emphasis on
the development, validation, and application of biologic markers or
determinants than can provide reliable prognostic information."
Laboratory and clinical models. The panel noted the need
for animal models as critical for defining the progression of the
disease and for testing preventive and therapeutic regimens.
Our recommendations are to develop more animal models that
truly recapitulate various aspects of prostatic cancer, Dr.
Tindall said. The group also urged greater attention to devising
additional prostate cancer cell lines that have predictable levels of
extrapolation to humans.
Staging and treatment of localized disease. Noting that
oncologists cannot now determine which localized prostate cancers
pose a threat so low that treatment can be deferred indefinitely, the
panel urged a major effort to improve staging and develop new
techniques to detect metastatic cells and determine their clinical
significance. It also called for new therapeutic approaches and said
that, among solid tumors, prostate cancer seems particularly suitable
for gene therapy.
Systemic therapies. Although hormonal therapy remains the only
recognized systemic treatment for advanced prostate cancer, research
has identified a number of promising mechanism-based approaches
worthy of clinical testing, the report said.
These include inhibiting signal transduction or specific steps in the
cell cycle, blocking angiogenesis and other specific steps in the
metastatic cascade, promoting apoptosis, inducing differentiation,
and stimulating the immune system by a variety of therapies.
Outcomes research. NCI was urged to increase outcomes
research in disease-specific and patient-focused endpoints to better
determine the results of various interventions.
Resources. "Progress in prostate cancer is severely
impeded by limitations in research funding, policies, and
practices," the committee concluded. "Several major areas
critically require investment and leadership: training and career
development, an informatics network linking repositories and
databases, clinical trials, translational research, laboratory and
clinical models, new technology, and patient education."
Finally, the committee called on the NCI to form a special prostate
cancer trials consortium to improve the design of clinical trials.