NCI Urged to Seize Opportunity for Prostate Cancer Research

 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 panel’s 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 doesn’t do justice to the enormous need."

The review group’s top priorities for prostate cancer research include:

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 don’t 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.