Planning National Agendas for Disease-Specific Research

Progress Review Groups

When I entered the clinical trial, my doctor said to me, "You are not going to die right away." This was a big surprise! I felt so bad and had been told that I could expect to live only a few more months. I just assumed I was at the end of the road. After several tries that failed, they finally found a treatment regimen that seems to have turned my cancer around - at least for now. This kind of thing is very unusual for pancreatic cancer. I have been so blessed and want others to know that there is hope.      - Christine, clinical trial patient

Each of the 1,268,000 Americans who will be diagnosed with cancer this year will battle a very specific, very personal disease. While the hundred-plus distinct diseases we call "cancer" have several essential attributes in common, each type of cancer has its own unique characteristics that affect how it arises, how it progresses, and how it can be most effectively treated.

And while we have learned much that is broadly applicable to all types of cancer through our core research programs and the initiatives of the Extraordinary Opportunities, we must be equally alert to the specific tendencies and behaviors of each cancer type. This is why NCI plans, promotes, and carries out an ambitious program of disease-specific research.

Top of Page

About NCI's Progress Review Groups

NCI charts the course for its disease-specific efforts primarily through advice from expert Progress Review Groups (PRGs). The PRGs are panels of 20 to 30 prominent members of the scientific, medical, and advocacy communities that assess the state of the science for a single type of cancer or a group of closely related cancers and make recommendations for future research.

Over a nine-month period, each PRG identifies:

• Gaps in our understanding of the disease under study
• Barriers to progress
• Key research priorities

The process culminates in the wide release of PRG findings and priorities in a comprehensive report. All PRG reports become road maps that guide NCI and the scientific community in their efforts to make progress against specific types of cancer. To date, six PRG reports have been issued. Six more PRGs are in progress or planned.

View a listing of completed and upcoming PRG's.

NCI's extensive slate of PRGs includes breast, prostate, lung, and other common types of cancer as well as less common diseases like pancreatic cancer, multiple myeloma, and brain tumors. By addressing these more unusual types of cancer through the PRGs, NCI hopes to raise awareness of the scientific opportunities afforded by each disease and to stimulate much-needed research.

Top of Page

Response and Communication

NCI responds rapidly and enthusiastically to PRG recommendations. For each PRG, NCI staff:

• Form an internal working group of disease-specific experts to spearhead the Institute's response to the recommendations, identify gaps in our understanding, and propose new programs and initiatives where needed.
• Thoroughly analyze the recommendations to determine the extent to which they are being addressed - or could be addressed - through existing programs or efforts.
• Reconvene the PRG to discuss what we learn through this analysis and to clarify what gaps remain.
• Develop strategies to implement the recommendations, particularly in gap areas.
• Communicate our decisions to the scientific community and enlist their active participation in the implementation process.
• Ensure that effective mechanisms are in place to implement decisions.
• Follow up to ensure that the recommendations continue to be addressed.
• Report on our results.

To ensure that researcher and advocacy communities are aware of NCI's disease-specific priorities, NCI is developing a comprehensive, systematic plan for disseminating and promoting the PRG reports. To promote the priorities identified by various PRGs, information related to the PRGs is distributed:

• At major medical meetings
• In journals and newsletters
• On the World Wide Web
• In partnership with several advocacy groups

Even with all these efforts in place, we recognize that the ultimate success of the PRG process depends on researchers' ability and willingness to undertake research projects in disease-specific areas of critical need. NCI encourages the scientific community to respond to its disease-specific priorities by:

• Treating the PRG reports as Broad Program Announcements that indicate the most pressing needs and opportunities, and
• Notifying the community about current funding opportunities that address the PRGs' recommendations through its Cancer Research Initiatives web site
• Giving special consideration in the funding exceptions process to grant applications that reference a PRG report.

Consumer advocates also play a key role in the PRGs and their follow-up. Advocates are involved throughout the PRG process, serving as PRG members and keeping their communities informed about the PRG and its recommendations and mobilizing in support of PRG priorities. They may also help raise awareness of the priorities among researchers and clinicians.

Top of Page

Highlights of PRG Recommendations

Based on review and analysis of the recommendations of the first six PRGs, it is clear that many of the recommendations are, or could potentially be, addressed by programs that are already in place. In some cases modification or supplementation of an existing program is sufficient to get the research on track. The PRGs have also pointed to obvious gaps in NCI's disease-specific programs. For example:

• The Breast Cancer PRG noted that our lack of understanding of the biology and developmental genetics of the normal breast was a significant barrier to progress against the disease. The NCI responded by joining several other NIH Institutes to release a Program Announcement (PA) seeking applications for research on normal breast development, as well as on changes in the breast throughout the development of early and advanced cancer. This PA has generated eight new research projects.



• The Prostate Cancer PRG told us that the lack of validated animal models of prostate cancer was severely impeding progress. Since then, four separate research teams have begun work on models of prostate cancer through NCI's Mouse Models of Human Cancers Consortium.



• The Leukemia, Lymphoma, and Myeloma PRG found that the infrastructure for developing new treatments of hematologic malignancies, particularly those exploiting molecular targets, is inadequate. They called for the development of consortia that would bring together experts across multiple disciplines and institutions to participate in the rapid discovery and development of cancer therapies. The ultimate goal of the program would be to shorten drug development time of five to ten years to about two years through an alliance among academia, industry, government, and patients. NCI is currently investigating ways to create and support these novel consortia.

Furthermore, NCI is taking steps to address a number of broad scientific needs noted by several PRGs, such as the need for research training and the development of biomarkers of disease. For example:

• NCI is currently expanding the Specialized Programs of Research Excellence (SPOREs) program to cover a number of the cancers addressed by the PRGs, including gynecologic cancers, brain tumors, leukemia, lymphoma, and myeloma.

  Examples of advances from the SPORE Program

• Several PRGs have recognized a need for the identification of biomarkers of disease. The Early Detection Research Network (EDRN) is dedicated to meeting this need. Projects specifically related to prostate, lung, and ovarian cancers are among those well under way, with others planned.

  Example of advances from the EDRN

• Several PRGs discussed the importance of more accurate diagnosis and staging of cancer. Research conducted through the The Director's Challenge: Toward a Molecular Classification of Tumors will facilitate diagnosis at the molecular level, enabling greater precision in diagnosis and treatment. To date, the Director's Challenge has stimulated some 22 supported projects covering a diverse array of cancers including breast, prostate, lung, brain, ovary, colon, and leukemia and lymphoma.

  Example of advances from The Director's Challenge

Top of Page

Assessing the Impact of the PRGs

It is too early to fully assess this, but the early signs are encouraging. NCI has recently begun the critical task of assessing the impact of the PRG effort within the research community. As part of a system for evaluating the PRG process and outcomes, the Institute will analyze changes in grant applications, funding levels, and types of research funded that occur after the completion of a PRG.

Starting with the Breast and Prostate PRGs, NCI will issue a status report two to three years after each PRG, and the groups will reconvene to:

• Discuss the status of the recommendations and NCI's response
• Consider further action

This process will provide valuable information and insight about our directions in disease-specific planning.

While the process may be refined over time, it is clear that the combined perspectives of PRG members, NCI staff, researchers, and cancer advocates will continue to influence the future direction of both broad-based and disease-specific research. By working together, we can ensure the most effective use of resources focused on both needs and opportunities for advances against all cancers.

Top of Page

People's Stories

• Pancreatic cancer
• Multiple Myeloma
• Brain tumors
• Prostate cancer
• Lung cancer
• Breast cancer

Pancreatic cancer continues to affect thousands.

"My father died from pancreatic cancer. My brother and I wonder if we've inherited a high risk for this awful disease. Are scientists working on ways to prevent this cancer, and find out who's at risk?"

Pancreatic cancer is a particularly devastating disease because it:

• Spreads quickly
• Seldom causes clear symptoms until it is advanced
• Is almost universally fatal

In 2001, an estimated 29,200 new cases will be diagnosed, with most patients living six months or less after diagnosis. Severe wasting and pain are tragic hallmarks of pancreatic cancer.

Recognizing the urgent need for improved detection, treatment, and symptom management of this disease, NCI convened a Pancreatic Cancer PRG in 2000. The PRG stressed the need to better understand how the normal pancreas develops and functions -- an essential foundation for research on how pancreatic cancers arise and the environmental and other factors that may influence their growth and spread.

Top of Page

Multiple myeloma incidence is on the rise.

My doctor said I had multiple myeloma, and I said, "What's that?" When she said it was cancer, I was stunned. I had never even heard of this disease.

Multiple myeloma is a cancer of blood plasma cells that grow out of control and form tumors, usually in the bone marrow. These tumors interfere with the blood-forming functions of the marrow, and the abnormal plasma cells cease producing infection-fighting antibodies.

Multiple myeloma is one of the blood system cancers that are rising in incidence - new cases are increasing by nearly one percent per year. An estimated 14,400 new cases will be diagnosed in 2001. Deaths from this disease also are increasing, and the average patient survives only three years from diagnosis. Typically a disease of the elderly, myeloma is now striking people as young as their twenties and thirties.

Multiple myeloma was one focus of NCI's Leukemia, Lymphoma, and Myeloma (LLM) PRG, whose report was released in May 2001. The group recommended:

• A large case-control study to investigate the etiology of the three diseases
• The development of an infrastructure and methodologies to better understand the interaction among immune function, infectious agents, environmental toxins, and lifestyle factors that can lead to the diseases' development

Top of Page

Brain tumors pose unique challenges for researchers and patients.

"We have to carefully weigh the potential benefit of every brain tumor surgery, chemotherapy, or radiation treatment against the risk of mental and functional damage. And with children, we worry about future learning or developmental problems."

Many cancers have one or more subtypes, but brain and central nervous system (CNS) tumors are extraordinary in this regard -- more than 125 types are known to exist, and their symptoms, aggressiveness, treatment, and outcome vary greatly. Because brain tumors affect the organ that is the essence of the "self," surgical approaches for treating most other cancers -- removing the tumor and a border of normal tissue if not the entire affected organ -- often cannot be used without damaging vital mental processes or brain functions.

Moreover, many brain and CNS tumors are highly resistant to radiation and chemotherapy. The Brain Tumor PRG convened by NCI noted these special challenges in its report, published in 2000, and called for the development of novel treatment agents and approaches, including:

• New chemotherapies
• Treatments that target the immune system
• Gene therapy
• Antiangiogenesis agents
• Viral agents

Top of Page

New drugs provide hope for prostate cancer patients with bone metastases.

When prostate cancer spreads, it often invades the bones, where it causes severe, debilitating pain. However, several drugs currently under study may combat bone metastases, slowing the spread of the cancer and improving the patient's quality of life.

For example, the class of drugs known as bisphosphonates has already been established as effective against breast cancer and multiple myeloma, but these drugs have not been considered particularly effective against prostate cancer -- until now.

• Clodronate, a bisphosphonate, has shown activity against prostate cancer metastasis, opening the door for further studies involving more potent bisphosphonates, or higher doses of the drug.
• A second drug, Atrasentan, targets the protein endothelin-1, which promotes cell growth in bone and which is overactive in prostate cancer cells.
• A combination of chemotherapy and a bone-targeted radiation drug, strontium-89 (Sr-89), may prolong the lives of men with prostate cancer that has spread to the bones. Sr-89 is a radioactive substance used to relieve bone pain caused by metastatic prostate cancer. When injected by vein, Sr-89 moves into bones and delivers radiation directly to cancer that has spread there.

Metastasis was also a key topic of interest for the Prostate Cancer PRG.

Top of Page

New imaging technology improves early detection for lung cancer.

Spiral CT is a promising new technique that can be used to detect lung cancer at a very early stage, before it has had a chance to spread. This technique uses X-rays to scan the entire chest quickly, in 15 to 20 seconds, during a single breath-hold. It is safe -- the amount of radiation during a spiral CT scan is about the same as that absorbed during a mammogram -- and simple.

But will detecting these early tumors reduce the likelihood of dying from lung cancer? The NCI is working to find out. The year-long Lung Screening Study (LSS), part of the Institute's landmark Prostate, Lung, Colorectal, and Ovarian Cancer screening trial, began in the fall of 2000 to gauge the feasibility of a larger, more definitive study down the road.

Through the LSS, we will learn, first and foremost, whether smokers will be willing to be randomized to receive something other than a spiral CT scan in a comparative study. The LSS will also provide important information about the medical follow-up of people who have the scans, as well as the costs involved.

The Lung PRG, whose report was released in August 2001, discussed the topic of screening extensively, calling for the rapid evaluation of spiral CT as a means of detecting cancer early and ultimately reducing deaths from lung cancer.

Top of Page

New initiatives aim to improve breast cancer treatment.

The findings of clinical trials in breast cancer over the last ten years have provided physicians and their patients with a wealth of new information to guide their treatment choices - but at the same time, have also complicated their decision making. To help oncologists and patients choose between radiation therapy, chemotherapy, or hormone therapy to try to eliminate cancer cells left behind after surgery, NCI co-sponsored a consensus conference at the end of 2000 to synthesize the information from recent research and make recommendations for routine cancer care.

The breast cancer experts participating in the conference provided advice on the factors that should guide the choice of adjuvant therapy, as these follow-up treatments are known, and made recommendations about which patients should consider hormonal, chemotherapy, or radiation therapy. In addition, consensus conference participants also considered the side effects and quality of life experienced by patients undergoing the various forms of adjuvant therapy and promising new directions for this research.

In other research, NCI is sponsoring clinical trials to compare the effects of removing only one or a few lymph nodes during breast cancer surgery to the standard, more invasive practice of removing more lymph nodes.

Top of Page