The teleconference of the Advisory Committee to the Director, National Cancer Institute, was convened on July 10, 2002, at 2:30 p.m. EST at the National Institutes of Health, Building 31, Conference Room 11A03.

Advisory Committee members participating in the teleconference:
Andrew von Eschenbach, M.D., Director, National Cancer Institute (Chair)
Frederick R. Appelbaum, M.D., Fred Hutchinson Cancer Research Center (Board of Scientific Advisors)
Barbara LeStage, Chair, Director's Consumer Liaison Committee, National Cancer Institute
Larry Norton, M.D., Memorial Sloan-Kettering Cancer Center, (Acting Chair, National Cancer Advisory Board)
Craig Thompson, M.D., University of Pennsylvania Cancer Center (Board of Scientific Counselors)

Ex Officio members participating:
Marvin Kalt, Ph.D., National Cancer Institute
Alan S. Rabson, M.D., Deputy Director, National Cancer Institute

Executive Secretary:
Lisa Stevens, Ph.D., National Cancer Institute

Other participants:
Heather Burns, National Cancer Institute
Norma Davis, National Cancer Institute
Deborah Duran, Ph.D., National Cancer Institute
Jorge Gomez, M.D., Ph.D., National Cancer Institute (Executive Director, Kidney/Bladder Cancers Progress Review Group)
Joanne Hawana, The Blue Sheet
Peter H. Jones, Ph.D., University of Southern California (Co-Chair, Kidney/Bladder Cancers Progress Review Group)
Cherie Nichols, M.B.A., National Cancer Institute
Nicholas Vogelzang, M.D., University of Chicago (Co-Chair, Kidney/Bladder Cancers Progress Review Group)

The purpose of the teleconference was to present to the Advisory Committee to the Director (ACD), for its discussion and acceptance, the draft report of the Kidney/Lung Cancers Progress Review Group (PRG). ACD must formally accept the report to enable NCI to develop an implementation plan based on the report's recommendations. Dr. Andrew von Eschenbach, Chair, ACD, welcomed those in attendance.

Dr. Jones noted that the Kidney/Bladder Cancers PRG included 16 or 18 urologists, including several department chairs. After two days of deliberations and presentations, they had met in a plenary session that proposed a number of conclusions and recommendations for action by NCI. The PRG concluded that kidney and bladder cancers make a significant contribution to cancer mortality, yet they are relatively understudied. They also found that pathways played a central role in both cancers and provided a unifying theme for the PRG's deliberations. The recent discovery of the role of the VHL gene in familial kidney cancer should open the door to targeted therapies. In bladder cancer, which lacks this familial trait, the use of p53 mutations as a molecular marker is now in prospective clinical trials.

Dr. Jones also noted that there is at present no advocacy group for bladder cancer and suggested that it would make sense to create one. There is a limited amount of cooperative research on these cancers, and there is a need for better ways to collect samples, detect the cancers at an earlier stage, and follow patients. There is also a need to strengthen urology research and to develop useful animal models.

Dr. Vogelzang summarized the PRG's recommendations in the area of cancer control, which focused on the need for (1) conducting behavioral and quality-of-life research on long-term survivors; (2) identifying and validating molecular markers of disease and treatment; and (3) identifying gaps and difference in standards of care that contribute to different outcomes. He noted that there are many long-term survivors available for study, but kidney patients die decades earlier than bladder patients. He also noted that urine is a readily available biologic reagent.

Dr. Jones summarized the PRG's recommendations in the area of discovery, which focused on (1) understanding the environmental risk factors in kidney and bladder cancers; (2) identifying the genomic changes and pathways that lead from molecular defect to pathological condition; (3) understanding the role of the stroma and its cellular signaling; and (4) developing transgenic (mouse) models for the pathways in kidney and bladder cancers, which lags far behind mouse models of other cancers. He noted that the high incidence of bladder cancer in the dye industry is well known but poorly understood, as is the connection with smoking, schistosomiasis, and arsenic in drinking water. He suggested that the tumor should be thought of as an organ, not just a collection of malignant cells.

Dr. Jones summarized the PRG's recommendations in the area of translational research, which focused on the opportunity to develop "smarter" therapies based on molecular markers for the genetic changes and pathways involved in kidney and bladder cancers. These cancers are a natural area for translational research because of the accessibility of the tumors, the availability of urine as a diagnostic fluid, and the ease of introducing therapeutics. One barrier in this area is the lack of serially available specimens for following the course of disease. Confidentiality of patient clinical data is also becoming an issue.

Dr. Vogelzang summarized the PRG's recommendations in the area of treatment, which focused on (1) developing treatment strategies using mechanism- or pathway-based agents; (2) developing novel markers for treatment, as well as diagnosis (e.g., functional imaging for staging); and (3) developing evidence-based, hypothesis-driven research in palliative care. NCI is well positioned to encourage the first area through collaborative research, and it could partner with other institutes to pursue the third.

Finally, Dr. Vogelzang summarized the PRG's findings with regard to the resources that would be required to pursue these recommendations. These include better animal and cell-based models, longitudinal samples of tissue, serum and urine; and international collaboration in the creation of specimen banks. Also needed are urinary markers, standardized assays, and high-throughput tests, and - in general - the capability to develop and screen small molecules. Better bioinformatics and biostatistics will be needed for data management, as well as a centralized database and data network to integrate the three largest clinical trials already underway and to link these databases with SEER to evaluate standards of care. Other needed technological resources include multimedia approaches to screening and noninvasive imaging to evaluate staging and treatment. Needed institutional resources include more flexible funding mechanisms, increased number of investigators working on kidney and bladder cancers, and enhanced training on quality of life issues for physicians, nurses and social workers.

In conclusion, Dr. Vogelzang said that the PRG found an enormous opportunity for advances in the detection and treatment of kidney and bladder cancers that could significantly reduce mortality. Better understanding of the causes and pathways involved in these cancers should lead to better treatment. Discovery of urinary markers could lead to earlier diagnosis and better outcomes. He concluded by saying that these four areas - cancer control, discovery, translation, and treatment - are part of a continuum, and that all four areas should be pursued in both types of cancer.

In response to questions from ACD members, Drs. Jones and Vogelzang explained that the PRG had not "prioritized its priorities," but that there were two areas where NCI could make the most difference by removing a roadblock or providing the foundation for further advances. These two areas were (1) identifying the genomic changes and pathways through which molecular defects lead to pathological conditions, and (2) developing transgenic mouse models of these pathways in kidney and bladder cancer. Similarly, they identified the single most important resource or infrastructure as the creation of disease-based centers and networks that would be "more than a cooperative group but less than a SPORE." They believe that there is a real need for this kind of multi-institutional mechanism to connect and support researchers in "orphan" fields such as kidney and bladder cancers.

The co-chairs also explained that the PRG did not focus on the role of the immune system because they considered this to be "plowed ground." However, they agreed that the report should give more attention to the proteomics of urine for screening and prognostics, and they indicated that they would write an addendum to the report to reflect this topic. Ms. LeStage suggested that the Director's Consumer Liaison Group could help researchers identify long-term survivors, and that it might also be able to assist in establishing a bladder cancer advocacy group.

ACD members unanimously accepted the report of the Kidney/Bladder Cancers PRG for transmittal to NCI for consideration and development of an implementation plan. Dr. Stevens stated for the record that ACD members had been determined to have no conflicts of interest with respect to the matters under discussion at this meeting. She added that the PRG report can be modified.

Dr. von Eschenbach thanked the PRG co chairs and executive director and the ACD members for their work. A follow up meeting will be held with the PRG to discuss both the recommendations and the proposed implementation strategy.

The teleconference was adjourned at 3:50 p.m. EST..