URINARY BLADDER CANCER PROGRAM AREA REPORT
September 1, 1977 to December 31, 1978

Program Coordinators: Dr. George T. Bryan
Dr. Osamu Yoshida


Administrative Report

During this year's reporting period, the following activities took place.

MEETINGS, SEMINARS, AND CONFERENCES
The "Seminar on Clinical Evaluation Multimodal Therapy, and Cooperative Studies of Bladder Cancer" was convened in Sarasota, Florida on December 10 to 13, 1978. A detailed report, including an agenda of the meeting and the participants, is presented in Conference Reports following this Program Area Report. Following this meeting, the participants attended the "Annual National Bladder Cancer Project Investigators' Workshop", December 13 through 15, 1978.

EXCHANGE OF SCIENTISTS
The following Japanese scientists visited the United States during this reporting period as ex-change scientists for the U.S.-Japan Cooperative Cancer Research Program: 1. Dr. Y. Ohno; Department of Preventive Medicine, Nagoya University School of Medicine visited Dr. A.S. Morrison, Harvard University School of Public Health, September 1977; and Dr. G.T. Bryan, University of Wisconsin Center for Health Sciences, October 1977.
The following scientists visited the following laboratories with support from other sources:
1. Dr. T. Iwasaki; Department of Urology, Faculty of Medicine, Kyoto University visited Dr. R. Oyasu, Department of Pathology, North-western University, June 1976 to October 1977.
2. Dr. Y. Hirao; Department of Urology, Nara Medical College visited Dr. R. Oyasu, Department of Pathology, Northwestern University, beginning October 1978.
3. Dr. S. Fukushima; Deportment of Pathology, Nagoya City University Medical School visited Dr. G. Friedell, Department of Pathology, St. Vincent Hospital, Worcester, beginning October 1977.
4. Dr. K. Hirao; Department of Urology, Nara Medical College visited Dr. G. Friedell, Department of Pathology, St. Vincent Hospital, Worcester, December 1975 to August 1977.
5. Dr. S. Sugihara; Cancer Center, Nara Medical College visited Dr. J. Leighton, Medical College of Pennsylvania, Pennsylvania, June 1975 to June 1978.
6. Dr. M. Arai; Department of Pathology, Nara Medical College visited Dr. G. Friedell, Department of Pathology, St. Vincent Hospital, Worcester, September 1974 to October 1977.
7. Dr. Y. Kamiryo; Department of Urology, Faculty of Medicine, Yamaguchi University visited Dr. G.T. Bryan, University of Wisconsin Center for Health Sciences, August 1976 to August 1978.
8. Dr. N. Yamamoto: Department of Urology, Faculty of Medicine, Yamaguchi University visited Dr. G. T. Bryan, University of Wisconsin Center for Health Sciences, beginning August 1978.
9. Dr. M. Matsushima; Department of Urology, Toho Medical College visited Dr. G.T. Bryan, University of Wisconsin Center for Health Sciences, beginning August 1978.
10. Dr. T. Shirai; Department of Pathology, Nagoya City University Medical School visited Dr. C. King, Michigan Cancer Foundation, Michigan, beginning April 15, 1978.
11. Dr. M. Takahashi; Department of Pathology, National Institute for Public Health visited Dr. P. Shubik, The Eppley Institute, Nebraska, Aprll 9, 1975 to April 26, 1977.
12. Dr. C.J. Grubbs; IIT Research Institute (IITRI), visited Dr. N. Ito, Department of Pathology, Nagoya City University Medical School, August 7, 1977 to August 21, 1977.
13. Dr. A.G. Lurie; University of Connecticut Health Center, Connecticut visited Dr. N. Ito, Department of Pathology, Nagoya City University Medical School, May 31, 1978 to June 16, 1978.

EXCHANGE OF RESOURCES AND MATERIALS
No extraordinary materials exchange has occurred this year. However, previous meetings and exchanges of scientists have permitted researchers in the U.S. and Japan to meet and become familiar with each others work. Through this direct scientist-to-scientist involvement, progress has been achieved for both sides.

Scientific Summary of Program Area

SUMMARY OF YEAR'S ACTIVITIES
This year was marked by individual bilateral personnel exchanges and planning for the forth-coming meeting. Personnel exchanges have continued and should result in future publications.

SPECIFIC OBJECTIVES ACCOMPLISHED
During this reporting period, the following objectives were accomplished:
1. A third bilateral meeting was planned
2. Bilateral scientist exchanges occurred
3. Exchanges of resources and materials continue
4. Joint publications are in progress.

COOPERATIVE AND COLLABORATIVE ACTIVITIES RESULTING FROM PAST MEETINGS AND DISCUSSIONS
1. Dr. N. Ito and Drs. G. Friedell and S.M. Cohen-through exchanges of personnel and materials.
2. Dr. M. Okada and Drs. C.C. Irving and G.T. Bryan-through exchanges of personnel and materials.
3. Dr. O. Yoshida and Dr. R. Oyasu-through exchange of personnel.
4. Dr. O. Yoshida and Dr. G.T. Bryan-through exchanges of personnel and materials.
5. Dr. Y. Ohno and Drs. A. Morrison and G.T. Bryan-through exchanges of personnel.
6. Dr. M. Ichikawa and Dr. G.T. Bryan-through exchanges of personnel and materials.
7. Dr. S. Sugihara and Dr. J. Leighton-through exchanges of personnel and materials.
8. Dr. N. Ito and Dr. C. King - through exchange of personnel.
9. Dr. M. Takahashi and Dr. P. Shubik - through exchanges of personnel.

Future Program Developments
A strong base of productive and collaborative basic and clinical science activities has been established in many interdisciplinary study areas dealing with bladder cancer. These include activities dealing with initiation and promotion, pathogenesis, epidemiology, detection, diagnosis, therapy, and rehabilitation. This base could be strengthened in future years to consolidate joint efforts initiated in these areas.

Five-Year Summary Administrative Report

MEETINGS, SEMINARS, AND CONFERENCES
1, "Experimental Models for Bladder Cancer,"
December 6 to 9, 1975, Honolulu, Hawaii
Participants: 10 from the United States
6 from Japan

2. "Etiology of Bladder Cancer,"
September 20 to 28, 1976, Kyoto, Japan
Participants: 7 from the United States
9 from Japan

3. "Clinical Evaluation Multimodal Therapy and Cooperative Studies of Bladder Cancer," December 10 to 13, 1978, Sarasota, Florida
Participants: 19 from the United States
11 from Japan

EXCHANGE OF MATERIALS
During the past five years, the Japanese have been most gracious in providing U.S. scientists with a large variety of chemicals for a variety of purposes. Of the many exchanges taking place, most occurred directly between the individual investigators.

EXTENT AND MANNER OF IMPACT OF ACTIVITIES
This program has enabled basic and clinical scientists possessing interests and skills in several areas dealing with bladder cancer to meet, ex-change information, exchange scarce resources and collaborate on research programs. Effective bilateral personnel exchanges have occurred. These generally have been of the long-term variety and have resulted in collaborative published work. We owe a debt of gratitude to those sponsors who willingly and enthusiastically provided the resources of their laboratories and communities to these young scientists. Through these exchanges, we have successfully laid the groundwork for continuous collaboration throughout the careers of these individuals. This aspect has been most gratifying.
We anticipate that the U.S.-Japan Cooperative Cancer Research Program will lead to continuous interactive projects in many scientific areas dealing with bladder cancer. At least nine collaborative and cooperative activities of a continuous nature have been developed from past meetings and discussions. These include activities dealing with initiation and promotion of bladder cancer, and studies of pathogenesis, epidemiology, detection, diagnosis, therapy, and rehabilitation. It would be most unfortunate if the lines of communication that have been forged were allowed to decay because of changes of program emphasis.
Drs. O. Yoshida and G.T. Bryan expressed their pleasure in their participation, thereby helping to create a strong, viable program between Japan and the United States, and wish the U.S.-Japan Cooperative Cancer Research Program every success in the future.


SEMINAR ON CLINICAL EVALUATION, MULTIMODAL THERAPY, AND COOPERATIVE STUDIES OF BLADDER CANCER
Sarasota, Florida
December 10-13, 1978

AGENDA
Monday, December 11
8:30 a.m. OPENING SESSION
Opening Statement of Goals and Purpose of Meeting 		Dr. G. T. Bryan and Dr. O. Yoshida
9:30 a.m. Comparison of Bladder Cancer in Japan and United States CHAIRMAN: Dr. W. F. Whitmore, Jr.
9:30 a.m. Epidemiology and Screening for Bladder Cancer Dr. Alan Morrison
10:00 a.m. Morphological Comparison of Bladder Cancer in the U.S. and Japan Dr. Nobuyuki Ito
10:30 a.m. COFFEE BREAK
11:00 a.m. Pathology of Bladder Cancer Dr. George M. Farrow
11:30 a.m. Discussion
1:00 p.m. Approaches to Therapy-Surgery CHAIRMAN: Dr. Nobuyuki Ito
1:00 p.m. Patient Selection Dr. Ceorge R. Prout
1:30 p.m. Role of Curative Surgery Dr. Takao Sonoda
2:00 p.m. Surgical Management Dr. Willet F. Whitmore, Jr.
2:30 p.m. Partial and Radical Cystectomy Dr. Yoshio Aso
3:00 p.m. Discussion
3: 15 p.m. COFFEE BREAK
3:30 p.m. Approaches to Therapy-Radiation CHAIRMAN: Dr. George Prout
3:30 p.m. Dr. Sachio Mochizuki
4:00 p.m. Dr. Morris J. Wizenberg
4:30 p.m. Discussion

Tuesday, December 12
8:00 a.m. Approaches to Therapy-Chemotherapy and Immunotherapy CHAIRMAN: Dr. O. Yoshida
8:00 a.m. Approaches to Developing Effective Systemic Therapy Dr. Mark Soloway
8:30 a.m. Chemotherapy and Immunotherapy in Japan Dr. Tadao Niijima
9:00 a.m. Discussion
COFFEE BREAK
9:30 a.m. Approaches to Therapy-Chemotherapy and Immunotherapy CHAIRMAN: Dr. Tadao Niijima
9:30 a.m. Chemotherapy for Metastatic Disease Dr. Richard G. Hahn
10:00 a.m. Intravesical Therapy in Japan Dr. Teruo Mishina
10:30 a.m. Intravesical Therapy and Cis-retinoic Acid Dr. W. Koontz
11:00 a.m. Discussion
1:00 p.m. Design and Conduct of Clinical Trials and Collaborative Studies CHAIRMAN: Dr. Robert E. Greenfield
1:00 p.m. Clinical Studies in Japan Dr. O. Yoshida
1:30 p.m. Planning and Organizing Collaborative Studies Mr. Arthur G. Hilgar
2:00 p.m. Design of Clinical Studies Dr. Ceorge R. Prout
The Urologists Point of View Dr. Kenneth Cummings
The Radiologists Point of View Dr. William Shipley
The Chemotherapists Point of View Dr. Albert Einstein
The Pathologists Point of View Dr. George Penick
3:40 p.m. COFFEE BREAK
4:00 p.m. The Statistical and Data Management Needs of Collaborative Studies Dr. Sidney Cutler
4:40 - 5:00 p.m. Discussion

Wednesday, December 13
9:00 - 12:00 a.m. Strategies for Mutually Designed Clinical Studies CO-CHAIRMEN: Drs. O. Yoshida and G. T. Bryan
Discussion by all Participants

Wednesday evening through Friday (December 13-15, 1978)
ANNUAL NATIONAL BLADDER CANCER WORKSHOP - All Participants


MINUTES OF THE SEMINAR ON CLINICAL EVALUATION MULTIMODAL THERAPY AND COOPERATIVE STUDIES OF BLADDER CANCER
Sarasota, Florida
December 10 to 13, 1978

The meeting began with registration and an in-formal social gathering on Sunday, December 10. 1978. Drs. G. T. Bryan and O. Yoshida welcomed guests and visitors. The list of invited participants and observers follows this conference report. Observers were encouraged to participate during all open discussion periods of free time.
The opening session on December 11, 1978, began with a description of the organization and purposes of the Joint U.S.-Japan Cooperative Cancer Research Program. The purposes and goals of the present meeting are: (1) to discuss and demonstrate knowledge and concepts concerning clinical evaluation and multimodal therapeutic approaches to bladder cancer; (2) to share concepts and approaches involved in cooperative clinical trials In bladder cancer; and (3) to seek opportunities for joint collaborative clinical trials to be developed in the future. The participants had been invited to submit an abbreviated abstract of the con-tents of their assigned topics. Most were kind enough to prepare such abstracts. Following each block of presentations, discussion was comprehensive and vigorous. These discussions involved the full time allotted and continued through free periods and mealtimes.
Two highlights of the meeting are deserving of special commendation. Dr. Sachio Mochizuki reported on the use of radiotherapy for bladder cancer in Japan. He clearly demonstrated the use of intraoperative irradiation of small solitary bladder tumors, exposed by cystotomy, to a high energy electron beam therapy. The U.S. urologists and radiotherapists expressed enthusiastic interest in this approach. It is likely that this might serve as a focus for cooperative studies. The second major contribution involved the presentation of the design and conduct of clinical trials and collaborative studies. These reports largely dealt with the five-year experience of the U.S. National Bladder Cancer Project Collaborative Group A activities. Mr. Arthur Hilgar described the numerous considerations to be confronted in planning and organizing the collaborative clinical studies. This was followed by comments by Collaborative Group A participants of the roles of the urologist, radiotherapist, chemotherapist, pathologist, and statistician in such a complex program. Much interest was expressed in this portion of the seminar.
The meeting enjoyed the involvement and participation of each member of the delegations. The participant selection was excellent, and each counterpart member found a scientific colleague to interact with. Members of both delegations expressed interest in seeking new avenues to develop mutually shared clinical trials and to continue scientific exchanges in the future. It is clear that ways to facilitate such continued interactions must be developed.
The Japanese participants as well as the U.S. hosts continued to interact during the period December 13 to 15, 1978, while attending the National Bladder Cancer Project Investigators' Workshop. More than 300 individuals attended and participated in this meeting. Dr. O. Yoshida very kindly presented aspects of clinical bladder cancer research activities in Japan at a principal session of the meeting.
These meetings were excellent and the purposes described were met. Ample time was provided for exchange of ideas, and preliminary steps were taken toward continued interactions. Finally, Professors Yoshida and Bryan wish to thank their advisors for providing the strength and direction to carry out these activities. The advisors from Japan are Dr. N. Ito and Dr. M. Okada. From the United States, the advisors are Drs. G.H. Friedell and C.M. King. It is appropriate that they should share in any successes; we accept responsibility for any shortcomings. The Japan Society for the Promotion of Science and the U.S. National Cancer Institute have been steadfast in their sup-port and encouragement of this program and that support is gratefully acknowledged.

JAPANESE PARTICIPANTS

Dr. Yoshio Aso
Professor of Urology
Hamamatsu University School of Medicine
3600 Handa-cho Hamamatsu-shi, Japan

Dr. Masao Hirose
Research Feliow of Pathology
Nagoya City University Medical School
1 Kawasumi, Mizuho-cho, Mizuho-ku
Nagoya 467, Japan

Dr. Nobuyuki Ito
Professor of Pathology
Nagoya City University Medical School
1 Kawasumi, Mizuho-cho, Mizuho-ku Nagoya 467. Japan

Dr. Takuo Iwasaki
Instructor of Urology
Kyoto University Hospital
54 Kawara-cho, Shogo-in
Sakyoku, Kyoto, Japan

Dr. Kenkichi Koiso
Assistant Professor of Urology
Faculty of Medicine
The University of Tokyo
7-3-1 Hongo. Bunkyo-ku
Tokyo. 113 Japan

Dr. Toshihiko Kotake
Chief of Urology
Center for Adult Disease
Nakamichi 1-1-3, Higashinari-ku
Osaka 537, Japan

Dr. Teruo Mishina
Associate Professor of Urology
Kyoto Prefectural University of Medicine
Kawaramachi-Hirokoji, Kamigyo-ku
Kyoto, Japan 602

Dr. Sachio Mochizuki
Professor of Radiology
Jikei University School of Medicine
3-25-8 Nishi-shinbashi, Minato-ku
Tokyo, Japan

Dr. Tadao Niijima
Professor of Uroiogy
Faculty of Medicine
The University of Tokyo
7-3-1, Hongo, Bunkyo-ku
Tokyo, 113 Japan

Dr. Tomoyuki Shirai
Visiting Scientist
Department of Chemicai Carcinogenesls
Michigan Cancer Foundation
Meyer L. Prentis Cancer Center
110 E. Warren Avenue
Detroit. Michigan 48201

Dr. Takao Sonoda
Professor of Urology
Osaka University Hospital
Fukushima 1-1-50, Fukushima-ku
Osaka 553, Japan

Dr. Osamu Yoshida
Professor of Urology
Kyoto University Hospital
54 Kawara-cho, Shogoin
Sakyo-ku, Kyoto, Japan

UNITED STATES PARTICIPANTS

Dr. George T. Bryan
Professor of Human Oncology
Department of Human Oncology
University of Wisconsin Center for Health Sciences
Madison, Winconsin 53792

Dr. Samuel Cohen
Department of Pathology
St. Vincent Hospital
Worcester, Massachusetts 01604

Dr. Kenneth Cummings
Department of Urology
Virginia Mason Research Center
Mason Clinic
1000 Seneca Avenue
Seattle, Washington 98101

Dr. Sidney Cutler
NBCCGA Statistical Center
Suite 527
2233 Winconsin Avenue
Washington, D.C. 20007

Dr. Albert B. Einstein
Maso Clinic
1100 Ninth Avenue
Seattle, Washington 98101

Dr. George Farrow
Department of Pathology
Mayo Clinic
Rochester, Minnesota 55901

Dr. Gilbert H. Friedell
Department of Pathology
St. Vincent Hospital
Worcester, Massachusetts 01604

Dr. Robert E. Greenfield
National Bladder Cancer Project
St. Vincent Hospital
Worcester, Massachusetts 01604

Dr. Richard G. Hahn
Department of Clinical Oncology
Mayo Clinic
Rochester, Minnesota 55901

Mr. Arthur G. Hilgar
National Bladder Cancer Project
St. Vincent Hospital
Worcester. Massachusetts 01604

Dr. Warren Koontz
Professor of Urology
Medical College of Virginia
Richmond, Virginia 23219

Dr. Alan Morrison
Department of Epidemiology
Harvard School of Public Health
677 Huntington Avenue
Boston, Massachusetts 02115

Dr. George Penick
Department of Pathology
University of Iowa Hospitals and Clinics
Iowa City, Iowa 52242

Dr. George R. Prout
Urological Service
Massachusetts General Hospital
32 Fruit Street
Boston, Massachusetts 02114

Dr. William Shipley
Department of Radiation Medicine
Massachusetts General Hospital
32 Fruit Street
Boston, Massachusetts 02114

Dr. William Straile
Program Director, National Bladder Cancer Program
853 Westwood Building National Cancer Institute
Bethesda, Maryland 20014

Dr. Mark Soloway
Department of Urology
University of Tennessee
Center for the Health Sciences
800 Madison Avenue, Box 63635
Memphis, Tennessee 38163

Dr. Willet F. Whitmore
Chief, Urologic Service
Memorial Sloan-Kettering Cancer Center
425 East 67th Street
New York, New York 10021

Dr. Morris J. Wizenberg
Department of Radiation Sciences
University of Oklahoma Health Science Center
P. O, Box 26901
Oklahoma City, Oklahoma 73190