Statement of Thomas V. Holohan, M.D.

STATEMENT OF

THOMAS V. HOLOHAN, M.D., F.A.C.P.

CHIEF PATIENT CARE SERVICES OFFICER

VETERANS HEALTH ADMINISTRATION

DEPARTMENT OF VETERANS AFFAIRS

BEFORE THE

SENATE SPECIAL COMMITTEE ON AGING

HEARING ON

PROSTATE CANCER DETECTION AND TREATMENT

SEPTEMBER 23, 1997

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Mr. Chairman and Committee Members:

I am pleased to have the opportunity to discuss the Department of Veterans Affairs' (VA) Prostate Cancer Detection and Treatment Programs. Cancer is second only to cardiovascular disease as a cause of mortality and morbidity in veterans. Because of this significant health challenge to veteran patients, a number of formal programs as well as specific designations of facilities based upon the available expertise in treating cancer have been established. Throughout VA, 103 facility-based cancer programs treat an estimated 50,000 new cases each year. Of those, approximately 9,000 are patients with newly-diagnosed prostate cancer. The total number of all cases of prostate cancer under care by VA is approximately 70,000; about 6,000 are treated on an inpatient basis each year. More than 60 VA facility-based cancer programs are approved by the American College of Surgeons (ACoS) Commission on Cancer. VA's Under Secretary for Health, Dr. Kenneth W. Kizer, has communicated his expectation of a significant increase in the number of sites achieving that recognition.

In 1992, VA headquarters prepared a set of standards for oncology programs that were based upon the ACoS requirements and were subsequently published in VA's policy manual. It is worthwhile to provide some details regarding this process, since promulgation of standards, such as those of the ACoS, is critical to provision of the highest quality of medical care. The goals of establishing those criteria for VA facilities were:

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to provide state-of-the-art multidisciplinary and humane care;
to improve patient access to comprehensive care;
to ensure coordination of approaches to cancer care among the numerous specialists;
and to develop cost-effective outpatient programs, including access to lodging facilities where appropriate.

Three levels of cancer care were established. Each medical center is classified as providing primary, secondary, or comprehensive cancer care. It is our intent that each of VA's 22 Veterans Integrated Service Networks (VISN) will have at least one Comprehensive Cancer Center (CCC) which is either certified by the College of Surgeons or possesses conditional approval. Currently, 40 facilities are designated as Comprehensive Cancer Centers.

Briefly defined, a primary care center has diagnostic capabilities focused on screening and prevention programs and has a referral relationship with a Comprehensive Cancer Center.

A secondary level program treats over 100 new cancer cases annually and has the capability to provide some chemotherapy and cancer surgery. Prevention and screening programs are available, as are routine radiology, nuclear medicine, and pathology diagnostic services. Radiation oncology services must be available either in the facility itself or by contract or sharing agreements with an adjacent entity.

A Comprehensive Cancer Center treats over 300 new cancer cases annually. In addition, three additional broad groups of requirements are met.

First, the center meets specified staffing requirements, personnel possess expertise in cancer management, and the center provides a wide range of services to assure the provision of state-of- the-art care. This encompasses diagnostic services including a complete clinical laboratory with cytology, immunopathology and blood bank capabilities, with access to other more specialized testing capabilities. Diagnostic services include invasive and noninvasive radiology, including

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computerized tomography, magnetic resonance imaging services, and nuclear medicine capabilities; single photon emission computed tomography (SPECT) is recommended.

Second, these centers must provide a complete range of therapeutic services including:

surgical oncology and surgical subspecialties (e.g., thoracic, head and neck surgery, urologic surgery etc.) ;
medical oncology with chemotherapy, including demonstrated familiarity and experience with investigational protocols, and a frill complement of internal medicine specialties and services (e.g., pulmonary medicine, cardiology, dialysis, etc.);
radiation therapy services including electron beam and interstitial therapy;
a nutritional support team;
a number of specific residency training programs;
a complete pharmacy service that specializes in the preparation of chemotherapeutic agents (using laminar flow hood equipment).

Each CCC program is encouraged, but not required, to have an inpatient oncology unit or its equivalent.

Finally, Comprehensive Cancer Centers are also expected to provide:

social work services; counseling; pain management; nutritional education and support;
in- and outpatient rehabilitation;
formal interaction with available hospice services;
special lodging arrangements for ambulatory patients receiving extended treatment.

Leadership is provided by a multidisciplinary committee which includes representatives from medical and radiation oncology, diagnostic radiology, surgery, and pathology. The committee's responsibility is to monitor quality management and provide for improved care, and to supervise the cancer registry. Interdisciplinary cancer conferences, wherein specific patient case management issues are discussed, are required at regular intervals; these must comprise a

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minimum of 10 percent of all cases seen at the Center. We have previously provided the Committee a portion of the annual cancer report from the VA Medical Center Long Beach, California, which illustrates the clinical and research activities underway at such centers.

Formal cancer registries are considered critical elements in a cancer program. They provide important epidemiologic information, data on staging, patient demographics, survival statistics; and other clinical outcome data. Currently, there are more than 85 VA healthcare facilities with formal cancer registries, and more than 55 certified tumor registrars. Establishment of a central tumor registry is underway and will enable compilation of accurate incidence statistics, planning

for resource allocation, comparison of incidence and outcomes with national standards, analyses of specific management and outcomes, assistance in reporting to the VA Secretary and Under Secretary for Health, and Congress, and contributions to the National Cancer Data Base.

Diagnostic and Treatment Options for Prostate Cancer:

Despite the high prevalence of prostate cancer, there are significant gaps in the evidence base regarding screening, diagnosis and treatment. While the number of diagnosed cases of prostate cancer has increased, there has not been a concomitant increase in mortality rates; therefore, some investigators have concluded the data include a disproportionate number of diagnoses of "non-lethal" cancers. Autopsy studies have demonstrated that a large fraction of elderly men die with, but not from, prostate cancer, and a number of population-based studies have indicated that more cases of prostate cancer that seem to have little likelihood of reducing survival are being detected in screening studies. The essence of the problem is that many early non-aggressive cancers that have limited potential to affect survival are detected (and likely treated); moreover, the early detection of aggressive cancers and those that have already spread and are poorly responsive to current treatment is unlikely to improve outcomes. Indeed, it is still uncertain whether radical prostatectomy or radiation therapy for many early stage prostate cancers will result in survival superior to that provided by careful observation without immediate treatment. Earlier detection of malignancy that is unresponsive to any treatment will result in an apparent increase in survival time (so-called lead-time bias) which is totally unrelated to any

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intervention(s). Notwithstanding, providing no active treatment to all early stage disease may obviate potentially curative treatment for some cases destined to otherwise progress.

There are a number of appropriate treatment options for each stage of prostate cancer. Selection of specific therapy is therefore dependent upon patient-specific clinical factors, the patient's personal preferences, the clinician's experience and best judgement, and the available technology.

For Stages I and II prostate cancer, it remains uncertain as to whether prostatectomy (with or without lymph node dissection), external beam radiotherapy, brachytherapy, or careful observation will provide the longest survival. Under various circumstances, all approaches could be supportable based upon current evidence. Stage III disease has spread beyond the gland, and the results of prostatectomy are much poorer than in Stages I and II. Nonetheless, for selected patients surgery may be appropriate. Radiation therapy is the most common treatment for this stage, and offers the possibility of cure. Acceptable options also include, for carefully selected cases, observation with treatment provided only for symptoms.

Advanced prostate cancer presents significant therapeutic difficulties. Surgery is not indicated save for local symptomatic problems such as pain or urinary obstruction. Radiation may prove beneficial for the same purposes. Hormonal therapy will provide palliation, and possibly extend survival, but is not curative; and chemotherapy remains primarily investigational at this time. For asymptomatic patients, careful observation may be appropriate.

Therefore, it is not possible to construct definitive statements selecting any specific treatment plan for any stage of prostate cancer. Indeed, if clinicians always selected the most appropriate treatment for each individual patient, it would be apparent that for any patient classification scheme - by disease stage, by age, etc. - a wide variety of therapeutic strategies would be employed in each category.

The major difficulty in formulating rational treatment plans is the nearly total absence of

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randomized, controlled trials of various therapies. Almost all of the data exist in the form of case series, usually with inadequate description of patient selection criteria and absent direct comparisons of alternative treatments. Patient selection factors often have influenced the choice of treatment and thus make comparisons of therapeutic strategies problematic; for example, it appears that Stage I and II patients treated with radiation therapy have had worse prognostic factors than those provided surgery. Unfortunately, such data constitute the foundation upon which some clinicians have formed their opinions regarding clinical management. Patients, too, form their own convictions based upon incomplete information, which may often derive from sources of questionable reliability and accuracy.

Screening for prostate cancer is a topic of great contemporary interest. The value of early detection and treatment of prostate cancer remains unclear, and the issue is controversial. Routine screening is not recommended by the U.S. Preventive Services Task Force, the Canadian Task Force on the Periodic Health Examination, or the American College of Physicians. Also, the American Cancer Society does not promote mass screening. Screening is, however, recommended by the American Urological Association, and the American College of Radiology. Prior to its demise, the U.S. Congress' Office of Technology Assessment concluded that the choice to accept or forego screening should depend on an individual patient's values. Current VA policy regarding prostate cancer screening for veterans is contained in an Information Letter issued by the Under Secretary for Health on January 8, 1997. That document states that the decision to screen, using modalities such as digital rectal examination, prostate-specific antigen (PSA), and transrectal ultrasound imaging with or without ultrasound-directed biopsies, should be made by the patient subsequent to an explanation by the physician of the controversy regarding the value of such testing and the potential benefits and risks of screening.

Clinical Guidelines:

It is our intent that physicians routinely provide the best available care to every one of the 9,000 new prostate cancer patients seen in VA healthcare facilities every year. VA is cognizant of the

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utility of guidelines for the purpose of providing best practices to our patients. The development of useful clinical practice guidelines is a complex and difficult procedure. Recommended best practices can only be as valid and reliable as the evidence upon which they are based. Moreover, guidelines require frequent review and revision as new information becomes available, and thus obsolescence is a constant problem. In addition, the guidelines must be promulgated and disseminated widely and in a timely fashion, be easily accessible, and "user-friendly" to busy clinicians. For all of these reasons, as part of a newly developed VA National Cancer Strategy requested by VA Under Secretary for Health, Dr. Kenneth W. Kizer, we have selected the Physicians Data Query system (or PDQ), provided by the National Cancer Institute through the National Library of Medicine as representing the standard of care to be provided by VA. In essence, PDQ is our national cancer care guideline. PDQ recommended diagnostic and therapeutic interventions are the result of a comprehensive review process by an editorial board of cancer experts and are based on published studies which are carefully evaluated according to the strength of their evidence (see enclosed PDQ statement). PDQ statements and their supporting evidence are re-assessed by the editorial boards at two-to-four-month intervals, thus assuring contemporaneous information. This database is stored by the National Library of Medicine in electronic format and is available virtually instantaneously, 24 hours a day, at every VA medical facility. The information can be reviewed on a personal computer, or hard copies can be printed for future reference. This database provides an up-to-date summary of the best practices in oncology.

Prostate Disease Research in VA:

Recognizing the importance of prostate disease to the veteran population and the large number of unresolved questions from basic biology to its optimal treatment, VA has committed substantial resources to research on prostate disease. Prostate disease research expenditures have grown from $3 million in FY 1995 to over $9 million in FY 1996, an estimated $12.8 million in FY 1997, and a projected $15. 1 million in FY 1998. An additional $7.3 million was obtained by VA investigators from non-VA sources in FY 1996 to support prostate cancer research projects,

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further leveraging the VA's direct investment in this field.

Selected examples of VA research include:

Clinical Trials - An ongoing project, The Prostate Cancer Intervention Versus Observation Trial (PIVOT), is a collaboration between VA's Cooperative Study Program, the National Cancer Institute, and the Agency for Health Care Policy and Research. Men 75 years of age or younger who have clinically localized prostate cancer are eligible for the study. Participants are randomly assigned to receive radical prostatectomy with additional treatment for residential or recurrent disease or expectant management with treatment for symptomatic progression or metastatic disease. The goal is to determine which treatment approach is better for patients.

Risk, Screening, and Treatment Preferences - A research investigator in Houston is studying relatives of men with prostate cancer to determine the familial risk of prostate cancer. Investigators in West Haven are evaluating the effectiveness of screening for prostate specific antigen (PSA) for identifying patients with early prostate cancer. They hope to determine whether screening can improve survival rates. A Gainesville investigator is using endorectal magnetic resonance imaging of the prostate as a new way to screen for prostate cancer and to monitor response of the prostate to cancer therapy. Research investigators in Milwaukee are analyzing patient preferences for treatment of localized prostate cancer. They found that the most important factors in making a treatment decision were the doctor's recommendation, life expectancy, and experience of friends or family. Another Houston project is assessing patient preferences associated with treatment of advanced prostate cancer. Since no available treatment can cure these patients, analysis of quality of life among the patients choosing particular treatments might help future patients to make treatment choices.

Basic Medical Research - Research investigators are identifying markers for differential diagnosis and aggressiveness of prostate tumor cells (Washington) while others are developing a panel of biomarkers that will detect individuals at high risk for development of prostate cancer

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(Oklahoma City). Stimulation and inhibition of growth of prostate cells is influenced by hormones and by various growth factors and their receptors. Studies focusing on specific growth factors include fibroblast growth factor (New York), insulin-like growth factor (Seattle), epithelial growth factor receptor (Birmingham), and transforming growth factor and parathyroid hormone (Loma Linda). Other projects (Minneapolis, Chicago) are focused on enzymes that may increase the ability of prostate tumor cells to grow in new sites in the patient (metastasis). A Madison group is studying the role different cells have in initiating prostate tumor cell growth. The investigators believe that naturally-occurring enzymes may allow the cells to grow in different parts of the body. These studies may provide new targets for better anticancer treatments.

Other research investigators are concentrating on hormones and their receptors on prostate (Washington) to understand the mechanisms underlying the transition of prostate cell growth from androgen-dependent (treatable) to androgen-independent (fatal).

Some projects concentrate on animal models such as the rat (Atlanta) or mouse (Iowa City) for prostate cancer. Other studies are looking at the role of the immune system and its interaction with prostate cells. Projects include the development of active immunization against prostate cancer cells (Baltimore) and the use of immune cells to destroy prostate cancer cells (Iowa City).

In addition to the ongoing projects described above, a joint VA/DoD planning committee has been formed to set priorities for prostate disease research, issue invitations for investigators to submit proposals, and conduct scientific reviews of proposals prepared by VA and DoD investigators. This committee has drafted a Request for Proposals for a VA/DoD Collaborative Research Program on prostate diseases including cancer that is now undergoing concurrence by both agencies. Scientific review committees are also being assembled to conduct the review of proposals anticipated in response to this RFP. Separately, the VA Cooperative Studies Program is preparing an Announcement soliciting proposals for new treatment trials of prostate cancer that will be released by the second quarter of FY 1998.

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VA has recently established three Epidemiological Research Information Centers (ERIC's) through its Health Services Research and Development program. Within the ERICs, one study on "Risk of Mortality in Prostate Cancer" has already been funded (West Haven), a "Prospective Cohort Study of Early Stage Prostate Cancer" is projected to be funded in FY 1998 (Boston/Brockton), and a proposal for a "Case Control Study of Prostate Cancer in Black and White U.S. Veterans" is now pending review for scientific merit (Durham).

These new initiatives will continue the strong trend of increasing VA funding of prostate cancer research into FY 1998.

Interagency Agreement with the National Cancer Institute (NCI):

We believe veteran patients should be provided with the most recent state-of-the-art care and should have the option of participating in promising, novel treatment plans which may become the standard of care for the future. To that end, VA and NCI have signed an Interagency Agreement. The purposes of this agreement are to provide veteran patients with access to the frill range of new approaches to prevention, diagnosis and treatment, while increasing VA clinical research and accrual of patients into NCI-sponsored national clinical trials. This agreement will build upon already existing cooperation between VA and NCI. There are currently 22 VA hospital affiliations with NCI-designated cancer centers and 90 formal associations between VA medical centers and various NCI Cooperative Study Groups.

That concludes my statement, Mr. Chairman. Dr. Feussner and I will be pleased to answer any questions you or Members of the Committee may have.

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