Statement of

Col. David G. McLeod, M.D.

Chief Urology Service

Walter Reed Army Medical Center

Washington, D.C.

For a hearing on

Prostate Cancer Prevention and Treatment

Before the

Special Committee on Aging

United States Senate

September 23, 1997

The opinions and assertions contained herein are the private views of the author and are not to be
construed as reflecting the views of the U.S. Army or the Department of Defense.

Mr. Chairman and Members of the Committee:

My name is Colonel David G. McLeod, M.D. I am Chief of Urology at Walter Reed Army Medical Center and Director of the Center for Prostate Disease Research at the Uniformed Service University of the Health Sciences.

The Center for Prostate Disease Research (CPDR) was established in 1991 to manage cooperative research efforts of the Tri-Service Medical Centers. The CPDR is currently funded through the U.S. Army Medical Research and Materiel Command and the Henry M. Jackson Foundation for the Advancement of Military Medicine. Over the years, Congress has provided a total of $23 million for CPDR activities. The Center is currently involved in a variety of activities including the implementation of a multi-center data base to analyze treatment outcomes on prostate cancer patients, the establishment of a clinical research center, and establishment of collaborative epidemiological and basic research on prostate cancer. The Center is rapidly becoming a vital resource for the improved understanding of prostate disease.

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I am here today to discuss the treatment of prostate cancer and the role that innovations in treatment are playing in improving patient outcomes.

As Doctor Crawford mentioned in his testimony—prostate cancer is very common among older men. One-in-five men will develop prostate cancer in their lifetime. Most prostate cancer patients will be over 65 when they are diagnosed and will survive 10 or more years with the disease. However, a significant percentage will be diagnosed when they are still relatively young. For most prostate cancer patients, their survival will depend on whether they get early detection or treatment. Many patients will be diagnosed late or to have a rapidly-progressing form of the disease.

The good news about prostate cancer is that when detected early in a low stage and grade, it can be effectively "cured" in 80 to 90 percent of patients through surgery or radiation. This is a remarkable result when you think of how rare it is with cancer that we are able to talk about "cures".

There is even more good news: with the advent of the PSA test, a larger proportion of patients is coming to us at earlier stages of the illness. This detection has helped us provide earlier treatment with a greater rate of success. This year, the Congress extended Medicare coverage to early detection of prostate cancer, effective in the year 2000. You and your colleagues are to be commended on this significant step, because it will

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make prostate cancer tests completely available to that large portion of men with the disease who are of Medicare age. I only wish that we could advance the date when Medicare will begin paying for these tests.

There is a portion of patients whose treatment will be effective in eliminating the prostate cancer; however, they will have side-effects from treatment that may affect their quality of life—mostly urinary incontinence or impotence. For these reasons, not all patients diagnosed with prostate cancer will choose definitive treatment. For older patients, with less than 10 years of life expectancy or those with serious health problems, it may be more appropriate to monitor the progress of the disease and withhold surgery or radiation if the disease does not appear to progress rapidly. It is particularly important that patients be given information about their treatment options and participate actively in the decision-making.

While there are complications for some patients, treatment outcomes for prostate cancer are improving dramatically. The advances we are making in forms of treatment are improving the effectiveness of treatment while reducing complications for patients. Earlier detection of the disease and better patient outcomes from early treatment are lessening many of the concerns that were raised in the past about prostate cancer detection and treatment.

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I would like to start my discussion of treatment advances by describing how we stage and grade prostate cancer and how this information is used to guide the choice of treatment. Doctor Crawford talked about detection—using the PSA blood test and the digital rectal exam (DRE). A positive result from the PSA and/or DRE is generally followed by a biopsy where we take samples of tissue from the prostate for the pathologist to examine. There are two important questions we need answered in this process:

• Stage — Is the cancer still confined to the prostate gland or has it extended beyond the gland and into adjoining tissue, pelvic lymph nodes, or bone?
• Grade — Is the form of the cancer cell—the degree of cell differentiation—one that would suggest very rapid progression or one that will progress slowly?

Well-differentiated cancers which are still confined to the prostate gland have the greatest chance of successful treatment. A recent study published in the Journal of the American Medical Association, for example, showed that 75 to 97 percent of the patients with organ-confined, well-

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differentiated cancer were still alive 10 years after radical prostatectomy¹. Cancers that have spread beyond the prostate are much less likely to be eradicated. Cancer that has metastasized to the bone will nearly always be fatal.

Once we know the stage and grade of the cancer, as much as can be determined from our clinical evaluation, we discuss treatment options with the patient and his family. There are four basic treatment choices: surgery, radiation, "watchful waiting," and hormonal therapy.

• Surgery — surgical removal of the entire prostate gland (radical/total prostatectomy) -- is a treatment that is appropriate if the cancer is still clinically confined to the prostate. Survival is quite good, and only a minority of men have complications.
• Radiation — an alternative to surgery, that may also be effective with some cancers that have spread beyond the prostate gland to surrounding tissue. Outcomes and complications are generally similar to those for surgery.
• Watchful waiting — a form of treatment in which the physician actively monitors the disease - through regular patient visits and

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1. Krongrad A, Lai H, Lai S. "Survival after radical prostatectomy," Journal of the American Medical

Association. 1997;278:44-46.

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• testing. With this approach, surgery or radiation will be withheld unless the disease begins to progress.
• Hormonal therapy — blocks male hormones that "feed the cancer" thus slowing the growth of the cancer. The optimal treatment for advanced prostate cancer involves combination hormonal therapy (including oral anti-androgens) to completely block production of male hormones. Treatment of advanced prostate disease cannot cure the cancer, but it has been shown to extend life expectancy and improve quality of life for men with late stage cancer. One study I was involved with showed that the addition of oral anti-androgens in combination with an injectable hormonal compound (an LHRH agonist) to block production of testosterone from the testicles improved survival of patients with advanced prostate cancer by 26 percent. Other studies have shown mixed results in the use of anti-androgens in combination with orchiectomy (surgical castration).

In a perfect world, we would limit surgery to cases in which we were sure the cancer was entirely confined to the prostate. Unfortunately, we cannot always be sure of the stage prior to surgery. Occasionally we

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discover cancer in surrounding tissue or pelvic lymph nodes when we examine the prostate and nodes after surgery. Significant improvements in diagnosis and staging prior to surgery are helping to reduce the number of prostate cancers that are found to extend outside the prostate. For example, laproscopic surgery can now be used in selected patients to remove the pelvic lymph nodes prior to prostatectomy or radiation to determine whether they contain cancer cells. Surgery can be avoided in patients with evidence of cancer in the lymph nodes.

In recent years, we have made a number of significant strides in treating prostate cancer. I would like to briefly describe these for you and then discuss their importance in improving the chances that treatment will be effective in curing the cancer with minimal side effects.

• "Nerve-sparing" prostatectomy — a surgical technique that was pioneered several years ago by Dr. Patrick Walsh at Johns Hopkins to reduce the chances of impotence or incontinence in patients having surgery. In the past, surgeons generally cut through the nerve bundles around the prostate gland to remove the gland. In the nerve-sparing approach, the surgeon attempts to keep the nerves intact that are critical to potency. Studies of this technique have indicated that it reduces impotence and incontinence rates

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• among men having surgery. Unfortunately, there are still relatively few surgeons with extensive training in this technique.
• Cryosurgery — an old technique that has recently become popular again, involving the freezing of the prostate gland to kill cancer cells. Since a fellow panelist is discussing cryosurgery, I will not elaborate on it here.
• External Beam Radiotherapy — Better methods are being developed to localize the prostate for radiation treatment (conformal radiotherapy). Also, techniques utilizing different types of radiation energy are being investigated—neutron and proton therapy.
• Brachytherapy — a form of radiation therapy where radioactive seeds are implanted in the prostate gland to kill cancer cells. Patients have the seeds implanted during one sitting, rather than coming in repeatedly for external beam radiation. The latest technique in brachytherapy is one whereby seeds are placed in the prostate with ultrasound guidance.
• Neoadjuvant hormonal therapy — Recently, the FDA has approved the use of combination hormonal therapy with radiation in the treatment of early stage cancer. The hormonal therapy slows

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• the growth of the cancer and shrinks the prostate to enable more effective therapy by radiation. Studies are on-going using neoadjuvant therapy prior to radical prostatectomy.
• Chemotherapy — Chemotherapeutic agents have usually been used with patients who have metastatic prostate disease and are no longer responding to hormonal therapy. Recently a chemotherapy drug was approved by the FDA for use in managing pain and reducing PSA levels for patients with advanced prostate disease.
• Immunotherapy and Gene Therapy — There is a potential for the use of immunotherapy and gene therapy in preventing prostate cancer. Additional research money is needed to realize this potential.

These treatment advances are encouraging, and offer great hope that we can be quite successful in curing prostate cancer for many patients at some point in the not too distant future. Unfortunately, there are a number of government imposed barriers that may stand in our way. Let me discuss a few of these barriers that I am most concerned about.

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• Delayed Medicare coverage of early detection with the PSA test: Unfortunately, when the Congress extended coverage to the PSA test earlier this year, they stopped short of putting it into effect immediately along the other preventive benefits. The 3-year wait before the new coverage goes into effect seem unnecessary. A patient who appears at the doctor’s office after they have begun to experience pain or difficulty in urination may have prostate cancer that is too advanced for a cure. Early detection has been very helpful in getting patients in early enough to treat them effectively. I would think Medicare costs would be lower if these patients were detected early and treated early than if they were to progress to advanced cancer and have significant, and expensive, complications associated with end-stage disease. Congress should accelerate the timetable to put this benefit into effect in 1998.
• Inadequate Medicare coverage of treatment — Medicare does not cover some forms of prostate cancer treatment. Of particular concern is the failure of Medicare to cover oral anti-androgens that are now showing promise in neo-adjuvant therapy with radiation and possible with surgery. Back in 1993, when the Congress enacted coverage for oral cancer drugs, it neglected to cover oral

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• anti-androgens. This omission is because the definition was limited to drugs that substituted for injectable drugs, and it did not include drugs (like oral anti-androgens) that supplement injectable drugs. As a result, there is a considerable bias in Medicare payment in favor of less-effective forms of treatment. Medicare should not be in the business of picking some forms of treatment over others. It should cover all approved and effective treatments for prostate cancer and let the medical community decide what is appropriate care for particular patients.
• Underfunding for prostate cancer research — Until last year, prostate cancer research received only one-fourth as much funding as breast cancer research. Then in fiscal year 1997, Congress appropriated $38 million for prostate cancer research through the Department of Defense. Unfortunately, the appropriation for fiscal year 1998 is still uncertain at this time. When signs are pointing to the chance for significant breakthroughs in prostate cancer detection and treatment, we should not be starving the research community dedicated to this problem. We have made great progress, but we need to make much more progress to begin to control this cancer that ravages so many older men.

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I commend the Chairman and Senator Shelby, and appreciate the interest other members of the Committee have shown in having this hearing today. I will be pleased to support any activities this Committee can undertake to help us solve the remaining problems in tackling prostate cancer.

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