Home: PCU3|2002: Col David G McLeod, Sr, MD

	Col David G McLeod, Sr, MD
		Chief, Urologic Oncology Director of the Urology Residency Program Walter Reed Army Medical Center Professor of Surgery Uniformed Services University of Health Sciences Professor, Department of Surgery (Urology) Georgetown University Medical School President, American Foundation of Urologic Disease President, Mid-Atlantic Section of the American Urologic Association

Edited comments by Dr McLeod

Local therapy decision-making: The case of a retired US Army General

General Norman Schwarzkopf has publicly disclosed information about his prostate cancer experiences, so I am not violating patient confidentiality by discussing his case. After returning from Desert Storm in 1994, he had a routine DRE, which revealed a prostatic nodule. His PSA was low — approximately 1.2 ng/mL. Prostate biopsy demonstrated organ-confined disease, with areas of Gleason 4 and Gleason 6 prostate cancer.

When I met with him, a paramount concern of his was the risk of urinary incontinence due to local therapy. He was a relatively young, very active man, who wanted to maintain his lifestyle. He had prior consultations at a number of medical centers with specialists in prostate cancer, and he knew all of the treatment options. His perspective was consistent with his military experiences. He knew that he could never gather "perfect intelligence." He had to evaluate information from physicians, friends and family and make a decision with the data that was available.

He elected to have a radical prostatectomy, and seven years postsurgery, he has no evidence of recurrent disease and is continent.

Multimodality therapy

Some urologists believe that prostate cancer can be cured through prostatectomy alone, without reliance upon adjuvant therapy. However, dependent upon which prostatectomy series you read, 30-50% of patients will have extracapsular disease, and the location of the prostate limits the margin width that can realistically be accomplished. In the past, prostatectomy was followed by adjuvant radiation therapy. Presently, we have shifted to simply monitoring the PSA, and urologists are reluctant to utilize adjuvant therapy.

Prostate Cancer Journal Club

Bicalutamide as immediate therapy either alone or as adjuvant to standard care of patients with localized or locally advanced prostate cancer: First analysis of the early prostate cancer program.

See WA et al. J Urol 2002;168(2):429-35. Abstract

Status of the EPC trials

The EPC trial — evaluating bicalutamide 150 mg versus placebo — is the largest prostate cancer study ever conducted. There is a misconception that the trial is completed. It is still ongoing and data are still being collected and analyzed. This will be an extremely valuable prostate cancer database, which will allow us to stratify patient and disease characteristics and determine the patients with greatest risk/benefit ratio for bicalutamide.

Physicians want to know whether bicalutamide will result in an improvement in mortality, but currently there have not been enough deaths to evaluate this endpoint. In the North American trial, there is only about two years of followup. However, evidence is accumulating that time to progression is reduced by bicalutamide 150 mg.

Optimal duration of 150 mg adjuvant bicalutamide

This is an important question to be addressed in randomized trials. In the adjuvant breast cancer trials, five years of tamoxifen was better than two years. That was the rationale for why this trial was designed to be a pooled analysis and evaluate bicalutamide for five or more years in Europe and two years in the United States.

Preliminary efficacy results of bicalutamide 150 mg versus placebo in patients managed with no local therapy (“watchful waiting”)

In the Scandinavian trial — which was predominantly watchful waiting — 29% of the patients on placebo had objective progression as opposed to 16% who were on bicalutamide 150 mg — almost a 50% reduction in objective progression for patients receiving bicalutamide. This will be one of the critical results from the trial.

The value of delaying time to biochemical failure

Patients are emotionally devastated after PSA relapse. Several years earlier, they made an emotional and physical investment in primary local therapy. PSA recurrence is as if they are being told that they have cancer again, and many patients want to be treated for a rising PSA.

The Pound article demonstrated that, on average, there is a 13-year interval from PSA rise until the patient dies of metastatic disease. However, that is a mean — for some patients it will be shorter, for others a longer period until death.

Also, delaying the time until a patient develops metastases is clinically meaningful. Some of the adverse side effects of an LHRH agonist can be avoided with a therapy such as bicalutamide 150 mg. I take into consideration comorbid illnesses, life goals, sexual and social functioning, etcetera when deciding on whether to treat these patients.

Quality-of-life advantage of bicalutamide 150 mg compared to medical or surgical castration

LHRH agonists may have debilitating side effects. Even with intermittent therapy, testosterone does not necessarily return to normal levels and alleviate symptoms. Additionally, osteoporosis may be an important issue in 60-yearold men treated with castration. There are preliminary studies that suggest that bicalutamide 150 mg does not have an adverse impact on bone density.

One trial demonstrated that bicalutamide was equivalent to medical or surgical castration in M0 disease, but with fewer side effects — anemia, osteoporosis, muscle-wasting, hot flashes, etcetera.

In terms of the expected side effects from bicalutamide 150 mg, I tell patients, “You have a 75% chance of having breast pain and/or nipple tenderness.” In all probability it will be a nuisance, and most patients will plateau. The breast tenderness typically resolves after therapy is completed. It does not become a major impediment to their lifestyle.

Gynecomastia can be managed with low-dose radiation prior to beginning treatment with bicalutamide. If a patient does develop breast enlargement, it typically plateaus after one year. If the gynecomastia is disturbing to the patient, then a mastectomy or liposuction can be performed, with cosmetically favorable results.

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Editor’s Note: “Visiting Professors”

Adam P Dicker, MD, PhD
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Eric A Klein, MD
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Col David G McLeod, Sr, MD
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Mary-Ellen Taplin, MD
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