Prostate cancer drug

Doctors frequently prescribe an inappropriate drug to men with early prostate cancer. Though the consequences of this treatment are severe, most men reported a high degree of satisfaction with their care. These paradoxical findings come from the first major study to look at the quality of life for men who were not treated surgically or with radiation therapy.

This study is an important contribution to the debate about whether the prostate-specific antigen (PSA) screening test for prostate cancer causes more harm than good. As its use increased dramatically over the last decade, so too has the diagnosis of early prostate cancer. The blood test is now routinely given to men with no symptoms, though studies show that most prostate cancers remain dormant an entire lifetime. Consequently, many men are treated unnecessarily. Previous studies of men with early disease who remained untreated showed that their prostate cancer death rate was similar to that of men given a prostatectomy. Neither the PSA test, nor any other, can accurately identify the minority of prostate cancers destined to be fatal. And there is no proof that treating the potentially fatal version at an early-stage saves lives.

There is a consensus among researchers, though not among urologists, that the decision to remain untreated is a valid choice. This used to mean: no treatment until symptoms occur ("watchful waiting"). But now it appears that many men who forego a radical prostatectomy or radiation therapy are being treated with a drug that stops their production of the male hormone, androgen. Known as androgen deprivation therapy (ADT), the treatment amounts to a medical castration, usually with the injectable drug, Lupron.

Lupron has been tested and proven useful only as a palliative treatment for men with advanced prostate cancer. A palliative treatment means that the drug can only alleviate symptoms. And now the drug is being prescribed for early-stage cancer in men without symptoms--at a great physical cost, according to the new study published recently in the Journal of the National Cancer Institute (3/20/02). "There is no definitive evidence that early ADT alone improves length or quality of life in men with clinically localized prostate cancer," according to the study's authors, Arnold L. Potosky, PhD, and colleagues.

All of the men who agreed to take part in this study had been newly diagnosed in 1994-5 with cancer that had not spread beyond the prostate gland. They are participants in a much larger project called the Prostate Cancer Outcomes Study (PCOS), initiated by the National Cancer Institute to investigate variations in the treatment of prostate cancer and to determine how the men fared afterward. Significantly, the PCOS is primarily following men who were treated at community medical practices, as opposed to a research-based cancer center. The participants include men under 60, as well as African-Americans and Hispanics, represented in higher proportions than white men over the age of 60.

Out of the PCOS database of over 3,000 men, Dr. Potosky and colleagues concentrated on the 661 who had not been treated with surgery, radiation, or cryotherapy (destruction of the gland by freezing it) and were followed for at least one year. They found that an astonishingly high proportion--37%--had been given ADT alone as their primary treatment, which was described as "an indication authoritatively endorsed nowhere in the medical literature," by James A. Talcott, MD, in an editorial that accompanied the new study.

Compared with men who were just observed--that is, given no treatment, the ADT-treated men were five times more like to have breast swelling and hot flashes. Those who were sexually potent prior to ADT were more than twice as likely to be impotent afterward. The overall physical functioning and vitality tended to be poorer among the men given ADT.

Though no scientific evidence supports the use of ADT for preventing or delaying onset of symptoms, Potosky and colleagues were able to identify a rationale for the doctors' prescription by going through the men's medical records. The ADT-treated men were more likely to have palpable tumors, more poorly differentiated tumors and a baseline PSA values over 10 ng/dL. In other words, their condition at diagnosis was viewed as worse than men with non-palpable, well differentiated tumors and a PSA under 10 ng/dL. The characteristics of the ADT-treated men indicate that their cancers could have spread outside the prostate.

Though it seems logical to treat the men whose cancer might be slightly more advanced, it is illogical to prescribe a drug that can only relieve symptoms in men who have none. Surprisingly, despite the distressing side effects, more ADT-treated men (56%) reported that they were "pleased" or "delighted" with their treatment (56%) than men who decided to remain untreated (45%). Additionally, the ADT-treated men believed themselves to be free of cancer at a 12% higher rate.

This study indicates that--for many men--the need for treatment may be more important than whether it actually works. The 661 participants came from a far larger pool of men with early-state disease participating in the Prostate Cancer Outcomes Study. The overwhelming majority of the PCOS participants have been treated with either surgery or radiation for early-stage prostate cancer. They face a dilemma with no scientific evidence to guide them because there has been no head-to-head comparison of the different options. Most men become permanently impotent no matter which treatment is chosen, and urinary incontinence or bowel symptoms are common depending upon the choice of treatment.

The new ADT study and the PCOS provide information that all men should consider before they consent to a PSA screening test. This test was prematurely introduced into medical practice before it could be determined whether it saves lives or whether its benefit outweighs the considerable harm of being unnecessarily treated. Significantly, most organizations that promulgate screening guidelines do not recommend the PSA test for symptomless men. Even the American Cancer Society withdrew its recommendation and now says that men should be offered the test and be informed of the benefit and risks.

But many physicians appear to be convinced of the test's merit as it has become commonplace in medical practice. In fact, it is often included within the blood testing for other purposes, such as cholesterol, without the patient's knowledge. A survey of internists and family physicians found that the frequency with which doctors ordered PSA tests rose from 73% of the time in 1993 to 81% of the time in 1998.

John D. Voss, MD, and colleagues, who published the survey results at the end of last year in the Journal of General Internal Medicine, concluded that the decision to test is not always driven by concerns related to a patient's health. They believe that the pressure on doctors to screen for prostate cancer is in response to a decade of lobbying for the test by the American Cancer Society and the American Urological Association.

--- MaMaryann Napoli is the associate director of the Center for Medical Consumers in New York City.