Progress in Prostate Cancer Treatment and Research
by William J. Catalona, M.D.

"Now, we almost never diagnose prostate cancer with distant metastates"

Dr. Catalona was the keynote speaker for the Florida Cancer Education Network’s Gala 2001. Other participants included Senator Connie Mack and Senator Bob Dole (via videotape). Dr. Catalona’s speech on the progress made in prostate cancer treatment and research and possible directions for the future was as follows.

Today, we are all living longer because deaths from heart disease and stroke have decreased dramatically over the past 25 years. One of the consequences of a longer life span is that now more men live long enough to develop prostate cancer – although this disease also strikes men in their forties and fifties.

As the most common internal cancer in men, accounting for more than 30 percent of cancer cases in men, prostate cancer is a concern for all men.

It is estimated that nearly 200,000 new cases of prostate cancer will be diagnosed in the US this year – which is one new case every three minutes. One man in six will be diagnosed with prostate cancer during his lifetime.

The cause of prostate cancer is not known for certain, but both genetic and environmental factors are involved. The prevalence of prostate cancer varies greatly in different racial and ethnic groups.

I first became interested in prostate cancer as a resident at Johns Hopkins, where my mentor, Dr. Patrick Walsh, developed the nerve-sparing radical prostatectomy, in the early 1980s. This operation allows for excellent cancer control while preserving sexual potency and urinary continence in the majority of patients.

Since I began performing nerve-sparing prostatectomy, I have collected follow-up information on all of my patients in a database and have periodically published my results in medical journals.

Improved outcomes have resulted in increased demand for treatment and I have now performed nearly 3000 nerve-sparing radical prostatectomies.

A major problem that we encountered before the PSA test was widely used for screening was that more than two thirds of men had incurable cancer that had spread beyond the prostate at the time of diagnosis. We clearly needed more accurate methods for early detection.

In 1986, the PSA test was approved for monitoring patients who already had been diagnosed with prostate cancer; however, it was not believed that PSA testing could be useful as a screening test for prostate cancer.

The reason was that many men without prostate cancer had elevated PSA levels and some with prostate cancer had normal levels.

Researchers were looking for a test like a pregnancy test that was always positive when the patient had cancer and negative when he did not. Thus, the PSA test was disregarded because it was not perfect.

In 1988, the National Cancer Institute sponsored a workshop in Maine to assess new diagnostic and management procedures for prostate cancer. I was asked to serve as co-chair of that meeting. The goal of the National Cancer Institute was to decrease the death rate from prostate cancer by the year 2000.

One of the sessions focused specifically on early diagnosis. Several experts presented papers on the PSA test, all concluding that it could not be used for early detection.

I had measured PSA levels on several hundred of my patients who had been diagnosed with either prostate cancer or benign prostate enlargement. My calculations showed that among men who had a PSA reading higher than 4 nanograms per milliliter (ng/ml), a substantial proportion had potentially curable prostate cancer.

My calculations suggested that a PSA elevation by itself justified performing a biopsy – an idea that seemed very radical at the time.

My calculations also suggested that the PSA test might be better than the digital prostate examination or the ultrasound scan for the early detection of prostate cancer. I presented these findings to the group assembled at the workshop.

I told them that I believed that we could diagnose more curable cancers through PSA testing than we were currently diagnosing using traditional methods. I suggested that this idea should receive further study.

My colleagues remained skeptical. Therefore, after the meeting, I was determined to launch a PSA study of my own in St. Louis.

My study opened in July 1989, and eventually enrolled over 35,000 men. However, after rolling the first 1600 men, it became obvious the PSA test was the most accurate first-line screening for prostate cancer available.

I was fortunate enough to have my study published in the New England Journal of Medicine in 1991. Thereafter, word spread and patients began to ask for the PSA test.

In 1994, a national multicenter trial formally tested PSA at seven major medical centers across the US. The results were uniformly similar and, based on this multi-center trial, PSA was the first blood test ever to be approved by the US Food and Drug Administration (FDA) as an aid to early detection of cancer.

Presenting this evidence to the FDA was challenging, and I was relieved when it was over and delighted with the unanimous recommendation to approve the PSA for detection.

In 1997, a similar trial was performed on the free PSA test which increases the accuracy of PSA testing, eliminating up to 20% of unnecessary biopsies. This study was published in the Journal of the American Medical Association, and in 1998, the free PSA test was also approved by the FDA.

PSA testing has been controversial from the outset. Medical societies are divided in their recommendations for PSA testing.

Prospective, randomized clinical trials to see if PSA testing saves lives are underway in the US and Europe, but the results will not be available for years. The situation is difficult because to prove the point, some men are required not to get PSA testing, and many men do not want to participate in such a study.

Widespread use of PSA testing is increasing throughout the world. In the US, more than 60% of men over the age of 50 have received a PSA test.

One early consequence of PSA screening was a dramatic decrease in the percentage of advanced prostate cancer cases at the time of diagnosis. We have actually had almost a complete reversal, from 70% being incurable at diagnosis to 70-80% being curable.

We almost never diagnose prostate cancer with distant metastases these days; whereas, this diagnosis used to be quite common.

In the mean time, prostate cancer death rates, after having increased steadily for 30 years, stabilized between 1991-1994 and then started to fall. They have declined 4.7 % per year through 1998, and overall more than a 16% decline in prostate cancer death rates has occurred in the post-PSA era.

Where do we go from here? The next step is to get to the root of the prostate cancer problem. To make some headway, we had to await the completion of the human genome project, with all of its exciting new technology.

All cancer is fundamentally a genetic disease. Some of the genetic changes that cause cancer are inherited from our parents and some are acquired during life from interactions with the environment; such as our diet, our exposure to carcinogenic chemicals, and our exposure to viruses.

A tremendous opportunity is before us today in cancer research. We are better equipped than ever to carry on the fight against cancer. I believe that when the final story is told, a series of genes will be discovered that, alone or in concert with other genes or environmental factors, predispose men to prostate cancer.

When it is learned how these genes work, we will have important insights into what causes cancer, why it sometimes behaves aggressively and sometimes does not, what determines whether it will respond to radiation, hormones, or chemotherapy, and even how it might be prevented.