Prostate cancer is the most common cancer in men, and I firmly believe that if you want to make an important contribution, you must work on an important problem. It also combined two major interests that I had: one was molecular endocrinology, and that’s important because hormone therapy has been a mainstay for the treatment of advanced prostate cancer, and the other is surgery. And so those two irresistible attractions made it very clear: important problem and two fascinating things to work on. Subsequently, I became interested in the genetics of the disease, so that added a third facet.

A sequence of events: when I came to Johns Hopkins 31 years ago as the director of the Brady Urological Institute, radical prostatectomies were rarely performed, despite the fact that the operation was pioneered at Hopkins, because there were so many side effects. Every man was impotent. Life-threatening bleeding was common, and 10-25% of men were totally incontinent. So I set off to find out why these side effects occurred and whether they could be prevented.

It turns out they occurred because no one understood the anatomy surrounding the prostate. And so, over a period of about six years, I defined the vascular anatomy, thus reducing blood loss. I discovered where the nerves were located that were being injured, causing impotence, thus making it possible to preserve potency. And I defined the fascia around the sphincters and prostate, improving continence and cancer control.

All of a sudden, it was possible to cure prostate cancer with surgery with fewer side effects. In 1983, only 7% of men with localized cancer underwent surgery, but a decade later, 34% of men did, and radical prostatectomy became the most common operation at the Johns Hopkins Hospital.

The other major discovery that happened around that time was prostate-specific antigen (PSA). This made it possible to diagnosis men earlier with curable disease, providing a number of additional opportunities. I began to see a lot of young men who had prostate cancer and, talking to them, I realized that many of them had very strong family histories. Onset of disease at an early age is a marker of hereditary disease.

It was from seeing these men that I became captivated by the idea that prostate cancer ran in families, and set out to determine what the relationship of family history was to the risk for prostate cancer, to determine whether that risk was environmental or genetic, and to begin to determine where the susceptibility genes were located. We put together a team at Hopkins, assembled one of the largest groups of multiplex (multiple-affected) families in the world, and teamed up with excellent scientists. We now have over 3,000 families in our registry and over 200 families with DNAs.

The JAMA paper you mentioned is actually the sequel to the original paper we published in 1993 (Partin AW, et al., "The use of prostate specific antigen, clinical stage and Gleason score to predict pathological stage in men with localized prostate cancer.," J. Urol. 150:110-14, 1993). In the early 1990s, it was difficult to determine preoperatively whether a man had curable disease. After I had done 1,000 operations, I realized there was a pattern and identified three factors that together were prognostic: the patient’s PSA, the Gleason score, and the clinical stage.

PSA alone was not enough, because we learned that as the Gleason score went up (as tumors became more undifferentiated) tumors made less PSA per gram of tissue. Clinical stage provided a reasonable estimate of tumor volume. All of a sudden, patients themselves and their physicians, armed with three simple, readily available pieces of information, could determine whether they had curable disease and were a candidate for definitive treatment of localized prostate cancer.

Thus, these tables, called the Partin tables, became almost a household word. (Dr. Alan Partin was one of my residents and he is now my successor.) The 1997 paper looked at 4,000 men treated by several surgeons at three major academic medical centers and showed that the findings were applicable to the general population. So the reason it is an advance is that it spared many men from unnecessary surgery.

With the advent of baby boomers turning 60, there is going to be an epidemic of prostate cancer because it is the most common cancer in aging individuals. It is estimated that the number of new cases of prostate cancer and deaths from the disease will double or triple over the next 40 years unless there are major advances in prevention or treatment.

Our group at Hopkins has been very interested in understanding the etiology of the disease in an effort to develop new approaches to prevention. Drs. William Nelson, William Isaacs, and Angelo De Marzo have put together compelling evidence that inflammation may play a major role in etiology. We have cloned two susceptibility genes for prostate cancer, MSR1 (macrophage scavenger receptor one) and RNASEL, that are involved in the host defense mechanisms against infections (Xu J, et al., "Common sequence variants of the Macrophage Scavenger Receptor 1 gene are associated with prostate cancer risk," J. Hum. Genet. 72[1]: 208–12, published online December 6, 2002; and Carpten J, et al., "Germline mutations in the ribonuclease L gene in families showing linkage with HPC1," Nat. Genet. 30[2]: 181-4, 2002). This raises the tantalizing possibility that infections may, in some way, be responsible for this inflammation.

PSA velocity was first described in 1992 (Carter HB, et al., "Longitudinal evaluation of prostate-specific antigen levels in men with and without prostate disease," JAMA 267[16]: 2215-20, 1992). Why has it taken a decade for this to become more popular? It is more pertinent today now that we recognize that there are many men with prostate cancer who have PSA levels lower than 4 ng/ml and that the use of serial PSA measurements (PSA velocity) has proven to be a valuable means to detect cancer in these men.

As my title says, I’m the University Distinguished Service Professor of Urology. I stepped down last year after 30 years of being the director of the Brady Urological Institute. I’m spending more time operating, I have more time to think about research problems, and I’m currently revising my best-selling book for lay people, Dr. Patrick Walsh’s Guide To Surviving Prostate Cancer (Worthington, JF and Walsh PC. New York: Warner Books, 2002).