The Colgate Scene
September 2005

Improving the odds against a disease that strikes one in six American men

[Photo by Timothy D. Sofranko]

Andrew Stephenson '93 knows he wants to make an impact, and always has.

He was certain, for example, long before he started at Colgate in 1989, that he would go into medicine. Yet it wasn't until he took several classes in the university's neuroscience program that he realized he would not just make his mark in the operating room, but in the lab as well.

He recalls his time in the early 1990s working at the National Institutes of Health with the university's then-new off-campus study program, his various chemistry courses, and a summer "dissecting a lot of rats" with psychology professor Jun Yoshino with particular fondness: "I didn't come up with anything ground-breaking," he said with a chuckle, "but getting acquainted with the whole process of scientific discovery was a lot of fun."

It's a good thing Yoshino was able to convey to his pupil the joys of petri dishes and Bunsen burners -- Stephenson embarked on a career as a surgeon-scientist in urologic oncology as a result. Today, the energetic doctor spends his time both in the operating room treating patients with prostate cancer and in the laboratory studying the molecular events that lead to it. His work in the field, say his colleagues, is changing the way doctors treat the disease.

From neuroscience to urologic oncology
The decision to go into medicine may have been a no-brainer for Stephenson, but his choice of specialty was not as simple. After graduating from Colgate, he set his sights on a career at the opposite end of the anatomic spectrum from urology: neurology. As a molecular biology major, Stephenson explained, he had a lot of flexibility to take a wide range of classes in many disciplines, and he ended up taking a number of neuroscience courses -- and loving them. "Coming out of Colgate, I thought I wanted to be a neurologist because of all the work I had done in the area already, and because my professors were so outstanding."

That plan was short-lived. While he was earning his medical degree at the University of Western Ontario (he later completed his surgical training at McGill University in Montreal), it quickly became clear to Stephenson that he enjoyed the hands-on nature of the surgical specialties. "When I started doing my medical training in the mid-1990s, I became a little bit turned off by neurology because, for many neurological disorders, there was little one could offer therapeutically to patients after the diagnosis was made. With surgery, you can impact in a direct way the natural history of someone's disease and see an immediate effect, which I found appealing."

That led Stephenson to specialize in urologic surgery, and eventually to the challenging area of urologic oncology. His work in the field so impressed his colleagues in the medical establishment that he was awarded a three-year research fellowship and named an American Foundation for Urologic Disease (AFUD) scholar at one of the finest facilities in the world for cancer care and research, Memorial Sloan-Kettering Cancer Center. There, Stephenson has focused on prostate cancer, the second-most common and second-most deadly type of cancer found in American men according to the American Cancer Society (ACS). In 2005 alone, the ACS estimates, more than 230,000 new cases of prostate cancer will be diagnosed, and about 30,000 men will die of the disease.

Still, there's hope in the numbers; although it's likely that one in six men will get prostate cancer, only one in 34 will die. And those odds are improving by the moment, say doctors, thanks to breakthroughs like the ones Stephenson has made in the past two years.

"...we'll be able to determine the inherent biology of a patient's disease and then target him for aggressive treatment based on his particular cancer."

Closer to a cure
Determined to isolate the genes that contribute to the progression of prostate cancer, Stephenson dove headfirst into his research at Memorial Sloan-Kettering in 2002. He spent hours in the lab peering into microscopes, running genetic tests, analyzing numbers, and looking at combinations of genes that seemed to predict recurrence of the disease. But it was actually what he called a "side study" published in the prestigious Journal of the American Medical Association (JAMA) that first made waves with fellow doctors. (It was also covered by outlets such as CNN, CBS, ABC, and the Associated Press, among others.)

Stephenson and a team of researchers at Memorial Sloan-Kettering looked at 501 men who had a recurrence of prostate cancer after a radical prostatectomy (the surgical removal of the prostate gland) and were administered radiation therapy. Previously, the next step for patients who have had relapses of the disease had been to give them hormone therapy. The belief was that rising levels of a protein called prostate-specific antigen [PSA] meant that the cancer had not only returned but had spread to other parts of the body and was incurable. Patients generally were not offered radiation but were treated only with hormones, which can slow the disease but not stop it. But Stephenson's group found that after administering radiation therapy at the earliest sign of a relapse, about half the men lived at least four years without a recurrence of the disease.

"Many of us already know it's a good idea," Timothy Wilson, director of the prostate cancer program at the City of Hope Medical Center in Los Angeles, told the New York Times in March of 2004, when the JAMA paper appeared. "Now, hopefully, it [radiation therapy] will work its way into the medical literature and become the standard of care."

A second study of Stephenson's, published in the July 15 issue of the American Cancer Society's journal Cancer, may prove equally significant. He and a team of fellow scientists at Memorial Sloan-Kettering used DNA-scanning devices called gene chips, or micro-arrays, to survey prostate tumor specimens. The thin glass chips allowed them to analyze thousands of human genes or gene fragments at once, and identify very specific molecular profiles of prostate cancer that, in essence, predict how the disease will behave.

"What this means is that one day, at the time of diagnosis, we'll be able to take a blood sample or tissue from a biopsy specimen of someone's cancer, run it through a genomic analysis, and tailor therapy to the individual characteristics of that patient's cancer," he explained. "Basically, we'll be able to determine the inherent biology of a patient's disease and then target him for aggressive treatment based on his particular cancer."

How exactly Stephenson will use his newfound knowledge of the disease will bear out in the coming months. This fall he, his wife, and three children will move to Cleveland, where Stephenson will continue his work, as an attending surgeon and assistant professor at the Glickman Urological Institute of the Cleveland Clinic Foundation. One thing is certain: there are still plenty of prostate cancer patients for Stephenson to treat and new research to conduct -- and that means many more opportunities for him to make an impact on the thousands of men who suffer from the disease.

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