BETHESDA, Md—Rapid advances in managing prostate cancer over the last decade have created dilemmas for clinicians as they attempt to determine which treatment is best for each patient, said Patrick Walsh, MD, director, Department of Urology, Johns Hopkins University School of Medicine. Such dilemmas will not be resolved fast enough through randomized trials, he said.
"We’re facing not a light at the end of a tunnel, but a tunnel at the end of the light," Dr. Walsh quipped during his presentation at a conference sponsored by the National Cancer Institute and the Society of Urologic Oncology.
The use of prostate-specific antigen (PSA) provides not only earlier diagnosis at curable stages but also objective criteria for earlier identification of treatment failure, permitting multiple points for intervention. "There are multiple options for treatment and multiple definitions of success," he said, "too many for anyone to say which is best, and too many to evaluate now in randomized trials."
The dilemma is not just about choosing the best treatment to cure the disease; physicians must also determine if the patient’s disease is, in fact, curable. Is the patient well enough to be cured? Will the treatment be effective? Will the potential added years of life be quality years?
Even increased awareness of the disease and treatment options can create problems, he noted. When a well-known public figure is diagnosed with the disease, people may assume that the treatment the famous individual receives is the best treatment for every patient.
Dr. Walsh called prostate cancer "a moving target," with treatment options and outcomes changing over the years. Data from 1982 to 1999, covering 2,400 men, show that prior to the advent of PSA testing (1982 to 1989), only 30% of men undergoing a radical prostatectomy at Johns Hopkins had organ-confined disease. Today, that figure is 80%.
Furthermore, Dr. Walsh said, those diagnosed more recently have higher actuarial survival. In men who underwent surgery from 1982 to 1988, at 10 years, 66% had an undetectable PSA; from 1989 to 1999, 80% had a PSA of less than 0.2 ng/mL at 10 years.
This change over time has created problems in comparing therapies, he said. Interpretation of study results has to be adjusted not only for disease stage but also for the era of diagnosis. Further, he said, it is hard to randomize patients between aggressive treatments like radical prostatectomy and brachytherapy. How, then, can valid comparisons be made among treatment modalities? he asked.
Usually, such evaluation calls for randomized controlled trials, Dr. Walsh said. However, conducting such trials in prostate cancer will require far too many treatment arms and will take too much time before results are available. "Randomized controlled trials are important, and eventually should be done, once we know what should be compared, but a nonrandomized comparison will provide the quickest answer," he said.
Blue-Ribbon Registry
Dr. Walsh called for a "blue-ribbon registry" to enroll patients and record data. Those involved would have to agree on the selection of patients; definition of cancer control ("whether undetectable PSA or a certain nadir, or ASTRO or other criteria"); and instruments for evaluating quality of life, both pre- and postoperatively. "We should enlist all centers of excellence and entrust the registry to collate and compare data," he said, adding that a multidisciplinary team would do the final evaluation of treatment alternatives.
