NEWS

PSA as a Treatment Marker for Prostate Cancer?

Mike Miller

Since the use of prostate specific antigen testing for prostate cancer exploded in the late 1980s, PSA has made the diagnosis and treatment of the disease more complex. In the past few years, the PSA test has played an even more pervasive role as a treatment marker, even though its benefits as a detection tool still await the outcome of several randomized clinical trials.

Indeed, of the 54 abstracts presented at the recent American Society of Clinical Oncology meeting that dealt with prostate cancer, two-thirds used PSA as a marker for gauging whether or not a treatment worked.

Nicholas James, Ph.D., and his colleagues in the department of pathology, University of Birmingham, England, for example, used PSA to gauge the effectiveness of a new immunotherapy for patients with late-state prostate cancer, which takes advantage of the Her2 gene's overexpression in a majority of patients with advanced disease. The immunotherapy targets a Her2-specific-antibody to the aggressive Her2-positive tumor cells along with granulocyte macrophage-colony-stimulating factor. James used what's called a " bispecific antibody" (MDX-H210 in this case) that attaches itself to both cancer cells and to immune cells. This approach, the investigators say, ultimately helps the immune system attack the cancerous cells while the GM-CSF aids in the production of immune cells.



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Dr. Nicholas James

 
"In one third of the patients we've followed for the longest time, PSA levels declined by about 50% and the others showed at least a decline in the rate of the rise of their PSA." If the velocity, or rate of PSA change, can be considered a reasonable surrogate marker in this population, James suggested, then this treatment could "be the first immunotherapy to show real promise for prostate cancer." James is also hopeful that this antibody may also work in breast cancer.

In another study presented at ASCO, Christopher Nauman, M.D., Boston University, Jamaica Plain, Mass., conducted a retrospective examination of 108 patients with elevated PSAs (and/or abnormal digital rectal exams) and looked at the utility of prostatic intraepithelial neoplasia, or PIN, as a physiological marker that could be used to enhance diagnostic accuracy in certain patients. The long term significance of high PIN readings has been unknown because it is generally considered to be a nonmalignant lesion and thus not a top priority for study.



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Dr. Christopher Nauman

 
Nauman said that, "PIN is found in 5% to 15% of biopsies performed but we have little information on how this lesion impacts on survival." Starting in 1989 Nauman followed 108 patients for 5 years, finding cancer in 49% of patients in the PIN group versus 21% in a control group. The initial mean PSA levels were 8.9 in the PIN group and a somewhat high 7.1 in the control group, leaving the long-term diagnostic capabilities of PSA in this study less than satisfactory. However,with the analysis of PIN results showing that cancer developed in over twice as many patients as controls, Nauman said that "our study shows that high grade PIN predicts cancer growth within 2 years."

As an additional point of comparison, Nauman also looked at PSA levels at the time of cancer diagnosis. Of those people in the study who developed cancer, the PIN group had a 14.1 PSA level versus 9.3 in the control group, pointing out the better utility of PSA as a marker versus a diagnostic tool.

Nauman added a major caveat when he noted that since there is little mortality associated with PIN, no survival benefit was found for men with a high PIN level. Deborah Kuban, M.D., Eastern Virginia Medical School, Norfolk, Va., remarked that Nauman's findings about PIN's prognostic capabilities help identify which patients to watch most carefully but the findings do not mean surgery or other forms of treatment are needed.

When looking at how prostate cancer treatment can cause other problematic conditions, researchers noted that the increased use of PSA testing has led an increasing number of men to choose hormonal drug therapy, which shuts down their testosterone and androgen production, significantly lowering PSA levels in many cases.

According to Celestia Higano, M.D., University of Washington, Seattle, Wash., "patient choice has been driving the increased use of hormone therapy. Since it lowers PSA levels, even though it's still a controversial therapy, it's much in demand, with a conservative estimate of over 100,000 men receiving this treatment annually." For many men, a low PSA level also gives them a much lower level of anxiety about mortality due to prostate cancer.



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Dr. Celestia Higano

 
Higano said doctors must be aware of the effects such hormonal treatments produce, including bone loss of 2% to 3% similar to that seen in women who are post-menopausal and undergoing breast cancer therapy. Higano urged that men on hormone suppression therapy be closely monitored and treated with bisphosphonates if their bone density readings become too low.

She noted that bone loss in men was reversed after stopping hormone therapy. She argued strongly for "patients having baseline bone densitometry tests before starting hormone therapy. That way we can closely monitor for negative effects and adjust treatments accordingly."



             
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