New treatments escalate war on metastatic prostate cancer

"Looking back, the momentous achievement since the last consultation is that, for the first time, cytotoxic chemotherapy has been shown to prolong survival in men with prostate cancer," said committee chair William Nelson, MD, professor of oncology, medicine, pathology, pharmacology, and molecular sciences at Johns Hopkins' Brady Urological Institute.

Dr. Nelson and fellow committee members predicted that the next few years will continue to see a great deal of clinical research on docetaxel (Taxotere) in combination with many different agents, including calcitriol, bevacizumab, and many others, as current phase II trials progress. They also said a better understanding of metastasis is evolving that will lead ultimately to better cancer treatment. For example, a recent New England Journal of Medicine study (2005; 352:1977-84) suggested that treatment of the primary cancer lesion by radical prostatectomy decreased the risk for metastasis and prolonged survival.

"This will have profound implications for how we treat [metastases] in the future," he said.

A metastatic timetable

The median time for developing bone metastases in men who have undergone radical prostatectomy is 8 years, according to the committee. In the United States, these patients often are treated with androgen deprivation therapy (ADT).

"This has provided us with a new group of men with prostate cancer who have castrate levels of antigens but still have a rising serum PSA as their only manifestation of disease. It is amazing, but, often, this scenario is associated with very minimal prostate cancer progression," said Dr. Nelson.

In a study of the natural history of a rising serum PSA despite adequate androgen deprivation therapy, published in the Journal of Clinical Oncology (2005; 23:2918-25), only 33% of patients had developed bone metastases and only 21% had died within 2 years of follow-up. The median time to first bone metastasis and the overall survival were not reached by 2 years. For these men, the PSA velocity independently predicted the time to bone metastasis.

"For many men, androgen-independent prostate cancer is manifested only with a rise in serum PSA and is quite an indolent disease," Dr. Nelson said.

The committee defined four categories of systemic prostate cancer:

Many androgen deprivation strategies have become available for the first two disease categories, and the role of estrogens is being re-evaluated.

"What do we know about the optimal use of androgen deprivation therapy for prostate cancer? Not as much as we probably should," Dr. Nelson said.

Important issues about targeting androgen signaling pathways remain unresolved. For example, in the United States, many men with rising serum PSA levels receive androgen deprivation.