Rapidly rising PSA is good indicator of metastasis

Orlando, FL-How likely are patients who have undergone radical prostatectomy to present with rising PSA levels and subsequent metastatic progression? Researchers at Memorial Sloan-Kettering Cancer Center employ a computerized tool called a nomogram to find the answer.

The nomogram takes into account several prognostic factors to predict the probability of metastasis 8 years after a biochemical failure, said Zohar A. Dotan, MD, PhD, a urologic oncology fellow at Memorial Sloan-Kettering, working with Michael Kattan, PhD, and colleagues.

Of the 220,000 new cases of prostate cancer diagnosed each year, up to 75% are treated by local therapy. Some 50,000 to 60,000 of these patients experience biochemical failure, or biochemical recurrence, the point at which PSA levels begin to rise following initial treatment. The risk of progression over time has been difficult to predict until the nomogram was introduced, Dr. Dotan told attendees at the 2005 Multidisciplinary Prostate Cancer Symposium.

On multivariate analysis, six factors predicted metastatic progression: presence of extracapsular extension of tumor (p=.05), seminal vesicle invasion (p=.0016), Gleason score 8 to 10 (p<.00017), PSA doubling time (p<.001), high PSA value at the time of biochemical recurrence (p<.001), and lack of using salvage radiation therapy for biochemical failure (p<.001).

"The nomogram has very good discrimination ability, and it can identify entry point to clinical trial, based on the probability of progression," Dr. Dotan said.

The nomogram may be downloaded at http://www.mskcc.org/mskcc/html/10088.cfm.

Note PSA velocity In a related study, conducted at Massachusetts General Hospital Cancer Center and Harvard Medical School, researchers have found a link between rapidly rising PSA levels and an increased risk of bone metastasis among prostate cancer patients.

"While rising PSA during hormone therapy is fairly common, this study shows that the key factors to look for are high baseline PSA and the rate of PSA rise," said Matthew R. Smith, MD, PhD, assistant professor of medicine at Harvard.

Dr. Smith and colleagues looked at 201 prostate cancer patients who were found to have rising PSA levels despite hormonal therapy but whose cancer had not yet metastasized. Men with a high baseline PSA or rapidly rising PSA were believed to be at increased risk of bone metastases and death. The numbers confirmed this suspicion.

Among men with a baseline PSA of greater than 24.0 ng/mL or a PSA doubling time of less than 6 months-one-third of the cohort-median metastasis-free survival was only about 12 months, whereas for the rest of the group it was 30 months.

"Baseline PSA and PSA velocity independently predict time to first bone metastasis and survival" in men with non-metastatic prostate cancer, Dr. Smith said.

He added that these indications appear to provide a reliable method to help physicians and patients estimate risk and the need for additional treatment.

Identifying patients for whom further treatment is indicated is a critical item in prostate cancer management, said Philip Kantoff, MD, professor of medicine at Harvard Medical School and director of the Lank Center for Genitourinary Oncology at the Dana-Farber Cancer Institute, Boston. Commenting on the two trials, he noted that the Sloan-Kettering study is a retrospective look at patients who have undergone radical prostatectomy, whereas the Harvard research is a prospective, randomized study of patients who have not had radical prostatectomy but were treated with hormone therapy and do not yet have metastases.

Dr. Kantoff said Dr. Dotan's findings confirm that approximately one-third of individuals who undergo radical prostatectomy will have a biochemical recurrence after the surgery.