ORLANDOA new nomogram may help physicians predict the
probability of prostate cancer metastasis in patients with a biochemical
recurrence after radical prostatectomy, nomogram codeveloper Zohar A. Dotan,
MD, PhD, reported at the 2005 Multidisciplinary Prostate Cancer Symposium
(abstract 162). "The nomogram’s prediction power was significantly higher than
that of currently available prediction tools," said Dr. Dotan, a clinical
fellow in the Department of Urology at Memorial Sloan-Kettering Cancer Center.
Among the study coauthors were Peter Scardino, MD, and Michael Kattan, PhD.
About 50,000 to 60,000 new patients experience biochemical
failure annually, Dr. Dotan said. Physicians lack a reliable way to determine
probability of metastasis in these men. Some patients do well, while other
patients’ cancers may spread rather quickly.
In developing the computerized tool, the researchers queried
Sloan-Kettering’s multidisciplinary prostate cancer database for patients
initially treated with surgery who later developed biochemical failure. They
defined biochemical failure as a PSA of 0.2 ng/mL and rising, a single PSA of
0.4 ng/mL or higher, or the use of a secondary treatment for a rising PSA.
Investigators excluded patients who had received preoperative radiotherapy,
hormonal therapy, or chemotherapy.
From a database of 4,438 patients, they identified 675
patients with biochemical failure after radical prostatectomy. Of these 675
patients, 141 developed metastasis. About half of the men were receiving
hormonal therapy at the time of metastatic progression. Median follow-up from
identification of biochemical failure to the end of the study was 5.2 years.
Median time from radical prostatectomy to biochemical failure was 1.4 years.
Fifty-four percent of the patients with biochemical failure
had a preoperative PSA greater than 10 ng/mL; 74% had a Gleason score of 7 or
higher. As secondary treatment for PSA progression, 191 received radiation
therapy, and 300 were given hormonal therapy.
Constructing the Nomogram
Using a Cox proportional hazards analysis, the team looked
at the following predictive factors: preoperative PSA; time from surgery to
biochemical failure; pathologic findings (such as surgical margin,
extracapsular extension, seminal vesicle invasion, lymph node metastases, and
pathologic Gleason score); PSA doubling time; and PSA value at the time of
biochemical failure. They also considered secondary treatments, such as
radiation therapy and hormonal therapy, as time-dependent covariates.
Patients with extracapsular extension, seminal vesicle
invasion, a Gleason score of 8 to 10, higher PSA levels at time of biochemical
failure, and a short PSA doubling time were significantly more likely to
develop metastasis. Those receiving radiation therapy as a second treatment
were significantly less likely to have their cancer spread.
"Interestingly, radiation therapy was associated with
reduction of metastatic progression," Dr. Dotan said at a media briefing. "It
is, as far as we know, the first linkage to reduction of metastatic progression
following another type of local therapy for patients with biochemical failure.
Unfortunately, hormonal therapy, the most common systemic therapy for prostate
cancer, was not associated with reduction of metastatic progression."
To construct the nomogram, Dr. Dotan and his colleagues
incorporated the predictive variables that were significant on multivariate
analysis, as well as preoperative PSA, surgical margins, lymph node status, and
time from surgery to biochemical failure. The resulting nomogram has a
concordance index of 0.88; internal validation showed its accuracy. Dr. Dotan
said that the nomogram has a discrimination ability significantly superior to
categorical PSA doubling time of 10 months and the Pound models of 1999 and
2003. He is now using an external database to validate the findings from this
"The nomogram can be used to identify high-risk patients for systemic
progression, to identify patients who will need systemic and local therapy,
and, most important, to identify entry point for clinical trials based on the
probability of progression," Dr. Dotan said.