Context In men who develop an elevated serum prostate-specific antigen leve
l (PSA) after having undergone a radical prostatectomy, the natural history
of progression to distant metastases and death due to prostate cancer is u
nknown.
Objective To characterize the time course of disease progression in men wit
h biochemical recurrence after radical prostatectomy.
Design A retrospective review of a large surgical series with median (SD) f
ollow-up of 5.3 (3.7) years (range, 0.5-15 years) between April 1982 and Ap
ril 1997,
Setting An urban academic tertiary referral institution.
Patients A total of 1997 men undergoing radical prostatectomy, by a single
surgeon, for clinically localized prostate cancer. None received neoadjuvan
t therapy, and none had received adjuvant hormonal therapy prior to documen
ted distant metastases.
Main Outcome Measures After surgery, men were followed up with PSA assays a
nd digital rectal examinations every 3 months for the first year, semiannua
lly for the second year, and annually thereafter. A detectable serum PSA le
vel of at least 0.2 ng/mL was evidence of biochemical recurrence. Distant m
etastases were diagnosed by radionuclide bone scan, chest radiograph, or ot
her body imaging, which was performed at the time of biochemical recurrence
and annually thereafter.
Results The actuarial metastasis-free survival for all 1997 men was 82% (95
% confidence interval, 76%-88%) at 15 years after surgery, Of the 1997 men,
315 (15%) developed biochemical PSA level elevation. Eleven of these under
went early hormone therapy after the recurrence and are not included in the
study. Of the remaining 304 men, 103 (34%) developed metastatic disease wi
thin the study period. The median actuarial time to metastases was 8 years
from the time of PSA level elevation. in survival analysis, time to biochem
ical progression (P<.001), Gleason score (P<.001), and PSA doubling time (P
<.001) were predictive of the probability and time to the development of me
tastatic disease. An algorithm combining these parameters was constructed t
o stratify men into risk groups. Once men developed metastatic disease, the
median actuarial time to death was 5 years. The time interval from surgery
to the appearance of metastatic disease was predictive of time until death
(P<.02).
Conclusions Several clinical parameters help predict the outcomes of men wi
th PSA elevation after radical prostatectomy. These data may be useful in t
he design of clinical trials, the identification of men for enrollment into
experimental protocols, and counseling men regarding the timing of adminis
tration of adjuvant therapies.