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Adverse Prognosis
Associated With "Detectable" PSA Following Prostatectomy (February 2007)
The "Natural History of
Disease Progression in Patients Who Fail to Achieve an Undetectable
Prostate-Specific Antigen Level after Undergoing Radical Prostatectomy" (CANCER
Dec 1, 2004) is defined in a classic article by Alan Partin et al. in a
study of 160 men whose PSA remained above 0.1 ng/mL 3 months after
surgery. The study cohort had clinically localized disease, T1 to T3a, and
had staging pelvic lymphadenectomies. This retrospective analysis assessed
the percentage of men who developed clinically evident metastatic
disease without any prior adjuvant intervention, mainly
based on a positive bone scan. "The probability of distant metastases-free
survival was 68% at 3 years; 49% at five years; and 22% at 10 years," and
the median time to distant metastases was 5 years. (The classic estimate
by Walsh of 8 years was measured from a rising PSA after surgery to
clinical metastases).
Partin's analysis
utilized the parameters of Gleason score, and involvement of seminal
vesicles and/or lymph nodes to create three predictive subgroups: 1)
Gleason score 6 and 7 (3+4) and SV-/LN- or SV+/LN- or SV-/LN+; 2) Gleason
score 7 (4+3); and 3) Gleason score 8-9 or Gleason score 6 and 7(3+4) and
SV-/LN+. In group 1 the median time to the development of distant
metastases was 9 years; in group 2, 6 years; and in group 1 the interval
was 4 years.
The determination of PSA
"undetectability" can be made at six weeks post surgery, but PSA
interpretation can be confounded by remaining normal prostate tissue,
which Partin acknowledges can account for a PSA up to 0.3 ng/mL. However,
this level should be stable over time. Hence the diagnostic importance of
the measurement of the rate of any upward change in the PSA value
during the ensuing 3 - 13 months after surgery, i.e. the graphic "slope"
of the PSA over time. Partin regards this observation as "the best
predictor of time to distant metastases." The critical breakpoint is >0.05/yr,
which is associated with a median time to metastases of 3.5 years,
compared to 13 years for a PSA slope <0.05/yr.
This
retrospective analysis is an important contribution to the conceptual data
on which adjuvant therapy is founded.
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