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A Nomogram Integrating Variables Affecting
Outcome Of Salvage Radiation Therapy Post-Rp:
The decision of
whether to offer "salvage" XRT to men showing only biochemical evidence
of recurrence post-RP is currently and will remain an inexact science.
The distinction of whether there is a systemic component in addition to
local recurrence is just too subtle for clear analysis with our current
diagnostic modalities. Even though the great majority of men, possibly
as many as 85%, undergoing salvage XRT will show a marked PSA decline,
thus indicating some component of local recurrence, subsequently PSA
failure reoccurs in well over 50%. The prudent desire to avoid the
morbidity of local XRT has spawned a great plethora of studies each with
its unique set of chosen variables and resulting guideline. A promise of
assistance in this this decision appears in abstract #1577 in the 2003
ASCO Proceedings wherein a consortium of prominent specialists
collaborated to create a nomogram (to be published soon) integrating
multiple variables to predict the outcome of salvage XRT. The
pre-treatment variables selected are: pre-RP PSA, pre-XRT PSA, pre-XRT
PSA doubling time, Gleason sum, pathologic stage, surgical margin
status, time to biochemical recurrence, neoadjuvant hormone therapy, and
XRT dose. Their model is based on 375 men, 108 exhibiting a persistently
post-RP elevated PSA (above 0.1 ng/ml) and a second group of 267 who
developed biochemical recurrence defined as a PSA rising above 0.1 ng/ml.
The median follow-up post XRT was 35.8 months, the median time to
recurrence was 11.6 months, and the median freedom from progression was
32.2 months. In keeping with many other studies, the highly significant
variables were Gleason sum, P=0.0002; pre-XRT PSA, P=0.001; PSA doubling
time, P=0.002; positive surgical margins, P=0.003; and neoadjuvant
hormone therapy, P=0.003. Overall the 2-year and 5-year actuarial
biochemical progression free probability was 57% and 31% respectively.
Many good studies
have addressed this issue and the familiar gestalt for successful
application of salvage XRT is in situations of low grade cancer and a
slow and low rise in PSA. Shild from the Mayo Clinic selected a rise of
PSA above 1.1 ng/ml as the critical point. He is somewhat unique in
reporting usefulness for the Prostascint scan: a negative scan was
associated with a 70% "biochemical control rate" which fell to 22% for a
positive scan. However, in his opinion its value was unclear when the
PSA was <1 ng/ml. A second study by Do, UCI Medical Center, reported on
73 men with adverse pathological features on the RP specimen who
underwent salvage XRT for rising PSA. This group showed a 45% bRFS at 10
years. These two studies and many more are difficult to compare. The
difficulty of arriving at a unified generalization results from small
sample sizes, selection of different variables, and different
definitions of end points, and different means to exclude systemic
disease.
And therein lies
the value of the forthcoming "Kattan" nomogram, which has ample sample
size and incorporates the most important predictive factors. Most
importantly the nomogram permits data point entry along a spectrum of
continuous variables instead of entry into a grouping of
values, such as "PSA 4 - 10". In this way each element is allowed to
influence the final outcome prediction according to its own degree of
adversity for affecting outcome. The clinician is still left with the
decision of how to employ this risk data in his management choice, but
with the nomogram he can feel that the factors of known significance
have been given due weight.
Bottom Line: The Kattan nomogram
will be published soon to help in the decision about offering salvage
XRT post-RP in situations of rising PSA.
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