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PSA "Bounce" Following Permanent Seed Brachytherapy - A Challenge To
Identify And A Cause Of Anxiety For Patients.
(January 2008)
The optimal outcome after radical
prostatectomy is an undetectable PSA several weeks following surgery.
However, brachytherapy leads to a prolonged process of cell kill with a
potential nadir often taking 2 - 5 years. During this period 30% - 40%
of patients experience a temporary rise in PSA termed a "bounce", or
"spike". This worrisome event was analyzed by, Juanita Crook et al.,
Princess Margaret Hospital, Toronto, in 292 men in their report "PSA
Kinetics and PSA Bounce Following [125I] Permanent Seed Prostate
Brachytherapy," Int.J.Rad.Oncol.Biol.Phys., Vol 69
(2), 2007.
These authors define
"bounce" as a "benign temporary increase in PSA level of varying
magnitude that spontaneously decreases without therapeutic intervention
to a level at or less than the pre-bounce PSA reading." They were
careful to define their terms: specifying "bounce" as a temporary rise
in PSA level of > 0.2 ng/mL; PSA nadir as a post treatment PSA
value of < 0.1 ng/mL or three consecutive stable readings
separated by at least 3 months; and PSA failure as a PSA value > 2 ng/mL
above the nadir. The median follow-up in the study was 44 months (range
8 - 81 months); median patient age, 64 years; and median baseline PSA,
5.6 ng/mL. All but 4 patients had Gleason score 6 or less, and 65% of
men were tumor clinical stage T1c and 35% T2a. Initial follow-up was
every 3-6 months for the first two years and then less frequently. "The
median nadir was 0.05 ng/mL (range 0.01 - 0.2 ng/mL) and was reached at
a median of 40.8 months."
Many studies have found, as did Crook et
al., that younger men are more likely to experience a bounce. Crook
cited a study by Critz (J Urol 2000,
163) that reported a bounce in 57% of men aged < 65; in 41%
between age 61-70; and in 26% of men > 71 years.
The median onset
of a bounce was at 15.2 months; the median magnitude, 0.76 ng/mL; and
the median duration was 6.8 months. In the Crook study a graph shows a
bell shaped curve depicting the distribution for time of onset
for the bounce with the median onset at 15.2 months. The trailing
edge of the curve shows that the onset of all bounces had essentially
returned to baseline at 36 months. PSA failure, of course, occurred much
less frequently and the same graph shows the failure events curve as a
low, slow rise and fall with the the median onset of PSA failure at 30
months (based on ASTRO definition). By using the "nadir + 2 ng/mL"
definition the median onset of PSA failure is 22.3 months. While median
time to bounce occurs earlier than the median time to PSA failure (by
both definitions for failure), there is considerable overlap for these
two curves so that an early PSA rise can be suggestive of, but not
conclusive for, designating a bounce.
The magnitude of the
bounce varies greatly, but in general the higher the PSA rises the less
likelihood that a bounce is the explanation.
"The magnitudes of the
bounce were <1 ng/mL in 64%, 1-2 ng/mL in 21%, and >2 ng/mL in 15%."
Thus in Crook's series "15% of subsequently resolved benign bounces
would have been mistakenly called failures using a "PSA nadir +2"
definition for biochemical failure." Critz's article reported one bounce
of 15.8 ng/mL!
Unfortunately, despite
close scrutiny by many researchers, the only prospective hint
that a PSA rise will ultimately be a "bounce" is the time of onset for
the PSA rise. The PSA doubling time prior to a PSA rise has not proved
to be a reliable indicator of bounce. Prostate biopsies in the 2 or so
years following brachytherapy may still show cancer cells even in cases
where in the ultimate outcome is favorable, so the authors discourage
biopsies in an effort to resolve the issue during this time period.
What management
suggestions do the authors present? When a PSA rise occurs the patient's
PSA should be monitored every 3 months, and if the level doesn't correct
by 30 months a biopsy should be considered. If the PSA level rises to
>10 ng/mL they suggest systemic investigations.
During the period of inconclusiveness as to bounce or failure, a patient
needs the perspective and supportive counseling of an experienced
clinician to help weather this anxiety laden event.
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