Home: PCU
2|2003: Mitchell Benson, MD
Edited comments by Dr Benson
Defining PSA failure after radical prostatectomy
The classic endpoint for radical prostatectomy has always been
undetectable serum PSA following surgery. This came into question
because of claims that a small subset of patients with low but detectable
serum PSA following surgery may maintain this low level of PSA.
The source of this PSA is debated.
The antibody for detecting PSA may cross-react with another protease
in the serum — a false detection. Some claim that periurethral
glands produce detectable levels of PSA. The explanation of greatest
concern is that benign prostate was left behind at the time of radical
surgery.
My clinical experience at Columbia University is that 98.7 percent
of patients following radical prostatectomy achieve an undetectable
PSA following their surgeries, and all patients not achieving undetectable
PSA require additional therapy.
Total androgen ablation in patients with residual
PSA
I am a very strong believer in total androgen ablation. In my
practice, many patients who are on monotherapy had detectable PSA
until an anti-androgen was added. This tells me that testosterone
or other androgens in the serum secreted by the adrenals are not
blocked by LHRH agonists. Removing the effects of those androgens
causes PSA to decrease further.
Even the SWOG study of orchiectomy with or without anti-androgen
therapy, which showed no difference in survival in the two groups,
did show a difference in PSA response in the two groups.
The most recent meta-analysis also indicates that there's a statistically
significant improvement in survival using combined androgen blockade
over monotherapy. I believe anti-androgens do provide a benefit
beyond blocking tumor flare.
| Maximum
androgen blockade in advanced prostate cancer: Conclusions from
an overview of the randomised trials |
"These results, which involve 98% of the worldwide
randomised evidence, suggest that in advanced prostate cancer,
the addition of an antiandrogen will improve the absolute
5-year survival by about 2% or 3%, with a range of uncertainty
that runs from about 0% to about 5%.
One particular limitation is that most of the evidence was
from patients who already had definite metastases when randomised,
and some investigators have hypothesised that the benefits
of MAB might be larger in other types of patients.
If, after AS in advanced prostate cancer, the addition of
an antiandrogen for 2 or 3 years does produce an improvement
of about 2% or 3% in overall survival, more effective hormonal
regimens might produce somewhat greater absolute benefits,
particularly if ways to identify the prostate cancers most
likely to respond to prolonged hormonal treatment become available
(as has happened with breast cancer)."
AS = androgen suppression |
| SOURCE:
Prostate Cancer Trialists’ Collaborative Group. Maximum
androgen blockade in advanced prostate cancer: An overview of
the randomised trials. Lancet 2000;355:1491–98.
Abstract |
Duration of androgen deprivation
Studies have shown that three to four months of androgen deprivation
are inadequate, and we are awaiting data to tell us whether eight
to nine months is sufficiently long.
The next data point that we have information on is from a European
study looking at two years of androgen deprivation versus two years
of androgen deprivation plus mitoxantrone in patients with metastatic
disease or at high risk. Mitoxantrone was not efficacious in metastatic
disease, but there was a statistically improved PSA failure-free
survival in the group receiving combination therapy in an adjuvant
setting.
Three years is the first time point showing a significant survival
advantage from the Bolla paper published in the New England Journal
of Medicine. Three years of MAB was both statistically and clinically
significant in terms of longterm survival.
So three years is enough, two years might be enough, eight to
nine months may be enough, but less than eight to nine months is
clearly inadequate. We use two years of therapy with the hope that
the preliminary mitoxantrone data will prove correct.
DERIVED FROM: Bolla M et
al. Long-term results with immediate androgen suppression
and external irradiation in patients with locally advanced
prostate cancer (an EORTC study): a phase III randomised trial.
Lancet 2002;360:103-08. |
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