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PSADT And Androgen Deprivation
(August 2005)
Can the PSADT provide much needed guidance to the vexing
decision as to the optimal timing for initiation of androgen deprivation
(AD) after failure of primary and salvage therapy - a judgment that
often is an ill defined tradeoff between psychology and biology?
This issue was addressed at the 2005 ASCO Prostate Cancer
Symposium by Dr. Philip Kantoff, Chief, Division of Solid Tumor
Oncology, Dana Farber Cancer Institute: “Biochemical failure - The case
for Androgen Deprivation Therapy”, and Dr. Kantoff kindly forwarded his
slides to me for review. A major focus was on the predictive utility of
PSADT, which he regarded as a “dominant determinant of outcome in this
population” [exhibiting a rising PSA after BCR].
He illustrated the large difference in outcomes for PSADT
calculations resulting from small differences at low PSA values by
comparing two situations: #1) PSA 0.04, 0.3, and 0.5 at 12, 15, and 18
months - PSADT 2.6 months; #2) PSA 0.09, 0.3, 0.4 at 12, 15, and 24
months - PSADT 13.4 months. His conclusion: “Measuring PSADT in an
individual in real time can be fraught with error particularly with
limited values and lower numbers”. [Some studies have even extended
consideration of PSADT measured in the range only reflected in the
“ultrasensitive postprostatectomy PSA” determination.]
Dr. Kantoff maintained that the hypothesis of benefit for
the early application of AD was established in two well
recognized major randomized trials: (1) the “Bolla” study comparing RT
alone vs RT + 6 months AD in early high-risk cancer. The overall
survival for the combination was 78% at 5 years vs. 62% for RT alone;
and (2) the “Messing” study comparing immediate, sustained AD vs.
delayed AD for node-positive men post RP. Early and sustained AD led to
an overall survival of ~ 88% at 5 years vs. ~76% for delayed AD, and
this superiority increased with time.
The success of early AD in these studies of high-risk men
suggests the possibility that some parameter of PSA might be identified
in the pattern of PSA rise in men showing only biochemical failure that
would guide a beneficial initiation of androgen deprivation.
D’Amico’s analysis of prognosis in patients with a
rising PSA (JNCI, April 7, 2004) was presented. His study found
that PSADT values of 3, 6, 9, 12 months were associated with: 1) a
median time to metastases of 2, 4, 6, 8 years, respectively; and, 2)
median survivals of 6, 8, 10, and 12 years, respectively.
The only randomized study addressing this question was
carried out by the British Medical Research Counsel in which 938 men
with locally advanced and M+ prostate cancer were treated with immediate
or delayed AD. A survival advantage was found for early AD, but
methodological deficiencies flawed the study. In the absence of
randomized prospective trials studying the timing of AD in the setting
of early biochemical failure following primary and salvage therapy, any
recommendations are essentially inferential.
In Dr. Kantoff’s conclusion he
summarized: 1) “PSA velocity is the dominant determination of outcome in
this population” [i.e. men with biochemical failure]; 2) “Measuring
PSADT in an individual in real time can be fraught with error
particularly with limited values and lower numbers”. Lastly, he
acknowledged the need for “greater refinement” of guidance data.
However, in his opinion if a patient’s PSADT was < 12 months he would
“strongly consider intervention with ADT or a clinical trial of ADT plus
other agents such as chemotherapy.”
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