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Hormone and Radiation as Post - RP Adjuvant Treatment (Journal Review)
(March 2004)
"Use Of Neoadjuvant and Adjuvant Therapy To Prevent Or Delay Recurrence
Of Prostate Cancer In Patients Undergoing Surgical Treatment For
Prostate Cancer," Gomella, Zeltzer, and Valicenti, UROLOGY Vol 62
December 29, 2004. (Contained in “The Conundrum Of Rising
Prostate-Specific Antigen: Prevention and Treatment”, a special
supplement to Vol. 62 edited by Ken Pienta) .
Please treat the reviews below as "Cliff Notes" that carry a "caveat
emptor" - for the full story read the source articles.
Surgical treatment of
pathologic stage pT2N0 yields long term biochemical control of 84% to
90%, whereas capsular penetration or positive surgical margins, pT3,
degrades the outcome to 37% to 70%. Men with high risk features,
(D'Amico - stage T2c, PSA >20 ng/mL, or Gleason > 8) have
a 14.2 X relative risk of cancer-specific mortality.
Does evidence based
information exist to guide a decision to intervene with various adjuvant
therapies to attempt to reduce this risk? This article reviews the
options.
NEOADJUVANT HORMONAL
THERAPY: At a follow-up period of 3 and 4 years there is no evidence of
benefit for 3 or 8 months of neoadjuvant androgen deprivation, except as
reported in the Canadian study, which found a significantly reduced risk
of PSA recurrence at 4 years in the subgroup of intermediate-risk
disease.
RADICAL PROSTATECTOMY
WITH ADJUVANT HORMONAL THERAPY: Two studies address this issue. Wirth
and Froehnew, 1999, reported improved progression free survival at 4
years in pT3 patients receiving flutamide 250 mg tid vs control of 90%
vs 69%, P = 0.0029. The second study is the 2002 interim report (median
follow-up 3 years) of the European Early Prostate Cancer Trial comparing
Casodex 150 mg/day to control for post RP patients with Gleason >7, PSA
>10 (regardless of T stage), which showed a 42% superiority in
progression free survival for the Casodex group. Survival information
requires further follow-up.
ADJUVANT EXTERNAL BEAM
RADIATION THERAPY (administered within 3 to 6 months after RP): "The
clear benefit of adjuvant EBRT in radical prostatectomy has not been
established in a prospective study. It is controversial whether early
adjuvant EBRT improves survival in men with pT3 disease with or without
positive surgical margins." However, there are 5 retrospective
"matched pair" studies which compare EBRT to control for advanced stage
PC. The Anscher trial (1995) of 159 men with T3/4 disease at 10 year
follow-up showed a benefit in bPFS for EBRT over no treatment: 55% vs
37% at 10 years, and 48% vs 33% at 15 years. The Valicenti report of 72
T3N0 patients whose post-op PSA was undetectable (36 treated vs 36
controls) showed a 5-year bPFS of 89% for EBRT vs 55% control. The other
three studies also showed a benefit for EBRT. Schild presented data in
support of improved outcome with an irradiation dose of >64 Gy.
Forthcoming studies addressing this issue in pT3N0 men are the phase III
randomized SWOG/INT0086 trial, which is completed and in follow-up, and
the active EROTC 2291 trial.
Available evidence for
benefit for EBRT in patients with pathologic seminal vesicle invasion is
mixed at best. A study by Schild (1994) found no benefit from EBRT in
this disease state; a Valicenti study (1998) found benefit only if the
PSA was undetectable at 3 months post op. EBRT is associated with a poor
outcome in men with SV involvement if the PSA is >.3 ng/mL at 6 weeks.
Valincenti reported EBRT in stage pT3b was associated with only a 36%
bPFS at 4 years, and a 20% bPFS when the PSA was persistently elevated
post surgery.
ADJUVANT EXTERNAL BEAM
RADIATION THERAPY WITH HORMONAL THERAPY: There are no reported
prospective randomized trials in this area. The schema for the active
RTOG 0011 trial compares EBRT + androgen blockade vs EBRT alone after RP
in men with capsular penetration, Gleason score >7, positive
surgical margins, or seminal vesicle invasion. Eligibility requires that
the postop PSA levels are <.2 ng/mL. The RTOG 85-31 (1999) studied post
RP pT3 men and compared the combination of RT and immediate androgen
suppression therapy to immediate RT with androgen suppression only upon
relapse. A retrospective analysis found a slight improvement in long
term PSA control in the early androgen suppression group, but no clear
comparative benefit in local control or overall survival. Until RTOG
0011 is reported there is no definitive answer to this issue.
Bottom Line:
In the important area of adjuvant treatment to improve outcome in
surgically treated men with high risk prostate cancer there is a need
for well supported evidence based guidelines.
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