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Adjuvant and Salvage Radiotherapy After Prostatectomy: Starting
Treatment at PSA < 1 ng/mL Unifies Outcome of Two Management Strategies
It is very satisfying
when basic tumor biology serves to link two major radiotherapy
strategies: immediate adjuvant irradiation (AR) for management of high
risk of recurrence cancer found at prostatectomy, and salvage
radiotherapy (SR) applied at the time of rising PSA post surgery. Such a
link was reported by Hagan et. al, "Comparison of adjuvant versus
salvage radiotherapy policies for post prostatectomy radiotherapy",
Int.J.Rad.Oncol.Bio.Phys.,Vol.59(2), 2004. The unifying biological
premise is that the level of the PSA is proportional to the bulk of
cancer from which it arises. Hagan emphasizes that the radiotherapy goal
is to irradiate the prostatic bed with the lowest practical
postoperative tumor burden, and presents evidence demonstrating that
there is a very ėnarrow range of PSA values [0 to < 1 ng/ml] which
results in durable control.
Their major findings
was that with either policy if radiotherapy was initiated
when the PSA was < 1 ng/mL the outcome was not statistically different
whether measured as OS (p = 0.26), disease-specific survival (p = 0.82),
or the time to the appearance of metastatic disease (p = 0.34). The
5-year bRFS% (analyzed from the date of surgery) when comparing pre-RT
PSA values of < 1 was 70% for AR and 79% for SR (p = 0.36). When RT was
started when the PSA was > 1 ng/ml the 5 year bRFS figures were 36% vs
31% for AR and SR, respectively. Of interest is the lack of outcome
difference for post-op adjuvant treatments started when the PSA was
undetectable vs. < 1 ng/mL. Since some patients in the AR group did not
achieve an undetectable post-op PSA value it was possible to make
further comparisons between the AR and SR policies in cohorts where the
PSA values were >1 to < 2, > 2 to < 4, and > 4. The declining outcomes
were not statistically different for AR vs. SR.
This study was based on
the experience of 158 men (AR, 50; SR, 118) from two institutions. At
the University of Florida the predominant policy was adjuvant treatment
prompted by considerations of microscopically positive surgical margins
(63%), seminal vesicle involvement (50%), extracapsular disease (57%),
or a combination of these factors, (62%). The median time from surgery
to AR was 2.9 months, and the median pre-RT PSA was .86 ng/mL. At the
Medical College of Virginia a policy of salvage radiotherapy was
followed, applied in the setting of a rising, but not uniform, value PSA
value. For this group the median time to RT was 40.3 months and the
median pre-RT PSA value was 4.5 ng/mL. Of the AR group 47% were
low-moderate grade cancers and 53% high grade, and in the SR group the
breakdown was 66% and 34%, respectively. Seminal vesicle vesicle
involvement was higher in the AR cohort, 50% vs.14%, as was
extracapsular extension, 57% vs. 30%. The salvage group was more likely
than the adjuvant group to have received a radiotherapy dose of > 64 Gy,
73% vs. 18%, but all received a minimum dose of > 60 Gy. Both groups
were free of nodal metastases. The 5-year actuarial survival for the
adjuvant group was 87%, which was not significantly different from 81%
for the salvage group.
Bottom Line:
The unifying message: (1) adjuvant and salvage radiotherapy after
prostatectomy achieve similar outcomes if RT is initiated
when the pre-RT PSA is < 1 ng/mL.; and, (2) outcomes for both strategies
significantly, and progressively decline when RT is commenced as PSA
values rise above > 1 ng/mL.
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