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Salvage Radiotherapy for Recurrent Prostate Cancer: The Earlier the
Better (May 2004)
The quote above is the
title of the editorial accompanying the recent JAMA article (March 17,
2004 -Vol. 291, 1325) jointly authored by 16 leading prostate cancer
gurus retrospectively analyzing the outcome of 501 men treated with
"salvage" radiotherapy (SRT) after PSA relapse following radical
prostatectomy. The data base represents pooled information from five
leading institutions. Although much has been written on this subject,
this study is the largest and most comprehensive to date and provides an
excellent reference for clinicians. A second worthy reference is the
review, "Salvage radiotherapy following radical prostatectomy" by Catton
and Milosevic, writing from the Princes Margaret Hospital and University
of Toronto (World J Urol (2003)21: 243-252). Both articles conclude that
salvage radiotherapy to the prostatic fossa is underused (and too often
offered too late), and should be considered for all men who present with
a PSA relapse. The treatment is considered well tolerated and is the
only potentially curative modality available for this group of men. Of
particular interest is that both groups offer data supporting an
expansion of the customary parameters that heretofore have been
considered requisite for the optimal chance of success.
Not surprisingly, the
basic recommendations from prior studies remain reinforced: the optimal
outcome from SRT is achieved in men with Gleason scores of <8, the PSA
doubling times (PSADT) of >10 months, whose PSA relapse occurs >2 years
post RP; and in situations where the surgical margin s positive,
and there has been no invasion of seminal vesicles or lymph nodes. The
optimal pre-SRT PSA is between 1 and 2 ng/ml. (ASTRO recommends <1.5 ng/ml).
The JAMA data found that men who had all of the favorable features
enjoyed a 77% freedom from PSA relapse at 4 years median follow-up.
Relapse was designated at a PSA >.1 ng/ml. above post SRT nadir, and
confirmed by a second consecutive rise or by continued rise in PSA after
treatment. The rate of progression following SRT is significantly
greater (<0.001) when SRT was initiated at PSA values >2 ng/ml. The
authors conjecture that the frequency of initially isolated local
recurrences may be underestimated, and that early application of SRT
offers the possibility of preventing progression to metastatic disease
for even some patients at highest risk. In their outcome analysis they
found that "for patients with the poor prognostic features of either
high Gleason score or a short PSADT, early treatment (i.e. before the
PSA level reached 2 ng/ml) more than doubled the 4-year progression free
survival." During the 4 year median follow-up of the 501 men, 50%
experienced progression, 10% developed metastases, 4% died from prostate
cancer, and 4% died of other causes. The median time to progression
after SRT was 12.5 months and 92% of these relapses occurred within 4
years.
What is the major new
concept that emerges from the JAMA analysis? The researchers discovered
that a positive surgical margin is a favorable finding that
"suggests a greater likelihood that recurrence is due to residual pelvic
disease...even for patients with aggressive features such as Gleason
score of 8 to 10 or a rapid PSADT". Early SRT for this group of men with
positive margins and Gleason scores 8-10 achieved a 4 year freedom from
PSA relapse of 81% if the PSADT was > 10 months, but only 37% for a
shorter PSADT. The rapidity of the PSA rise is a very significant
indicator for risk of PSA failure. For example, when SRT was commenced
at PSA <2 ng/ml in men whose Gleason score was 4 to 7 and whose PSADT
was <10 months, those with positive margins had a 4-year PSA control of
64% compared to 22% control for men with negative margins. The article
provides a very clear graphic algorithm that sets out the four-year
actuarial progression-free survival after SRT and charts all the various
permutations of the major risk parameters so that a clinician could
easily identity the likely outcome from SRT for any individual patient.
The authors acknowledge that "no comparative study has shown that SRT
improves survival or prevents metastatic disease", but they believe that
SRT can offer the possibility of cure for even some high risk for
recurrence patients who heretofore would not have been considered
promising candidates for SRT, or at least SRT can alter the natural
history of the disease.
The Catton article
addresses treatment complications with the following comment: "Acute
complications of diarrhea, urinary frequency and urgency were reported
as common events, but no grade 3 or 4 acute morbidity was reported. Late
grade 3 and 4 complications were identified in less than 2% of the
patients."
Bottom Line:
The JAMA authors conclude: "patients with positive surgical margins who
experience relapse after radical prostatectomy should be strongly
considered for salvage radiotherapy, even those with high grade disease
[Gleason sum 8 - 10] and/or rapid [< 10 month] PSADT.
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