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Is
External Beam Radiotherapy A Necessary Supplement To Brachytherapy?
(June 2006)
The
question: "Permanent Prostate Brachytherapy: Is Supplemental External-Beam
Radiation Therapy Necessary?" is the title of a review article authored by
Drs. Blasko, Wallner, and Merrick in the May issue of ONCOLOGY, and
the same issue is discussed in Merrick's "Monotherapeutic Brachytherapy
for Clinically Organ-Confined Prostate Cancer, in West Virginia Medical
Journal, July/August 2005. The authors share the opinion that the
appropriate application of supplemental XRT is best narrowed to instances
of high-risk disease predicted to have extensive involvement of the
seminal vesicles and/or pelvic lymph node disease. Their collective data
indicates that for low- and intermediate-risk, and some carefully selected
high-risk tumors, despite a prediction of extra capsular extension,
high-quality brachytherapy as a single modality produces excellent
treatment outcomes. The review in ONCOLOGY is particularly informative
because it explains the radiobiologic basis of the "favorable biochemical
control rates" achieved by optimal implant techniques, which incorporate "intraprostatic
dose escalation", "generous periprostatic brachytherapy treatment
margins", and scrupulous post-implant CT verification of seed location
combined with accurate dosimetric analytic confirmation of the planned
dose distribution. Merrick and Blasko report that in their hands 35%-40%
of seeds are placed into periprostatic tissue, thereby extending the field
of effective irradiation to 5-8 mm beyond the prostatic capsule and
covering the proximal 6-10 mm of the seminal vesicles. Blasko points to
pathologic data indicating that "the mean extent of extraprostatic
extension [is] in the range of 1 to 3 mm; [and] thus brachytherapy margins
of 5 mm should encompass all sites of extracapsular extension in 99% of
cases". Their CT-based dosimetry demonstrates "post-implant treatment
margins of 6.5 mm at the 100% isodose line". The target radiation doses
are 140 Gy for I-125 and 100 Gy of Pd-103. The "adverse pathologic
features (eg. high Gleason score, perineural invasion and extensive
tumor)" become of less consequence in the face of improvements in
radiation delivery." Because ... radiation dose decreases by up to 20 Gy/mm
at the periphery of the target volume"
it is recommended that "patients at significant risk for seminal vesicle
and/or lymph node involvement are likely to benefit from supplemental XRT".
Merrick claims, with a whiff of hubris that risks over generalization,
that in his hands "cancercidal treatment margins [are] substantially
larger than those obtainable with radical prostatectomy".
Results:
In Merrick's series of 202 men with clinical T1b-T2c disease, with
biochemical failure set at PSA > 0.4 ng/mL, the 8 year bPFS (median
follow-up 5.2 years) for therapy with Pd-103 and I-125 was: low-risk (143
men), 98.0% and 93.4%; and for a combined intermediate- (51 men) and
high-risk (8 men) group, 96.3% and 93.2%, respectively. The data graphs at
this stage of maturity show a clear plateau with no failures after the 3
year mark.
Treatment
results from the Seattle Prostate Institute have been widely reported.
Representative results for men treated with contemporary technique:
low-risk patients (I-125, at 10 years) ~ 88% bPFS, with no improved by
supplemental XRT; intermediate-risk patients (Pd-103, at 9 years) - 82%
bPFS, also not improved by supplemental XRT; and high-risk (PSA > 20ng/mL,
Pd-103, at 9 years ), bPFS 65%.
The
ability to avoid supplemental XRT confers the advantage of avoidance of
the 5 weeks required for administration of an additional 45 Gy of XRT to
the prostatic bed and adds significant additional cost, which is
considerable if IMRT technique is used. Long-term adverse effect on
urinary quality of life may occur, but is lessened with experienced
brachytherapists. Long-term bowel dysfunction occurs infrequently, but can
be a very serious problem.
Not all
radiotherapists agree with the strategic recommendations incorporated in
the two articles referred to above, and two critical reviews are included
in the ONCOLOGY issue. One objection focuses on the heterogeneity inherent
in the "intermediate-risk" grouping and maintains that a more careful
stratification in this cohort is needed to allow optimally informed
individual treatment decisions. Another concern relates to the choice of
the treatment modality for high-risk patients, where uncertainty in
biopsy-based prognostic estimates of the true pathologic extent of disease
might make a strategy external beam XRT alone the safest choice. Another
caveat is that these excellent reported results come from work by very
experienced brachytherapists, results that may not be achieved by
physicians earlier in their learning curves.
All
parties agree that the information that will emerge from RTOG Trial 0232,
designed to investigate the usefulness of XRT supplemental to
brachytherapy, will provide clarity in these areas of controversy.
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