Radiation After Prostatectomy Reduces Risk of Recurrence
Medscape Medical News 2006. © 2006 Medscape
November 14, 2006 ? The optimal management of prostate cancer after a
radical prostatectomy remains unclear, even though adjuvant radiation has
been used in such patients for more than 40 years. Only now has a
long-term, controlled study spelled out the benefits and drawbacks of this
approach to treatment. Published in the November 15 issue of the Journal of
the American Medical Association, the study shows that adding radiation
reduces the risk of disease recurrence but does not appear to significantly
improve survival.
"The results of this study provide guidance for clinicians and patients in
weighing options for adjuvant radiotherapy for pathologically advanced
disease," the authors write.
Cancer Had Already Spread Outside of Prostate
Conducted by Ian Thompson, MD, and colleagues at the University of Texas
Health Science Center, San Antonio, the study followed 425 men for a median
of 10.6 years. It was supported by grants from the National Cancer
Institutes of the United States and Canada.
All participants had been diagnosed with prostate cancer and had opted for a
radical prostatectomy, during which the cancer was found to have already
spread outside the prostate. This happens in 38% to 52% of patients, the
authors comment, and this proportion hasn't changed in recent years,
despite a stage shift to earlier cancer stages and lower volumes.
Patients were randomized to receive radiotherapy (n = 214) or usual care and
observation (n = 211). Radiation was delivered by external beam at a dose
of 60 to 64 Gy in 30 to 32 fractions.
The primary study end point was metastasis-free survival, and the difference
between the groups was not statistically significant. The median estimates
for metastasis-free survival were 14.7 years in the radiotherapy group vs
13.2 years in the observation group (P = .06).
These metastasis-free survival times were much longer than had been
anticipated at the start of the trial (in August 1988) ? at that time the
median metastasis-free survival in the observation group was expected to be
around 6 years, the researchers comment. There were 35 cases of metastatic
disease noted in the observation group and 17 in the radiotherapy group, a
much lower rate than expected, they add.
Significant Reduction in Disease Recurrence
Radiotherapy significantly reduced the risk of disease recurrence, which was
defined as any evidence of measurable or evaluable disease (eg, bone
lesions). In the radiotherapy group, 84 of 214 patients (39.3%) experienced
a disease recurrence, compared with 111 of 211 patients (52.6%) in the
observation group (P = .001). The median recurrence-free estimates were
13.8 years for radiotherapy vs 9.9 years for observation.
Radiotherapy also significantly reduced the risk of a biochemical relapse,
measured by levels of prostate specific antigen (PSA). Nearly twice as many
patients in the observation group had a biochemical relapse (112 of 175, or
64%), compared with those in the radiotherapy group (60 of 172, or 34.9%; P
< .001). However, the implications of this are unknown, the authors
comment, as there is currently a debate raging about whether a PSA response
to treatment can serve as a surrogate for disease-related outcomes. "This
study demonstrates the potential inconsistency of PSA relapse and the
primary end point, with a significant reduction in the former but no
significant relation in the risk of metastatic disease," they add.
*No significant effect was seen on overall survival.* A total of 71 of 214
patients (33.2%) in the radiotherapy group died, compared with 83 of 211
patients (39.3%) in the observation group (P = .16). Median survival was
14.7 vs 13.8 years, respectively.
Significantly more complications occurred in patients receiving radiotherapy
(51 of 214, or 23.8%) compared with those on observation (25 of 211, or
11.9%; P = .002). About twice as many were affected, and the authors note
in particular the following complications: rectal complications such as
proctitis or rectal bleeding, which occurred in 3.3% of radiotherapy group
vs none in the observation group (P = .02); urethral stricture (17.8% vs
9.5%, P = .02), and total urinary incontinence (6.5% vs 2.8%, P = .11).
Guidance for Both Doctors and Patients
In commenting that the results of this study provide guidance, the authors
write: "Arguments in favor of radiation include the approximately 50%
reduction in risk of PSA relapse or disease recurrence and perhaps the
nonsignificant reduction in the risk of metastasis-free survival, the
primary study end point."
However, among the arguments against adjuvant radiotherapy is the fact that
the study had negative findings ? there was no significant reduction in
metastatic disease. "Despite prolonged follow-up of these patients, the
rate of metastatic disease was significantly less than anticipated."
One option that has been advocated is to delay the radiotherapy: not
administer it immediately after the prostatectomy (within 10 days in this
study), but to follow these patients and offer radiotherapy only if PSA
levels increase. This is, ultimately, the approach that was used in the
observation group in the current study, the authors point out, as one third
of these patients eventually had radiotherapy. "With a lack of a
statistically significant improvement in metastasis-free and overall
survival in the 2 study groups, this approach may be a reasonable
alternative," they comment.
JAMA. 2006;296;2329-2335.
Radiation After Prostatectomy 
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