EURURO Vol. 72 No. 2

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Re: Radiation With or Without Antiandrogen Therapy in
Recurrent Prostate Cancer
Shipley WU, Seiferheld W, Lukka HR, et al
N Engl J Med 2017;376:417–28
Experts’ summary:
This double-blind randomized controlled trial assesses
the effect on long-term survival from the addition of antian-
drogen (AA) therapy to salvage radiotherapy (sRT) [1]. Seven
hundred and sixty men with biochemical recurrence (BCR:
0.2–4 ng/ml) following radical prostatectomy for T2/T3 N0 M0
disease were enrolled to receive either sRT 64.8 Gy in 36 frac-
tions alone, or with the addition of 24 mo of bicalutamide
150 mg (AA) daily with 516 men completing the study.
When comparing the sRT + AA arm with the sRT alone
arm, there was a significant improvement in overall survival
of 76.3% versus 71.3% (hazard ratio [HR] = 0.77, p = 0.04,
numbers needed to treat [NNT] = 20); death from prostate
cancer 5.8% versus 13.4% (HR = 0.49, p < 0.001, NNT = 13);
incidence of metastases 14.5% versus 23% (HR = 0.63,
p = 0.005, NNT = 5); incidence of a second BCR was 44%
versus 67.9% (HR = 0.48, p < 0.001, NNT = 4.2), was observed
in favor of the combination arm. Posthoc subgroup analysis
suggests the greatest benefit formenwith aggressive disease.
The incidence of gynecomastia was significantly higher with
bicalutamide (69.7%) compared with radiotherapy alone
(10.9%), with little difference in the incidence of other
adverse events. Twenty-five percent of men in the treatment
arm withdrew, compared with 11% in the placebo arm.
Experts’ comments:
The results of this study, in addition to those of GETUG-AFU 16
[2] have shown that the addition of hormonal therapy (either
androgen deprivation therapy [ADT] or AA), to sRT in men
with detectable prostate-specific antigen levels improves
long-term outcomes [1,2]. Clinicians are therefore faced with
the question: should this become standard of care for all men
with BCR undergoing sRT?
We believe the answer to this question is no, for the
following reasons. First, and in common with all studies of
localized prostate cancer [3,4], clinical practice has
evolved since this study was conceived, and therefore
the results may not be applicable today. Ultrasensitive
prostate-specific antigen testing, imaging (including
prostate-specific membrane antigen-positron emission
tomography), and radiotherapy dose and techniques have
all moved on since the authors began recruiting patients
back in 1998, and more refined risk stratifications for the
prediction of adverse outcomes have been developed.
Second, applying a one-size-fits-all approach of applying
combined sRT and ADT/AA to all men with BCR would likely
overtreat some patients in this setting. Furthermore, there
will be a group of men with BCR in this cohort who may
benefit from ADT alone as the source of their BCR may be
outside the pelvis.
There does, however, appear to be increasing evidence of
benefit to a combination approach for men with higher risk
disease in whom it might be advisable to recommend 2 yr of
hormonal therapy in addition to radiotherapy. However, it
is likely that such ADT rather than AA therapy will be the
preferred approach for those who adopt a combination
approach. For men with lower risk disease, the addition of
hormonal therapy may be of limited benefit [5].
Whilst in principal, the use of using ADT with sRT may be
sound; in practice, the data from this study will require
careful interpretation in light of more recent advances and
ongoing studies [6] in the diagnosis and management of
these patients.
Conflicts of interest: The authors have nothing to disclose.
References
[1]
[2]
[3]
[4]
.
[5]
[6]
Benjamin W. Lamba, John Violetb, Shankar Sivab,c,
Declan G. Murphya,c,d,*
a Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne,
Australia
bDivision of Radiation Oncology, Peter MacCallum Cancer Centre,
Melbourne, Australia
cThe Sir Peter MacCallum Department of Oncology, University of Melbourne,
Melbourne, Australia
dAustralian Prostate Cancer Research Centre, Epworth Healthcare,
Melbourne, Australia
*Corresponding author. Division of Cancer Surgery, Peter MacCallum
Cancer Centre, 305 Grattan Street, Melbourne, Victoria 3002,
Australia.
E-mail address: (D.G. Murphy).
# 2017 European Association of Urology.
Published by Elsevier B.V. All rights reserved.
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