radiographic progression-free survival (rPFS) and overall
survival (OS).
A total of 1717 patients were recruited. The enzaluta-
mide group had a significantly better rate of rPFS at 12 mo,
65%, compared with 14% in the placebo group (hazard ratio
[HR]: 0.19;
p
<
0.001). In addition, the risk of death was
reduced by 29% with enzalutamide (HR: 0.71;
p
<
0.001).
Enzalutamide was also superior in times to initiation of
chemotherapy, to first skeletal-related event, and to pros-
tate-specific antigen progression as well as in rates of
complete and partial soft tissue disease response.
After reviewing interim results, the trial was premature-
ly terminated, and enzalutamide was offered to eligible
patients receiving the placebo. The authors concluded that
enzalutamide had significant benefits for patients with
mCRPC who are chemotherapy naı¨ve.
Experts’ comments:
This important randomised controlled trial has been eagerly
awaited and does not disappoint. It demonstrates that enza-
lutamide, a well-tolerated and easily administered oral agent,
provides very significant reductions in rPFS and OS in men
with mCRPC prior to chemotherapy. The respective HRs of
0.19 and 0.71 are most impressive. The other interesting agent
in this disease space, abiraterone, is also well tolerated and
easily administered (but requires concomitant use of prednis-
olone); however, it failed to demonstrate an OS advantage
when its phase 3 study was published in a similar patient
population
[1]
. This may be explained by the trial stopping
early due to the very impressive reductions in rPFS at interim
analysis; however, it is noted that the PREVAIL study was also
stopped early for similar reasons.
One might expect that in the increasingly competitive
mCRPC market, the data from the PREVAIL study would
lead to enzalutamide becoming the first choice for
therapy in this patient population. This may be so;
however, CRPC is still progressive in many patients, and
multiple agents may be required to offer a maximum
survival benefit. The optimal sequence and combination
of therapies to ensure maximum survival, maximum
quality of life, and maximum cost effectiveness are still
far from clear
[2]
.W
i
thsu
chap
l
e
th
o
r
ao
fth
e
r
a
p
i
e
s
available, it may be some time before the optimal
sequence and combination of therapies is established.
In the meantime, this excellent study gives us further
hope that a well-tolerated and easily administered agent
can offer a very significant survival benefit for patients in
this otherwise perilous situation.
Conflicts of interest:
The authors have nothing to disclose.
References
[1]
Ryan CJ, Smith MR, de Bono JS, et al. Abiraterone in metastatic
prostate cancer without previous chemotherapy. N Engl J Med
2013;368:138–48.
[2]
Heidenreich A, Bastian PJ, Bellmunt J, et al. EAU guidelines on
prostate cancer. Part II: treatment of advanced, relapsing, and
castration-resistant prostate cancer. Eur Urol 2014;65:467–79.
Ken Chow
a
, Declan G. Murphy
a,b,c,
*
a
Department of Urology, Royal Melbourne Hospital, Melbourne, Australia
b
Division of Cancer Surgery, Peter MacCallum Cancer Centre,
University of Melbourne, Melbourne, Australia
c
Epworth Prostate Centre, Epworth Healthcare, Richmond, Australia
*Corresponding author. Division of Cancer Surgery, Peter MacCallum
Cancer Centre, St. Andrews Place, East Melbourne,
Victoria 3002, Australia.
E-mail address:
declan.murphy@petermac.org
(D.G. Murphy).
Re: Testosterone Lab Testing and Initiation in the United
Kingdom and the United States, 2000 to 2011
Layton JB, Li D, Meier CR, et al.
J Clin Endocrinol Metab 2014;99:835–42
Experts’ summary:
The retrospective cohort study by Layton and colleagues
sought to describe the patterns of testosterone testing and
testosterone prescriptions in men in the United Kingdom and
the United States. The authors utilized data from general
practitioner health care records in the United Kingdom and
from both commercial and Medicare insurance claims in the
United States between 2000 and 2011. This study found that
testosterone testing rates increased in both countries and
that new testing in untreated patients rose threefold in the
United Kingdom and more than fourfold in the United States.
This study observed that a significant proportion of men in
their reproductive years received testosterone supplementa-
tion. Men aged 18–39 yr accounted for a significant minority
of new testosterone prescriptions (United Kingdom: 16%;
United States: 12%), and a higher proportion of US men with
normal or high serum testosterone levels received testoster-
one prescriptions (United Kingdom: 1%; United States: 4–9%).
This discrepancy in testing and diagnosis was also evident
from the fact that in the United Kingdom, 88% of men who
were prescribed testosterone were diagnosed with clinical or
laboratory hypogonadism compared with only 60% of men in
the United States.
Experts’ comments:
The study by Layton et al., using data from both UK and US
cohorts, highlights the discrepancies between a definitive
diagnosis of hypogonadism and interventional treatment. This
study, along with an analysis performed by Baillargeon and
colleagues
[1]
, provides evidence for what we already see in
clinical practice, namely, that the number of testosterone
therapy prescriptions has risen dramatically over the past
decade. Because practitioners have become more aware of
hypogonadism, we would hope to see an increase in labora-
tory testing but with a smaller increase in testosterone thera-
py. These data, however, demonstrate an alarming trend. A
subset of patients are not receiving adequate testing
[2]
prior
to initiation of testosterone therapy, and more men are being
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