EURURO Vol. 71 No. 4

543 692

Platinum Priority – Editorial
Referring to the article published on pp. 534–542 of this issue
The Effect of Enzalutamide and Bicalutamide on Patient-reported
Quality of Life Outcomes: Results from the TERRAIN Study
Mark D. Tyson Alan Bryce
a Department of Urologic Surgery, Vanderbilt University Medical Center, Nashville, TN, USA; bDivision of Hematology and Oncology, Mayo Clinic, Phoenix, AZ,
USA
The last decade has ushered in a litany of systemic
treatments for men with metastatic prostate cancer. While
numerous high-quality studies have established the oncol-
ogic efficacy of these treatments in the metastatic castrate-
resistant prostate cancer (mCRPC) population, decidedly
much less is known about how these medications impact a
man’s quality of life (QoL). Given the relative equipoise
regarding timing and sequence of systemic therapies for
mCRPC patients understanding how these medications
impact QoL will undoubtedly facilitate data-driven decision-
making.
In this issue of European Urology, Heidenreich et al
describe patient-reported outcomes from the TERRAIN trial,
a phase 2 study comparing enzalutamide to bicalutamide in
mRCPC. Building on the recently published main analysis
, the authors provide an in-depth post hoc comparison of
these two medications with respect to several different QoL
metrics. Somewhat expectedly, the authors show that
enzalutamide is superior to bicalutamide in mitigating the
expected decline in several domains of function, probably
because of lower rates of symptomatic progression of
disease. In a sensitivity analysis in which the authors do not
assume that missing data are missing at random via
modeling with multiple imputation, the results look even
more promising for enzalutamide.
Nevertheless, there are a few points worth noting. While
TERRAIN was conducted at the request of European
regulators who desired a comparison with bicalutamide,
bicalutamide is frequently used at a higher dose of 150 mg
in Europe on the basis of randomized trials in the
nonmetastatic setting that suggest that 150 mg has higher
efficacy . In TERRAIN, the protocol compares 160 mg of
enzalutamide to 50 mg of bicalutamide. While higher doses
of bicalutamide are unlikely to be as effective as enzalu-
tamide and are also associated with more side effects than
low-dose bicalutamide, the question regarding whether the
differences observed in the current study could be due to
differences in dose remains. Second, enzalutamide remains
significantly more expensive than bicalutamide, by at least
an order of magnitude, and this study does not report on the
relative value of the two drugs, or on the impact of following
bicalutamide with enzalutamide. It is possible that initial
treatment with bicalutamide followed by enzalutamide on
progression can lead to equal outcomes at a much lower
cost. Nevertheless, the fact that the grade 3–4 toxicity rate
was slightly higher for enzalutamide is entirely mitigated
by the superior Functional Assessment of Cancer Therapy–
Prostate scores for enzalutamide patients, emphasizing the
value of composite QoL assessments over isolated analysis
of individual toxicities.
This article makes a very important contribution to the
literature in that it further defines the benefit of enzalu-
tamide in the mCRPC population, uses a high-quality
randomized design to minimize bias, and applies longitu-
dinal, psychometrically validated quality-of-life instru-
ments. Studies like this are imperative before any new
treatment regimen receives the collective imprimatur of the
urologic community.
Conflicts of interest: The authors have nothing to disclose.
ava ilable at
journal homepage:
DOI of original article: .
* Corresponding author. Department of Urologic Surgery, Vanderbilt University Medical Center, A1302 Medical Center North, Nashville, TN 37203,
USA. Tel. +1 615 3222880; Fax: +1 615 3439815.
E-mail address: (M.D. Tyson).
0302-2838/# 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.