EURURO Vol. 73 No. 1

21 148

Platinum Priority – Editorial
Referring to the article published on pp. 11–20 of this issue
Randomised Controlled Trials Remain the Key to Progress in
Localised Prostate Cancer
Alison Tree, David Dearnaley
The Royal Marsden NHS Foundation Trust and Institute of Cancer Research, Sutton, UK
Over the last 2 yr, there has been an unprecedented wealth
of randomised controlled trials (RCTs) illuminating out-
comes in localised prostate cancer (PCa). Several thousand
patients have been included, spanning low-risk to advanced
localised disease. The ProtecT trial is the only substantial
study comparing management options in screen-detected,
predominantly low-risk disease. Favourable 10-yr survival
was demonstrated whether using active monitoring,
prostatectomy, or conventionally fractionated external-
beam radiotherapy (EBRT) with a short course of androgen
deprivation therapy (ADT). The excess risk of metastasis
developing in the active monitoring group is a concern but
may be mitigated by improvements in the surveillance
pathway using, for example, magnetic resonance imaging
(MRI) to identify disease progression, and by exploration of
biomarkers to better select patients. The ProtecT study also
gives important information on patient-reported outcomes;
no intervention can be distinguished on overall health-
related quality of life, but unbiased observers may note
some advantage for nonsurgical intervention. In a second
group of studies, more than 5000 patients have been
included in radiotherapy (RT) studies of modest hypo-
fractionation . The patients included had predominantly
intermediate- or high-risk disease. Treatment using frac-
tions of 3 Gy/d to a total dose of 60 Gy over 4 wk was as
effective and with similar late side effects as conventional
2-Gy daily fractions delivered to doses of 74–78 Gy,
whether or not short-course ADT was used. Very impor-
tantly, treatment techniques using intensity-modulated RT
(IMRT), with or without image guidance (IGRT) and with
mandated normal tissue dose constraints, have reduced
gastrointestinal side effects by approximately 50%. The
shorter schedule is expected to become the new standard of
care, with considerable benefits in terms of patient
convenience and use of health care resources. Results of
more extreme (eg, 5 fractions) hypofractionation studies in
Sweden (HYPRO trial ISRCTN85138529) and UK/Canada
(PACE ISRCTN17627211) are awaited.
The improved outcome using ADT observed in the CHHiP
trial (with ADT) compared to the PROFIT study (without
ADT) mirrors the advantage shown for ADT in the recent
EORTC trial report using high-dose EBRT. It appears that
short-course ADT impacts on micro-metastases as well as
local tumour control. The results of ‘‘super-ADT’’ have just
been reported for the Medical Research Council STAMPEDE
trial. Standard of care (SOC) in patients with locally
advanced or metastatic prostate cancer was compared with
SOC plus abiraterone acetate and prednisolone (AAP) . An
overall survival advantage was shown, but, very strikingly,
the hazard ratio (HR) for failure-free survival, was 0.29
(p < 0.4 10 61) in favour of SOC + AAP, with an even lower
HR of 0.21 in the M0 group. This will probably translate into
a long-term survival advantage and opens up a new era in
the successful treatment of advanced, high-grade localised
disease.
Despite these large trials and their practice-changing
results, we remain left with the quandary of which patients
are best treated with primary surgical or RT options. In this
issue of European Urology, Wallis and colleagues address
this issue in their international review of surgery or RT. They
appropriately conclude that we just do not have the
evidence from RCTs to reach a sound judgement. They
comment that it has been shown that surgery prolongs
survival compared to watchful waiting in clinically localised
ava ilable at
journal homepage:
DOI of original article: .
* Corresponding author. Division of Radiotherapy and Imaging, Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, Downs
Road, Sutton SM2 5PT, UK. Tel. +44 208 6613458; Fax: +44 208 6438809.
E-mail address: (D. Dearnaley).
0302-2838/# 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.