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disease in the SPCG-4 trial, at least for younger age groups.
The firming up of this conclusion with >10-yr long-term
follow-up is instructive. However, there has been no similar
RT RCT for this group. Similarly, RT with long-course ADT
prolongs survival in advanced localised disease , but
there are no surgical RCTs in this group. The key issue to
appreciate is that both local modalities produce good
efficacy, and differences in survival outcomes are likely to
be small at most. It is questionable whether large enough
phase 3 trials will be ever be performed in appropriate
patient subgroups. Therefore, the temptation is to turn to
observational data. As Wallis et al point out in their
review, such data are confounded by both known and
unknown variables. Statistical tools attempt to correct the
known imbalances; propensity score analysis is frequently
used. However, it is salutary to note that it has been shown
that these techniques are ineffective in localised PCa and
we believe the resulting comparative data are flawed and
certainly unsuitable for making decisions on health care
delivery. Globally, it has been reported that PCa is the major
cause of ‘‘years lived with disability’’ among men . This
emphasises the importance of reducing treatment-related
effects as far as possible. Treatment should be avoided when
not needed, and focal therapies need to be studied and their
efficacy and side effect profiles more rigorously assessed. RT
techniques continue to evolve and improve, with IMRT and
IGRT becoming widely available. Focal boost treatments
directed using high-quality MRI can be given to maximise
local control, and randomised trials are under way using
both standard and moderately hypofractionated schedules
(FLAME trial NCT01168479, PIVOTALboost CRUK/16/018).
ADT should not be used unless shown to improve outcome.
We need better imaging, tissue, and plasma biomarkers to
separate patients with intermediate risk into appropriate
favourable and unfavourable groups, which can then be
assessed prospectively to validate biomarker-led hypothe-
ses. Whichmen really need long-course hormone treatment
and which subgroups would benefit from the addition of
‘‘super-ADT’’ with abiraterone or the new generations of
potent anti-androgens are relevant questions.
Another way of looking at the choice between prosta-
tectomy and RT is to ask the question ‘‘After RT, which
patients will develop life-shortening or symptomatic local
recurrence?’’ With modern, high-quality RT techniques, the
proportion will be small, but prospective collection of
potentially predictive biomarkers including genetic hetero-
geneity may be of assistance. The use of patient-
reported outcomes, particularly using the EPIC instrument,
as noted by Wallis et al , may help us to advise patients of
the likely outcomes for different treatment modalities.
Patient choice after appropriate counselling remains central
to decision-making. We believe that this is best performed
in well-functioning, multidisciplinary teams that can
deliver both high-quality surgery and RT.
Conflicts of interest: David Dearnaley has received advisory board/
consultancy fees from Takeda, Amgen, Astellas, Sandoz, and Janssen; is
an employee of the Institute of Cancer Research, where abiraterone acetate
was developed; has an intellectual property in a pending patent
(EP1933709B1); and is the recipient of a Cancer Research UK Programme
Grant and an NIHR Royal Marsden Hospital/Institute of Cancer Research
Biomedical Research Centre quinquennial grants (2007-2012 and 2012-
2017). Alison Tree has received research and travel funding from Accuray
and Elekta, research funding from MSD, and honoraria from Bayer and
Janssen.
Acknowledgments: The authors gratefully acknowledge the support of
the NIHR Royal Marsden/Institute of Cancer Research Biomedical
Research Centre.
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