EURURO Vol. 73 No. 1

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1. Introduction
For three decades, management options for patients with
clinically localized prostate cancer (PCa) have remained the
same: surgery, radiotherapy, and observation. Many men,
particularly those who are older or have low-risk PCa, will
not benefit from active intervention . For men with long
life expectancy (>10 yr), treatment is recommended for
those with intermediate- or high-risk PCa . Both surgery
and radiotherapy (now usually in combination with
androgen deprivation therapy, ADT) have been used in
the treatment of PCa for more than 100 yr. While other
treatments such as high-intensity frequency ultrasound and
cryotherapy are gaining prominence, the volume of
evidence for intermediate- and long-term outcomes
remains insufficient to guide treatment decision-making.
Accordingly, these treatments are not routinely recom-
mended in clinical practice guidelines
Without significant supportive evidence, surgery and
radiotherapy (generally in combination with ADT) have
been advocated as having similar oncologic efficacy. Thus,
treatment counseling and decision-making have been
complex and predominately centered on the risks of urinary
incontinence and erectile dysfunction and other radiation-
specific side effects (and increasingly the side effects of ADT
as we have become aware of them in the past decade). The
importance of localized PCa management is highlighted by
its selection by the Institute of Medicine as one of the top
25 priorities for comparative effectiveness research . In
the past few years, a significant body of literature assessing
survival and complications following treatment of localized
PCa has emerged. In this collaborative narrative review, we
summarize historical and contemporary data evaluating
survival outcomes and complications following radical
prostatectomy and radiotherapy in the treatment of
clinically localized PCa, including consideration of the role
and toxicity of ADT co-administered in most modern
radiotherapy regimes.
2. Evidence acquisition
Medline was systematically searched from inception
until December 2016 using the following terms: ‘‘radical
prostatectomy’’, ‘‘radiotherapy’’, ‘‘brachytherapy’’, ‘‘survival’’,
‘‘complications’’, and ‘‘outcomes’’, along with free-text,
related, derivative, and exploded terms. The lead author
compiled a proposed bibliography and manuscript frame-
work that was iteratively revised by all co-authors. Following
agreement on the manuscript structure, the first and senior
authors drafted this narrative review that was critically
revised by all co-authors. The final manuscript represents the
consensus of the authors.
3. Evidence synthesis
3.1. Oncologic outcomes in PCa research
Many cancer-related outcomes have been used in compar-
ative effectiveness studies of PCa treatments, including
biochemical recurrence (BCR), clinical recurrence, metasta-
sis, PCa-specific mortality, and overall mortality. All-cause
(overall) mortality is the most reliable endpoint of any
oncology study and, according to the US Food and Drug
Administration, is the preferred endpoint owing to its
precision and lack of ascertainment bias . Previous work
has shown that PCa may be reliably ascertained as a cause of
death from administrative records . Thus, PCa-specific
survival is an alternative outcome that may more directly
assess the oncologic efficacy of PCa therapies.
BCR is the outcome most commonly used in studies of
PCa treatment efficacy as it develops relatively early
following treatment While BCR is an important clinical
event, most notably as it triggers further therapy with
significant costs and quality-of-life (QoL) detriments ,
it is limited as a meaningful research outcome. First,
approximately 10% of men with BCR will develop clinical
progression and <5% at 5 yr will ultimately die of the
disease Thus, BCR is a poor surrogate measure for
survival. Second, innumerable definitions of BCR exist. A
systematic review of the literature in 2007 identified
53 different definitions of BCR following radical prostatec-
tomy and 99 different definitions of BCR following
radiotherapy making it difficult to compare outcomes
between studies. Finally, given the intrinsically different
definitions of BCR for patients treated initially with surgery
and radiotherapy, the use of BCR to compare outcomes
following treatment with the two modalities is inherently
problematic. Both the Phoenix criterion and ASTRO criteria
as a definition of BCR systematically overestimate BCR-free
survival for patients following radical prostatectomy
. Furthermore, Lee et al showed that among men
with comparable 5-yr risks of BCR, those treated with
better PCa control cannot be definitively answered now or in the near future. Complications
following PCa treatment are relatively common regardless of treatment approach. These
include the commonly identified issues of urinary incontinence and erectile dysfunction,
and others including hospitalization and invasive procedures to manage complications and
secondary malignancies. Population-based outcome studies, rather than clinical trial data,
will be necessary for a comprehensive understanding of the relative benefits and risks of
each therapeutic approach.
Patient summary: Surgery and radiotherapy are the most common interventions for men
diagnosed with prostate cancer. Comparisons of survival after these treatments are limited
by various flaws in the relevant studies. Complications are common regardless of the
treatment approach.
# 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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