EURURO Vol. 73 No. 1

16 148

Finally, there is growing evidence that radiotherapy
may exert systemic effects. That radiotherapy has effects
beyond the treatment field is relatively well established .
A combination of systemic effects and local toxicity to
the femur and pelvis may explain an association observed
between radiotherapy and fracture risk among women
with pelvic malignancies . There is recent evidence
demonstrating an independent association between
radiotherapy and fracture risk among men treated for
PCa although others have not demonstrated this
relationship In addition, we recently observed an
independent association between radiotherapy for clini-
cally localized PCa and the development of coronary artery
disease, myocardial infarction, and sudden cardiac death
although this requires further validation.
3.5. Effect of ADT
ADT is often co-administered with radiotherapy because of
evidence that it improves overall survival Thus,
most radiation administered is in fact combination therapy.
Long-termADT (2 or 3 yr) is recommended for patients with
locally advanced disease rather than short-term therapy
(6 mo) . However, among patients with localized
disease, short-term ADT appears sufficient Nonethe-
less, both the ProtecT study and Lennernas et al treated all
patients receiving radiotherapy with ADT.
ADT is associated with detriments in bone health,
cardiovascular disease, diabetes, sexual function, mental
health, and cognition Furthermore, ADT causes sexual
dysfunction in more than 90% of treated men in terms of a
decrease in sexual interest (libido) and erectile function
ADT has also been associated with decreases in penile
length and testicular size which may be psycho-
logically distressing and associated with treatment regret. At
1 yr after treatment, ADT was associated with significant
impairments in HRQoL and greater psychological distress
than conservative management, while no differences were
found between either surgery or radiotherapy and conser-
vative management .
Most studies assessing ADT toxicity were conducted
among men with advanced or metastatic disease and
without consideration of local treatment. Recently, adverse
cardiovascular and skeletal-related effects of ADT have been
demonstrated among patients with localized disease
undergoing definitive local treatment in an observational
cohort . Among patients with intermediate- and high-
risk clinically localized PCa in the DART 01/05 randomized
trial, longer ADT duration (24 mo) was associated with
higher risk of cardiovascular events when compared to
short duration (4 mo) . However, comparing treatment
with ADT to no ADT, a recent meta-analysis of randomized
trials showed no increase in the risk of cardiovascular death
. Adjuvant ADT may potentiate the bowel and sexual
toxicity of radiotherapy (either EBRT or brachytherapy)
and the urinary and sexual toxicity following radical
prostatectomy . Furthermore, adjuvant ADT has been
associated with significant impairments in HRQoL .
Among patients undergoing radiotherapy, neoadjuvant ADT
resulted in significant impairment in sexual- and vitality-
related QoL within 2 mo of initiating ADT
3.6. Evolving treatment modalities
3.6.1. Changes in surgical approach
Most survival and oncologic data for surgically treated
patients reported in this manuscript are derived from
patients treated with open retropubic radical prostatec-
tomy. To the best of our knowledge, there exists only one
trial that randomized patients to open or robotic radical
prostatectomy . To date, only early perioperative
outcomes are available. When assessed at 6 and 12 wk
after surgery, there were no significant differences in
urinary or sexual function. Conclusions regarding positive
margin rates could not be drawn.
Several population-based observational cohort studies
have compared open and robotic approaches. In terms of
oncologic outcomes, robotic prostatectomy has been associ-
ated with a lower risk of positive surgical margins and of
requiring additional cancer therapies but no differ-
ence in overall or PCa-specific mortality was observed
Using PRO measures, O’Neil et al found that
patients treated robotically had better urinary and sexual
function at 6 mo after surgery when compared to those
treated with open surgery. The difference in sexual function
persisted, while differences in urinary function disappeared
by 12mo. By contrast, Barry et al found no differences in
continence or sexual function between operative techniques.
Owing to a combination of pro-innovation bias and
changes in surgical training, it is likely that robotic
prostatectomy will remain the preferred surgical approach.
Centralization of care may lead to improved outcomes
because of the established association between surgical
volume and outcomes Furthermore, operative
advances, including the use of a modified nerve-sparing
technique and neurovascular structure-adjacent
frozen-section examination , may contribute.
3.6.2. Changes in radiotherapy delivery
Over the past two decades, IMRT has largely supplanted
three-dimensional conformal radiotherapy for EBRT and
has been associated with lower gastrointestinal toxicity but
comparable genitourinary toxicity Accompanying
the transition to IMRT has been a trend towards dose
escalation, which improved biochemical control and re-
duced metastases in some randomized trials ,
although mortality appeared to be comparable .
Early reports indicated that dose escalation may be
associated with greater gastrointestinal toxicity ;
however, a recent review concluded that toxicity profiles
were probably similar for dose-escalated and non–dose-
escalated therapy . Hypofractionation is associated with
similar oncologic outcomes and toxicity to conventional
regimes . Stereotactic body radiotherapy (SBRT)
combines dose escalation and hypofractionation. While
randomized comparisons to IMRT are ongoing, observational
data suggest that SBRT has similar oncologic outcomes
to IMRT although SBRT but may be associated with
E U R O P E A N U R O L O G Y 7 3 ( 2 0 1 8 ) 1 1 – 2 0 16