EURURO Vol. 71 No. 4

624 692

PCa patients. Late Grade 2 GI and GU toxicities of 18.2% and
26.2% were noted with HFX compared to 11.4% and 20.5%
using conventional fractionation Patient reported
toxicity outcomes are awaited. Another [10_TD$DIFF]randomised trial,
using a higher dose per fraction of 3.4 Gy delivered to a total
dose of 64.6 Gy (HYPRO trial), has demonstrated increased
G3 and higher late urinary toxicity particularly in patients
with pre-existing urinary symptoms . HFX delivered
with fewer treatments can increase the convenience for the
patient and lower costs for the health care system, but only
evidence based fractionation schedules should be used
outside of clinical trials.
HFX requires meticulous quality assurance, excellent
image guidance, and close attention to organ-at-risk dose
constraints to minimise the long-term toxicity risk. Extreme
HFX (5–10 Gy per fraction) in which radiation is delivered in
five to seven fractions should still be considered as
investigational.
10.1. Low-risk prostate cancer
Offer dose-escalated IMRT (74–78 Gy) without ADT.
10.2. Intermediate-risk prostate cancer
Patients suitable for ADT should be given combined dose-
escalated IMRT (76–78 Gy) with short-term ADT (4–6 mo)
For patients unsuitable for ADT (eg, due to comorbid-
ities) or unwilling to accept ADT (eg, to preserve their sexual
health), the recommended treatment is IMRT at a dose of
76–80 Gy or a combination of IMRT and brachytherapy.
10.3. Localised high-risk prostate cancer
The high risk of relapse outside the irradiated volume
makes it mandatory to use a combined modality approach,
consisting of dose-escalated IMRT, possibly including the
pelvic lymphatics and long-termADT, generally for 2 to 3 yr.
The duration of ADT has to take into account performance
status, comorbidities, and the number of poor prognostic
factors.
10.4. Locally advanced prostate cancer: T3–4 N0, M0
The standard of care for patients T3–4 N0, M0 locally
advanced PCa is IMRT combined with long-term ADT for at
least 2 to 3 yr as it results in better OS The
combination is clearly better than EBRT or ADT mono-
therapy . In both high-risk localised and locally
advanced PCa, an upfront combination with docetaxel only
improves relapse-free survival, with no survival benefit at
9 yr .
10.5. Lymph node irradiation
In men with cN0 PCa, RCTs failed to show a benefit from
prophylactic pelvic nodal irradiation (46–50 Gy) in high-
risk cases . In men with cN1 or pN1 the outcome of RT
alone is poor, and these patients should receive RT plus
long-term ADT, as shown by the STAMPEDE trial, in which
the use of RT improved failure-free survival in men with N+
PCa
10.6. Postoperative external-beam radiation therapy after
radical prostatectomy
Extracapsular invasion and positive surgical margins are
associated with a risk of local recurrence and progression.
Adjuvant RT was associated with improved biochemical
progression-free survival in three RCTs , although
only SWOG 8794 suggested improved OS. Thus for
patients classified as pT3 pN0 with a high risk of local failure
with positive margins (highest impact), pT3a and/or pT3b
with a postoperative PSA <0.1 ng/ml, two options can be
offered in the framework of informed consent. Either
immediate EBRT to the surgical bed after recovery of urinary
function or monitoring followed by early salvage RT before
the PSA exceeds 0.5 ng/ml .
10.7. Side effects of definitive radiation therapy
The Memorial Sloan Kettering Cancer Center group reported
data on late toxicity from their experience in 1571 patients
with T1–T3 disease treated with either 3D-CRT or IMRT at
doses between 66 Gy and 81 Gy, with a median follow-up of
10 yr . The use of IMRT significantly reduced the risk of
late grade 2 or higher gastrointestinal (GI) toxicity to 5%
compared with 13% with 3D-CRT. The incidence of grade 2
late genitourinary (GU) toxicity was 20% in patients treated
with 81 Gy IMRT versus 12% with lower doses. The overall
incidences of late grade 3 toxicity were 1% and 3% for GI and
GU toxicity, respectively.
Systematic review and meta-analysis of observational
studies comparing patients exposed or unexposed to
radiotherapy in the course of treatment for PCa demon-
strate an increased risk of developing second cancers for
bladder (OR: 1.39), colorectal (OR: 1.68), and rectum (OR:
1.62) with similar risks over lag times of 5 and 10 yr.
Absolute risks over 10 yr are small (1–4%) but should be
discussed with younger men in particular .
11. Brachytherapy
Low-dose rate (LDR) brachytherapy uses permanent radio-
active seeds implanted into the prostate and is an option for
those with low-risk disease and selected cases with
intermediate-risk disease (low-volume GS 3 + 4), prostate
volume <50 cm3
[4_TD$DIFF], and an IPSS 12 Up to 85% relapse-
free survival at 10 yr is demonstrated . LDR as a boost
with EBRT can be used to dose escalate radiation in
intermediate- and high-risk patients. Although seen as a
low-impact treatment modality, some patients experience
significant urinary complications following implantation,
such as urinary retention (1.5–22%), postimplantation
transurethral resection of the prostate (TURP) (8.7% of
cases), and incontinence (0–19%) . Careful selection of
patients using uroflowmetry can avoid these significant
side effects Previous TURP for BPH increases the risk of
E U R O P E A N U R O L O G Y 7 1 ( 2 0 1 7 ) 6 1 8 – 6 2 9 624