EURURO Vol. 72 No. 5

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of postoperative RT only in patients with more aggressive PCa.
In particular, aRT was associated with a 10.3% improvement in
the 10-yr cancer-specific survival rates exclusively in men
with at least two of the following characteristics: lymph node
invasion, seminal vesicle invasion, and Gleason score 8–10.
These retrospective results appeared to be valid in a
population-based study, where the NNT to prevent one death
at 10-yr follow-up was 10 among men with two or more of the
aforementioned features
Patients with lymph node invasion were not included in
the randomized trials evaluating aRT. However, recent
evidence suggests a potential role of aRT on oncologic
outcomes in this setting . reports the
characteristics of six retrospective investigations addres-
sing this issue. Five studies concluded that there might be a
benefit of aRT in node positive patients while
only one population-based analysis reported negative
findings However, the lack of details regarding dose
administered, RT technique, PSA levels at RT, and the
definition of aRT might preclude its generalizability. The
rationale for using aRT in men with lymph node invasion
would be to maximize loco-regional disease control,
assuming that not all patients with node-positive PCa
would be invariably affected by systemic spread
. Proper patient selection is mandatory in this
setting. When considering a large multi-institutional
retrospective cohort of node-positive patients, Abdollah
et al reported a beneficial impact of aRT only in men
with two or less positive lymph nodes with high-grade
nonorgan confined PCa and in those with three to four
positive lymph nodes, regardless of local disease character-
istics. These findings were externally validated in patients
included in the Surveillance, Epidemiology, and End Results
database . However, as most patients treated by RP do
not undergo an extended lymph node dissection, rigorous
rules based on such a series may not be applicable
. More recently, Tilki et al suggested that aRT
might be associated with improved BCR- and metastasis-
free survival in a cohort of 773 node positive patients
treated with RP and extended nodal dissection. Of note,
whole-pelvis RT was beneficial in all node positive patients
regardless of the number of positive nodes. Nonetheless, the
short follow-up duration (median: 33.8 mo) limits their
findings and results of randomized trials assessing strong
oncologic outcomes are needed to address the role of aRT in
selected patients with pN1 disease .
Currently available selection criteria for the adminis-
tration of aRT are based on clinical characteristics.
However, the introduction of novel biomarkers may allow
clinicians to individualize postoperative management
according to the risk of recurrence. In a retrospective
analysis, Ross et al suggested that the genomic
classifier score predicted the risk of metastases after RP
regardless of postoperative therapies. Moreover, men with
higher scores and more aggressive diseases were the ones
who benefitted the most from aRT. This was confirmed by
Zhao et al who developed a novel genomic classifier
based on 24 genes and reported a positive effect of aRT on
the risk of metastases only inmenwith higher scores (10-yr
incidence of metastases: 4% vs 35% for RT vs no RT,
respectively). Similarly, Den et al showed that patients
with a higher genomic classifier score did much better
when managed with aRT rather than sRT (5-yr incidence of
metastases: 6% vs 23% for aRT and sRT, respectively).
Therefore, genomic classifiers might provide important
information on RT timing in the postoperative setting.
Nonetheless, the rates of metastases in men managed with
aRT alone included in these studies raise questions about
whether they should have received ADT as well. Genomic
classifiers might therefore be useful also in selecting
patients for whom ADT might be omitted without
compromising oncologic outcomes.
Table 1 – Characteristics of randomized controlled trials assessing the role of adjuvant radiotherapy (aRT) after radical prostatectomy (RP) in
prostate cancer patients with aggressive disease characteristics
Inclusion
criteria
Patients
(N)
Timing Technique Dose
(median)
Study
period
Follow-up
(median)
Oncologic outcomes
Bolla et al
EORTC 22911
pT2 R1 N0
pT3 N0
1005 Within 16 wk
from RP
EBRT 50 Gy in 25
fractions +
10 Gy in
5 fractions
1992–2001 127 mo Postoperative RT significantly
improved biochemical
progression-free survival
compared with WS (198 vs
311 events); NNT at 10-yr:
overall survival was not
improved 5
Thompson et al
SWOG 8794
pT3 N0 425 Within 16 wk
from RP
EBRT 60–64 Gy
in 30–32
fractions
1988–1997 152 mo RT significantly improved
metastasis-free survival (93 vs
114 events); NNT at 10-yr: 10
RT significantly improved
overall survival (88 vs
110 events); NNT at 10-yr: 13
Wiegel et al
ARO 96–02/
AUO AP 09/95
pT3 N0
Postoperative
PSA <0.5 ng/ml
368 aRT began
between
6 wk and
12 wk after RP
3D-CRT 60 Gy in
30 fractions
1997–2004 112 mo vs
113 mo
for aRT vs
WS
At 10-yr, progression-free
survival was 56% for aRT and
35% for WS; NNT: 5
EBRT = external-beam radiotherapy; EORTC = European Organization for Research and Treatment of Cancer; NNT = number needed to treat; PSA = prostate-
specific antigen; RP = radical prostatectomy; RT = radiotherapy; SWOG = Southwest Oncology Group; WS = wait-and-see; 3D-CRT = three-dimensional-
conformal radiotherapy.
E U R O P E A N U R O L O G Y 7 2 ( 2 0 1 7 ) 6 8 9 – 7 0 9 693