EURURO Vol. 72 No. 5

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a role in the development of side effects. Van Praet et al
reported that the incidence of acute and late GI toxicity was
higher among patients undergoing whole pelvis IMRT.
However, Jereczek-Fossa et al showed no differences
in toxicity among men treated with IMRT delivered to the
prostatic bed only versus the whole pelvis.
The association between the type of RT (ie, aRT vs sRT)
and the risk of adverse events has also been investigated.
Jereczek-Fossa et al reported that patients undergoing
aRT are at higher risk of acute and late Grade 3-4 GU toxicity
compared with their counterparts receiving sRT. However,
no differences in GI toxicity were observed. Similarly, a
retrospective study by Zaffuto et al suggested that men
undergoing aRT had lower 3-yr continence and erectile
function recovery rates compared with those treated with
sRT. Conversely, Cozzarini et al reported similar rates of
Grade 2 and 3 late urinary toxicity among patients treated
with aRT and sRT. Sowerbi et al also failed to show
differences in the rates of incontinence among men treated
with aRT and sRT. However, these studies might be limited
by the relatively small number of patients included and by
the short follow-up interval.
Finally, an association between postoperative RT and the
risk of secondary malignancies has been proposed
. Abdel-Wahab et al reported an increased risk
of secondary cancers within the irradiated field (eg, rectum
and bladder cancers) in PCa patients receiving postopera-
tive RT included in the Surveillance, Epidemiology, and End
Results registry. Singh et al evaluated the same cohort
and showed an increased risk of bladder cancer among men
treated with RP and postoperative RT. Ciezki et al
reported an increased incidence of secondary bladder and
rectal cancers among patients treated with RP and
postoperative RT compared with those treated with surgery
alone at 20-yr follow-up (0.74% vs 1.06% and 1.7% vs 2.7%,
respectively). More recently, Wallis et al performed a
systematic review and meta-analysis of second malignan-
cies after RT for PCa. The authors concluded that there was
an increased risk of cancers of the bladder, colorectum, and
rectum with hazard ratios of 1.70, 1.80, and 1.8 compared
with those unexposed to RT. They also noted that the
absolute risk varied from 0.1% to 4.2% for studies reporting
the lowest risk compared with those reporting the highest
risk. However, almost all of these studies suffer from a
methodological flaw, namely the use of patients treated by
RP as a control group to estimate the risk of second cancers
after RT. An example of this point is provided in an analysis
of more than 18 000 men treated by RP reported by Eifler
et al The authors showed that the rate of deaths from
second cancers was lower in men treated with RP than in
the general American population (standardized mortality
ratio: 0.47). Thus, if men in the general population have
twice the risk of deaths from second cancers compared to
RP, then most if not all of the estimates from studies
supporting an association between postoperative RT and
secondary malignancies could be explained by this selec-
tion bias. Thus, although radiation can result in second
cancers, the true risk is still unknown and is likely to be
substantially lower that many studies have suggested.
4. Conclusions
Immediate RT reduces the risk of recurrence after RP in
patients with aggressive pathologic characteristics. How-
ever, this approach is associated with an increase in the
10-yr cumulative risk of Grade 2 or higher GU toxicity of 8%
and of Grade 2 or higher GI and GU toxicity of 3%. Therefore,
accurate patient selection is mandatory and genomic
classifiers might provide information on RT timing in the
postoperative setting and on the need for systemic
therapies. Although evidence from randomized trials is
lacking, observation followed by sRT administered at the
first sign of recurrence might be associated with durable
cancer control in selected patients. Dose escalation, WPRT,
novel RT techniques, and the concomitant use of ADT might
improve the long-term outcomes of postoperative RT.
Author contributions: Giorgio Gandaglia had full access to all the data in
the study and takes responsibility for the integrity of the data and the
accuracy of the data analysis.
Study concept and design: Gandaglia, Briganti, Clarke, Karnes, Graefen,
Ost, Zietman, Roach.
Acquisition of data: Gandaglia, Briganti, Clarke, Karnes, Graefen, Ost,
Zietman, Roach.
Analysis and interpretation of data : Gandaglia, Briganti, Clarke, Karnes,
Graefen, Ost, Zietman, Roach.
Drafting of the manuscript: Gandaglia, Briganti, Clarke, Karnes, Graefen,
Ost, Zietman, Roach.
Critical revision of the manuscript for important intellectual content:
Briganti, Clarke, Karnes, Graefen, Ost, Zietman, Roach.
Statistical analysis: None.
Obtaining funding : None.
Administrative, technical, or material support : None.
Supervision: None.
Other: None.
Financial disclosures: Giorgio Gandaglia certifies that all conflicts of
interest, including specific financial interests and relationships and
affiliations relevant to the subject matter or materials discussed in the
manuscript (eg, employment/affiliation, grants or funding, consultan-
cies, honoraria, stock ownership or options, expert testimony, royalties,
or patents filed, received, or pending), are the following: None.
Funding/Support and role of the sponsor: None.
Appendix A. Supplementary data
Supplementary data associated with this article can be
found, in the online version, at
.
References
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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 9 705