EURURO Vol. 72 No. 5

711 860

and sophisticated biomarkers, such as the recently intro-
duced genomic classifiers, may be extremely helpful in
further refining assessment of the biologic aggressiveness
and propensity of residual PCa after RP to spread systemi-
cally, theoretically leading to more accurate and timely
identification of better candidates for aRT than for sRT.
Notwithstanding, there is still quite a long list of open
questions in the field of postoperative RT that have not yet
been definitively answered. We still do not know, for
example, if the prognosis for all patients with a rising PSA
after RP is invariably poor or, conversely, if some form of
salvage treatment should be promptly proposed even for
patients with rising PSA even if their level is 0.20 ng/ml, a
crucial issue in the current era of ultrasensitive PSA assays.
Furthermore, we do not know the possible need for
radiation doses higher than those currently delivered in
both the adjuvant and salvage settings, or the possible
hypothetical benefit of prophylactic irradiation of the pelvic
lymph-node area via so-called whole-pelvis RT (WPRT).
Both moderate dose escalation and WPRT could theoreti-
cally reduce the benefit, recently found in two phase 3 RCTs
(RTOG 9601 and GETUG-16) , of ADT added to
postoperative RT.
In any case, in the debate on aRT versus sRT it should be
acknowledged that the uro-oncology community has
apparently already made a choice by electing for salvage
as the better strategy, even in the absence of any level
1 evidence from RCTs. It is likely that the seemingly better
toxicity profile (both acute and long-term) of sRT when
compared to aRT played a crucial role in determining this
choice. It is undeniable that the detrimental effect of
delayed RT on post-surgical recovery of urinary function,
especially urinary continence, is much lower than that of RT
delivered only a few weeks after RP.
The issue of immediate versus deferred post-RP RT for
the likely growing subset of patients with high-risk disease
after radical surgery is becoming increasingly important in
uro-oncology. Clinical data and early evidence from genetic
profiling suggest that for patients with (very) high-risk
features at final pathology, immediate RT may confer
a survival advantage compared to RT delayed until rising
PSA occurs. Nevertheless, only a very comprehensive
cost-benefit analysis, for which the primary endpoint must
be avoidance of any even minimal risk of potential
overtreatment, in conjunction with a significant improve-
ment in the therapeutic ratio for both aRT and sRT, will
allow uro-oncologists to adequately tailor the management
of patients at higher risk of post-RP recurrence.
Conflicts of interest: The authors have nothing to disclose.
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