EURURO Vol. 72 No. 5

Introduction

Radical prostatectomy (RP) represents one of the treat-

ments of choice for patients with localized prostate cancer

(PCa) and is associated with excellent long-term outcomes

[1,2]

. Nonetheless, more than 30% of contemporary patients

treated with RP will harbor aggressive disease character-

istics (ie, extracapsular extension, seminal vesicle invasion,

or lymph node invasion) at final pathology

[3,4]

. In some of

these individuals, surgery alone might not provide adequate

long-term oncologic control

[5–8]

. Therefore, a multimodal

approach that includes radiotherapy (RT) should be

considered. Adjuvant RT (aRT) is defined as the administra-

tion of RT to the prostatic bed the seminal vesicle bed and

the pelvic lymph node area delivered typically 1–6 mo after

surgery in the absence of signs of recurrence

[9]

. Prospective

randomized trials support a role for aRT in reducing the risk of

biochemical recurrence (BCR). Nonetheless, more than 40% of

patients managed with initial observation will not recur at

10-yr follow-up

[6,7]

. Potential short- and long-term side

effects associated with aRT, as well as patient inconvenience

and expense, significantly limit its adoption

[10–12]

. Conse-

quently, aRT is administered in approximately 20% of contem-

porary patients with aggressive pathologic features in the USA

[3]

. By contrast, initial observation followed by RT in the case

of BCR (ie, salvage RT [sRT]) represents an increasingly adopted

option even in the absence of strong data from randomized

trials

[13]

. Several improvements in patient selection criteria,

radiation dose, techniques of radiation delivery, and use of

hormonal therapies have been introduced over the last decades

and might impact on patient outcomes. The aim of our review

is to analyze the current role and future perspectives of

postoperative RT in PCa patients treated with RP.

Evidence acquisition

2.1.

Search strategy

The literature review was performed in September 2016

according to the Preferred Reporting Items for Systematic

Reviews andMeta-analysis guidelines

[14]

. The Medline and

EMBASE databases were searched for relevant articles

between January 2009 and August 2016. The search strategy

included the terms prostate cancer, radical prostatectomy,

adjuvant radiotherapy, salvage radiotherapy, alone or in

combination.

2.2.

Inclusion and exclusion criteria

Inclusion criteria were: (1) English language, (2) more than

100 patients enrolled, (3) original articles, (4) cohorts of PCa

patients treated with RP postoperative RT, (5) studies

reporting on oncologic outcomes (BCR, progression-free

survival, cancer-specific mortality, and overall mortality)

and/or patient-reported side effects, and (6) prospective

randomized trials and/or retrospective studies. Exclusion

criteria were: (1) other types of articles (ie, reviews, conference

abstracts, letters to editor, and editorials), (2) insufficient

details provided, and (3) possible data overlap with articles of

the same group. If multiple publications evaluating the same

cohort were available, the most recent one was selected. After

an analysis of the abstracts and recovery of all full texts,

additional references were identified. Cited references from

selected articles retrieved in our search were also used to

identify manuscripts that were not included in the initial

search. Two authors (G.G. and M.R.) selected studies for

inclusion. Discrepancies between the two authors were

resolved via discussion with all coauthors. The articles that

provided the highest level of evidence were then evaluated and

selected with the consensus of all participating authors

( Fig. 1

2.3.

Assessment of risk of bias

The risk of bias in the included randomized controlled trial

was assessed using the Cochrane risk of bias assessment

tool for randomized controlled trials

[15]

. Risk of bias in

nonrandomized comparative studies was assessed using

the modified Cochrane tool. Publication bias for studies

comparing progression-free survival after aRT versus sRT

was assessed using a funnel plot.

2.4.

Data extraction

The following information was abstracted: the number of

patients, age, study design, primary treatment, pathologic

stage and grade, type of RT after surgery, administration of

androgen deprivation therapy (ADT), median follow-up,

oncologic outcomes, and short- and long-term side effects.

Evidence synthesis

3.1.

Characteristics of the studies included in the review process

Overall, three randomized controlled trials comparing

immediate postoperative RT and initial observation

[6–8]

one randomized trial assessing the impact of dose

intensification in the salvage setting

[16]

, and two

randomized controlled trials comparing the use of RT alone

versus RT plus ADT

[17,18]

were identified. Overall, six

nonrandomized comparative studies evaluating the role of

postoperative RT in node positive patients

[19–24] ,

and

seven nonrandomized studies comparing aRT and sRT were

included in the review process

[13,25–30] .

Finally, seven

case series reporting predictors of oncologic outcomes after

aRT

[31–37] ,

21 case series reporting the outcomes of sRT

[38–58] ,

and 20 studies describing postoperative RT side

effects have been identified

[10–12,28,59–74]

3.2.

Risk of bias assessment of the included studies

Fig. 2

presents the risk of bias assessment of six randomized

controlled trials included in our systematic review

[6–8, 16–18] .

The risk of selection, detection, and reporting biases

was low. The risk of bias related to the blinding of

participants and personnel when evaluating patient-

reported outcomes (performance bias) was high. When

considering nonrandomized comparative studies, we ob-

served a high risk of selection, performance, and detection

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