Background: It has been reported that compared with no local therapy (NLT), patients treated with local therapy (LT) using radiotherapy (RT) possess higher survival rate in metastatic prostate cancer (mPCa). The aim of this meta-analysis was to evaluate the impact of RT on prognosis in patients with mPCa. Methods: We retrieved the literature in PubMed, Embase, and Cochrane Library databases until June 2019 using structured search terms. Several studies were included, which evaluated patients with mPCa who received RT versus NLT. Results: A total of 14,542 patients were analyzed in 7 included papers (2 randomized controlled trials [RCTs] and 5 cohort retrospective studies [CRS]), and 2,232 mPCa patients were treated with RT and 12,310 with NLT. The data of RCTs and CRS were analyzed separately. In RCTs, RT was associated with no significant difference in overall survival (OS) (pooled hazard ratio [HR] = 0.96; 95% confidence interval [CI]: 0.85–1.09; p = 0.55; I2 = 42%) relative to NLT, while survival benefit was observed in the low-metastatic burden group (pooled HR = 0.68; 95% CI: 0.54–0.86; p = 0.001; I2 = 0%), and no survival benefit was observed in the high-metastatic burden group (pooled HR = 1.07; 95% CI: 0.92–1.24; p = 0.39; I2 = 0%). In CRS, RT results in lower cancer-specific mortality (CSM) (pooled HR = 0.49; 95% CI: 0.34–0.75; p < 0.00001; I2 = 0%) and higher OS (pooled HR = 0.61; 95% CI: 0.55–0.68; p < 0.00001; I2 = 0%) relative to NLT. Subsequent analysis demonstrated that high level of M-stage or N-stage was associated with increased CSM (pooled HR = 2.08; 95% CI: 1.69–2.55; p < 0.00001; I2 = 0% and pooled HR = 1.16; 95% CI: 1.03–1.30; p < 0.00001; I2 = 0%; respectively). Conclusions: Our observations in aggregate indicated that RT at least does not appear to be harmful and may be beneficial for low-metastatic burden patients and better condition patients. More prospective and randomized studies evaluating RT for mPCa are warranted.

1.
Siegel
RL
,
Fedewa
SA
,
Miller
KD
,
Goding-Sauer
A
,
Pinheiro
PS
,
Martinez-Tyson
D
, et al.
Cancer statistics for Hispanics/Latinos, 2015
.
CA Cancer J Clin
.
2018
;
65
(
6
):
457
80
.
2.
Schröder
FH
,
Hugosson
J
,
Roobol
MJ
,
Tammela
TL
,
Zappa
M
,
Nelen
V
, et al.
Screening and prostate cancer mortality: results of the European Randomised Study of Screening for Prostate Cancer (ERSPC) at 13 years of follow-up
.
Lancet
.
2014
;
384
(
9959
):
2027
35
.
3.
Gandaglia
G
,
Karakiewicz
PI
,
Briganti
A
,
Passoni
NM
,
Schiffmann
J
,
Trudeau
V
, et al.
Impact of the site of metastases on survival in patients with metastatic prostate cancer
.
Eur Urol
.
2015
;
68
(
2
):
325
34
.
4.
Cornford
P
,
Bellmunt
J
,
Bolla
M
,
Briers
E
,
De Santis
M
,
Gross
T
, et al.
EAU-ESTRO-SIOG guidelines on prostate cancer. Part II: treatment of relapsing, metastatic, and castration-resistant prostate cancer
.
Eur Urol
.
2017
;
71
(
4
):
630
42
.
5.
Bayne
CE
,
Williams
SB
,
Cooperberg
MR
,
Gleave
ME
,
Graefen
M
,
Montorsi
F
, et al.
Treatment of the primary tumor in metastatic prostate cancer: current concepts and future perspectives
.
Eur Urol
.
2016
;
69
(
5
):
775
87
.
6.
Yuan
Y
,
Kishan
AU
,
Nickols
NG
.
Treatment of the primary tumor in metastatic prostate cancer
.
World J Urol
.
2019 Dec
;
37
(
12
):
2597
2606
.
7.
Löppenberg
B
,
Dalela
D
,
Karabon
P
,
Sood
A
,
Sammon
JD
,
Meyer
CP
, et al.
The impact of local treatment on overall survival in patients with metastatic prostate cancer on diagnosis: a national cancer data base analysis
.
Eur Urol
.
2017
;
72
(
1
):
14
9
.
8.
Dall’Era
MA
,
Lo
MJ
,
Chen
J
,
Cress
R
,
Hamilton
AS
.
Nine-year prostate cancer survival differences between aggressive versus conservative therapy in men with advanced and metastatic prostate cancer
.
Cancer
.
2018
;
124
(
9
):
1921
8
.
9.
Wang
Y
,
Qin
Z
,
Wang
Y
,
Chen
C
,
Wang
Y
,
Meng
X
, et al.
The role of radical prostatectomy for the treatment of metastatic prostate cancer: a systematic review and meta-analysis
.
Biosci Rep
.
2018 Jan 17
;
38
(
1
):
BSR20171379
.
10.
Carneiro
A
,
Baccaglini
W
,
Glina
FPA
,
Kayano
PP
,
Nunes
VM
,
Smaletz
O
, et al.
Impact of local treatment on overall survival of patients with metastatic prostate cancer: systematic review and meta-analysis
.
Int Braz J Urol
.
2017
;
43
(
4
):
588
99
.
11.
Shrier
I
,
Boivin
JF
,
Steele
RJ
,
Platt
RW
,
Furlan
A
,
Kakuma
R
, et al.
Should meta-analyses of interventions include observational studies in addition to randomized controlled trials? A critical examination of underlying principles
.
Am J Epidemiol
.
2007
;
166
(
10
):
1203
9
.
12.
Higgins
JP
,
Altman
DG
,
Gøtzsche
PC
,
Jüni
P
,
Moher
D
,
Oxman
AD
, et al.
The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials
.
BMJ
.
2011
;
343
:
d5928
.
13.
Stang
A
.
Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses
.
Eur J Epidemiol
.
2010
;
25
(
9
):
603
5
.
14.
Kirtane
AJ
,
Gupta
A
,
Iyengar
S
,
Moses
JW
,
Leon
MB
,
Applegate
R
, et al.
Safety and efficacy of drug-eluting and bare metal stents: comprehensive meta-analysis of randomized trials and observational studies
.
Circulation
.
2009
;
119
(
25
):
3198
206
.
15.
Abdel-Rahman
O
,
Cheung
WY
.
Impact of prior local treatment on the outcomes of metastatic hormone-sensitive prostate cancer: secondary analysis of a randomized controlled trial
.
Clin Genitourin Cancer
.
2018 Dec
;
16
(
6
):
466
72
.
16.
Patel
DN
,
Jha
S
,
Howard
LE
,
Amling
CL
,
Aronson
WJ
,
Cooperberg
MR
, et al.
Impact of prior local therapy on overall survival in men with metastatic castration-resistant prostate cancer: results from Shared Equal Access Regional Cancer Hospital
.
Int J Urol
.
2018 Dec
;
25
(
12
):
998
1004
.
17.
Parker
CC
,
James
ND
,
Brawley
C
,
Clarke
NW
,
Attard
G
,
Chowdhury
S
, et al.
Radiotherapy (RT) to the primary tumour for men with newly-diagnosed metastatic prostate cancer (PCa): survival results from STAMPEDE (NCT00268476)
.
Br J Cancer
.
2018
;
119
(
1
):
37
.
18.
Boevé
L
,
Hulshof
M
,
Vis
A
,
Zwinderman
K
,
Twisk
J
,
Delaere
K
, et al.
Pd10-10 a prospective, randomized controlled trial evaluating overall survival in patients with primary bone metastatic prostate cancer (mPCA) receiving either androgen deprivation therapy (ADT) or adt combined with concurrent radiation therapy to the prostate, final data from the HORRAD trial
.
J Urol
.
2018
;
199
(
4S
):
e231
2
.
19.
Bianchini
D
,
Estelles
DL
,
Rescigno
P
,
HOS
,
Kolinsky
MP
,
Sumanasuriya
S
, et al.
Loco-regional treatment (LRT) for Ml at diagnosis prostate cancer (PCa) patients (pts) and impact on overall survival (OS): a retrospective analysis
.
J Clin Oncol
.
2016
;
34
(
2
):
280
.
20.
Pompe
RS
,
Tilki
D
,
Preisser
F
,
Leyh-Bannurah
S-R
,
Bandini
M
,
Marchioni
M
, et al.
Survival benefit of local vs. no local treatment for metastatic prostate cancer: impact of baseline PSA and metastatic substages
.
Eur Urol Suppl
.
2018
;
17
(
2
):
e1849
.
21.
Leyh-Bannurah
SR
,
Gazdovich
S
,
Budäus
L
,
Zaffuto
E
,
Briganti
A
,
Abdollah
F
, et al.
Local therapy improves survival in metastatic prostate cancer
.
Eur Urol
.
2017
;
72
(
1
):
118
24
.
22.
Culp
SH
,
Schellhammer
PF
,
Williams
MB
.
Might men diagnosed with metastatic prostate cancer benefit from definitive treatment of the primary tumor? A SEER-based study
.
Eur Urol
.
2014
;
65
(
6
):
1058
66
.
23.
Antwi
S
,
Everson
TM
.
Prognostic impact of definitive local therapy of the primary tumor in men with metastatic prostate cancer at diagnosis: a population-based, propensity score analysis
.
Cancer Epidemiol
.
2014
;
38
(
4
):
435
41
.
24.
Parikh
RR
,
Byun
J
,
Goyal
S
,
Kim
IY
.
Local therapy improves overall survival in patients with newly diagnosed metastatic prostate cancer
.
Prostate
.
2017
;
77
(
6
):
559
72
.
25.
Fossati
N
,
Trinh
QD
,
Sammon
J
,
Sood
A
,
Larcher
A
,
Sun
M
, et al.
Identifying optimal candidates for local treatment of the primary tumor among patients diagnosed with metastatic prostate cancer: a SEER-based study
.
Eur Urol
.
2015
;
67
(
1
):
3
6
.
26.
Satkunasivam
R
,
Kim
AE
,
Desai
M
,
Nguyen
MM
,
Quinn
DI
,
Ballas
L
, et al.
Radical prostatectomy or external beam radiation therapy vs no local therapy for survival benefit in metastatic prostate cancer: a SEER-Medicare analysis
.
J Urol
.
2015
;
194
(
2
):
378
85
.
27.
Rusthoven
CG
,
Jones
BL
,
Flaig
TW
,
Crawford
ED
,
Koshy
M
,
Sher
DJ
, et al.
Improved survival with prostate radiation in addition to androgen deprivation therapy for men with newly diagnosed metastatic prostate cancer
.
J Clin Oncol
.
2016
;
34
(
24
):
2835
42
.
28.
Cho
Y
,
Chang
JS
,
Rha
KH
,
Hong
SJ
,
Choi
YD
,
Ham
WS
, et al.
Does radiotherapy for the primary tumor benefit prostate cancer patients with distant metastasis at initial diagnosis?
PLoS One
.
2016
;
11
(
1
):
e0147191
.
29.
Bianchini
D
,
Lorente
D
,
Rescigno
P
,
Zafeiriou
Z
,
Psychopaida
E
,
O’Sullivan
H
, et al.
Effect on overall survival of locoregional treatment in a cohort of de novo metastatic prostate cancer patients: a single institution retrospective analysis from the royal marsden hospital
.
Clin Genitourin Cancer
.
2017
;
15
(
5
):
e801
7
.
30.
Pompe
RS
,
Tilki
D
,
Preisser
F
,
Leyh-Bannurah
SR
,
Bandini
M
,
Marchioni
M
, et al.
Survival benefit of local versus no local treatment for metastatic prostate cancer-Impact of baseline PSA and metastatic substages
.
Prostate
.
2018
;
78
(
10
):
753
7
.
31.
Boeve
LMS
,
Hulshof
M
,
Vis
AN
,
Zwinderman
AH
,
Twisk
JWR
,
Witjes
WPJ
, et al.
Effect on survival of androgen deprivation therapy alone compared to androgen deprivation therapy combined with concurrent radiation therapy to the prostate in patients with primary bone metastatic prostate cancer in a prospective randomised clinical trial: data from the HORRAD trial
.
Eur Urol
.
2019
;
75
(
3
):
410
8
.
32.
Parker
CC
,
James
ND
,
Brawley
CD
,
Clarke
NW
,
Hoyle
AP
,
Ali
A
, et al.
Radiotherapy to the primary tumour for newly diagnosed, metastatic prostate cancer (STAMPEDE): a randomised controlled phase 3 trial
.
Lancet
.
2018
;
392
(
10162
):
2353
66
.
33.
Kyriakopoulos
CE
,
Chen
YH
,
Carducci
MA
,
Liu
G
,
Jarrard
DF
,
Hahn
NM
, et al.
Chemohormonal therapy in metastatic hormone-sensitive prostate cancer: long-term survival analysis of the randomized phase III E3805 CHAARTED trial
.
J Clin Oncol
.
2018
;
36
(
11
):
1080
7
.
34.
Boeri
L
,
Sharma
V
,
Karnes
RJ
.
Radiotherapy for newly diagnosed oligometastatic prostate cancer
.
Lancet
.
2018
;
392
(
10162
):
2327
8
.
35.
Gillessen
S
,
Attard
G
,
Beer
TM
,
Beltran
H
,
Bossi
A
,
Bristow
R
, et al.
Management of patients with advanced prostate cancer: the report of the advanced prostate cancer consensus conference APCCC 2017
.
Eur Urol
.
2018
;
73
(
2
):
178
211
.
36.
Parker
CC
,
James
ND
,
Brawley
CD
,
Clarke
NY
,
Hoyle
AP
,
Ali
A
, et al.
Radiotherapy to the primary tumour for newly diagnosed, metastatic prostate cancer (STAMPEDE): a randomised controlled phase 3 trial
.
Lancet
.
2018
;
392
(
10162
):
2353
66
.
37.
Rusthoven
CG
,
Jones
BL
,
Flaig
TW
,
Crawford
ED
,
Koshy
M
,
Sher
DJ
, et al.
Improved survival with prostate radiation in addition to androgen deprivation therapy for men with newly diagnosed metastatic prostate cancer
.
J Clin Oncol
.
2016
;
34
(
24
):
2835
42
.
38.
Cho
Y
,
Chang
JS
,
Rha
KH
,
Hong
SJ
,
Choi
YD
,
Ham
WS
, et al.
Does radiotherapy for the primary tumor benefit prostate cancer patients with distant metastasis at initial diagnosis?
PLoS One
.
2016
;
11
(
1
):
e0147191
.
39.
Barocas
DA
,
Alvarez
J
,
Resnick
MJ
,
Koyama
T
,
Hoffman
KE
,
Tyson
MD
, et al.
Association between radiation therapy, surgery, or observation for localized prostate cancer and patient-reported outcomes after 3 years
.
JAMA
.
2017
;
317
(
11
):
1126
40
.
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