Introduction: The objective of this study was to determine effects of adjuvant chemotherapy (AC) on survival outcomes compared to surgery alone without AC for upper tract urothelial carcinoma (UTUC) patients with variant histology (VH). Methods: We conducted a systematic review and meta-analysis of studies investigating AC for UTUC in Medline, Embase, the Cochrane Library up to January 2023. Population, intervention, comparator, and outcome were UTUC patients with VH, radical nephroureterectomy with AC, radical nephroureterectomy only, and oncological survival, respectively. Results: Four retrospective studies were included. Regarding overall survival (OS), the pooled hazard ratio was 0.61 (95% confidence interval: 0.42–0.87; p = 0.007) across two studies. Regarding cancer-specific survival (CSS), the pooled hazard ratio was 0.46 (95% confidence interval: 0.25–0.84; p = 0.01) across three studies. All included studies had a high quality based on the Newcastle-Ottawa Scale. Certainty of evidence for OS was low. Certainty of evidence for CSS was moderate due to a strong association (hazard ratio <0.5). Publication bias was not significant for any studies. Conclusion: In UTUC patients with VH, administration of AC after surgery might have better survival outcomes than surgery alone. Our study provides evidence for decision-making of clinicians who treat UTUC patients with VH.

1.
Rouprêt
M
,
Seisen
T
,
Birtle
AJ
,
Capoun
O
,
Compérat
EM
,
Dominguez-Escrig
JL
, et al
.
European association of urology guidelines on upper urinary tract urothelial carcinoma: 2023 update
.
Eur Urol
.
2023
;
84
(
1
):
49
64
.
2.
Margulis
V
,
Shariat
SF
,
Matin
SF
,
Kamat
AM
,
Zigeuner
R
,
Kikuchi
E
, et al
.
Outcomes of radical nephroureterectomy: a series from the upper tract urothelial carcinoma collaboration
.
Cancer
.
2009
;
115
(
6
):
1224
33
.
3.
Kang
M
,
Kim
HS
,
Jeong
CW
,
Kwak
C
,
Kim
HH
,
Ku
JH
.
Conditional survival and associated prognostic factors in patients with upper tract urothelial carcinoma after radical nephroureterectomy: a retrospective study at a single institution
.
Cancer Res Treat
.
2016
;
48
(
2
):
621
31
.
4.
Zigeuner
R
,
Pummer
K
.
Urothelial carcinoma of the upper urinary tract: surgical approach and prognostic factors
.
Eur Urol
.
2008
;
53
(
4
):
720
31
.
5.
Birtle
A
,
Johnson
M
,
Chester
J
,
Jones
R
,
Dolling
D
,
Bryan
RT
, et al
.
Adjuvant chemotherapy in upper tract urothelial carcinoma (the pout trial): a phase 3, open-label, randomised controlled trial
.
Lancet
.
2020
;
395
(
10232
):
1268
77
.
6.
Quhal
F
,
Mori
K
,
Sari Motlagh
R
,
Laukhtina
E
,
Pradere
B
,
Rouprêt
M
, et al
.
Efficacy of neoadjuvant and adjuvant chemotherapy for localized and locally advanced upper tract urothelial carcinoma: a systematic review and meta-analysis
.
Int J Clin Oncol
.
2020
;
25
(
6
):
1037
54
.
7.
Zalay
O
,
Yan
M
,
Sigurdson
S
,
Malone
S
,
Vera-Badillo
FE
,
Mahmud
A
.
Adjuvant radiotherapy for upper tract urothelial carcinoma: systematic review and meta-analysis
.
Curr Oncol
.
2022
;
30
(
1
):
19
36
.
8.
Mori
K
,
Janisch
F
,
Parizi
MK
,
Mostafaei
H
,
Lysenko
I
,
Kimura
S
, et al
.
Prognostic value of variant histology in upper tract urothelial carcinoma treated with nephroureterectomy: a systematic review and meta-analysis
.
J Urol
.
2020
;
203
(
6
):
1075
84
.
9.
Flaig
TW
,
La Rosa
FG
,
McKinney
K
,
Maroni
P
,
Wilson
S
.
A man with changes in the urinary bladder: benign metaplasia or adenocarcinoma
.
Oncology
.
2009
;
23
(
2
):
177
80
.
10.
Moher
D
,
Shamseer
L
,
Clarke
M
,
Ghersi
D
,
Liberati
A
,
Petticrew
M
, et al
.
Preferred reporting items for systematic review and meta-analysis protocols (prisma-p) 2015 statement
.
Syst Rev
.
2015
;
4
(
1
):
1
.
11.
Wells
GA
,
Shea
B
,
O’Connell
D
,
Peterson
J
,
Welch
V
,
Losos
M
, et al
.
The newcastle-ottawa scale (nos) for assessing the quality of nonrandomised studies in meta-analyses
;
2000
.
12.
Guyatt
GH
,
Oxman
AD
,
Vist
GE
,
Kunz
R
,
Falck-Ytter
Y
,
Alonso-Coello
P
, et al
.
Grade: an emerging consensus on rating quality of evidence and strength of recommendations
.
BMJ
.
2008
;
336
(
7650
):
924
6
.
13.
Parmar
MK
,
Torri
V
,
Stewart
L
.
Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints
.
Stat Med
.
1998
;
17
(
24
):
2815
34
.
14.
Higgins
JP
,
Thompson
SG
,
Deeks
JJ
,
Altman
DG
.
Measuring inconsistency in meta-analyses
.
BMJ
.
2003
;
327
(
7414
):
557
60
.
15.
DerSimonian
R
,
Kacker
R
.
Random-effects model for meta-analysis of clinical trials: an update
.
Contemp Clin Trials
.
2007
;
28
(
2
):
105
14
.
16.
Kim
JK
,
Moon
KC
,
Jeong
CW
,
Kwak
C
,
Kim
HH
,
Ku
JH
.
Variant histology as a significant predictor of survival after radical nephroureterectomy in patients with upper urinary tract urothelial carcinoma
.
Urol Oncol
.
2017
;
35
(
7
):
458.e9
458.e15
.
17.
Murakami
Y
,
Matsumoto
K
,
Ikeda
M
,
Hirayama
T
,
Utsunomiya
T
,
Koguchi
D
, et al
.
Impact of histologic variants on the oncological outcomes of patients with upper urinary tract cancers treated with radical surgery: a multi-institutional retrospective study
.
Int J Clin Oncol
.
2019
;
24
(
11
):
1412
8
.
18.
Tully
KH
,
Krimphove Md
MJ
,
Huynh
MJ
,
Marchese
M
,
Kibel
AS
,
Noldus
J
, et al
.
Differences in survival and impact of adjuvant chemotherapy in patients with variant histology of tumors of the renal pelvis
.
World J Urol
.
2020
;
38
(
9
):
2227
36
.
19.
Lo
CW
,
Li
WM
,
Ke
HL
,
Chang
YH
,
Wu
HC
,
Chen
IHA
, et al
.
Impact of adjuvant chemotherapy on variant histology of upper tract urothelial carcinoma: a propensity score-matched cohort analysis
.
Front Oncol
.
2022
;
12
:
843715
.
20.
Gandhi
J
,
Chen
JF
,
Al-Ahmadie
H
.
Urothelial carcinoma: divergent differentiation and morphologic subtypes
.
Surg Pathol Clin
.
2022
;
15
(
4
):
641
59
.
21.
Chalasani
V
,
Chin
JL
,
Izawa
JI
.
Histologic variants of urothelial bladder cancer and nonurothelial histology in bladder cancer
.
Can Urol Assoc J
.
2009
;
3
(
6 Suppl 4
):
S193
8
.
22.
Netto
GJ
,
Amin
MB
,
Berney
DM
,
Compérat
EM
,
Gill
AJ
,
Hartmann
A
, et al
.
The 2022 world health organization classification of tumors of the urinary system and male genital organs: part b: prostate and urinary tract tumors
.
Eur Urol
.
2022
82
(
5
):
469
82
.
23.
Green
DA
,
Rink
M
,
Xylinas
E
,
Matin
SF
,
Stenzl
A
,
Roupret
M
, et al
.
Urothelial carcinoma of the bladder and the upper tract: disparate twins
.
J Urol
.
2013
;
189
(
4
):
1214
21
.
24.
Mori
K
,
Abufaraj
M
,
Mostafaei
H
,
Quhal
F
,
Karakiewicz
PI
,
Briganti
A
, et al
.
A systematic review and meta-analysis of variant histology in urothelial carcinoma of the bladder treated with radical cystectomy
.
J Urol
.
2020
;
204
(
6
):
1129
40
.
25.
Zamboni
S
,
Foerster
B
,
Abufaraj
M
,
Seisen
T
,
Roupret
M
,
Colin
P
, et al
.
Incidence and survival outcomes in patients with upper urinary tract urothelial carcinoma diagnosed with variant histology and treated with nephroureterectomy
.
BJU Int
.
2019
;
124
(
5
):
738
45
.
26.
Nogueira
LM
,
Yip
W
,
Assel
MJ
,
Tracey
AT
,
Wong
NC
,
Alvim
RG
, et al
.
Survival impact of variant histology diagnosis in upper tract urothelial carcinoma
.
J Urol
.
2022
;
208
(
4
):
813
20
.
27.
Varinot
J
,
Colin
P
,
Rouprêt
M
,
Leroy
X
,
Comperat
E
.
[pathologic analysis of upper tract urothelial carcinomas: state of the art review for the yearly scientific report of the French national association of urology]
.
Prog Urol
.
2014
;
24
(
15
):
954
65
.
28.
Zaghloul
MS
,
Nouh
A
,
Nazmy
M
,
Ramzy
S
,
Zaghloul
AS
,
Sedira
MA
, et al
.
Long-term results of primary adenocarcinoma of the urinary bladder: a report on 192 patients
.
Urol Oncol
.
2006
;
24
(
1
):
13
20
.
29.
Zhai
QJ
,
Black
J
,
Ayala
AG
,
Ro
JY
.
Histologic variants of infiltrating urothelial carcinoma
.
Arch Pathol Lab Med
.
2007
;
131
(
8
):
1244
56
.
30.
Budía Alba
A
,
Queipo Zaragozá
JA
,
Pérez Ebrí
ML
,
Fuster Escrivá
A
,
Vera Donoso
DC
,
Vera Sempere
FJ
, et al
.
[comparative study of pure epidermoid carcinoma of the bladder and transitional cell carcinoma with squamous or mixed differentiated foci]
.
Actas Urol Esp
.
1999
;
23
(
2
):
111
8
.
31.
Amin
MB
.
Histological variants of urothelial carcinoma: diagnostic, therapeutic and prognostic implications
.
Mod Pathol
.
2009
;
22
(
Suppl 2
):
S96
118
.
32.
Margulis
V
,
Puligandla
M
,
Trabulsi
EJ
,
Plimack
ER
,
Kessler
ER
,
Matin
SF
, et al
.
Phase ii trial of neoadjuvant systemic chemotherapy followed by extirpative surgery in patients with high grade upper tract urothelial carcinoma
.
J Urol
.
2020
;
203
(
4
):
690
8
.
33.
Leow
JJ
,
Chong
YL
,
Chang
SL
,
Valderrama
BP
,
Powles
T
,
Bellmunt
J
.
Neoadjuvant and adjuvant chemotherapy for upper tract urothelial carcinoma: a 2020 systematic review and meta-analysis, and future perspectives on systemic therapy
.
Eur Urol
.
2021
;
79
(
5
):
635
54
.
34.
Gayed
BA
,
Thoreson
GR
,
Margulis
V
.
The role of systemic chemotherapy in management of upper tract urothelial cancer
.
Curr Urol Rep
.
2013
;
14
(
2
):
94
101
.
35.
Chitale
S
,
Mbakada
R
,
Irving
S
,
Burgess
N
.
Nephroureterectomy for transitional cell carcinoma - the value of pre-operative histology
.
Ann R Coll Surg Engl
.
2008
;
90
(
1
):
45
50
.
36.
Tae
JH
,
Ha
MS
,
Chi
BH
,
Chang
IH
,
Kim
T-H
,
Myung
SC
, et al
.
Neoadjuvant versus adjuvant chemotherapy in upper tract urothelial carcinoma: a nationwide cohort study
.
BMC Urol
.
2022
;
22
(
1
):
175
.
37.
Galsky
MD
,
Iasonos
A
,
Mironov
S
,
Scattergood
J
,
Donat
SM
,
Bochner
BH
, et al
.
Prospective trial of ifosfamide, paclitaxel, and cisplatin in patients with advanced non-transitional cell carcinoma of the urothelial tract
.
Urology
.
2007
;
69
(
2
):
255
9
.
38.
Siefker-Radtke
AO
,
Gee
J
,
Shen
Y
,
Wen
S
,
Daliani
D
,
Millikan
RE
, et al
.
Multimodality management of urachal carcinoma: the m. D. Anderson cancer center experience
.
J Urol
.
2003
;
169
(
4
):
1295
8
.
39.
Ogbue
O
,
Haddad
A
,
Almassi
N
,
Lapinski
J
,
Daw
H
.
Overview of histologic variants of urothelial carcinoma: current trends and narrative review on treatment outcomes
.
Transl Androl Urol
.
2022
;
11
(
6
):
877
901
.
40.
Seiler
R
,
Ashab
HAD
,
Erho
N
,
van Rhijn
BWG
,
Winters
B
,
Douglas
J
, et al
.
Impact of molecular subtypes in muscle-invasive bladder cancer on predicting response and survival after neoadjuvant chemotherapy
.
Eur Urol
.
2017
;
72
(
4
):
544
54
.
41.
McGregor
BA
,
Campbell
MT
,
Xie
W
,
Siefker-Radtke
AO
,
Shah
AY
,
Venkatesan
AM
, et al
.
Phase ii study of nivolumab and ipilimumab for advanced bladder cancer of variant histologies (BCVH)
.
American Society of Clinical Oncology
;
2019
.
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