PROGNOSTIC ROLE OF HYDRONEPHROSIS

IN THE TREATMENT OF PATIENTS WITH

LOCALLY ADVANCED CERVICAL CANCER: A
RETROSPECTIVE COHORT

Presenter:
Dr. Dwi Cahya Puspitasari

Department of Obstetrics and Gynecology

RSUP Dr. Mohammad Hoesin
Faculty of Medicine Sriwijaya University
2021
2
 INTRODUCTION
CERVICAL
CANCER

2nd most diagnosed 4th cause of death

malignant tumor women worldwide

anemia, sciatica, infection,

vesicovaginal and rectovaginal
fistula, rectal and bladder
Complication
involvement, ureteral
obstruction with hydronephrosis,
and renal failure
Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: Cancer J Clin
2018;68:394–424.
Sankaranarayanan R, Budukh AM, Rajkumar R. Effective screening programmes for cervical cancer in low- and middle-income developing countries. Bull World Health Organ 2001;79:954–
62. 3
Hopkins MP, Morley GW. Prognostic factors in advanced stage squamous cell cancer of the cervix. Cancer 1993;72:2389–93.
 INTRODUCTION
22-48% locally
Obstructive
DIARE INFEKSI
uropathy
advanced cervical cancers

compromising leading to worse

renal failure
Virus Parasit
therapeutic options outcomes

Option to restore
renal function First line treatment
Urinary diversion (ureteral radiotherapy with
stents, percutaneous cisplatinbased
nephrostomy or other) chemotherapy
Chao KSC, Leung W-man, Grigsby PW, et al. The clinical implications of hydronephrosis and the level of ureteral obstruction in stage IIIB cervical cancer. Int J Radiat Oncol Biol Phys 1998;40:1095–100.
Rose PG, Ali S, Whitney CW, et al. Impact of hydronephrosis on outcome of stage IIIB cervical cancer patients with disease limited to the pelvis, treated with radiation and concurrent chemotherapy: a Gynecologic
Oncology Group study. Gynecol Oncol 2010;117:270–5.
Patel K, Foster NR, Kumar A, et al. Hydronephrosis in patients with cervical cancer: an assessment of morbidity and survival. Support Care Cancer 2015;23:1303–9. 4
Chemoradiotherapy for Cervical Cancer Meta-Analysis Collaboration. Reducing uncertainties about the effects of chemoradiotherapy for cervical cancer: a systematic review and meta-analysis of individual patient data
from 18 randomized trials. J Clin Oncol 2008;26:5802–12
 AIM
AIM THIS STUDY

• Evaluate the prognostic

impact of hydronephrosis and
urinary diversion in patients
with locally advanced cervical
cancer undergoing
concurrent radiotherapy
and/or chemotherapy.
5
 METODE treated with
chemotherapy
and/or
Women with locally radiotherapy
Barretos Cancer
A retrospective cohort advanced cervical cancer Hospital
study (FIGO 2018 stage IIIB to January 2009-
IVA) June 2018

group I – patients with locally advanced cervical

cancer without hydronephrosis
Cases
group II –with uropathy
patients with prior
locally advanced cervical
Non-probability to cervical
cancer cancer, lost to
with hydronephrosis who underwent a urinary
3 groups of
convenience sampling follow-up, or with diversion
missing patient
groupdata
III – in the records
patients with locally advanced cervical
Excludecancer with hydronephrosis but no urinary diversion.

6
 VARIABLES EVALUATED
Race (white,
Disease stage by
Age black, pardo or Histological type
MRI and/or CT
other)

The presence of Pelvic or

Type of cancer
Tumor size parametrial retroperitoneal
treatment
involvement lymph nodes

Obstruction were analyzed:

Creatinine laterality, classification of
clearance pyeloectasis, ype of urinary
diversion 7
Data Colection Statistical
Analysis
The REDCap
database Catagorical
data parametric data
Outcome The normality of ordinary oneway
overall survival distributions was analysis of variance
and progression- tested by the with Tukey’s multiple
free survival Shapiro-Wilk test comparisons test
based on the χ2
presence of or
hydronephrosis Fisher’s Non-parametric
and urinary exact test data
diversion the Kruskal-Wallis
IBM-SPSS software v.21.0 test+Dunn’s post
hoc test

8
Retroperitoneal
Table 1. Clinicopathological features 6 (9.7)
by hydronephrosis 3(6.8)
status 2 (4.4)
lynphadenopathy‡ RESULT
Table 1. Clinicopathological features by hydronephrosis status
No-Hydronephrosis hydronephrosis
Creatinine clearanceNo-Hydronephrosis
Table 1. Clinicopathological Group atfeatures
I97 (80.5–117)
(n=62)
hydronephrosis
With64(34-98.5)
relief status
by hydronephrosis )¶ Without
77 (58-103)**
relief
admission (mL/min) § Group I (n=62) With relief Without relief
No-Hydronephrosis Group II (n=44) hydronephrosis
Group III (n=45)
Treatment‡ Group II (n=44) Group III (n=45)
Histological degree‡ Group I (n=62) With relief Without relief
Stage‡ There was no statistically significant difference between
CCRT
I 3 (4.8) 60 (96.8) 0Group38 (86.4) 32III(71.1)**
2(4.4)
II (n=44)stage,
Group (n=45) type
the groups analyzed for disease histological
RT IIIB
Alone 16 (25.8)
or 2 (3.2)
grade, tumor 11 (25)
size, 6 (13.6)
parametrial 8 lymph
or (17.8)
12 (26.7)**
node
II Age* 44 (71)
53.6±15.2 30(68,2)
47.2±4.6† 30 (66.7)
52.3±14.7
IIIC1 involvement.
33 (53.2) 21 (47.7) 23 (51.1)
CT Alone
III Race‡ 15 (24.2) 0 0
14(31.8) 1 (2.2)
13 (28.9)
Data expressed
IIIC2 as number (%);5mean±SD;
(8.1) median (IQR) 3 (6.8) 2 (4.4)
*Analysis
Tumor White of variance
size (cm) § with post hoc Tukey’s
6.2(54.8)
34 multiple
(5.75–7.3) comparisons
6.2 test.
(5-7.6)
26 (59.1) 256.3 (5.5-8.1)
(55.5)
†Group I vs II - p<0.05.
IVAexact test or Χ2 test. 8 (12.9)
‡Fisher’s
9 (20.5) 12 (26.7)
Parametrial
Black 761 (98.4)
(11.3) 43 (97.7)
4 (9.1) 345(100)
(6.7)
§Kruskal-Wallis test with post hoc Dunn’s multiple comparisons test.
¶Group
Histological type‡
I vs II - p<0.001.
involvement‡
Pardo 20 (32.3) 14 (31.8) 17 (37.8)
**Group I vs III - p<0.05.
ADC, SCC
adenocarcinoma; CCRT, 57 (91.9) chemoradiation43
concurrent (97.7)CT, chemotherapy;
therapy; 43 (95.6)RT, radiation
9
PelvicOther 142
(1.6)
therapy; SCC, squamous cell carcinoma.
(67.7) 24(54.5)
0 026 (57.8)
 RESULT
Table 2. Hydronephrosis and urinary diversion profile
hydronephrosis
Table 2. Hydronephrosis and urinary diversion profile
With relief Without relief
hydronephrosis
Group
With relief II Without
Group relief
III
(n=44)
Group (n=45)
II Group III
Urinary Ureteral stents L 23 (52.3)
(n=44) NA
(n=45)
diversion
Laterality Unilateral L 12 (27.3)* 22 (48.9)
Percutaneous R
R 17 (34.1)
15 (38.6) NA(37.8)
17
Classification nephrostomy
Bilateral 17 (38.6)* 6 (13.3)
Other
Mild 4 (15.9)
7 (9.1) NA
9 (20)
Data expressed as number (%);
*Group II vs III - p<0,05. 10
Moderate
†Fisher’s exact test or χ2 test.
23 (52.3) 21 (46.7)
RESULT

11
 RESULT
Tumor
Table 3size 1.085 by(0.988
Prognostic factors 0.088 1.127hazard
Cox proportional (1.016 0.023
regression 1.145 0.019 1.180 (1.050 to 0.006

Factor to 1.192)
Univariate analysis to 1.249) (1.023
Multivariate to
analysis 1.326)

OS PFS OS 1.281) PFS

Pelvic HR1.536 (0.926
P value 0.097 2.257 (1.173
HR (95%CI) 0.015 HR (95%CI)
P value 1.918 P value
0.029 HR2.203
(95%CI)
(1.089 P
to value
0.028
lymphadenopathy (95%CI)
to 2.55) to 4.34) (1.071 to 4.456)
(yes
Racevs (black
no) vs 1.22 0.619 1.109 (0.439 to 0.826 3.436)

Hydronephrosis
others) 2.253
(0.558 to (1.336 0.002 0.958
2.804) (0.541 0.882 2.063 0.02 NS
(yes vs no) to 3.799)
2.667) to 1.694) (1.121 to

Cell type 1.51 0.485 0.388 (0.165 to 0.03 3.795)

Creatinine
(squamous 0.995
cell (0.475 to (0.988 0.177 1.003
0.913) (0.995 0.431
clearance
carcinoma to 1.002)
vs 4.802) to 1.012)
others)
Concurrent 0.315 (0.181 <0.00 1.178 (0.5 to 0.707 0.43 0.019 NS
chemoradiotherapy to 0.547)
Tumor degree (3 1.109 1 1.2412.774)
(0.644 to 0.519 (0.212 to
(yes
vs 1 vs
andno)
2) (0.637 to 2.389) 0.873

HR, hazard ratio; NS,

1.93)
not significant; OS, overall survival; PFS, progression-free surviva 12
 DISCUSSION
Summary of Main
Results

Patients with locally advanced

Performing urinary diversion had
cervical cancer with
no impact on overall survival or
hydronephrosis had no difference
progression-free survival.
in progression-free survival

The most frequent intervention for

A large proportion of women had relief of ureteral obstruction was
moderate to severe ureteral cystoscopic ureteral stent
ectasia. placement followed by
percutaneous nephrostomy 13
 DISCUSSION
Results in the Context of
Published Literature

Rose et al demonstrated an association

Findings of a systematic
of worse overall survival and
review support the negative
progression-free survival in IIIB patients
impact of hydronephrosis on
with hydronephrosis (received similar
the overall survival of patients
doses of radiation and cisplatin-based
with cervical cancer;
chemotherapy)

Hydronephrosis in our analysis remained an unfavorable prognostic

factor in multivariate analysis irrespective of creatinine clearance
levels, corroborating findings from other studies.
14
 DISCUSSION
Results in the Context of
Published Literature

Rose et al demonstrated an association

Findings of a systematic
of worse overall survival and
review support the negative
progression-free survival in IIIB patients
impact of hydronephrosis on
with hydronephrosis (received similar
the overall survival of patients
doses of radiation and cisplatin-based
with cervical cancer;
chemotherapy)

Hydronephrosis in our analysis remained an unfavorable prognostic

factor in multivariate analysis irrespective of creatinine clearance
levels, corroborating findings from other studies.
Chao KSC, Leung W-man, Grigsby PW, et al. The clinical implications of hydronephrosis and the level of ureteral obstruction in stage IIIB cervical cancer. Int J Radiat Oncol Biol Phys 1998;40:1095–100.
Rose PG, Ali S, Whitney CW, et al. Impact of hydronephrosis on outcome of stage IIIB cervical cancer patients with disease limited to the pelvis, treated with radiation and concurrent chemotherapy: a Gynecologic
Oncology Group study. Gynecol Oncol 2010;117:270–5
15
Pradhan TS, Duan H, Katsoulakis E, et al. Hydronephrosis as a prognostic indicator of survival in advanced cervix cancer. Int J Gynecol Cancer 2011;21:1091–6.
 DISCUSSION
Results in the Context of
Published Literature

Creatinine clearance levels The reliable cut-off creatinine

were not associated with clearance level is still a
worse overall survival or subject of controversy for
progression-free survival. decision-making for relief of

Gynecologic oncology patients with <20%of renal function may recover from

Acute kidney injury after placement of a stent or percutaneous
Nephrostomy tube.
Klaipetch A, Namwongprom S, Ekmahachai M, et al. Excretory urography and renal scintigraphy for chronic obstructed kidney: does nonopacity mean nonsalvageability?. Singapore Med
J 2013;54:267–70
Liang B, Lange SS, Massad LS, et al. Do gynecologic oncology patients with severely diminished renal function and urinary tract obstruction benefit from ureteral stenting or 16
percutaneous nephrostomy?. Gynecol Oncol Rep 2019;28:136–40.
 DISCUSSION
Results in the Context of This study did not
Published Literature
Rose et al reported a confirm these
correlation between relief of findings
ureteral obstruction and
improved overall survival and
progression-free survival5

Patients with obstructive uropathy are at increased risk of chronic kidney

disease and, due to chemotherapy nephrotoxic properties, they often need
dose reduction or omission
Patel K, Foster NR, Kumar A, et al. Hydronephrosis in patients with cervical cancer: an assessment of morbidity and survival. Support Care Cancer 2015;23:1303–9.
Rose PG, Ali S, Whitney CW, et al. Impact of hydronephrosis on outcome of stage IIIB cervical cancer patients with disease limited to the pelvis, treated with radiation and concurrent
chemotherapy: a Gynecologic Oncology Group study. Gynecol Oncol 2010;117:270–5
17
 DISCUSSION
Complication Some authors consider early
hydronephrosis urinary diversion in cases of Risk of urinary adverse:
bilateral hydronephrosis with Low urinary symptoms
low creatinine clearance Hematuria
(<50mL/min) Urinary incontinence and
Urinary tract infections
Chronic low back pain Radiotherapy retention
Nausea induce acute Renal colic
Vomiting urinary
Nephrolithiasis
obstructive
Bleeding disease. Obstruction
Chronic kidney failure Multiple interventions
Hospitalization
Infections
Shekarriz B, Shekarriz H, Upadhyay J, et al. Outcome of palliative urinary diversion in the treatment of advanced malignancies. Cancer 1999;85:998–1003
Goldfarb RA, Fan Y, Jarosek S, et al. The burden of chronic ureteral stenting in cervical cancer survivors. Int Braz J Urol 2017;43:104–11.
Horan G, McArdle O, Martin J, et al. Pelvic radiotherapy in patients with hydronephrosis in stage IIIB cancer of the cervix: renal effects and the optimal timing for urinary diversion?. 18
Gynecol Oncol 2006;101:441–4
 Original Research
Strength Weaknesses

retrospective
Patients with locally
advanced cervical A patient population nature
cancer (FIGO 2018 from a single
stage IIIB to IVA) institution with
according to presence consistent patterns of
or absence of practice
hydronephrosis. the sample size

19
Implications for Practice and Future Research

Patients with locally advanced cervical

cancer (FIGO 2018 stage IIIB to IVA)
according to presence or absence of
hydronephrosis.

20
 Conclusions
Hydronephrosis in locally However, limited data
advanced cervical cancer support urinary diversion as
may be an ominous a treatment of ureteral
predictor of poor overall obstruction to improve
survival based on overall survival and
retrospective literature. progression-free survival.

Potential risks must be

balanced against possible
A comprehensive medical
benefits from expectant
evaluation must be
management and ureteral
performed
stenting or percutaneous
nephrostomy. 21
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• Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and
mortality worldwide for 36 cancers in 185 countries. CA: Cancer J Clin 2018;68:394–424.
• Sankaranarayanan R, Budukh AM, Rajkumar R. Effective screening programmes for cervical cancer in low- and
middle-income developing countries. Bull World Health Organ 2001;79:954–62.
• Hopkins MP, Morley GW. Prognostic factors in advanced stage squamous cell cancer of the cervix. Cancer
1993;72:2389–93.
• Chao KSC, Leung W-man, Grigsby PW, et al. The clinical implications of hydronephrosis and the level of ureteral
obstruction in stage IIIB cervical cancer. Int J Radiat Oncol Biol Phys 1998;40:1095–100.
• Rose PG, Ali S, Whitney CW, et al. Impact of hydronephrosis on outcome of stage IIIB cervical cancer patients with
disease limited to the pelvis, treated with radiation and concurrent chemotherapy: a Gynecologic Oncology Group
study. Gynecol Oncol 2010;117:270–5.
• Patel K, Foster NR, Kumar A, et al. Hydronephrosis in patients with cervical cancer: an assessment of morbidity
and survival. Support Care Cancer 2015;23:1303–9.
• Chemoradiotherapy for Cervical Cancer Meta-Analysis Collaboration. Reducing uncertainties about the effects of
chemoradiotherapy for cervical cancer: a systematic review and meta-analysis of individual patient data from 18
randomized trials. J Clin Oncol 2008;26:5802–12.
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• Liang B, Lange SS, Massad LS, et al. Do gynecologic oncology patients with severely diminished renal
function and urinary tract obstruction benefit from ureteral stenting or percutaneous nephrostomy?. Gynecol
Oncol Rep 2019;28:136–40.
• Tan S, Tao Z, Bian X, et al. Ureteral stent placement and percutaneous nephrostomy in the management of
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THANK YOU