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Indian Journal of Cancer Ca Endometrium: July 2015

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Indian Journal of Cancer ca endometrium

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Praveen S Rathod Uttam D Bafna


Kidwai Cancer Institute Kidwai Memorial Institute of Oncology
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Original
journal A retrospective clinicopathological study of 131 cases with
Article endometrial cancers – Is it possible to define the role of
retroperitoneal lymphadenectomy in low‑resource settings?
Rathod PS, Reddihalli PV, Krishnappa S, Devi UK, Bafna UD
Department of Gynecologic Oncology, Kidwai Memorial Institute of Oncology, Bangalore, Karnataka, India
Correspondence to: Dr. Praveen S Rathod, E‑mail: rathodps2003@yahoo.com

Abstract
AIM: The study objectives were evaluation of clinicopathological characteristics, correlations between the preoperative and postoperative tumor
grades, and their implications on lymph node metastasis. MATERIALS AND METHODS: We conducted a retrospective descriptive study of 131 cases
of endometrial cancer examined and treated at a tertiary regional cancer institute between the years 2003 and 2009. We reviewed the oncology
database as well as the clinical records and surgico‑pathological registry of all these patients. STATISTICAL METHODS USED: All the summary
measure computation and Chi‑square test for comparing more than one proportion was done in spreadsheet (Excel). RESULTS: The multiparity
association with endometrial cancer was commonly seen 113/131 (86.2%). Twelve (9.7%) patients preoperatively diagnosed as Grade 1
tumors upgraded to Grade 3 changes in postoperative specimens and six of these 12 patients (50%) had lymph node metastasis. A total of
14/131 (10.6%) cases had lymph nodes metastasis. CONCLUSIONS: There is a poor correlation between the preoperative and the postoperative
tumor grades. Routine pelvic lymphadenectomy may be a valuable method in low‑risk cases and para‑aortic lymphadenectomy may be limited
to high‑risk endometrial cancers.
Key Words: Low‑resource settings, myometrial invasion, parity, retroperitoneal lymphadenectomy, tumor grade

Introduction of high‑risk factors, particularly radiographic imaging and


frozen section assessment, the role of complete surgical
Endometrial carcinoma (EC) is the second most common staging may be beneficial.
gynecologic cancer worldwide. Most cases (75%) are
diagnosed when the disease is still limited to the uterus Study objectives were: evaluation of clinicopathological
(International Federation of Gynecology and Obstetrics characteristics in endometrial cancer, the correlations between
[FIGO] Stages I‑II). [1,2] Ninety percent of patients with the preoperative and postoperative tumor grades, and their
endometrial cancer will have abnormal vaginal bleeding, implications on lymph node metastasis.
most commonly postmenopausal bleeding, and the Materials and Methods
bleeding usually occurs early in the course of the disease.
Intermenstrual bleeding or heavy prolonged bleeding in We conducted a retrospective descriptive study of 131 cases
perimenopausal or anovulatory premenopausal women of endometrial cancer examined and treated between the
should arouse suspicion. Occasionally, vaginal bleeding years December 2003 and December 2009. We reviewed the
does not occur because of cervical stenosis, particularly in oncology database as well as the clinical, histopathological
thin, elderly, estrogen‑deficient patients. In some patients records and surgico‑pathological registry of all these
with cervical stenosis, a hematometra develops, and a small patients from the hospital Inpatients’ files. The applied
percentage has a purulent vaginal discharge resulting from treatments were surgery with or without platinum‑based
a pyometra.[3‑5] chemotherapy with or without radiotherapy (brachytherapy/
Many aspects of the management of endometrial cancer external pelvic radiotherapy) and with or without hormone
remain controversial and at the discretion of the individual therapy (medroxyprogesterone acetate). The departmental
physician. Clinical decision‑making is influenced by the policy for all the patients with endometrial cancer is
initial histological diagnosis from endometrial tissue extrafascial hysterectomy with bilateral salpingo‑opherectomy
obtained by biopsy or dilatation and curettage (D and with pelvic lymphadenectomy, peritoneal washings, and
C). High‑grade endometrioid adenocarcinomas are more recently from the beginning of the year 2008, the patients
frequently associated with nodal metastasis, [6] and a having tumor Grade 3 changes underwent para‑aortic
preoperative diagnosis of this type would likely prompt lymphadenectomy. Type II/III radical hysterectomy was
a complete surgical staging procedure, including pelvic done for clinically suspected cases of cervical extensions.
and para‑aortic lymphadenectomy. It has been suggested All the surgico‑pathological diagnosis was conducted by
that complete surgical staging may not be necessary in pathologist‑gynecologic oncologists, according to the
patients with low‑risk endometrial carcinoma who have histopathological criteria defined by the World Health
disease limited to the uterus without Grade 3 or deep Organization (WHO).[9] This review included endometroid/
myometrial invasion.[7,8] However, proper selection of such papillary adenocarcinoma Grade 1, 2, 3, clear cell carcinoma,
low‑risk patients remains problematic. In situations where adenosquamous, papillary serous adenocarinomas and
there is limited preoperative and intraoperative assessment undifferentiated carcinomas. The mixed malignant mullerian
tumors, carcinosarcomas, endometrial stromal sarcoma and
Access this article online
adenosarcoma endocervix were excluded. The postoperative
Quick Response Code: Website: specimen tumor grade was used to evaluate the association
www.indianjcancer.com
with lymph node metastasis. The cases with no residual
DOI:
tumors in postoperative specimens were included in the
10.4103/0019-509X.134628
study. Patients’ staging was carried out according to the
PMID:
*******
classification established by the FIGO for endometrial
cancer in 1989. Finally, clinical management and follow‑up
54 Indian Journal of Cancer | January–March 2014 | Volume 51 | Issue 1
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journal Rathod, et al.: The role of retroperitoneal lymphadenectomy in endometrial cancers in low resource settings

of patients was conducted on a multidisciplinary basis. All tumors were upgraded to Grade 3 changes in postoperative
the summary measure computation and Chi‑square test for specimens and six (50%) of these 12 patients had pelvic
comparing more than one proportion (J L Fleiss) was done lymph nodes’ metastasis. Similarly, 23 patients preoperatively
in a spreadsheet (Excel).[10] diagnosed as Grade 1 tumors were upgraded to Grade 2 in
Results postoperative specimens but none of them had lymph nodal
metastasis.
The patients’ mean age at the time of diagnosis was A total of 14/131 (10.6%) [Table 3] cases had lymph nodes
56.4 (range 30‑80) years [Table 1].The mean parity metastasis. Eight cases of 14 had tumor confined to the
was three (range 1‑8) and only 18/131 (13.7%) cases uterus, six of 14 had serosal invasion but none of these
were nulliparous. Postmenopausal metrorrhagia with or
14 patients had ovarian metastasis or positive peritoneal
without abnormal vaginal discharge was the most frequent
cytology. One case with Grade I tumor had lymph node
symptom; it was present in 84.7% (111/131) of patients,
metastasis, and three cases with Grade 2 tumor had
18 patients (13.7%) presented only with abnormal vaginal
lymph node metastasis, 9/42 (21.4%) cases with Grade 3
discharge without vaginal bleeding. Only two of 131 (1.5%)
tumor had lymph node metastasis and one case with
patients presented with abdominal pain and dysuria that
undifferentiated carcinomas had lymph node metastasis. The
were detected incidentally (endometrial thickening in
only patient who had para‑aortic lymph node metastasis
gynecological ultrasound). Surgery was the initial treatment
actually had Stage IIIC, Grade 3 changes, serosal invasion
for all patients, the majority, 90/131 (68.7%) cases had
but no extra‑uterine disease and no clinically palpable
Type I extra‑fascial hysterectomy, 15 cases had Type I
para‑aortic nodes during the intraoperative period. Similarly,
extra‑fascial hysterectomy with infracolic omentectomy,
all the nine patients with high‑risk group (Grade 3, clear
14 cases had laparoscopic‑assisted vaginal hysterectomy, six
cell type, uterine papillary serous and undifferentiated
cases had Type II and another six cases had Type III radical
carcinomas) who had para‑aortic lymphadenectomy did
hysterectomy. All except seven cases with high risk medical
not show the palpable para‑aortic nodes. None of the
co morbid conditions had bilateral pelvic lymph node
13 patients with superficial myometrial invasion (MI)
dissection and nine cases had para–aortic lymphadenectomy.
had lymph node metastasis, 2/61 (3.3%) cases with <½
The incision type was pfannenstiel, Mayolard and lower
midline vertical in 77, 11, and 29 cases each respectively. MI, 7/41 (17%) cases with >½ MI and 5/14 (35.7%)
The average duration of surgery was 135 min with a range cases with serosal involvement had lymph node metastasis.
between 120 and 270 min. The majority 89/131 (67.9%) of None of the 131 cases showed positive peritoneal cytology.
the patients did not require any blood transfusion and only The FIGO surgical staging [Table 1] was Stage I in
one case required 3 units of blood. 93/131 (70.9%) cases (A = 15, B = 50, C = 30); Stage
II in 21 (16.2%) (A = 12, B = 9) and Stage III in
Table 2 describes the preoperative and postoperative 17 (12.9%) (A = 2, B = 1, C = 14).
histopathological types and grades of tumors. Twelve of
123 (9.7%) patients preoperatively diagnosed as Grade 1 The Chi‑square test was used to analyze the correlation
between tumor grade and lymph nodes metastasis. The
Table 1: Clinico‑pathological features testing of more than two proportions, tumor grades 1, 2,
No. of patients 131 3, and undifferentiated carcinomas was significantly different
Mean age (range) year 56.4 (30‑80) (P < 0.043011). Further, to find out the significantly
Nulliparous 18/131 (13.7%) different categories the four categories were subdivided into
Multiparous 113/131 (86.2%) two groups (tumor Grade 1 and Grade 2 formed Group 1
Mean parity (range) 3 (1‑8) and the remaining two categories, that is tumor Grade 3
Symptoms (%) and undifferentiated carcinomas formed Group 2). It was
B PV* with or without DPV** 111/131 (84.7) found that there is no significant difference in between
Only abnormal DPV 18/131 (13.7) Grade 1 and Grade 2 in the Group 1 and between Grade 3
Pain abdomen and dysuria 02/131 (1.5) and undifferentiated carcinomas in the Group 2; but the
Surgical stage difference between the two groups is statistically significant
I 93/131 (70.9%)
IA 15 Table 2: Histopathological features
IB 48 Preoperative Postoperative
IC 30 Hyperplasia 08 ‑
II 21/131 (16.2%) Adenocarcinoma 109 120
IIA 12 Adeno‑ squamous ca 10 07
IIB 9 Clear cell carcinoma 04 02
III 17/131 (12.9%) No residual malignancy ‑ 02
IIIA 2 Grades (%)
IIIB 1 I 48/123 (39) 31/129 (24)
IIIC 14 II 33/123 (26.8) 50/129 (38.7)
Positive peritoneal cytology 0/131 III 27/123 (21.9) 42/129 (32.5)
*Bleeding per vagina, **Discharge per vagina, BPV=Bleeding per vagina;
Undifferentiated carcinomas 15/123 (12.2) 6/129 (4.6)
DPV=Discharge per vagina

Indian Journal of Cancer | January–March 2014 | Volume 51 | Issue 1 55


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journal Rathod, et al.: The role of retroperitoneal lymphadenectomy in endometrial cancers in low resource settings

Table 3: Correlation between tumor grade and lymph node metastasis


Group 1 Grade 1 Grade 2 P<0.005024
LN positive LN negative LN positive LN negative
01/31 (3.2%) 30 03/50 (6%) 47
Group 2 Grade 3 Undifferentiated carcinomas
LN positive LN negative LN positive LN negative
09/42 (21.4%) 33 01/6 (16.6%) 05
LN=Lymph node

(P < 0.005024)[Table 3]. The number of lymph nodes’ Several studies reported that lymphadenectomy was required
metastasis in Grade 3 and undifferentiated carcinomas was not only for accurate surgical staging but suggested
significantly more than Grade 1 and 2 tumors. therapeutic benefit. [14,15] A large population‑based study
from the National Cancer Institute (United States) reported
Discussion
that patients who underwent lymphadenectomy had better
This study confirmed that there is a poor correlation disease‑free survival than those who did not, except for
between the preoperative and the postoperative tumor Stage I (Grades 1 and 2).[16] In contrast, the results of A
grades. Eight cases (6.1%) with endometrial hyperplasia Study in the Treatment of Endometrial Cancer (ASTEC)
with atypia actually had endometrial adenocarcinoma failed to demonstrate a survival benefit from pelvic
in the postoperative specimen. The preoperative tumor lymphadenectomy.[17]
grades in 123 cases, Grade 1, 2, 3, and undifferentiated Preoperative imaging such as magnetic resonance or
carcinomas was 48 (39%), 33 (26.8%), 27 (21.9%) and positron emission tomography scan has been proposed
15 (12.2%), and the corresponding grades in postoperative to identify myometrial invasion, extra‑uterine disease, and
specimen was 31 (24%), 50 (38.7%), 42 (32.5%) and macroscopic node metastasis. However, the disadvantage is
6 (4.6%) respectively. Two of the 123 cases had no residual undetectable microscopic node metastasis, low sensitivity
malignancy in the postoperative specimen. The 12/123 rates and expense. Intraoperative assessment based on gross
(9.7%) patients preoperatively diagnosed as Grade 1 inspection and palpation is inaccurate to detect the patients
tumors were upgraded as Grade 3 changes in postoperative with risks for node metastasis. Frozen section is the most
specimens. Therefore, surgical specimen’s histopathological acceptable intraoperative assessment at this moment, but
study is the most precise method to identify the tumor it still has limitations. Adequate frozen section analysis
grades. may not be available, especially in developing countries.
A Gynecologic Oncology Group study reported that Special expertise in gynecologic pathology is an essential
pelvic lymph node metastasis was found in less than 3% component of the frozen section process and is often
of patients with Grade 1 disease confined to the inner lacking in limited medical environments.
third of the myometrium. The incidence of para‑aortic The present study demonstrated association of multiparity
node metastasis was less than 1%. [11] In this study, the in endometrial cancer patients was not uncommon. Patients
high‑risk patients, nine (9/42, 21.4%) with Grade 3 with only abnormal vaginal discharge without bleeding
tumor and one (1/6, 16.6%) with undifferentiated and asymptomatic women’s could also have endometrial
carcinomas had lymph node metastasis, and 7/41 (17%) cancer. The histological grade from the curettage specimen
cases with >½ MI and 5/14 (35.7%) cases with serosal is known preoperatively; however, this is unreliable. Thus,
involvement had lymph node metastasis. The only patient in situations where there are limited resources without
who had para‑aortic lymph node metastasis actually had preoperative imaging and intraoperative frozen section, pelvic
Stage IIIC, Grade 3 changes. The low‑risk patients, only lymphadenectomy may be a valuable method for determining
one (1/31, 3.2%) with Grade 1, three (3/50, 6%) with prognosis, postoperative management, and possibly, its
Grade 2, two (2/61, 3.3%) cases with <½ MI and none therapeutic value. The para‑aortic lymphadenectomy may be
of the 13 patients with superficial myometrial invasion limited to the high‑risk cases.[18]
had lymph node metastasis. Thus, these low‑risk patients
Acknowledgment
may not benefit from lymphadenectomy. However, these
low‑risk patients were diagnosed based on the final We would like to thank Dr Ramesh, Dept. of Statistics, Kidwai
histology from the surgical specimen. It is unreliable Memorial Institute of Oncology and Mr Marimuthu, Dept. Of
to predict these adverse prognostic factors before or Statistics, National Institute of Mental Health Sciences, Bangalore
for helping to analyze the data.
during surgery by various preoperative and intraoperative
assessments. Our study showed that 12 (9.7%) References
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