JOURNAL OF EVIDENCE BASED MEDICINE AND HEALTHCARE

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Year : 2021 Month : July Volume : 8 Issue : 29 Page : 2625-2632.

Clinicopathological Analysis of Carcinoma Endometrium at a Tertiary Care Centre in Chennai – A Retrospective Study

Shanmugasundaram Gouthaman1, Roshni Saravanan2, Sivasundari Maharajan3, Ravi Shankar Pitani4, Jagadesh Chandra Bose Soundarajan5

1, 5 Department of Surgical Oncology, Sri Ramachandra Medical College and Research Institute, Sri Ramachandra Institute of Higher Education & Research (Deemed University), Porur, Chennai, India.
2 Department of Human Genetics, Faculty of Bio-Medical Sciences, Technology and Research, Sri Ramachandra Institute of Higher Education & Research (Deemed University), Porur, Chennai, India.
3 Department of Obstetrics and Gynaecology, Saveetha Medical College and Hospital, Thandalam, Chennai, India.
4 Department of Community Medicine, Sri Ramachandra Medical College and Research Institute, Sri Ramachandra Institute of Higher Education & Research (Deemed University), Porur, Chennai, India.

CORRESPONDING AUTHOR

Dr. Sivasundari Maharajan, Department of OBG, Saveetha Medical College and Hospital, Thandalam, Chennai, India.
Email : sivasundarimdr@yahoo.com

ABSTRACT

Background

Endometrial carcinoma is a leading malignancy among females. Pre-operative imaging and biopsy are necessary to identify the disease. Clinicopathological analysis determines the extent of the disease. Complete surgical staging is advised for high-risk patients. The purpose of this study was to analyze the different clinical endpoints, prognostic factors and demographic details that will influence the survival patterns of the cases of carcinoma of endometrium who underwent surgery during the period from 2014 to 2017 at a tertiary care centre, Chennai, India.

 

Methods

Patients diagnosed with operable endometrial carcinoma were surgically staged based on the surgical procedures performed namely, total abdominal hysterectomy (TAH) with bilateral salphingo-oophorectomy (BSO), bilateral pelvic lymph node dissection, and para-aortic lymphadenectomy (patients with high-risk features). Post-surgical staging specimens were histopathologically examined in the Department of Pathology. Adjuvant radiation was given to patients with stage IA grade II and above. Patients with stage III disease received adjuvant chemotherapy. Descriptive analysis was done to show the distributions of patients accordingly. Kaplan-Meier survival analysis was performed for the overall median survival of the patients.

 

Results

The study consisted of a total of 35 patients with a mean age of 56 ± 8.64. Parameters such as age, clinicopathological features, stage (FIGO staging), tumor size, grade, lymphovascular invasion (LVI), myometrial invasion, cervical involvement, involvement of margins, lymph node ratio (LNR) and survival were studied. Tumor size and grade were found to be significant factors affecting the survival. Overall median survival period of patients who underwent surgery was found to be 31 months.

 

Conclusions

Tumor size and grade of the tumor are significant prognostic factors affecting the survival of the patients with carcinoma of endometrium. Lymph node ratio is a new concept in carcinoma endometrium to be pondered upon as a factor predicting survival in future studies thereby defining the role of lymph node dissection in surgical staging.

 

Keywords

Endometrial Cancer, FIGO Staging, Lymph Node Ratio, Prognosis, Survival Analysis

BACKGROUND

The second most common gynecological malignancy worldwide is endometrial carcinoma preceded by the breast.1 The first symptom for the diagnosis of the disease is abnormal vaginal bleeding, usually in postmenopausal women. Endometrial carcinoma comprises a spectrum of neoplasms with variable histologic differentiation ranging from well-differentiated to poorly differentiated carcinomas originating from glandular epithelial cells.2 The most common histological type of endometrial cancer is endometrioid carcinoma, estrogen-dependent grouped as type I having a better prognosis. Other histologic types include serous papillary carcinoma and mixed carcinoma (including clear cell carcinoma), being estrogen-independent grouped as type II having a poor prognosis.3 Most of the endometrial cancers are diagnosed at an earlier stage resulting in a 5-year survival rate for more than 95 % of the patients.

However, the same is lower when there is a regional spread or distant metastasis. Long-term exposure to endogenous or exogenous estrogens is considered as one of the most critical risk factors for endometrial carcinoma.4 Infertility, nulliparity, overweight, obesity, diabetes mellitus, hypertension, early menarche, late menopause and tamoxifen treatment are associated risk factors for the disease. Sporadic mutations increase the risk of endometrial cancer.

Lynch syndrome, a germline mutation caused in DNA mismatch repair gene MSH6, BRCA1, β-catenin, PIK3CA, K-ras, p53 mutations, Peutz-Jeghers syndrome (PJS) – STK11 gene mutation, Cowden syndrome (CS) contribute towards the disease. Physical activity, breastfeeding, multiparity, oral contraceptives are some of the known protective factors for endometrial carcinoma.3,5,6 The incidence of endometrial carcinoma in India is 4.3 per 100,000, which is lower compared to western statistics.7 Surgery for endometrial carcinoma includes a complete surgical staging procedure (staging laparotomy) with total abdominal hysterectomy  and bilateral salphingo-oophorectomy (BSO) including pelvic and para-aortic lymphadenectomy (regional lymph nodes) based on the risk categories and extent of disease. It has been suggested that complete surgical staging may not be necessary for patients with low-risk endometrial carcinoma who have disease limited to the uterus.8,9 Pre-operative imaging (transvaginal sonography and MRI Pelvis) and biopsy are essential to identify the disease. Parameters such as pathological staging namely the International Federation of Gynecology and Obstetrics (FIGO) and American Joint Committee on Cancer TNM staging (AJCC), histological grading, lymphovascular invasion (LVI), involvement of the margins (parametrial and vaginal cuff), cervical involvement, extent of myometrial invasion and lymph node ratio (LNR) are important for an expert pathological review to determine the extent of malignancy. Adjuvant therapy is guided for patients depending on the stage and variable risk groups suggested by the European Society for Medical Oncology (ESMO). Here we present a retrospective analysis of 35 consecutive cases operated in a tertiary care centre.

 

Aim

The aim of this study was to analyze different clinicopathological parameters of carcinoma of endometrium at a tertiary care centre.

 

Objectives

Primary Objective

The retrospective study primarily aimed to analyze different clinical endpoints that will influence the overall median survival patterns of the cases of carcinoma endometrium who underwent surgery during the period 2014 - 2017 at a tertiary care centre, Chennai, India using Kaplan-Meier survival analysis.

 

Secondary Objective

The study also aimed at descriptive analysis to show the distributions of patients according to various prognostic factors and demographic details.

METHODS

The study was approved by the institutional ethics committee (Reference Number: IEC-NI/19/NOV/71/93) and was carried out as per the ethical principles. Confidentiality and patient anonymity were maintained and informed consent was obtained.

This hospital-based study was carried out based on the descriptive statistical analysis, and median survival of patients who were operated from January 2014 to December 2017 at the Department of Surgical Oncology. Histologically confirmed patients with carcinoma of endometrium suitable for primary surgery were included in the study (stages I to IVA). All the samples collected were studied/observed to confirm with endometrial carcinoma, at the department of pathology. Patients with advanced stage IVB disease requiring neo-adjuvant or palliative therapy were excluded. Other types of malignancies including sarcomas were also excluded. Thus, a total of 35 consecutive patients who found to be satisfying the above criteria were included in the study.

The computerized hospital database helped in a thorough investigation of every particular case with respect to its clinical setting, medical history, prior investigations, diagnoses, treatments, last follow-up, and survival status of the subjects.

A follow-up protocol to update on the present status of the individual was followed. The patients were reviewed once in 3 months for the first three years, once in 6 months for the next two years and then annually in the forthcoming years. Clinical examination was done every visit and radiological imaging of the abdomen and pelvis was done annually. Computed tomography (CT) of whole abdomen and pelvis or positron emission tomography (PET-CT) for the whole body was done for patients with suspected recurrence or metastasis.

The medical records of 35 patients were reviewed, and parameters such as histopathological findings (tumor size, histology, type, grade, stage, myometrial invasion, lymphovascular invasion, the involvement of the cervix, and involvement of the margins, ESMO risk, and nodal status), age, parity, menopausal status, underlying co-morbidities, and clinical indications were recorded. Date of diagnosis, date of surgery, the last follow-up date, and the present status of the patient was also recorded.

Patients diagnosed with endometrial carcinoma were surgically staged. Total abdominal hysterectomy, bilateral salphingo-oophorectomy, staging laparotomy, including pelvic (external iliac, internal iliac, obturator and common iliac nodes) and para-aortic lymphadenectomy based on the risk categories and extent of disease was performed.

Para-aortic lymphnode dissection was done in patients with more than 50 % of myometrial invasion, tumor more than 2 cm with poorly differentiated histology, high grade lesions, clear cell and serous histology. Omentectomy was performed on serous and papillary tumor histology cases. Biological samples obtained from these specimens have been processed using the conventional method of paraffin embedding and hematoxylin and eosin staining was performed on three-micron thick sections cut from these blocks.

The histopathological findings were classified according to the world health organization (WHO), FIGO and ESMO classification.

 

Statistical Analysis

Statistical analysis was carried out using statistical package for social sciences (SPSS) software version 16.0. Descriptive and overall survival analysis was done.

RESULTS

Clinical Factors

We analyzed 35 cases of carcinoma of endometrium, who underwent surgery from 2014 to 2017 in our tertiary cancer care centre. The mean age of the patients was 56 ± 8.64 years (range 40 to 71 years).

Out of the total 35 patients, 21 (60 %) patients were postmenopausal. Co-morbid illness included diabetes mellitus in 21 (60 %) patients, systemic hypertension in 11 (31.4 %) cases and hypothyroidism in 8 (22.9 %) patients (Table 1).

9 (26.1 %) patients had other co-morbid illnesses such as asthma, anemia, depression disorder, bronchiectasis, tubal block, fibroid uterus, skin allergy, goiter, seizures, TB lymphadenitis, and H1N1 sepsis.

 

 

Surgical Factors

Based on the risk categories and extent of disease, different surgical procedures were opted. Total abdominal hysterectomy and bilateral salphingo-oophorectomy were performed on all 35 (100 %) patients, pelvic and para-aortic (Figure 1a & 1b) lymphadenectomy (regional lymph nodes) for 34 (97.1 %) patients and omentectomy for 4 (11.5 %) patients.

 

 

Pathological Factors

The average size of the tumor was calculated to be 3.79 cm. The predominant histology was endometrioid adenocarcinoma in 30 (85.7 %) cases. 4 (11.4 %) patients had papillary serous carcinoma. Mixed carcinoma histology was present in 1 (2.9 %) patient (Figure 2a, 2b & 2c). In other words, 30 (85.7 %) patients had type 1 endometrial carcinoma (Endometrioid Adenocarcinoma), while 5 (14.3 %) patients had type 2 (inclusive of papillary serous and mixed carcinoma).

18 (51.4 %) patients had grade I tumors, 10 (28.6 %) patients had grade II tumors, and grade III tumors in 6 (17.1 %) patients. The stage distribution was stage IA in 22 (62.9 %) patients, stage IB in 3 (8.6 %) patients, stage II in 3 (8.6 %) patients, stage III A in 2 (5.7 %) patients, 4 (11.3 %) patients in stage IIIC1 and stage IVA in 1 (2.9 %) patient. Based on the ESMO risk classification, 19 (54.2 %) patients had low risk, 2 (5.7 %) patients had intermediate and 3 (8.6 %) high-intermediate, 10 (28.6 %) patients were at high risk, and 1 (2.9 %) in the advanced risk category.

27 (77.1 %) patients had less than 50 % myometrial invasion, while 8 (22.9 %) patients had more than 50 % invasion. 1 (2.9 %) patient had lymphovascular space invasion. Cervical stromal involvement was present in 4 (11.4 %) patients. Margins were free of tumor in all (100 %) patients. The total nodes examined ranged from 7 to 42. The number of nodes examined differed with respect to each patient. 5 (14.7 %) patients had their nodes examined in the range 0 - 10, 17 (49.9 %) patients in the range 11 - 20, 5 (14.7 %) patients in the range 21 - 30, 6 (17.6 %) patients in 31 - 40 and 1 (2.9 %) patient in the range 41 - 50. 30 (85.7 %) patients had node-negative disease, and 4 (11.4 %) patients had node-positive disease. The nodal percentage was calculated based on the lymph node ratio, that is, the ratio of the total nodes involved (positive) to the total number of nodes examined. The highest nodal percentage in the study was 25, while the lowest was 0.