|Year : 2021 | Volume
| Issue : 3 | Page : 119-125
Endometrial carcinoma: A single institute experience
Asifa Andleeb1, Kaneez Fatima1, Shahida Nasreen1, Mushtaq Ahmad Sofi1, Sumyra Khurshid Qadri2
1 Department of Radiation Oncology, Sher-I-Kashmir Institute of Medical Sciences Soura, Srinagar, Jammu and Kashmir, India
2 Department of Pathology, Sher-I-Kashmir Institute of Medical Sciences Soura, Srinagar, Jammu and Kashmir, India
|Date of Submission||01-Jul-2021|
|Date of Acceptance||25-Jul-2021|
|Date of Web Publication||03-Sep-2021|
Dr. Asifa Andleeb
Department of Radiation Oncology, Sher-I-Kashmir Institute of Medical Sciences Soura, Srinagar, Jammu and Kashmir
Source of Support: None, Conflict of Interest: None
Aims: This study aims to assess the clinicopathological features, treatment, recurrence pattern, survival, and prognostic factors in patients with endometrial carcinoma (EC). Materials and Methods: This was a retrospective study of 64 patients with EC who were diagnosed and treated at our institute from January 2010 to December 2013 and were followed till December end 2019. Survival analysis was done using Kaplan–Meier estimates and significance between curves by using the log-rank test. Results: The mean age of diagnosis was 60 years. The most common complaint was vaginal bleeding (75%). More than half of the patients (52.6%) had high body mass index (BMI). The majority of patients underwent surgery (90.7%) and had the early-stage disease (Stage I in 82.9%). During a median follow-up of 79 months (range: 4–100 months), 18.8% of patients experienced recurrence and vaginal vault (33.3%) was the most common site for recurrence. The 5-year disease-free survival was 83% and the 5-year overall survival was 84.7%. Elderly age, high BMI, advanced disease stage, more than 50% of myometrial invasion, nonendometrioid histology, Grade II and Grade III tumors, lymphovascular space invasion, and lymph node involvement adversely affected long-term survival. Conclusion: EC is mainly a disease of postmenopausal women, and most of them are diagnosed at an early stage and have good survival outcomes.
Keywords: Early-stage disease, good prognosis, postmenopausal vaginal bleeding
|How to cite this article:|
Andleeb A, Fatima K, Nasreen S, Sofi MA, Qadri SK. Endometrial carcinoma: A single institute experience. J Radiat Cancer Res 2021;12:119-25
| Introduction|| |
Carcinoma of uterus is the most common gynecological malignancy in developed countries. However, when considering both developed and developing countries together, it is cervical cancer that tops the list followed by uterine cancer at second place. In India, the total number of estimated new cases of endometrial carcinoma (EC) in 2018 is 13,328 and 5010 deaths due to the same. The most common endometrial malignancy is endometrial adenocarcinoma, and based on clinicopathological features, it is broadly divided into two types: (a) Type I are low-grade endometrioid ECs. They include International Federation of Gynecology and Obstetrics (FIGO) Grade I and Grade II and are most common (85%) of all ECs. They are estrogen sensitive and typically preceded by atypical hyperplasia of the endometrium. They are often associated with obesity and overweight, present at early stages, and have a fairly good prognosis. (b) Type II includes high-grade endometrioid ECs (FIGO Grade III) and all nonendometrioid histological subtypes: serous, clear cell, mixed cell, and undifferentiated. Carcinosarcomas are also included in this group. They are insensitive to estrogen, have no association with obesity, and have a poor prognosis. Compared to Type I, they behave aggressively and usually present in advanced stages. Approximately one-third of Type II patients even without any myometrial invasion, when subjected to complete surgical staging, have an extrauterine disease.,, Although endometrial cancer is usually considered a disease in postmenopausal women, 14% of cases are diagnosed in premenopausal women and 5% of whom are <40 years at the time of diagnosis.,,,, The etiology of EC is multifactorial. The risk factors are broadly categorized as nonmodifiable and modifiable. Nonmodifiable risk factors are age, race, and genetic predisposition, while the modifiable lifestyle factors are unhealthy diet and physical inactivity.
The main treatment for EC is surgery; a standard staging surgical procedure established by FIGO includes total abdominal hysterectomy (TAH) with bilateral salpingo-oophorectomy (BSO) and pelvic/para-aortic lymph node (LN) dissection (LND). The decision for adjuvant treatment is taken as per the risk factors present, which are stage, age, grade, histologic type, and depth of myometrial invasion. Adjuvant treatment modalities include vaginal vault brachytherapy (VBT), pelvic external beam radiation therapy (EBRT), and/or chemotherapy (CT). Hormonal therapy (HT) is given selectively to few early-stage premenopausal patients desirous of childbearing for the time being till their family is complete and later they are subjected to standard surgical procedure. HT is also given in recurrent or metastatic EC, especially in endometrioid histology.
The present study aimed to assess various clinicopathological factors, overall survival (OS), and disease-free survival (DFS) in patients of endometrial cancer and to also determine various factors affecting prognosis in such patients.
| Materials and Methods|| |
We analyzed all cases of EC that were diagnosed in our institute from January 1, 2010, to December 31, 2013, and followed them till December 31, 2019. This study was initiated after the due clearance from the ethical committee of hospital. Patients who were diagnosed and operated on in some other institutes and were referred to our institute for further management were excluded from the study. Patients with uterine sarcomas, secondary uterine malignancy, and patients who died from diseases other than EC were also excluded.
The clinicopathological characteristics and survival of patients were studied by reviewing the hospital records and study notes present in patient files. Information regarding the details of the surgery, histopathology reports, and follow-up examinations was collected. The staging was done according to the 2009 FIGO system. Patients were evaluated in terms of age, date of diagnosis, menopausal status, age at menopause, body mass index (BMI), parity, presenting symptoms, type of surgery, stage, grade, histological type, depth of invasion, presence or absence of lymphovascular invasion (LVI), and details of LN involvement. BMI (is defined as weight in kilograms divided by height in meters squared) of all patients was calculated and entered into patient files at the time of diagnosis. Treatment details include date and type of surgery performed along with details: LND, adjuvant radiotherapy (pelvic EBRT and/or VBT), chemotherapy (CT), and HT if any. Patients who were not candidates for definitive treatment were managed on palliative lines which included radiotherapy, chemotherapy, HT, or best supportive care only. None of our patients had received preoperative pelvic radiation.
Patients were followed regularly in the radiation oncology outpatient department with 3-monthly physical examinations during the first 2 years of follow-up, 6 monthly during the 3rd–5th year, and yearly thereafter. Imaging was advised when clinically indicated to detect recurrence or when clinical concern for metastatic disease. OS was defined as the period from the time of diagnosis until death or until the last follow-up and DFS was calculated from the date of surgery or date of completion of adjuvant treatment if received till first symptom or sign of recurrence was documented. All patients underwent routine laboratory investigations: complete blood count, kidney function test, liver function test, and X-ray chest. If an X-ray chest was found suspicious, it was supplemented by noncontrast computerized tomography chest to confirm findings. To establish a site of origin and local extension of the tumor, pelvic magnetic resonance imaging (MRI) or transvaginal ultrasound (if MRI was contraindicated) was done. For metastatic evaluation, contrast-enhanced computed tomography (CT) of chest, abdomen, and pelvis was done in high-grade carcinomas and in patients who underwent hysterectomy for some other gynecological reasons and EC was an incidental finding. Other investigations such as bone scan, contrast-enhanced MRI brain ± spine, and positron emission tomography/CT were done when indicated by clinical suspicion.
Statistical analysis was done using SPSS V: 25 software (IBM SPSS, Chicago, USA). DFS and OS were evaluated using Kaplan–Meier estimates and compared by log-rank test. P < 0.05 was considered statistically significant.
| Results|| |
A total of 80 patients with EC were enrolled in the study, but 16 were excluded because they did not meet the inclusion criteria mentioned above. The results of the present study are based on the observations of these 64 patients. The detailed clinicopathological characteristics of these patients are shown in [Table 1]. The median age of diagnosis was 60 years (minimum: 25 years and maximum: 80 years). The mean age of menopause was 49.86 ± 2.16 years (minimum: 45 years to maximum: 55 years), with 14.1% as premenopausal patients and 85.9% as postmenopausal at the time of diagnosis. We observed a normal range BMI (18.5–24.9) in only 43.8% of patients and the rest were either overweight or obese; none of our patients was underweight (BMI <18.5). The median parity was 4, ranging from 0 to 7, and 10.9% of patients were nulliparous. The most common symptom at presentation was postmenopausal bleeding, seen in 48 (75.0%) patients. Thirty-three (51.6%) patients had Stage IA, 20 (31.2%) patients had Stage IB, 1 (1.6%) patient had Stage II, 2 (3.1%) patients had Stage III, and 8 (12.5%) patients had Stage IV disease. Grade I disease was seen in 24 (37.5%) patients, Grade II in 17 (26.6%) patients, and Grade III in 23 (35.9%) patients. We observed endometrial adenocarcinoma (endometrioid type) as the most common histological subtype, seen in 51 (79.7%) patients, followed by serious papillary carcinoma in 5 (7.8%) patients. Other less common histological subtypes were clear cell carcinoma (4.7%), undifferentiated (4.7%), and carcinosarcoma (3.1%). The depth of myometrial invasion was more than 50% in 24 patients (37.5%) and LVI was present in 11 (17.1%) patients. Five (7.8%) patients had positive pelvic LNs and none had positive para-aortic LNs. Various treatment modalities, recurrence pattern, and final outcome at closure of the study are shown in [Table 2]. Out of 58 (90.6%) patients who were operated on, 54 (84.4%) underwent standard TAH + BSO with pelvic ± para-aortic LND, and in 4 (6.2%) patients, only hysterectomy was done. These were the patients who had been operated on for some other gynecological reasons, and uterine carcinoma was an incidental finding. However, they were not subjected to completion surgery because of endometrioid histology, low grade, and the early stage of the disease. Six (9.4%) patients were not operated on as they were Stage IV at presentation. Adjuvant treatment was decided in multidisciplinary tumor board meetings with the radiation oncologist, surgical oncologist, pathologists, and medical oncologists after a thorough assessment of risk factors such as age, depth of myometrial invasion, LVI, grade, stage, and nodal involvement. Adjuvant radiotherapy was given as pelvic EBRT or VBT either singly or in combination as per risk factors present. After surgery, 16 (25.0%) patients received pelvic EBRT, 15 (23.4%) patients received VBT, and 5 (7.8%) patients received a combination of both modalities. Seven (10.9%) patients also received adjuvant chemotherapy. Palliative pelvic EBRT was given to six (9.4%) patients and palliative chemotherapy to ten (15.6%) patients. Four (6.2%) patients received palliative HT. There were two (3.1%) patients who had Grade 1 Stage IA (noninvasive) endometrial adenocarcinoma who received HT as a fertility-sparing treatment: one among them underwent surgery after completing childbearing, but another had a persistently positive uterine biopsy after 6 months of hormone treatment and she opted for surgery instead of continuing with HT. During the follow-up period, many patients had disease recurrence both locoregional and distant, with the vaginal vault being the most common site of relapse. The tumor recurrence rate was 18.7% (12 patients) and tumor-related mortality rate 9.4% (6 patients); 90.6% (n = 58) of patients were alive at the closure of the study and they continued with follow-up. The median observation time was 79 months (range: 4–100 months).
|Table 2: Treatment received, recurrence pattern, and final outcome of patients|
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The DFS at 5 years was 83% [Figure 1] and OS at 5 years was 84.7% [Figure 2]. The mean DFS (in months) was 36.78 ± 34.75. The mean OS (in months) was 43.09 ± 39.21. We evaluated various clinicopathological features as potential prognostic factors for survival. We observed that elderly age, high BMI, advanced disease stage, more than 50% of myometrial invasion, nonendometrioid histology, Grade II and Grade III tumors, lymphovascular space invasion, and LN involvement adversely affected long-term survival when analyzed by log-rank test [Table 3].
|Table 3: Disease-free survival and overall survival at 5 years for the variables analyzed by log-rank test|
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| Discussion|| |
In the present study, a thorough analysis of clinicopathological characteristics and various treatment modalities received by a cohort of 64 patients with EC was done. EC is known to be a disease of postmenopausal women, and in the present study, 14.1% of patients were premenopausal and 85.5% were postmenopausal. We observed that a median age of diagnosis was 60 years which is close to published literature, where a median age of 61 years was observed at the time of diagnosis. It has been seen that women of EC who are <50 years of age at the time of diagnosis are often at risk because of chronic anovulation and obesity. We observed that increased body weight is significantly associated with the risk of developing endometrial cancer. In the present study, only 43.8% of patients had normal BMI and the rest were either overweight or obese; none of our patients was underweight (BMI <18.5), confirming the fact that high BMI has a direct correlation with the occurrence of EC. It has been observed that while overweight women have double the risk of developing endometrial cancer, obese women have four to five times the risk compared to normal-weight women. The majority of patients in the present study were multiparous (89.1%). It has been seen that the risk of endometrial cancer is inversely related to parity and this risk is two to three times higher in nulliparous women. However, nulliparity is not an independent risk factor and the association seen is most likely due to the high number of anovulatory menstrual cycles in infertile and subfertile women. Postmenopausal vaginal bleeding was the most common symptom in our patients (75%) which is in accordance with published data., Hence, vaginal bleeding in a postmenopausal woman should alert a primary physician and such a patient must be evaluated thoroughly to exclude the possibility of EC.
Treatment for EC is mainly surgery; in our study, out of 64 patients, 54 underwent a standard primary surgical procedure (TAH with BSO + pelvic/para-aortic LND) and only 4 patients had a simple hysterectomy. After complete surgical staging, most of our patients had the early-stage disease (uterine confined, i.e., Stage I and Stage II) and whether to follow such patients with adjuvant treatment or not has remained a question of debate, which is beyond the scope of this paper. The GOG 99 and PORTEC trials have defined the risk factors for women who have high-intermediate risk for recurrence and can be benefited by adding adjuvant radiotherapy., The risk factors include age, depth of myometrial invasion, grade, and LVI, and these factors are continuous variables. After complete surgical staging, we discussed our patients in multispecialty tumor board meetings to decide for adjuvant treatment which included pelvic EBRT and VBT either alone or in combination as per risk factors present. However, some of our patients with advanced disease and some early-stage patients with a high risk of distant failure received chemotherapy in addition to radiotherapy. The role of adding chemotherapy to such patients has been proved by published data. In our study, DFS and OS rates at 5 years were 83% and 84.7%, respectively, which is similar to data published by Hirai et al. Ayhan et al. reported a 5-year survival of 86%, while the survival reported by Karateke et al. is only 76.9%., This difference in survival reported by various authors is mainly due to the difference in prognostic factors in the patient groups studied. Various studies reported that several clinicopathological features such as age, histologic grade, lymphovascular space involvement, depth of myometrial invasion, cervical invasion, and extrauterine involvement, including LN status, have prognostic significance for EC.,
In our study, we observed that elderly age, high BMI, advanced stage, more than half of myometrial invasion, nonendometrioid histology, Grade II and Grade III tumors, presence of lymphovascular space invasion, and LN metastasis were bad prognostic factors [Table 3].
| Conclusion|| |
Our study showed that EC mainly affected postmenopausal women, but luckily, most of them are diagnosed at an early stage as they often presented with the alarming symptom of vaginal bleeding. Hence, women need to be educated to report postmenopausal bleeding immediately to the primary health-care professional and it must be evaluated thoroughly by a primary physician to rule out the possibility of EC. Community-level awareness programs should be organized to educate females regarding the importance of maintaining normal body weight and adapting to healthy lifestyle modifications, such as healthy dietary habits and good physical activity from a very young age. Survival in our patients is very good and is comparable to best-reported survival in literature. We observed that young age, normal BMI, early-stage disease, endometrioid histology, Grade 1 tumor, less than half of myometrial invasion, absence of lymphovascular space invasion, and absence of LN involvement are good prognostic factors and all of these findings should be considered seriously while treating patients of EC, especially when deciding adjuvant treatment after surgery.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3]