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ORIGINAL ARTICLE
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Early endometrial carcinoma: Experience and outcomes


1 Department of Departments of Surgical Oncology, Radiation Oncology, Medical Oncology and Pathology, Homi Bhabha Cancer Hospital, Sangrur, Punjab, India
2 Department of Radiation Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India
3 Department of Nursing, Homi Bhabha Cancer Hospital, Sangrur, Punjab, India

Date of Submission07-Jun-2021
Date of Decision24-Aug-2021
Date of Acceptance21-Aug-2024
Date of Web Publication11-Nov-2022

Correspondence Address:
Sachin Khandelwal,
Homi Bhabha Cancer Hospital, Civil Hospital Campus, Sangrur - 148 001, Punjab
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jcrt.jcrt_920_21

 > Abstract 


Aim: Endometrial carcinoma (EC) data from India are very sparse. We did a retrospective analysis of our patients registered at this peripheral cancer center based in rural Punjab and studied their outcome.
Materials and Methods: Ninety-eight Stage I and II EC patients with endometroid histology registered at our institute from January 2015 to April 2020 were studied for demography, histopathology, treatment received, and outcomes. FIGO 2009 staging and new European Society for Medical Oncology (ESMO) risk group classification was used.
Results: Our patients had a median age of 60 years (range 32–93 years). There were 39 (39.8%), 41 (42.0%), 4 (4.1%), 12 (12.2%) patients in the low risk, intermediate risk (IR), high intermediate risk, and high risk groups, respectively, as per new ESMO risk classification. Two (2.0%) patients had incomplete information to assign them to a particular risk group. Fifty (46.7%) patients underwent complete surgical staging and 54 (50.5%) patients received adjuvant RT. With a median follow-up of 27.0 months, there were 1 locoregional and 2 distant recurrences. There were 8 deaths in total. Three-year overall survival for the entire group is 90.6%.
Conclusions: The risk group determines adjuvant treatment in endometrial cancer. Patients operated at dedicated cancer center tend to have better surgical staging and thus better outcome because of better risk stratification and grouping for adjuvant therapy. IR histology was more common in our group of patients, which is variable as compared to available literature.

Keywords: Early stage, endometroid carcinoma, rural center



How to cite this URL:
Goel P, Singh V, Sharma R, Chaudhary D, Chatterjee A, Dora T, Sancheti S, Goel A, Khandelwal S, Sali AP, Kaur H, Guru A, Kapoor R. Early endometrial carcinoma: Experience and outcomes. J Can Res Ther [Epub ahead of print] [cited 2022 Dec 9]. Available from: https://www.cancerjournal.net/preprintarticle.asp?id=361026




 > Introduction Top


Endometrial carcinoma (EC) is the most common gynecological malignancy in the developed countries[1] with increasing trend in developing countries like India.[2] It is the second most common gynecologic cancer worldwide after cervical cancer.[3] Cumulative risk for diagnosis of EC is 1.71%.[4] Most patients are postmenopausal and the median age at diagnosis is 63 years with more than 90% of cases seen between 60 and 70 years and only 2%–5% in <40 years of age.[5] Five-year survival rates are more than 95% in Stage I but significantly go down to 68% and 17% with regional and distant metastasis, respectively.[6]

The early diagnostic symptom is postmenopausal vaginal bleeding.[7] Some are diagnosed as an incidental finding on imaging or after hysterectomy. The most common method of tissue diagnosis is endometrial biopsy (office or dilation and curettage).

EC is divided into two types: Type I is the most common endometroid adenocarcinoma (80%– 90%) and Type II is nonendometroid subtypes such as serous, clear cell, carcinosarcoma, and undifferentiated carcinoma.[8] Type I are commonly associated with alterations in PTEN, KRAS, CTNNB1, PIK3CA, MLH1 promoter hypermethylation whereas serous carcinoma harbor TP53 mutation. Type I is estrogen dependent with good prognosis and Type II is gene mutation related with metastatic potential and poor prognosis. Favorable outcome has been seen in Type I because of minimal myometrial infiltration. The incidence of EC is increasing due to increase in the prevalence of obesity, decreased postmenopausal progestin use, diabetes[9] or hypertension,[10] nulliparity,[11] unopposed long duration estrogen therapy,[12] tamoxifen,[13] and hereditary factors such as Lynch syndrome.[14]

Risk groups have been stratified on the basis of clinicopathological prognostic factors for tailoring the adjuvant therapy. Established prognostic factors are age, FIGO stage, depth of myometrial invasion, tumor differentiation grade, tumor type, and lymphovascular space invasion (LVSI).[15]


 > Materials and Methods Top


A total of 179 patients with EC were registered at our institute from January 2015 to April 2020. Out of these, after excluding patients who had defaulted before complete assessment, Stage III and IV disease, and Type II histology, 107 patients were found to have Stage I and II endometroid carcinoma. Out of these, surgery data were available in only 98 patients; hence, they were included in the final analysis. All patients were evaluated in a multidisciplinary joint clinic. Electronic medical records were accessed for patient and treatment details. FIGO 2009 staging and new European Society for Medical Oncology (ESMO) risk groups classification was applied [Table 1]. Pattern of recurrence and deaths were studied and SPSS software Version 25.0. Armonk, NY: IBM Corp. was used for data analysis.
Table 1: European Society for Medical Oncology risk classification

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 > Results Top


Demographic data

Patient and treatment characteristics are summarized in [Table 2].
Table 2: Demographic profile

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Surgery details

Out of 98 patients who underwent surgery, 44 underwent surgery at our institute and 54 were referred to us after surgery. Among patients operated at our center, 37 (84.1%) underwent lymph node dissection, and among rest, only 12 (22.2%) had lymph node sampling.

Histopathology

Review of slides and blocks of all referred patients was done. At our institute, we did not have frozen section facility till 2018 to confirm grade and depth of invasion intraoperatively. Preoperative grade was available in 46 patients, which was concurrent with postoperative grade in 34 patients, 10 were upstaged to higher grades, and 2 were downstaged to lower grades. Seven patients were upstaged from Grade 1 to 2 and three from Grade 2 to 3. There was no propensity of cervical stromal invasion with any specific grade. Preoperative pelvic imaging was available in 57 patients. There was concurrence for radiological myometrial invasion versus histological invasion in 43 (75.4%), upstaging in 9 (15.8%), and downstaging in 5 (8.8%) patients.

Adjuvant treatment

Radiotherapy

After surgery, out of 98 patients, 88 patients followed the multidisciplinary clinic plan for adjuvant treatment and 10 patients defaulted [Table 3]. Whole pelvic radiotherapy was done using Co 60 machine or linear accelerator with 6–15 MV photons using 2- or 4-field technique or volumetric modulated arc therapy to dose of 50 Gy/25#/5 weeks at 200 cGy/fraction. Vaginal brachytherapy (VBT) alone was done using high dose rate brachytherapy 2100 cGy/3 fractions at 700 cGy/fraction once weekly. Boost can be delivered by brachytherapy to a total dose of 12 Gy in 2 fractions @ 600 cGy per fraction per week.
Table 3: Adjuvant treatment

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Chemotherapy

Two patients received adjuvant chemotherapy (both high risk [HR] Stage II, with simultaneous carcinoma ovary). The chemotherapy regimen used was paclitaxel and carboplatin.

Recurrences

One patient had vault and nodal recurrence for which she received palliative chemotherapy. She was intermediate risk (IR) and nodes were not evaluated and had received brachytherapy alone. Another patient with Stage II EC with simultaneous carcinoma ovary who received adjuvant chemotherapy followed by external beam radiotherapy (EBRT) developed abdominal metastasis and could not be evaluated further. Eleven patients were lost to follow-up and eight patients died (4 died of unknown reasons, 1 of portal cavernoma, 1 died of postoperative complications, and 2 died of abdominal recurrence).


 > Discussion Top


There is a paucity of Indian literature looking exclusively at early stage endometroid carcinoma. Mahantshetty et al. reported the clinical outcomes of 249 early stage endometroid carcinoma patients treated at Tata Memorial Hospital, Mumbai.[16] The median age in our study is 61 years, with more than 50% of our patients being less than 60 years of age. Nineteen patients were ≤ 50 years of age. The mean body mass index (BMI) in our study was 30.8 (information was available in 84 patients only), which puts them in obesity class as per the WHO BMI classification of nutritional status. Higher BMI is a known risk factor for endometrial cancers.[17] Diabetes mellitus[9] and hypertension[10] are uncertain risk factors for EC although obesity per se contributes as a confounding factor in most. In our series, it was present in almost half (44.9%) of our cases.

Earlier patients were divided into low risk (LR) as Stage I and Grade I with superficial invasion or Grade 2 without invasion and High risk as Stage I, Grade 3 with deep myometrial invasion and rest of combinations as Intermediate Risk. The prognostic role of LVSI and tumor Grade 3 within the IR group has been recognized;[18],[19],[20] hence, refined classification into LR, IR, high intermediate risk (HIR), and HR has been introduced by ESMO. Our study had more of IR patients[21] as compared to Western data, which had more of LR patients.

Although retrospective data supports systematic lymphadenectomy,[22] data from two RCTs do not support lymphadenectomy in early stage EC.[23],[24] SEPAL trial[25] showed survival benefit of paraaortic node clearance in IR and HR patients. Lymphadenectomy is not indicated in LR patients and should be done in all HR patients. Systematic pelvic lymphadenectomy should be done wherever indicated. PA node clearance, from level of inferior mesenteric artery till renal hilum, is indicated in HR cases. We could not find consistency in indication of nodal dissection in our series as significant numbers of patients were referred to us after hysterectomy.

Retrospective series have shown improved survival with a dissected lymph node count of more than 10.[26],[27] In our series, the mean lymph node count in patients operated within the institute was 12.72 as compared to 7.3 among referred patient.

Patients in the LR group can be observed in view of lower recurrence rate of < 5%. An RCT did not find benefit of VBT in LR EC.[28] In our series, 4 patients received VBT due to ambiguity in final histology. Two patients received EBRT outside our institute and were referred to us for VBT.

IR patients having a LR of distant and regional recurrence should be given VBT as adjuvant to decrease the risk of vaginal recurrences. PORTEC 2[29] trial mainly included patients with Grade 1–2 with deep myometrial invasion and no LVSI and showed brachytherapy alone provided excellent vaginal control compared to EBRT with favorable toxicity profile, the results of which were confirmed in another trial.[30] In our series, 8 patients defaulted, 6 received EBRT outside and then referred to us for brachytherapy, 1 received EBRT alone, and 2 received EBRT + brachytherapy at our institute due to ambiguous histology reports. Rest all received brachytherapy alone.

Adjuvant therapy in HIR is dependent on surgical nodal staging. If it has been performed, brachytherapy alone is sufficient. If no nodal surgical staging has been performed, EBRT is recommended for LVSI positive patients and adjuvant brachytherapy alone is sufficient for Grade 3 and LVSI negative. In our series, 3 patients received EBRT + brachytherapy and 1 received brachytherapy alone.

HR patients have increased risk of pelvic recurrences and distant metastasis. However, this category is heterogenous, including nonendometroid histology as well. Patients including Stage 1 and Stage 2 who were adequately surgically staged usually receive EBRT to decrease locoregional recurrence. PORTEC 3 trial studied the role of concurrent chemoradiotherapy versus radiotherapy in HR endometrial cancers. The updated analysis[31] demonstrated better overall survival (OS) and failure free survival with chemoradiotherapy. The role of adjuvant chemotherapy is under investigation in trials. In our series, all patients received EBRT followed by VBT except two patients who also received chemotherapy i/v/o simultaneous carcinoma ovary and two patients who defaulted.

The median follow-up in our study was 27.0 months (mean 28.6 months, 95% confidence interval from 21.03 to 32.9). Three-year OS for the entire group is 90.6% [Figure 1]. Five-year survival in the study from India[16] was 95% and Western data showed 5-year survival of 95% in Stage I endometroid histology.[32] These figures are very encouraging as we work in a rural setup where treatment compliance is an issue as most of our patients are either farmers or laborer.
Figure 1: Survival analysis

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 > Conclusions Top


Early stage endometroid carcinoma has a good survival and adjuvant therapy is to be planned depending on the risk of recurrence. To the best of our knowledge, our study is the only study from an Indian rural cancer center almost exclusively catering to patients of Punjab, India, specifically addressing early stage endometroid histology of EC. A limitation of its study is its retrospective nature.

Acknowledgments

Technical support was provided by our Information Technology team, Rahul Dev Dwivedi (Scientific officer “c”) and Manbir Singh Punia (Scientific officer “c”).

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

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Mahantshetty U, Aggarwal A, Ganesh B, Saoba S, Mulla S, Engineer R, et al. Clinical outcome of early-stage endometroid adenocarcinoma: A tertiary cancer center experience. Int J Gynecol Cancer 2013;23:1446-52.  Back to cited text no. 16
    
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[PUBMED]  [Full text]  
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Kilgore LC, Partridge EE, Alvarez RD, Austin JM, Shingleton HM, Noojin F 3rd, et al. Adenocarcinoma of the endometrium: Survival comparisons of patients with and without pelvic node sampling. Gynecol Oncol 1995;56:29-33.  Back to cited text no. 22
    
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