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ORIGINAL ARTICLE
Year : 2014  |  Volume : 51  |  Issue : 1  |  Page : 54-57
 

A retrospective clinicopathological study of 131 cases with endometrial cancers - Is it possible to define the role of retroperitoneal lymphadenectomy in low-resource settings?


Department of Gynecologic Oncology, Kidwai Memorial Institute of Oncology, Bangalore, Karnataka, India

Date of Web Publication18-Jun-2014

Correspondence Address:
P S Rathod
Department of Gynecologic Oncology, Kidwai Memorial Institute of Oncology, Bangalore, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-509X.134628

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 » 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.


Keywords: Low-resource settings, myometrial invasion, parity, retroperitoneal lymphadenectomy, tumor grade


How to cite this article:
Rathod P S, Reddihalli P V, Krishnappa S, Devi U K, Bafna U D. A retrospective clinicopathological study of 131 cases with endometrial cancers - Is it possible to define the role of retroperitoneal lymphadenectomy in low-resource settings?. Indian J Cancer 2014;51:54-7

How to cite this URL:
Rathod P S, Reddihalli P V, Krishnappa S, Devi U K, Bafna U D. A retrospective clinicopathological study of 131 cases with endometrial cancers - Is it possible to define the role of retroperitoneal lymphadenectomy in low-resource settings?. Indian J Cancer [serial online] 2014 [cited 2020 Dec 2];51:54-7. Available from: https://www.indianjcancer.com/text.asp?2014/51/1/54/134628



 » Introduction Top


Endometrial carcinoma (EC) is the second most common gynecologic cancer worldwide. Most cases (75%) are diagnosed when the disease is still limited to the uterus (International Federation of Gynecology and Obstetrics [FIGO] Stages I-II). [1],[2] Ninety percent of patients with endometrial cancer will have abnormal vaginal bleeding, most commonly postmenopausal bleeding, and the bleeding usually occurs early in the course of the disease. Intermenstrual bleeding or heavy prolonged bleeding in perimenopausal or anovulatory premenopausal women should arouse suspicion. Occasionally, vaginal bleeding does not occur because of cervical stenosis, particularly in thin, elderly, estrogen-deficient patients. In some patients with cervical stenosis, a hematometra develops, and a small percentage has a purulent vaginal discharge resulting from a pyometra. [3],[4],[5]

Many aspects of the management of endometrial cancer remain controversial and at the discretion of the individual physician. Clinical decision-making is influenced by the initial histological diagnosis from endometrial tissue obtained by biopsy or dilatation and curettage (D and C). High-grade endometrioid adenocarcinomas are more frequently associated with nodal metastasis, [6] and a preoperative diagnosis of this type would likely prompt a complete surgical staging procedure, including pelvic and para-aortic lymphadenectomy. It has been suggested that complete surgical staging may not be necessary in patients with low-risk endometrial carcinoma who have disease limited to the uterus without Grade 3 or deep myometrial invasion. [7],[8] However, proper selection of such low-risk patients remains problematic. In situations where there is limited preoperative and intraoperative assessment of high-risk factors, particularly radiographic imaging and frozen section assessment, the role of complete surgical staging may be beneficial.

Study objectives were: evaluation of clinicopathological characteristics in endometrial cancer, the correlations between the preoperative and postoperative tumor grades, and their implications on lymph node metastasis.


 » Materials and Methods Top


We conducted a retrospective descriptive study of 131 cases of endometrial cancer examined and treated between the years December 2003 and December 2009. We reviewed the oncology database as well as the clinical, histopathological records and surgico-pathological registry of all these patients from the hospital Inpatients' files. The applied treatments were surgery with or without platinum-based chemotherapy with or without radiotherapy (brachytherapy/external pelvic radiotherapy) and with or without hormone therapy (medroxyprogesterone acetate). The departmental policy for all the patients with endometrial cancer is extrafascial hysterectomy with bilateral salpingo-opherectomy with pelvic lymphadenectomy, peritoneal washings, and recently from the beginning of the year 2008, the patients having tumor Grade 3 changes underwent para-aortic lymphadenectomy. Type II/III radical hysterectomy was done for clinically suspected cases of cervical extensions. All the surgico-pathological diagnosis was conducted by pathologist-gynecologic oncologists, according to the histopathological criteria defined by the World Health Organization (WHO). [9] This review included endometroid/papillary adenocarcinoma Grade 1, 2, 3, clear cell carcinoma, adenosquamous, papillary serous adenocarinomas and undifferentiated carcinomas. The mixed malignant mullerian tumors, carcinosarcomas, endometrial stromal sarcoma and adenosarcoma endocervix were excluded. The postoperative specimen tumor grade was used to evaluate the association with lymph node metastasis. The cases with no residual tumors in postoperative specimens were included in the study. Patients' staging was carried out according to the classification established by the FIGO for endometrial cancer in 1989. Finally, clinical management and follow-up of patients was conducted on a multidisciplinary basis. All the summary measure computation and Chi-square test for comparing more than one proportion (J L Fleiss) was done in a spreadsheet (Excel). [10]


 » Results Top


The patients' mean age at the time of diagnosis was 56.4 (range 30-80) years [Table 1].The mean parity was three (range 1-8) and only 18/131 (13.7%) cases were nulliparous. Postmenopausal metrorrhagia with or without abnormal vaginal discharge was the most frequent symptom; it was present in 84.7% (111/131) of patients, 18 patients (13.7%) presented only with abnormal vaginal discharge without vaginal bleeding. Only two of 131 (1.5%) patients presented with abdominal pain and dysuria that were detected incidentally (endometrial thickening in gynecological ultrasound). Surgery was the initial treatment for all patients, the majority, 90/131 (68.7%) cases had Type I extra-fascial hysterectomy, 15 cases had Type I extra-fascial hysterectomy with infracolic omentectomy, 14 cases had laparoscopic-assisted vaginal hysterectomy, six cases had Type II and another six cases had Type III radical hysterectomy. All except seven cases with high risk medical co morbid conditions had bilateral pelvic lymph node dissection and nine cases had para-aortic lymphadenectomy. The incision type was pfannenstiel, Mayolard and lower midline vertical in 77, 11, and 29 cases each respectively. The average duration of surgery was 135 min with a range between 120 and 270 min. The majority 89/131 (67.9%) of the patients did not require any blood transfusion and only one case required 3 units of blood.
Table 1: Clinico‑pathological features

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[Table 2] describes the preoperative and postoperative histopathological types and grades of tumors. Twelve of 123 (9.7%) patients preoperatively diagnosed as Grade 1 tumors were upgraded to Grade 3 changes in postoperative specimens and six (50%) of these 12 patients had pelvic lymph nodes' metastasis. Similarly, 23 patients preoperatively diagnosed as Grade 1 tumors were upgraded to Grade 2 in postoperative specimens but none of them had lymph nodal metastasis.
Table 2: Histopathological features

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A total of 14/131 (10.6%) [Table 3] cases had lymph nodes metastasis. Eight cases of 14 had tumor confined to the uterus, six of 14 had serosal invasion but none of these 14 patients had ovarian metastasis or positive peritoneal cytology. One case with Grade I tumor had lymph node metastasis, and three cases with Grade 2 tumor had lymph node metastasis, 9/42 (21.4%) cases with Grade 3 tumor had lymph node metastasis and one case with undifferentiated carcinomas had lymph node metastasis. The only patient who had para-aortic lymph node metastasis actually had Stage IIIC, Grade 3 changes, serosal invasion but no extra-uterine disease and no clinically palpable para-aortic nodes during the intraoperative period. Similarly, all the nine patients with high-risk group (Grade 3, clear cell type, uterine papillary serous and undifferentiated carcinomas) who had para-aortic lymphadenectomy did not show the palpable para-aortic nodes. None of the 13 patients with superficial myometrial invasion (MI) had lymph node metastasis, 2/61 (3.3%) cases with <½ MI, 7/41 (17%) cases with >½ MI and 5/14 (35.7%) cases with serosal involvement had lymph node metastasis. None of the 131 cases showed positive peritoneal cytology. The FIGO surgical staging [Table 1] was Stage I in 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 17 (12.9%) (A = 2, B = 1, C = 14).
Table 3: Correlation between tumor grade and lymph node metastasis

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The Chi-square test was used to analyze the correlation between tumor grade and lymph nodes metastasis. The testing of more than two proportions, tumor grades 1, 2, 3, and undifferentiated carcinomas was significantly different (P < 0.043011). Further, to find out the significantly different categories the four categories were subdivided into two groups (tumor Grade 1 and Grade 2 formed Group 1 and the remaining two categories, that is tumor Grade 3 and undifferentiated carcinomas formed Group 2). It was found that there is no significant difference in between Grade 1 and Grade 2 in the Group 1 and between Grade 3 and undifferentiated carcinomas in the Group 2; but the difference between the two groups is statistically significant (P < 0.005024)[Table 3]. The number of lymph nodes' metastasis in Grade 3 and undifferentiated carcinomas was significantly more than Grade 1 and 2 tumors.


 » Discussion Top


This study confirmed that there is a poor correlation between the preoperative and the postoperative tumor grades. Eight cases (6.1%) with endometrial hyperplasia with atypia actually had endometrial adenocarcinoma in the postoperative specimen. The preoperative tumor grades in 123 cases, Grade 1, 2, 3, and undifferentiated carcinomas was 48 (39%), 33 (26.8%), 27 (21.9%) and 15 (12.2%), and the corresponding grades in postoperative specimen was 31 (24%), 50 (38.7%), 42 (32.5%) and 6 (4.6%) respectively. Two of the 123 cases had no residual malignancy in the postoperative specimen. The 12/123 (9.7%) patients preoperatively diagnosed as Grade 1 tumors were upgraded as Grade 3 changes in postoperative specimens. Therefore, surgical specimen's histopathological study is the most precise method to identify the tumor grades.

A Gynecologic Oncology Group study reported that pelvic lymph node metastasis was found in less than 3% of patients with Grade 1 disease confined to the inner third of the myometrium. The incidence of para-aortic node metastasis was less than 1%. [11] In this study, the high-risk patients, nine (9/42, 21.4%) with Grade 3 tumor and one (1/6, 16.6%) with undifferentiated carcinomas had lymph node metastasis, and 7/41 (17%) cases with >½ MI and 5/14 (35.7%) cases with serosal involvement had lymph node metastasis. The only patient who had para-aortic lymph node metastasis actually had Stage IIIC, Grade 3 changes. The low-risk patients, only one (1/31, 3.2%) with Grade 1, three (3/50, 6%) with Grade 2, two (2/61, 3.3%) cases with <½ MI and none of the 13 patients with superficial myometrial invasion had lymph node metastasis. Thus, these low-risk patients may not benefit from lymphadenectomy. However, these low-risk patients were diagnosed based on the final histology from the surgical specimen. It is unreliable to predict these adverse prognostic factors before or during surgery by various preoperative and intraoperative assessments. Our study showed that 12 (9.7%) patients preoperatively diagnosed as Grade 1 tumors were upgraded to Grade 3 changes in postoperative specimens and six of these 12 patients (50%) had lymph node metastasis. Several authors have concluded that lymphadenectomy should be performed in all patients except when there is the potential for major morbidity. [12],[13]

Several studies reported that lymphadenectomy was required not only for accurate surgical staging but suggested therapeutic benefit. [14],[15] A large population-based study from the National Cancer Institute (United States) reported that patients who underwent lymphadenectomy had better disease-free survival than those who did not, except for Stage I (Grades 1 and 2). [16] In contrast, the results of A Study in the Treatment of Endometrial Cancer (ASTEC) failed to demonstrate a survival benefit from pelvic lymphadenectomy. [17]

Preoperative imaging such as magnetic resonance or positron emission tomography scan has been proposed to identify myometrial invasion, extra-uterine disease, and macroscopic node metastasis. However, the disadvantage is undetectable microscopic node metastasis, low sensitivity rates and expense. Intraoperative assessment based on gross inspection and palpation is inaccurate to detect the patients with risks for node metastasis. Frozen section is the most acceptable intraoperative assessment at this moment, but it still has limitations. Adequate frozen section analysis may not be available, especially in developing countries. Special expertise in gynecologic pathology is an essential component of the frozen section process and is often lacking in limited medical environments.

The present study demonstrated association of multiparity in endometrial cancer patients was not uncommon. Patients with only abnormal vaginal discharge without bleeding and asymptomatic women's could also have endometrial cancer. The histological grade from the curettage specimen is known preoperatively; however, this is unreliable. Thus, in situations where there are limited resources without preoperative imaging and intraoperative frozen section, pelvic lymphadenectomy may be a valuable method for determining prognosis, postoperative management, and possibly, its therapeutic value. The para-aortic lymphadenectomy may be limited to the high-risk cases. [18]


 » Acknowledgment Top


We would like to thank Dr Ramesh, Dept. of Statistics, Kidwai Memorial Institute of Oncology and Mr Marimuthu, Dept. Of Statistics, National Institute of Mental Health Sciences, Bangalore for helping to analyze the data.

 
 » References Top

1.Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, et al. Cancer Statistics. CA Cancer J Clin 2008;58:71-96.  Back to cited text no. 1
    
2.International Federation of Gynaecology and Obstetrics (FIGO). Classification and staging of malignant tumours in the female pelvis. Int J Gynaecol Obstet 1989;28:189-93.  Back to cited text no. 2
    
3.Pacheco JC, Kempers RD. Etiology of postmenopausal bleeding. Obstet Gynecol 1968;32:40-6.  Back to cited text no. 3
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4.Lidor A, Ismajovich B, Confino E, David MP. Histopathological findings in 226 women with postmenopausal uterine bleeding. Acta Obstet Gynecol Scand 1986;65:41-3.  Back to cited text no. 4
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5.Fortier KJ. Postmenopausal bleeding and the endometrium. Clin Obstet Gynecol 1986;29:440-5.  Back to cited text no. 5
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6.Creasman WT, Morrow CP, Bundy BN, Homesley HD, Graham JE, Heller PB. Surgical pathologic spread patterns of endometrial cancer. A Gynecologic Oncology Group Study. Cancer 1987;60:2035-41.  Back to cited text no. 6
    
7.Mariani A, Webb MJ, Keeney GL, Haddock MG, Calori G, Podratz KC. Low-risk corpus cancer: Is lymphadenectomy or radiotherapy necessary?. Am J Obstet Gynecol 2000;182:1506-19.  Back to cited text no. 7
    
8.Geisler JP, Wiemann MC, Zhou Z, Miller GA, Geisler HE. Using FIGO histologic grade to determine when to perform lymphadenectomies in endometrioid adenocarcinoma of the endometrium. Eur J Gynaecol Oncol 1996;17:204-7.  Back to cited text no. 8
    
9.Silverberg SG, Mutter GL, Kurman RJ, Kubik-Huch RA, Nogales F, Tavassoli FA. Tumors of the uterine corpus: Epithelial tumors and related lesions. In: Tavassoli FA, Stratton MR, editors. WHO Classification of Tumors: Pathology and Genetics of Tumors of the Breast and Female Genital Organs. Lyon, France: IARC Press; 2003. p. 221-32.  Back to cited text no. 9
    
10.Fleiss JL, Levin B, Paik MC. Statistical Methods for Rates and Proportions. 1 st ed. New Jersey: John Wiley and Sons; 2003. p. 139-42.  Back to cited text no. 10
    
11.Boronow RC, Morrow CP, Creasman WT, Disaia PJ, Silverberg SG, Miller A, et al. Surgical staging in endometrial cancer: Clinical-pathologic findings of a prospective study. Obstet Gynecol 1984;63:825-32.  Back to cited text no. 11
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12.Frumovitz M, Slomovitz BM, Singh DK, Broaddus RR, Abram J, Sun CC, et al. Frozen section analyses as predictors of lymphatic spread in patients with early uterine cancer. J Am Coll Surg 2004;199:388-93.  Back to cited text no. 12
    
13.Goudge C, Bernhard S, Cloven NG, Morris P. The impact of complete surgical staging on adjuvant treatment decisions in endometrial cancer. Gynecol Oncol 2004;93:536-9.  Back to cited text no. 13
    
14.Kilgore LC, Partridge EE, Alvarez RD, Austin MJ, Shingleton HM, Noojin FI, et al. Adenocarcinoma of endometrium: Survival comparisons of patients with and without pelvic node sampling. Gynecol Oncol 1995;56:29-33.  Back to cited text no. 14
    
15.Cragun JM, Havrilesky LJ, Calingaert B, Synam I, Secord AA, Soper JT, et al. Retrospective analysis of selective lymphadenectomy in apparent early-stage endometrial cancer. J Clin Oncol 2005;23:3668-75.  Back to cited text no. 15
    
16.Chan JK, Wu H, Cheung MK, Shin JY, Osann K, Kapp DS. The outcomes of 27,063 women with unstaged endometrioid uterine cancer. Gynecol Oncol 2007;106:282-8.  Back to cited text no. 16
    
17.Kitchener H, Swart AM, Qian Q, Amos C, Parmar MK, the ASTEC study group. Efficacy of systemic pelvic lymphadenectomy in endometrial cancer (MRC ASTEC trial): A randomized study. Lancet 2009;373:125-36.  Back to cited text no. 17
    
18.Morrow CP, Bundy BN, Kurman RJ, Creasman WT, Heller P, Homesley HD, et al. Relationship between surgical-pathologic risk factors and outcome in clinical stage I and II carcinoma of the endometrium: A Gynecologic Oncology Group study. Gynecol Oncol 1991;40:55-65.  Back to cited text no. 18
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3]

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