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  In this article
 »  Abstract
 » Introduction
 »  Materials and Me...
 » Results
 » Tumor Site
 » Tumor Size
 » Discussion
 » Conclusion
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  Table of Contents  
ORIGINAL ARTICLE
Year : 2015  |  Volume : 52  |  Issue : 4  |  Page : 677-680
 

Discrepancy between clinicoradiological and surgicopathological staging in stage 1 carcinoma endometrium: Identification of risk factors


Department of Surgical and Gynaecological Oncology, Lakeshore Hospital, Cochin, Kerala, India

Date of Web Publication10-Mar-2016

Correspondence Address:
S Neetha
Department of Surgical and Gynaecological Oncology, Lakeshore Hospital, Cochin, Kerala
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-509X.178440

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 » Abstract 

INTRODUCTION: Carcinoma endometrium carries an excellent prognosis when diagnosed early. But controversies exist in the management of Ca endometrium confined to the uterus as to whether a complete surgical staging including lymph node dissection is needed always. This may increase unnecessary surgical morbidity for some. On the other hand, if not done it fails to recognize a subset of patients who require adjuvant treatment, thus affecting the outcome. Hence it is very important to categorize the patients to assess the need of complete surgical staging. AIM: The aim of the following study is to identify the risk factors influencing the upstaging of disease in clinicoradiologically stage 1 carcinoma endometrium. MATERIALS AND METHODS: A retrospective database evaluation of all cases of clinicoradiologically stage 1 carcinoma endometrium from January 2009 to September 2012. STATISTICAL ANALYSIS: Done using the statistical software SPSS − version 16 for windows (SPSS Inc. 233 South Wacker Drive, 11th Floor Chicago, IL 60606-6412) Independent samples test (t-test for equality of means) were done and (two-tailed) P < 0.05 − were significant. RESULTS: Carcinoma endometrium patients with grade 1, no or < 50% myometrial involvement, <2 cm size and no isthmus involvement had low risk of upstaging. CONCLUSION: Significant upstaging is seen in the present study with per-operative staging procedures. Until the standardization of magnetic resonance imaging (MRI) techniques and reporting, or until a more sensitive non-invasive technique is devised, staging lymphadenectomy appears to be invaluable in risk assessment and prognosis.


Keywords: Clinicoradilogical, discrepancy, risk factors, surgicopathological, upstaging Ca endometrium


How to cite this article:
Chitrathara K, Asima K, Neetha S, Neha S, Simi R. Discrepancy between clinicoradiological and surgicopathological staging in stage 1 carcinoma endometrium: Identification of risk factors. Indian J Cancer 2015;52:677-80

How to cite this URL:
Chitrathara K, Asima K, Neetha S, Neha S, Simi R. Discrepancy between clinicoradiological and surgicopathological staging in stage 1 carcinoma endometrium: Identification of risk factors. Indian J Cancer [serial online] 2015 [cited 2019 Dec 7];52:677-80. Available from: http://www.indianjcancer.com/text.asp?2015/52/4/677/178440





 » Introduction Top


Carcinoma endometrium tops the list in incidence among the gynecological cancers in the west. In India, it is the third most common cancer among a woman. It has an excellent prognosis as majority (69%) are diagnosed when the disease is confined to the uterus. However if the disease is diagnosed at an advanced stage, the prognosis is worse than that of advanced ovarian cancer. Hence, it is very important to identify the sites of disease spread. This is more so because the recurrence and survival is greatly influenced by the presence of extrauterine disease. It is also important to assess the need of adjuvant treatment.[1]

The current recommendations include a thorough surgical staging including pelvic and para-aortic lymph node dissection as the primary treatment when disease is confined to uterus. But many a time this is not practiced routinely. Lymph node dissection and proper staging are not being done widely. This results in under treatment and overtreatment as they are not properly staged. On the other hand, lymphadenectomy in low risk patients unnecessarily adds on to surgical morbidity. Hence, it is very important to categorize the patient to assess the need of a complete surgical staging.[2],[3],[4],[5],[6],[7] This paper is aiming at identifying the risk factors which influenced the upstaging of disease in clinicoradiologically stage 1 carcinoma endometrium. Literature did not reveal any of such studies reported from Indian Institutions.

Magnetic resonance imaging (MRI) is now widely accepted as the imaging modality of choice in the pre-operative staging of endometrial cancer. Sentinel node is less accurate than MRI.[8] In India, many medical colleges are lacking the support of MRI imaging. Even when the MRI imaging is available the resolution of the machine, the strict adherence to the carcinoma endometrium protocol, and the reporting expertise greatly affect the interpretation. Hence, it is better to have other clinicoradiological factors which increase the accuracy of prediction of lymph node involvement.


 » Materials and Methods Top


A retrospective data base evaluation of all cases of clinicoradiologically stage 1 carcinoma endometrium from January 2009 to September 2012 was conducted. A total of 59 patients with mean age of 58.5 years were included in the study. Detailed history was taken. General physical examination and per abdominal examination were done especially to rule out any signs of distant disease. Per speculum and bimanual pelvic examination were carried out and cervical and vaginal extension if any was noted. Size of the uterus, its mobility, presence of any adnexal mass, nodularity in the pouch of Douglas and the involvement of the parametrium were routinely assessed. All the routine blood investigations were done.  Pap smear More Details, endometrial and endocervical curettings were taken for having a tissue diagnosis. Pipelle sampling or hysteroscopy were done depending on the situation. Patients were initially evaluated with ultrasound scan and then with MRI. Only three patients did not have an MRI since they already had computed tomography (CT) scan from elsewhere before reference to our centre.

All the patients were surgically staged according to International Federation of Gynecologists and Obstetricians (FIGO) staging guidelines [8] [Table 1] which included peritoneal fluid collection for cytology, thorough intra-abdominal exploration with inspection and palpation of omentum, liver, peritoneal cavity especially cul-de-sac, paracolic gutters and diaphragmatic surface. Biopsy of suspicious areas were taken. Uterus was evaluated for breach in serosa. Total hysterectomy with bilateral salpingo-oophorectomy was the routine until 3 years back. We had local recurrence of two stage 1A patients in the first year. Even though one patient could be salvaged by radiation, since then a modified radical hysterectomy without ureteric skeletonization was used as the primary surgical procedure. Pelvic lymph node dissection with or without para-aortic node dissection was done. High medical risk including obesity, where a Maylards incision was usually put, is the main factor for deselection of cases for para-aotic dissection. Very rarely clinicoradiopathologic factors like low grade and very small area of endometrial involvement and insignificant pelvic nodes also influenced the decision. The main purpose of staging was to define the risk groups for adjuvant treatment. Staging defines the extent of disease better, minimizes over and under treatment, and it is a more accurate predictor of prognosis.
Table 1: Carcinoma of the endometriuma

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Statistical analysis

The assessment of outcome was done by following parameters. Upstaging of disease and their correlation with various risk factors. Statistical TE analysis was performed using SPSS version 16 independent samples test (

t-test for equality of means) were done and (two-tailed) P < 0.05 − were significant.


 » Results Top


Stage

There were a total of 43 patients with stage 1 Ca endometrium; out of these 16 patients were with more than stage 1 [Table 2].
Table 2: Distribution of patients in different stages

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The patients were categorized into two groups i.e., stage 1 and more than stage 1. Patients with stage 2, 3 and 4 disease were grouped together for statistical analysis as the number of patients were less in this group [Table 3].
Table 3: Distribution of patients in different stages

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Age

There were 25 patients with stage 1 disease in the 40-60 years age group whereas 16 patients in 60-80 years group. There were six and eight patients respectively with more than stage 1 disease. Both groups were comparable in age [Table 4].
Table 4: Age distribution

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Upstaging variables

The upstaging variables used were cervix invasion, pelvic node involvement, para-aortic node involvement, locoregional spread and distant metastasis. Majority of patients (37%) were upgraded because of pelvic lymph node involvement, followed by locoregional spread. Some had involvement of more than 1 factor for up gradation [Table 5].
Table 5: Upstaging variables

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Histology

The most common histological subtype in our study was endometrioid and followed by clear cell and carcinosarcoma. Amongst the endometrioid variant 10% of had nodal spread. P value was 0.53. Hence statistically not significant. Chi square test was used to know the significance [Table 6].
Table 6: Histology and pattern of spread

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Grade of the tumor

Higher the grade more is the chance of nodal spread. Nearly 33% of cases with nodal spread were having grade 3 tumor and 16% patients with grade 2. P value is 0.03, hence statistically significant [Table 7].
Table 7: Grading and pattern of spread

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 » Tumor Site Top


In 28% of the patients, tumor was involving full endometrial cavity. Out of this, 28.57% had nodal metastasis resulting in upstaging of disease. P value is 0.002 Chi-square test was used to know the significance. Nearly 19.04% had regional spread, and 14.28% had cervical stromal involvement. Cervical stromal involvement was more in posterior wall growths [Table 8].
Table 8: Tumor site and pattern of spread

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 » Tumor Size Top


The lymph nodal metastasis also correlates with the tumor size. Cervical involvement, regional spread and metastasis are also mostly seen in patients with larger tumors. Most of the upstaged patients were having tumor size of > 2 cm [Table 9].
Table 9: Tumor size and pattern of spread

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Variables influencing pattern of spread

Out of 59 patients, 19 had uterine isthmus involvement and out of these 19 (26%) had nodal spread and 21% had cervix involvement. Most of the patients were having >50% myometrial involvement and majority of patients were >50 years of age [Table 10].
Table 10: Variables influencing pattern of spread

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P value for Lymphvascular space involvement is 0.71. Not significant. Chi-square test was used.

P value for myometrial involvement is 0.06; hence not significant.

P value for cervical isthmus involvement is 0.01; so it is a significant risk factor influencing the upstaging.


 » Discussion Top


Early endometrial cancer even though highly curable is often highly mismanaged. Even patients presenting with postmenopausal bleeding are submitted to total hysterectomy or total hysterectomy with bilateral salpingo-oophorectomy without proper investigations for pre-operative diagnosis or staging. Many a time patients are given unnecessary radiotherapy because of unplanned surgery. The value of pre-operative staging is unquestionable since it helps to carry out adequate surgery. Pre-operative staging also identifies stage 2 patients where the patients can opt for a single curative treatment since post-operative radiation definitely increases the bladder and bowel morbidity. FIGO [9] and National Comprehensive Cancer Network (NCCN) guidelines [10] still adheres to per-operative staging lymphadenectomy. Despite many criticisms raised against the trial many oncologists argue in favor of the MRC-ASTEC trial [11] reported in 2009, which showed no survival advantage for systematic lymphadenectomy in their group of pre-operative stage 1 patients. A recent article [8] found only 82% and 54% sensitivity for myometrial invasion and cervical stromal invasion respectively for MRI, even when they reported the specificity for both as 100%. Under this circumstances the question of whether the use of MRI for pre-operative staging is enough to avert per-operative lymphadenectomy remains unanswered and requires further clarification. The value of positron emission tomography (PET)-CT is yet to be proved.

Most of the cases in the index study was in stage 1. This is in accordance with the published data. The factors which reached statistical significance in surgicopathologic upstaging was grade of the tumor, tumor site, tumor size and isthmus involvement whereas age and myometrial involvement didn't influence upstaging. We had only 10 case of type 2 cancers and probably because of this small number, histology failed to achieve statistical significance. According to Neubauer and Lurain [12] surgical staging not only identifies most patients with extrauterine disease, but also identifies patients with uterine risk factors for recurrence, including large tumor size, deep myometrial invasion, lymph vascular space invasion (LVSI), cervical extension, and positive peritoneal cytology. In our study, LVSI also did not attain statistical significance.

The advantage of modified radical hysterectomy in type 2 endometrial cancer is shown in some of the recently reported studies.[13],[14] This might hold true for type 1 endometrial cancer also especially when it involves lower uterus. Ideally, all gynecological cancer surgeries should be done by gynecology surgeons for better outcome, and they can modify procedures according to necessity thus reducing the morbidity. In their hands, the morbidity of lymphadenectomy also may be negligible.

However, at least in low resource settings and in developing countries, this ideal circumstance does not exist because of a dearth of expertise and specialized centers. Our study is relevant in this context. The referral to specialized centers can be minimized considering the risk factors for upstaging. Among the known risk factors grade can be found out easily from an endometrial sampling histology, an experienced sonologist can tell the size of the tumor. In addition to this, we could find an additional factor, the tumor site as an important significant predictor of surgicopathologic upstaging. Tumors involving entire wall, and filling the endometrial cavity appeared to be the most important significant factor in the present study. Furthermore, we found that post wall involvement is a good predictor of cervical stromal involvement and thus isthmial involvement also. Careful high resolution sonogram/hydrohysterosonogram can detect these findings with reasonable accuracy with the endometrial sampling histology of carcinoma. “Transvaginal ultrasound and MRI performed equally well in the pre-operative local staging of endometrial cancer, with no statistically significant differences between the two techniques” was the conclusion drawn by Savelli et al.[15] In a study reported by Antonsen et al.

[16] they found that PET/CT, MRI and 2dimentional ultrasound were comparable in predicting the myometrial invasion. However, they reported that for cervical invasion and lymph node metastases, PET/CT was the best and concluded that no currently available imaging method can replace surgical staging.


 » Conclusion Top


Significant upstaging is seen in the index study with per-operative staging procedures. Until the standardization of MRI techniques and reporting, or until a more sensitive non-invasive technique is devised, staging lymphadenectomy appears to be invaluable in risk assessment and prognosis. However, a more focused approach is essential to categorize the cases in order to assess the need of surgical staging especially lymphadenectomy. This is essential in low resource settings especially in low risk patient to optimize the surgical morbidity and refer needy patients only to lower the burden of specialized centers.

This study showed that carcinoma endometrium patients with grade 1, no or less than half of myometrial involvement had low risk of upstaging of the disease. In these patients lymph node dissection and the related increased surgical morbidity can be avoided.

 
 » References Top

1.
Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin 2009;59:225-49.  Back to cited text no. 1
    
2.
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. 2
    
3.
International Federation of Gynecology and Obstetrics Annual report on the results of treatment in gynecologic cancer: Corpus cancer staging. Int J Gynecocol Obstet 1989;28:189-93.  Back to cited text no. 3
    
4.
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. 4
    
5.
Mariani A, Webb MJ, Galli L, Podratz KC. Potential therapeutic role of para-aortic lymphadenectomy in node-positive endometrial cancer. Gynecol Oncol 2000;76:348-56.  Back to cited text no. 5
    
6.
ACOG Committee on Practice Bulletins. Management of Endometrial Cancer (Joint with the Society of Gynecologic oncologists). Obstet Gynecol 2005;106:413-25.  Back to cited text no. 6
    
7.
Soliman PT, Frumovitz M, Spannuth W, Greer MJ, Sharma S, Schmeler KM, et al. Lymphadenectomy during endometrial cancer staging: Practice patterns among gynecologic oncologists. Gynecol Oncol 2010;119:291-4.  Back to cited text no. 7
    
8.
Zamani F, Goodarzi S, Hallaji F, Zamiri A, Deilami T, Malek M, et al. Diagnostic value of pelvic MRI for assessment of the depth of myometrial invasion and cervical involvement in endometrial cancer: Comparison of new versus old FIGO staging. Iran J Radiol 2012;9:202-8.  Back to cited text no. 8
    
9.
Pecorelli S. Revised FIGO staging for carcinoma of the vulva, cervix, and endometrium. Int J Gynaecol Obstet 2009;105:103-4.  Back to cited text no. 9
    
10.
NCCN Clinical Practice Guideline Oncology-Uterine Neoplasms, 2011. Available from: http://www.nccn.org/professionals/physician gls/f guidelines.asp./NCCN guidelines for treatment of cancer by site/Uterine Neoplasms.  Back to cited text no. 10
    
11.
ASTEC study group, Kitchener H, Swart AM, Qian Q, Amos C, Parmar MK. Efficacy of systematic pelvic lymphadenectomy in endometrial cancer (MRC ASTEC trial): A randomised study. Lancet 2009;373:125-36.  Back to cited text no. 11
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12.
Neubauer NL, Lurain JR. The role of lymphadenectomy in surgical staging of endometrial cancer. Int J Surg Oncol 2011;2011:814649.  Back to cited text no. 12
    
13.
Sinorelli M, Lissonj AA, Cormio G, Katsaros D, Pelleqrino A, Selvaggi L, et al. Modified radical hysterectomy in the treatment of stage 1 endometrial cancer: Results from the ILIADE randomized study. Ann Surg Oncol 2009;16: 431-41  Back to cited text no. 13
    
14.
Hiura M, Nogawa T. The role of modified radical hysterectomy in endometrial carcinoma. Shikoku Cancer Center, Japan. Available from: http://www.intechopen.com./subjects/medicine/obstetricsand gynaecology/Hysterectomy edited by Ayman Al- Hendi/chapter 4  Back to cited text no. 14
    
15.
Savelli L, Ceccarini M, Ludovisi M, Fruscella E, De Iaco PA, Salizzoni E, et al. Preoperative local staging of endometrial cancer: Transvaginal sonography vs. magnetic resonance imaging. Ultrasound Obstet Gynecol 2008;31:560-6.  Back to cited text no. 15
    
16.
Antonsen SL, Jensen LN, Loft A, Berthelsen AK, Costa J, Tabor A, et al. MRI, PET/CT and ultrasound in the preoperative staging of endometrial cancer-A multicenter prospective comparative study. Gynecol Oncol 2013;128:300-8.  Back to cited text no. 16
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8], [Table 9], [Table 10]



 

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