Endometrial Carcinoma - Pretreatment Evaluation, Staging, and Surgical Treatment - UpToDate

5/7/2018 Endometrial carcinoma: Pretreatment evaluation, staging, and surgical treatment - UpToDate
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Endometrial carcinoma: Pretreatment evaluation, staging, and surgical treatment
Author: Steven C Plaxe, MD
Section Editor: Barbara Goff, MD
Deputy Editor: Sandy J Falk, MD, FACOG
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Apr 2018. | This topic last updated: Jun 01, 2017.
INTRODUCTION — Uterine cancer (picture 1) is the most common gynecologic malignancy in the United
States; annually there are approximately 46,470 new cases and 8120 deaths from the disease [1]. Women
have a 2.5 percent lifetime risk of developing endometrial carcinoma, which accounts for 6 percent of all
cancers in women. Fortunately, most cases are diagnosed at an early stage when surgery alone may be
adequate for cure. Fiveyear survival rates for localized, regional, and metastatic disease are 96, 67, and 17
percent, respectively.
Preoperative evaluation, staging, and posttreatment surveillance for endometrial carcinoma will be reviewed
here. Risk factors, clinical features, diagnosis, and histopathology, treatment with chemotherapy or radiation,
and uterine sarcoma are discussed separately. (See "Endometrial carcinoma: Epidemiology and risk factors"
and "Treatment of lowrisk endometrial cancer" and "Treatment of recurrent or metastatic endometrial cancer"
and "Uterine sarcoma: Classification, clinical manifestations, and diagnosis" and "Treatment and prognosis of
uterine leiomyosarcoma".)
PRETREATMENT EVALUATION — Prior to treatment, a complete pelvic and general physical examination
should be performed, with particular attention to the size and mobility of the uterus and the presence of
extrauterine masses or ascites; potential sites of nodal metastases should also be examined (eg,
supraclavicular nodes) [2]. Laboratory evaluation or imaging studies should be selected as appropriate for the
planned treatment (eg, major surgery, chemotherapy, radiation), patient comorbidities, and suspicion of
metastases. Cervical cancer screening should be performed as appropriate. (See "Preoperative medical
evaluation of the adult healthy patient" and "Preoperative evaluation and management of patients with
cancer" and "Screening for cervical cancer".)
Preoperative issues related to endometrial carcinoma staging are discussed in this section. Diagnosis of
endometrial carcinoma is discussed in detail separately.
Assessment for hereditary cancer syndromes — Lynch syndrome (hereditary nonpolyposis colon cancer)
is associated with a greatly increased risk of endometrial carcinoma, as well as colon and ovarian cancer and
other Lynchassociated malignancies. Synchronous tumors discovered intraoperatively are common in these
women. Synchronous tumors are simultaneously diagnosed primary tumors involving two different organs.
These tumors do not represent a metastasis from one organ to the other. Women with endometrial carcinoma
who have a family history suggestive of Lynch syndrome should be referred for genetic counseling and testing
and also have testing of their tumor specimen for the mismatch repair proteins which characterize this
syndrome. (See "Lynch syndrome (hereditary nonpolyposis colorectal cancer): Clinical manifestations and
diagnosis" and 'Testing of tumor specimen for mismatch repair deficiency' below.)
Tumor markers — Measurement of the serum tumor marker CA 125 is a clinically useful test for predicting
extrauterine spread of endometrial carcinoma. In a retrospective study of 141 women with endometrial
carcinoma, a CA 125 value of greater than 40 units/mL was reported to have a sensitivity of 78 percent and
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specificity of 81 percent for lymph node metastases [3]. These results have been confirmed by others, but the
optimal threshold (eg, >20, >35, >40 units/mL) has not been determined [48]. No significant difference in CA
125 levels between pre and postmenopausal women were found in the study cited; however, the average CA
125 value in premenopausal women is higher than it is in postmenopausal women.
Assay of serum CA 125 may also be useful for following patients after initial treatment, if levels were initially
elevated. (See 'Posttreatment surveillance' below.)
Imaging studies — Pelvic or abdominal imaging to assess myometrial invasion or cervical involvement is
unnecessary if surgical staging is planned. In the infrequent situation in which a patient is staged clinically,
contrastenhanced magnetic resonance imaging (MRI) appears to be the best radiographic modality for
detecting myometrial invasion or cervical involvement when compared with nonenhanced MRI, ultrasound, or
computed tomography (CT) [9,10]. The majority of studies reported the sensitivity of enhanced MRI as
approximately 80 to 90 percent (range 57 to 100 percent) for myometrial invasion; findings of sensitivity for
cervical invasion were inconsistent ranging from 56 to 100 percent. Thus, a negative study does not provide
assurance that complete surgical staging is not needed.
MRI is also the best imaging modality, compared with CT or positron emission tomography (PET) with or
without CT, for detecting lymph node metastases [1114]. However, preoperative imaging for this purpose is
not necessary. Lymph nodes should be assessed intraoperatively in all women with endometrial carcinoma.
This evaluation should consist of, at a minimum, palpation of pelvic and paraaortic nodes with biopsy or
removal of enlarged nodes. (See 'Lymph node evaluation' below.)
A chest radiograph should be performed as part of the initial assessment.
STAGING AND PRIMARY SURGICAL TREATMENT — Endometrial carcinoma is surgically staged
according to the joint 2010 International Federation of Gynecology and Obstetrics (FIGO)/TNM classification
system (table 1 and table 2) [15,16].
In the 2010 classification system, the definition of stage I was changed to include only two substages: IA
(tumor limited to the endometrium or invades less than onehalf of the myometrium) and IB (tumor invades
onehalf or more of the myometrium). In the previous surgical staging system for endometrial carcinoma,
stage I had three substages: IA (tumor limited to the endometrium); IB (tumor invades less than onehalf of
the myometrium); or IC (tumor invades onehalf or more of the myometrium). It appears that the 2010 staging
system is better able to predict prognosis than the prior system [17]. Therefore, when discussing studies
published prior to 2010, we will use the older surgical staging system.
Surgery alone is usually curative for women with low risk disease (endometrioid histology, grade 1 or 2,
confined to the endometrium [a subset of stage IA], no other risk factors for persistence or recurrence). (See
"Approach to adjuvant treatment of endometrial cancer".)
Surgical staging overview — Total extrafascial hysterectomy with bilateral salpingooophorectomy with
pelvic and paraaortic lymph node dissection is the standard staging procedure for endometrial carcinoma [18].
Vaginal, laparoscopic or robotassisted approaches are also possible (see 'Other surgical approaches' below).
As with other intraabdominal gynecologic malignancies, complete staging includes biopsy of any areas where
metastases are suspected; most surgeons record results of peritoneal cytology, but these are not part of
FIGO staging. Cytoreduction often is performed when metastases are evident. An omentectomy is frequently
done for patients with serous or clear cell histology. Pelvic and paraaortic lymph nodes sampling or removal
are performed selectively. At a minimum, these nodes are palpated and enlarged or suspicious lymph nodes
are removed [19].
Intraoperative gross inspection and frozen section — The uterine surgical specimen should be opened
in the operating room to evaluate disease extent. The extent of uterine disease provides some direction as to
the extent of surgical staging that is called for (ie, whether lymph node evaluation is needed), which, in turn,
may impact on recommendations for adjuvant treatment. A metaanalysis of 16 studies including 2567 women
with endometrial cancer evaluated the diagnostic performance of intraoperative gross inspection to determine
the depth of myometrial invasion and found a sensitivity of 75 percent and a specificity of 92 percent [20].
(See 'Prevalence of and risk factors for nodal metastases' below.)
Frozen section of the area of deepest invasion may provide additional information, but studies comparing
results of frozen section with final pathology have not reported consistently high concordance, especially in
lowstage and lowgrade disease [2126]. Variable concordance between specialist gynecologic pathologists
and general pathologists has also been reported and is of concern [27]. As an example, in a large study (n =
482) of women with grade 1 endometrial adenocarcinoma, the grade on final pathologic analysis was higher
than that from intraoperative frozen section in 15 percent of patients, 1 percent of whom had a grade higher
than 2 [28]. In contrast, another study (n = 784) found that clinically significant discordance between frozen
section and final pathology evaluation occurred in only 1.3 percent of cases [29].
Lymph node evaluation — One of the most important prognostic factors for endometrial carcinoma is the
presence of extrauterine disease, particularly pelvic and paraaortic lymph node metastases. The approach to
lymph node assessment is controversial, particularly in women presumed to have early stage disease.
Prevalence of and risk factors for nodal metastases — The rate of nodal spread varies with tumor
stage and grade. The risk is 3 to 5 percent in patients with welldifferentiated superficially invasive tumors,
while it is as high as 20 percent in poorly differentiated deeply invasive disease (table 3) [3032].
In addition, the presence of any of the following variables indicates a high risk of nodal disease, even in
apparent stage I disease; therefore, the presence of any of these features suggests a benefit for surgical
resection of the lymph nodes:
● Serous, clear cell, or highgrade histology
● Myometrial invasion greater than 50 percent
● Large tumor (>2 cm in diameter or filling the endometrial cavity)
In a study of women with serous endometrial carcinoma from a United States national cancer database, 19
percent of women with disease grossly confined to the uterus had nodal metastases [33].
Anatomy of pelvic and paraaortic nodes — According to the Gynecologic Oncology Surgical
Procedures Manual, pelvic node dissection includes removal of nodal tissue from the distal onehalf of each
common iliac artery, the anterior and medial aspect of the proximal half of the external iliac artery and vein,
and the distal half of the obturator fat pad anterior to the obturator nerve (figure 1 and figure 2). Some data
suggest that removal of the circumflex iliac nodes to the distal external iliac nodes increases the risk of
lymphedema [34].
Paraaortic node dissection consists of resection of nodal tissue over the distal vena cava from the level of the
inferior mesenteric artery to the mid right common iliac artery and between the aorta and the left ureter from
the inferior mesenteric artery to the left mid common iliac artery [35]. Some experts extend the paraaortic
lymph node dissection (LND) superiorly to the level of the renal veins [36].
In our practice, the nodal chains that we assess when staging endometrial carcinoma include the left and right
paraaortic and, in the pelvis, the left and right common, external and internal iliac and obturator chains.
Controversies in lymph node assessment — There is ongoing controversy over whether pelvic and
paraaortic node sampling or complete LND should be performed [3740]. The status of both the pelvic and
paraaortic lymph nodes should be assessed intraoperatively in all patients, as advised by the FIGO surgical
and pathologic staging system [19,4143]. However, the type and extent of LND were not specified.
Assessment of paraaortic nodes — Paraaortic nodes may be positive in the absence of positive
pelvic nodes [44,45]. Some data suggest that paraaortic LND is associated with a survival benefit in women
with intermediate or highrisk disease. This finding was reported in a retrospective cohort study of 671 women
with endometrial carcinoma of all stages who underwent either pelvic LND or combined pelvic and paraaortic
LND; median followup for both groups was approximately 7.5 years [46]. Eightyear diseasespecific survival
rates were significantly higher in the combined pelvic and paraaortic LND group compared with pelvic LND
alone for women with intermediate or highrisk disease (84 versus 69 percent), but not for women with low
risk disease (94 versus 93 percent). In addition, it appears that the potential benefit associated with paraaortic
LND increases with higher tumor grades. In a large series (n=1453) of women with endometrioid endometrial
carcinoma, there were 10 paraaortic recurrences, distributed as follows: 0/10 in grade 1 tumors; 1/10 in grade
2; 9/10 in grade 3 [47].
Node sampling versus resection — Lymph node sampling differs from lymphadenectomy in that the
goal of sampling is to obtain a representative biopsy, while the intent of lymphadenectomy is to remove all
nodebearing tissue in a specific anatomic distribution. When lymph node sampling is performed, data
suggest that patients who underwent multiple site sampling had better survival compared to those who had
limited site sampling, or no sampling at all [48]. Based on this report, it would be reasonable to conclude that
more accurate prognostic information may be obtained when nodes are dissected from several of the node
chains draining the uterus.
Surgery limited to TAHBSO with palpation of nodes with sampling of enlarged nodes for women with grade 1
or 2 disease that is presumed to be stage IA or B is advocated by some experts [32,4951]. These women
have a greater than 90 percent fiveyear survival rate following TAHBSO alone [52,53]. Of note, palpation or
inspection has not been found to be a sensitive method for detecting metastases. This was illustrated in a
classic report, in which fewer than 10 percent of node positive patients with endometrial carcinoma had
grossly involved nodes [30].
This limited approach for presumed early stage disease is supported by data from two large randomized trials
and a large retrospective cohort study [32,49,54]. The largest of these trials (n=1408), A Study in the
Treatment of Endometrial carcinoma (ASTEC) trial, found no survival benefit of staging with versus without
pelvic lymphadenectomy in women thought preoperatively to have stage I disease [32]. Of note, in the no
lymphadenectomy group, suspicious nodes were removed.
However, this trial does not provide information regarding the usefulness of pelvic LND for guiding treatment
after surgery since patients in the second phase of the trial were treated without taking into account lymph
node status. In addition, since all patients underwent paraaortic node palpation and sampling, it does not
address the benefit of paraaortic LND. The radiotherapy portion of this trial is discussed separately. (See
"Treatment of lowrisk endometrial cancer".)
Women who do not undergo at least sampling of pelvic and paraaortic lymph nodes at the time of surgery are
incompletely surgically staged.
Some experts believe that lymph node sampling should be performed in all women with endometrial
carcinoma, but not complete pelvic and paraaortic LND. When this approach is used, all clinically suspicious
nodes are sampled, but in the absence of suspicious nodes, a representative (not random) sampling is
performed. The benefit of this approach is that it gives information about nodal status while minimizing
procedurerelated morbidity. In particular, some experts believe that the morbidity associated with complete
LND outweighs the benefits when the likelihood of nodal disease is very low, such as in low risk stage I
disease. Lower extremity lymphedema and associated cellulitis are the primary posttreatment issues
associated with pelvic and paraaortic LND. The reported risk of lymphedema varies widely (5 to 38 percent)
[34,55]. Risk of lymphedema appears to increase with the number of nodes removed (10 or more is
associated with a risk of lymphedema of 3 to 10 percent) and with adjuvant radiation therapy [34,55]. (See
"Treatment of lowrisk endometrial cancer".)
Management of lymphedema and cellulitis following pelvic lymph node dissection is discussed in detail
separately. (See "Clinical staging and conservative management of peripheral lymphedema" and "Cellulitis
following pelvic lymph node dissection".)
Complete resection of lymph nodes in all patients is recommended by other experts because they believe that
sampling may miss positive nodes and that therefore fail to identify patients who may benefit from adjuvant
therapy [56,57]. (See "Treatment of lowrisk endometrial cancer".)
We suggest complete pelvic LND and extended paraaortic node dissection rather than selective nodal
sampling. Given the importance of lymph node involvement to staging and treatment decisions, lymph node
assessment is best performed by experienced surgeons, such as gynecologic oncologists [5860].
Sentinel node biopsy — Sentinel lymph node biopsy for endometrial carcinoma has become more
commonly performed, but its role is still not fully established. The National Comprehensive Cancer Network
guidelines state that sentinel lymph node biopsy may be considered for the staging of apparent uterine
confined malignancy when there is no metastasis demonstrated by imaging studies or no obvious extrauterine
disease at exploration [61].
A study of over 28,000 women who underwent surgical staging for endometrial carcinoma from 2011 to 2015
reported that 32.9 percent had no nodal assessment, 62.3 percent had lymphadenectomy, and 4.8 percent
had sentinel lymph node biopsy [62]. Metaanalyses of 25 or more observational studies have found a
sensitivity of 89 to 93 percent for the detection of lymph node metastases in women with endometrial
carcinoma; there are no randomized trials comparing sentinel lymph node biopsy with lymphadenectomy
[63,64]. As an example, in the largest multicenter prospective study (n = 340), women with clinical stage I
endometrial carcinoma (all histologies and grades) underwent sentinel lymph node biopsy followed by pelvic
lymphadenectomy (with or without paraaortic lymphadenectomy) [65]. Successful mapping of at least one
sentinel lymph node was achieved in 86 percent and the sensitivity of sentinel lymph node was 97.2 percent.
According to the sentinel lymph node hypothesis, tumor cells migrate from a primary tumor and colonize one
or a few lymph nodes (ie, the sentinel lymph node) before involving other lymph nodes. Peritumoral injection
of a dye or tracer permits identification of a sentinel lymph node in most patients, and its status accurately
predicts the status of the remaining regional nodes.
The site of injection of the tracer for endometrial carcinoma is controversial [66,67]. Studies have evaluated
cervical, subserosal, and hysteroscopicallyguided endometrial injection [6872]. The metaanalysis of 26
studies described above found that pericervical injection was associated with a significantly increased rate of
detecting any sentinel node and that hysteroscopic injection was associated with a significantly decreased
detection rate [63].
There is no consensus about the best surgical approach (open or laparoscopic) for sentinel lymph node
biopsy or the utility of preoperative imaging [67]. Further study is required to evaluate whether sentinel lymph
node biopsy is clinically useful and, if so, the optimal site for tracer injection and the accuracy of lymphatic
mapping in endometrial carcinoma.
Management of women with cervical involvement — Historically, it was thought that women with stage II
endometrial carcinoma (tumor invades stromal connective tissue of the cervix but does not extend beyond
uterus (table 1)) had a high risk of parametrial involvement; this was based upon an assumption that
endometrial carcinoma would follow a pattern of spread similar to cervical cancer [73]. Thus, these patients
have been treated with radical hysterectomy at some institutions. However, it appears that lymphovascular
space invasion is a better predictor of parametrial extension than cervical involvement. This was illustrated in
the largest study, a retrospective series of 334 women with endometrial carcinoma who underwent radical
hysterectomy [74]. Lymphovascular spread was present in all 28 women (8.4 percent) with parametrial
spread. Most of these women (26 of 28) had lymphovascular space invasion in addition to one or more of the
following findings: invasion of more than half the myometrial depth (19 women), cervical invasion (10), ovarian
metastases (six), or pelvic or paraaortic lymph node metastases (19), or positive peritoneal cytology (13).
Thus, for women with stage II endometrial carcinoma, we suggest performing a simple hysterectomy
(extrafascial class I) (table 4) with lymphadenectomy rather than radical hysterectomy. The exceptions to this
are women with gross cervical involvement in whom performing a simple hysterectomy would cut through the
tumor (all gross disease should be removed) and/or those in whom it is uncertain whether the primary is
cervical or uterine.
Cytoreduction — We suggest surgical cytoreduction in women who are found to have pelvic or intra
abdominal disease at exploration. Cytoreduction appears to confer a survival advantage to women with pelvic
or intraabdominal spread of endometrial cancer, but high quality data are lacking. The best available
evidence is a metaanalysis of 14 retrospective case series that included 10 studies of primary disease and
four studies of recurrent disease [75]. A higher proportion of women with complete cytoreduction were found
to be significantly associated with longer median survival. For women with primary disease, overall survival
rates were: complete cytoreduction (30 to 51 percent) and optimal cytoreduction, defined in individual studies
as ≤1 or ≤2 cm (15 to 51 percent).
Secondary cytoreduction is discussed in detail separately. (See "Treatment of recurrent or metastatic
endometrial cancer".)
Other surgical approaches — The traditional surgical approach to endometrial carcinoma staging is by
laparotomy. Alternative approaches may be appropriate in low risk patients or as data emerge regarding
laparoscopic staging.
Laparoscopy — Use of laparoscopy for staging and treatment of endometrial carcinoma decreases
perioperative morbidity and appears to result in comparable treatment effectiveness when compared with
laparotomy for women with early stage disease [7678]. A metaanalysis of eight randomized trials with early
stage endometrial carcinoma compared staging with laparoscopy or laparotomy and found no effect on
overall survival (three trials; 359 women; hazard ratio [HR] 1.14, 95% CI 0.622.10) or recurrencefree
survival, but the analysis lacked sufficient statistical power to detect a difference in this outcome (four trials;
2975 women; HR 1.13, 95% CI 0.901.42) [78]. There was no statistically significant difference in the rate of
perioperative death, blood transfusion, or bladder, ureteric, bowel, or vascular injury. However, the rate of
severe postoperative adverse events was lower in the laparoscopy group (relative risk 0.58, 95% CI 0.37
0.91). Laparoscopy resulted in less blood loss (mean difference, 106.82 mL less), and with longer operative
duration and shorter hospital stay; however, no pooled analysis was done for the latter two outcomes.
A previous metaanalysis compared women with endometrial carcinoma who underwent complete surgical
staging with laparoscopically assisted vaginal or total laparoscopic hysterectomy versus laparotomy [68,79].
Operative duration for laparoscopic procedures was longer (3.3 versus 2.2 hours), but resulted in fewer
perioperative complications, decreased blood loss (267 mL less), and shorter hospital stays (three versus four
days) and faster return to normal activity (28 versus 48 days). The number of pelvic and paraaortic lymph
nodes resected was the same with both techniques.
A subsequent large, multinational randomized trial (n = 760) of women with stage I endometrioid endometrial
carcinoma compared staging with total laparoscopic and total abdominal hysterectomy and found no
difference in diseasefree survival at 4.5 years (81.6 versus 81.3 percent) or overall survival (mortality: 7.4
versus 6.8 percent) [80]. This was the second largest trial to evaluate this question; a prior trial included 2616
women [81] and was included in the metaanalysis cited above [78].
In a case series from a single surgeon, the rate of conversion of laparoscopic endometrial carcinoma staging
procedures to an open or vaginal approach in a series of 235 patients was three percent overall and seven
percent in patients with a body mass index of 40 or higher [82].
An important potential limitation of laparoscopic endometrial carcinoma staging is the difficulty of using this
technique to dissect the paraaortic nodes above the inferior mesenteric artery (IMA). A prospective series
reported that 77 percent of patients with paraaortic nodal metastases have disease above the IMA [83]. As
noted above, some experts extend the paraaortic LND superiorly to the level of the renal veins. To reach this
level laparoscopically requires advanced skills, and possibly, special techniques [36].
Laparoscopic staging of endometrial carcinoma should only be performed by a surgeon with experience in
laparoscopic hysterectomy and lymph node sampling. To minimize potential seeding of cancer cells of the
peritoneal cavity, vaginal cuff, and port site during laparoscopic staging, some surgeons perform bilateral tubal
coagulation as the first surgical step and also avoid use of uterine manipulators [69,70]. Because of these
concerns, uterine morcellation typically is avoided; if the uterus is too large to remove vaginally, then an
abdominal hysterectomy is preferred. (See "Pelvic and paraaortic lymphadenectomy in gynecologic cancers"
and "Laparoscopic hysterectomy".)
Robotassisted or single port laparoscopy — Robotassisted and single port (also referred to as
laparoendoscopic singlesite surgery [LESS]) are newer laparoscopic techniques that have been used for
endometrial carcinoma staging. (See "Robotassisted laparoscopy" and "Abdominal access techniques used
in laparoscopic surgery", section on 'Singleincision surgery (SIS)'.)
Robotassisted laparoscopic endometrial carcinoma staging was compared with conventional laparoscopy
and laparotomy in a systematic review that included eight studies with a total of 589 patients [84]. The
advantages of robotic procedures were mainly in comparison with laparotomy. Blood loss was significantly
lower with robotic surgery than laparotomy (an average of 186 mL less) and conventional laparoscopy (an
average of 86 mL less, a difference that is unlikely be clinically significant). The rate of transfusion was not
significantly reduced compared with either laparotomy (OR 0.3, 95% CI 0.11.2) or conventional laparoscopy
(OR 0.5, 95% CI 0.1–2.2), but the study was underpowered to detect significant improvements of this
magnitude. The rate of wound and other complications (stroke, ileus, lymphedema, nerve palsy, acute renal
failure, lymphocyst, urinary retention) were significantly reduced for robotic surgery compared with laparotomy
(wound: OR 0.1, 95%CI 0.04–0.4 and other complications: OR 0.3, 95% CI 0.1–0.6), but not conventional
laparoscopy. The primary disadvantage of robotic procedures was longer operative duration (an average of
89 minutes longer than laparotomy).
Regarding LESS, use for surgical staging and lymphadenectomy for gynecologic cancers has been reported.
As an example, 13 of 15 women with endometrial carcinoma and five of six women with ovarian cancer were
staged with lymphadenectomy, when appropriate, using a LESS approach; the remaining procedures were
converted to conventional laparoscopy or laparotomy [85]. Median operative duration was 2.2 hours.
Another series evaluated use of LESS for staging of gynecologic malignancies with pelvic and paraaortic
lymph node dissection [86]. Successful procedures were reported in 20 of 21 patients with a mean operative
duration of 2.0 hours. Median pelvic and paraaortic node counts were 14 (range 7 to 19) and 6 (range 2 to
14), respectively.
Vaginal hysterectomy — Vaginal hysterectomy is not recommended, in general, for endometrial
carcinoma staging since it precludes examination of the abdomen and lymph nodes for metastases. However,
this surgical approach may be appropriate for women who are poor candidates for major abdominal surgery
(eg, obesity, medical comorbidities). In these populations, retrospective series have reported that vaginal
hysterectomy is associated with a low rate of perioperative complications and 5 to 10 year diseasespecific
survival rates of 80 percent or higher [87,88]. However, since stage is uncertain in these women, it is not
possible to compare these data with survival rates for other women.
In women who undergo vaginal hysterectomy, BSO should also be performed. Women who are at
intermediate (grade 3 or tumors that extend beyond onehalf of the myometrium) or greater risk of disease
recurrence may be advised to have adjuvant radiation therapy. (See "Adjuvant treatment of intermediaterisk
endometrial cancer", section on 'Definition of intermediate risk' and "Approach to adjuvant treatment of
endometrial cancer", section on 'Definition of risk based on histology and stage'.)
Testing of tumor specimen for mismatch repair deficiency — Endometrial carcinoma is often the sentinel
cancer for women with Lynch syndrome (hereditary nonpolyposis colon cancer). These women are also at
risk of colon cancer, ovarian cancer, and other Lynchassociated malignancies. Thus, to identify these
women, some experts advocate universal testing of endometrial carcinoma specimens using
immunohistochemistry for mismatch repair proteins, followed by single gene sequencing to establish a
diagnosis of Lynch syndrome [8991]. However, whether testing should be performed for all women with
endometrial carcinoma or only for those with family histories suggestive of Lynch syndrome is uncertain. (See
"Lynch syndrome (hereditary nonpolyposis colorectal cancer): Clinical manifestations and diagnosis".)
Loss of mismatch repair can also occur in sporadic cancers [9295]. However, sporadic tumors with defective
MMR do not contain MMR gene mutations; instead, they have somatic epigenetic changes such as promoter
hypermethylation that silence gene expression and result in microsatellite instability (MSI). Approximately 20
percent of endometrial carcinomas are MSIpositive; fewer than 5 percent are thought attributable to Lynch
syndrome [96].
SPECIAL CLINICAL SITUATIONS
Synchronous ovarian and endometrial cancer — Synchronous primary cancers of the endometrium and
ovary are found in 5 percent of women with endometrial carcinoma and 10 percent of women with ovarian
cancer and [97,98]. For women with endometrial carcinoma, the risk appears to be higher in premenopausal
women, in whom 5 to 29 percent have a synchronous ovarian malignancy [99].
Histology is often the same in both the endometrium and ovary, making it unclear whether there are two
separate primary tumors or a metastasis from the endometrium to the ovary, or, less frequently, from the
ovary to the endometrium. Metastatic disease to the ovary, rather than a synchronous primary, should be
suspected when ovarian disease is small, bilateral, or multinodular with surface implants and angiolymphatic
invasion at the ovarian cortex [100].
Staging and surgical treatment is the same regardless of whether the patient has metastatic disease or
synchronous primaries. In cases with synchronous primary tumors of both ovary and endometrium, treatment
is based on the combined treatment recommendations for each cancer according to stage.
Inoperable patients — For women with presumed stage I disease who are unfit or unwilling to have surgery,
primary radiation therapy may be acceptable. Clinical staging should be performed for these women
according the FIGO system adopted in 1971 [101]. Clinical staging procedures include examination under
anesthesia, sounding of the uterus, endocervical curettage, hysteroscopy, cystoscopy, proctoscopy, and
imaging studies. Adjuvant therapy for women with endometrial carcinoma who cannot tolerate surgery is
discussed in detail separately. (See "Approach to adjuvant treatment of endometrial cancer", section on
'Overview of treatment'.)
Fertility preservation — Women with stage I, grade 1 endometrial carcinoma who wish to preserve fertility
may be candidates for treatment with progestin therapy (eg, megestrol acetate). A thorough evaluation prior
to medical therapy (eg, dilation and curettage, imaging studies) is necessary to try to confirm that the lesion is
consistent with low grade, low stage disease. However, an important consideration is that highrisk features
may be found in the surgical specimen at the time of hysterectomy in women who were felt to have lowrisk
disease prior to surgery [102]. Fertility preservation for women with endometrial carcinoma is discussed in
detail separately. (See "Treatment of lowrisk endometrial cancer", section on 'Fertility preservation'.)
Surgical approaches to fertility preservation are not commonly used for women with endometrial cancer [103].
PROGNOSIS — The prognosis of endometrial carcinoma is determined primarily by disease stage and
histology (including both grade and histologic subtype). Fortunately, most women with endometrial carcinoma
have a favorable prognosis, since the majority have endometrioid histology and present with earlystage
disease.
In general, the rate of fiveyear survival for stage I disease is approximately 80 to 90 percent, for stage II is 70
to 80 percent, and for stages III and IV is 20 to 60 percent [17,104]. Survival rates by stage are presented in
the table (table 5).
POSTTREATMENT SURVEILLANCE — Posttreatment surveillance and other posttreatment issues,
including postmenopausal hormone therapy and sexual health, are discussed separately. (See "Overview of
approach to endometrial cancer survivors", section on 'Followup posttreatment'.)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, “The Basics”
and “Beyond the Basics.” The Basics patient education pieces are written in plain language, at the 5th to 6th
grade reading level, and they answer the four or five key questions a patient might have about a given
condition. These articles are best for patients who want a general overview and who prefer short, easyto
read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more
detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want
indepth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or email
these topics to your patients. (You can also locate patient education articles on a variety of subjects by
searching on “patient info” and the keyword(s) of interest.)
● Basics topics (see "Patient education: Uterine cancer (The Basics)")
● Beyond the Basics topics (see "Patient education: Endometrial cancer diagnosis and staging (Beyond the
Basics)")
SUMMARY AND RECOMMENDATIONS — Endometrial carcinoma is surgically staged according to the joint
International Federation of Gynecology and Obstetrics (FIGO)/American Joint Committee on Cancer (AJCC)
classification system (table 1 and table 2). (See 'Surgical staging overview' above.)
● We recommend total extrafascial hysterectomy with bilateral salpingooophorectomy performed either via
laparotomy or laparoscopy for staging and initial management of endometrial carcinoma (Grade 1B).
(See 'Surgical staging overview' above and 'Laparoscopy' above.)
● Women with apparent stage IA grade 1 endometrial carcinoma who wish to preserve fertility can opt to
avoid TAHBSO and undergo progestin therapy, but the optimum surveillance of these women is not
known and they are at risk for recurrent and synchronous disease. Thus, we recommend that these
women undergo TAHBSO after completion of childbearing, even in cases with demonstrated tumor
regression (Grade 1C). (See 'Fertility preservation' above.)
● We suggest surgical cytoreduction for women with pelvic or intraabdominal disease (Grade 2C). (See
'Cytoreduction' above.)
● The status of both the pelvic and paraaortic lymph nodes should be assessed intraoperatively in all
patients. Given the importance of identification of nodal metastases to staging and treatment decisions,
this assessment should be performed by experienced surgeons, such as gynecological oncologists. (See
'Lymph node evaluation' above.)
● Lymph node dissection provides the most comprehensive and precise evaluation of patients with
apparent stage I endometrial carcinoma (Grade 2B). It is reasonable not to remove lymph nodes in those
who do not have individual patient or tumor characteristics (eg, serous, clear cell, or highgrade
histology; myometrial invasion >50 percent; or a large tumor) associated with a high risk of nodal
metastases. Women with endometrial carcinoma who do not undergo at least sampling of pelvic and
paraaortic lymph nodes at the time of surgery are incompletely surgically staged. (See 'Prevalence of and
risk factors for nodal metastases' above.)
● For women with endometrial carcinoma who are undergoing lymph node evaluation, we suggest pelvic
and extended paraaortic lymph node dissection rather than nodal sampling alone (Grade 2C). (See
'Node sampling versus resection' above.)
● For women with stage II endometrial carcinoma, we suggest performing a simple hysterectomy
(extrafascial class I) (table 4) with lymphadenectomy rather than radical hysterectomy (Grade 2C). The
exceptions to this are women with gross cervical involvement in whom performing a simple hysterectomy
would cut through the tumor (all gross disease should be removed) and/or those in whom it is uncertain
whether the primary is cervical or uterine. (See 'Management of women with cervical involvement'
above.)
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Topic 3251 Version 37.0
GRAPHICS
Adenocarcinoma of the endometrium
This tumor, which occupies a small uterine cavity, grows primarily as a firm
polypoid mass.
Reproduced with permission from: Silverberg SG, Kurman RJ. tumors of the Uterine
Corpus and Gestational Trophoblastic Disease. AFIP Atlas of Tumor Pathology, version
2.0, American Registry of Pathology, Washington DC 1995.
Graphic 73416 Version 2.0
Staging uterine carcinoma* (TNM and International Federation of Gynecology and
Obstetrics [FIGO])
Primary tumor (T) (surgicalpathologic findings)
TNM FIGO
Definition
categories stages
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
Tis ¶ Carcinoma in situ (preinvasive carcinoma)
T1 I Tumor confined to corpus uteri
T1a IA Tumor limited to endometrium or invades less than onehalf of the myometrium
T1b IB Tumor invades onehalf or more of the myometrium
T2 II Tumor invades stromal connective tissue of the cervix but does not extend beyond uterus Δ
T3a IIIA Tumor involves serosa and/or adnexa (direct extension or metastasis)
T3b IIIB Vaginal involvement (direct extension or metastasis) or parametrial involvement
T4 IVA Tumor invades bladder mucosa and/or bowel mucosa (bullous edema is not sufficient to
classify a tumor as T4)
Regional lymph nodes (N)
TNM FIGO
Definition
categories stages
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 IIIC1 Regional lymph node metastasis to pelvic lymph nodes
N2 IIIC2 Regional lymph node metastasis to paraaortic lymph nodes, with or without positive pelvic
lymph nodes
Distant metastasis (M)
TNM FIGO
Definition
categories stages
M0 No distant metastasis
M1 IVB Distant metastasis (includes metastasis to inguinal lymph nodes intraperitoneal disease, or
lung, liver, or bone. It excludes metastasis to paraaortic lymph nodes, vagina, pelvic
serosa, or adnexa.)
Anatomic stage/prognostic groups
Carcinomas*
Stage 0 ¶ Tis N0 M0
Stage I T1 N0 M0
Stage IA T1a N0 M0
Stage IB T1b N0 M0
Stage II T2 N0 M0
Stage III T3 N0 M0
Stage IIIA T3a N0 M0
Stage IIIB T3b N0 M0
Stage IIIC1 T1T3 N1 M0
Stage IIIC2 T1T3 N2 M0
Stage IVA T4 Any N M0
Stage IVB Any T Any N M1
NOTE: cTNM is the clinical classification, pTNM is the pathologic classification.
* Carcinosarcomas should be staged as carcinoma.
¶ FIGO no longer includes Stage 0 (Tis).
Δ Endocervical glandular involvement only should be considered as Stage I and not as Stage II.
Used with the permission of the American Joint Committee on Cancer (AJCC), Chicago, Illinois. The original source for this
material is the AJCC Cancer Staging Manual, Seventh Edition (2010) published by Springer New York, Inc.
Uterine corpus carcinoma grades: degrees of histopathologic differentation
Cases of carcinoma of the corpus should be grouped with regard to the degree of
differentation of the adenocarcinoma as follows:
G1 5 percent or less of a nonsquamous or nonmorular solid growth pattern
G2 6 percent to 50 percent of a nonsquamous or nonmorular solid growth pattern
G3 More than 50 percent of a nonsquamous or nonmorular solid growth pattern
Used with the permission of the American Joint Committee on Cancer (AJCC), Chicago, Illinois. The original source for this
material is the AJCC Cancer Staging Manual, Seventh Edition (2010) published by Springer New York, Inc.
Incidence of pelvic and paraaortic lymph node metastases in clinical stage I
endometrial carcinoma
Depth of myometrial invasion
Histologic grade n
None Inner third Middle third Outer third
Percent pelvic lymph nodes involved
1 180 0 3 0 11
2 288 3 5 9 19
3 153 0 9 4 34
Percent paraaortic lymph nodes involved
1 180 0 1 5 6
2 288 3 4 0 14
3 153 0 4 0 24
Adapted from Creasman WT, Morrow CP, Bundy BN, et al, Cancer 1987; 60(8 Suppl):2035.
Lymph node groups in women
The green dots indicate the location of lymph nodes, which are found throughout the body.
Female pelvic lymphadenectomy
Lymph node dissection is begun by sharply and bluntly mobilizing the tissue lateral
to the external iliac artery and vein, and moving this tissue until the external iliac
artery can be identified. The dissection should be kept close to the artery to
facilitate the resection. Using Metzenbaum scissors and forceps, the lymphatic tissue
is then sharply dissected off the surface of the external and common iliac arteries,
and reflected medially. With lateral traction at this time, the external iliac vein and
obturator fossa can be identified.
Courtesy of William J Mann, Jr, MD.
Types of hysterectomy
Subtotal/supracervical
Subtotal/supracervical hysterectomy. The uterus is removed. The superior portion of the cervix is amputated, the
remainder of the cervix is conserved. Intrafascial hysterectomy is a subtype of subtotal hysterectomy in which the
uterosacral ligaments are conserved. [1]
PiverRutledgeSmith Classification [2]
Class l
Extrafascial hysterectomy. The fascia of the cervix and lower uterine segment, which is rich in lymphatics, is
removed with the uterus.
Class ll
Modified radical hysterectomy. The uterine artery is ligated where it crosses over the ureter and the uterosacral
and cardinal ligaments are divided midway towards their attachment to the sacrum and pelvic sidewall,
respectively. The upper onethird of the vagina is resected.
Class lll
Radical hysterectomy. The uterine artery is ligated at its origin from the superior vesical or internal iliac artery.
Uterosacral and cardinal ligaments are resected at their attachments to the sacrum and pelvic sidewall. The upper
onehalf of the vagina is resected.
Class lV
Radical hysterectomy. The ureter is completely dissected from the vesicouterine ligament, the superior vesical
artery is sacrificed, and threefourths of the vagina is resected.
Class V
Radical hysterectomy. There is additional resection of a portion of the bladder or distal ureter with ureteral
reimplantation into the bladder.
References:
1. Semm K. Hysterectomy via laparotomy or pelviscopy. A new CASH method without colpotomy (German).
Geburtshilfe Frauenheilkd 1991; 51:996.
2. Piver MS. Five classes of extended hysterectomy for women with cervical cancer. Obstet Gynecol 1974; 44:265.
Uterine carcinoma: FIGO surgical stage and overall survival
FIGO stage Fiveyear overall survival, percent
IA 90.3
IB 80.8
II 80.5
IIIA 68.5
IIIB 53.1
IIIC1 58.3
IIIC2 51.2
IVA 22.0
IVB 21.1
Data from: SEER database for patients treated in 1988 through 2006, staging in these patients includes
lymphadenectomy, staged according to the 2010 FIGO staging system (from Obstet Gynecol 2010; 116:1141).
FIGO: International Federation of Gynecology and Obstetrics; SEER: Surveillance, Epidemiology, and End Results.

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T3a IIIA Tumor involves serosa and/or adnexa (direct extension or metastasis)

T3b IIIB Vaginal involvement (direct extension or metastasis) or parametrial involvement

Stage IVB Any T Any N M1

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