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Adjuvant treatment of high-risk endometrial cancers

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Adjuvant treatment of high-risk endometrial cancers

Authors: Gini Fleming, MD, Paul A DiSilvestro, MD

Section Editors: Barbara Goff, MD, Don S Dizon, MD, FACP

Deputy Editor: Sadhna R Vora, MD

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Feb 2017. | This topic last updated: Sep 22, 2016.

INTRODUCTION — Adenocarcinomas of the endometrium are the most common gynecologic malignancy in

developed countries and the second most common in developing countries. Among the different histologic types

of adenocarcinomas, grade 1 and 2 endometrioid uterine cancers have a favorable prognosis and typically

present at an early stage. Other histologic types of uterine adenocarcinoma (eg, serous, clear cell) are

associated with a poorer prognosis.

The American Joint Committee on Cancer (AJCC) and International Federation of Gynecology and Obstetrics

(FIGO) combined staging system is used to designate cancer stage (table 1). In addition to stage, other

pathologic factors are used to assign risk for recurrent or persistent disease into low, intermediate, and high risk.

Women with high-risk endometrial cancer have a poor prognosis following surgery alone. Therefore, adjuvant

treatment is often administered, although the effect of any therapy following surgery on overall survival is unclear.

This review will focus on treatment of high-risk endometrial cancer.

An overview of endometrial cancer, including clinical features and an approach to diagnosis, the approach to

adjuvant treatment, and treatment of both low- and intermediate-risk endometrial cancer are discussed

separately.

®

®

● (See "Overview of endometrial carcinoma".)

● (See "Endometrial carcinoma: Clinical features and diagnosis".)

● (See "Approach to adjuvant treatment of endometrial cancer".)

● (See "Adjuvant treatment of intermediate-risk endometrial cancer".)

● (See "Treatment of low-risk endometrial cancer".)

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DEFINITION OF HIGH RISK — Patients are classified as having high-risk endometrial cancer if they have

serous or clear cell adenocarcinoma (any stage) or pathologic stages III/IV disease (table 1).

Some experts also include the presence of specific risk factors for women with early-stage endometrial cancer

(ie, deep myometrial invasion, grade 3 disease, tumor lymphovascular space invasion [LVSI]) (see 'High

intermediate-risk disease' below and "Adjuvant treatment of intermediate-risk endometrial cancer"). Results of

The Cancer Genome Atlas (TCGA) analysis suggest that a subset of grade 3 endometrioid cancers are

biologically similar to serous carcinomas, but this subgroup has not been well defined using conventional

clinicopathologic factors [1].

The evidence to support this definition of high risk is reviewed below.

Uterine serous or clear cell carcinoma — Compared with endometrioid adenocarcinomas, uterine serous and

clear cell carcinomas are more aggressive histologic types [2]. This was demonstrated in a Surveillance,

Epidemiology, and End Results (SEER) study of cases diagnosed from 1998 to 2001 [2]. The five-year survival

rate stratified by histologic type was 45, 65, and 91 percent for serous, clear cell, and endometrioid

adenocarcinomas, respectively.

This poorer prognosis was also seen when stratified by stage at presentation [2]:

Stage III disease — Compared with women with early-stage I or II endometrial cancer (table 1), patients with

surgical and pathologic stage III endometrial cancer have a lower five-year survival rate (60 versus 97 and 80

percent for stage I and II, respectively) [2]. However, outcomes appear to differ based on grade. Among women

with stage III disease, those with grade 1 adenocarcinoma have a higher five-year survival rate (83 versus 68

and 48 percent for women with grade 2 or 3 tumors, respectively).

High intermediate-risk disease — Individual experts and cooperative groups may also include women with

intermediate-risk endometrial cancer in clinical trials of high-risk endometrial cancer based on three tumorassociated

risk factors: grade 2 or 3 histology, outer-third myometrial invasion, or LVSI. The Gynecologic

Oncology Group (GOG) has used these factors to include women in clinical trials for high-risk endometrial cancer

as below:

● (See "Treatment of recurrent or metastatic endometrial cancer".)

Among women diagnosed with stage I serous, clear cell, or endometrioid cancers, the five-year survival rate

was 74, 88, and 95 percent.

● Among women with stage II cancers, it was 56, 67, and 86 percent, respectively.

● Among women with stage III cancers, it was 33, 48, and 67 percent, respectively.

● Among women with stage IV cancers, it was 18, 18, and 37 percent, respectively.

● Patients of any age with all three risk factors

● Patients 50 to 69 years old with at least two factors

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A discussion on the approach to women with high intermediate-risk endometrial cancer is covered separately.

(See "Adjuvant treatment of intermediate-risk endometrial cancer", section on 'High intermediate-risk disease'.)

TREATMENT APPROACH — Given the lack of high-quality data to help guide recommendations, there is no

uniform approach to the treatment of women with high-risk endometrial cancer. For women with surgically and

pathologically defined high-risk endometrial cancer, we take into account whether disease is confined to the

uterus (stage I/II) or whether disease extends outside of the uterus (stage III) (table 1).

Women with bulky stage III disease not amenable to surgery cannot be cured by nonsurgical therapy alone, and

these patients are treated similarly to women with recurrent or metastatic endometrial cancer. (See "Treatment of

recurrent or metastatic endometrial cancer".)

Serous carcinoma — The risk of recurrence and death for women with serous carcinoma is dependent on the

extent of tumor involvement. For women with early-stage disease (stage I to II), our approach is discussed

below. The approach to women with fully resected stage III disease is discussed separately. (See 'Stage III

disease, regardless of histology' below.)

Stage IA disease without myometrial invasion — Although the data are limited, women with endometrial

serous carcinoma without myometrial invasion (subset of stage IA) are at a lower risk of recurrence compared

with women with myometrial invasion (9 versus 29 percent) [3]. Therefore, we prefer to treat these patients with

vaginal brachytherapy (VBT) alone (with or without radiation therapy [RT]). However, given the overall low risk of

recurrence, observation may be a reasonable alternative. A review of cases of stage IA polyp- or endometriumlimited

endometrial cancers of clear cell, serous, or mixed histology who received a variety of adjuvant therapies

showed a three-year progression-free survival (PFS) rate of 94.9 percent and no impact of histologic subtype on

adjuvant treatment [4].

An analysis of stage IA noninvasive serous carcinomas showed that adjuvant chemotherapy or pelvic radiation

had no impact on outcome in patients who had undergone lymphadenectomy. There was an improved outcome

for unstaged patients, but this effect was likely due to occult spread to lymph nodes in a number of these

patients. The overall risk of recurrence in staged patients with no adjuvant therapy was 23.5 percent with a

median follow-up time of 52 months [5]. Surgical staging, including lymph node assessment, for patients with

endometrial cancer is discussed elsewhere. (See "Endometrial carcinoma: Pretreatment evaluation, staging, and

surgical treatment", section on 'Staging and primary surgical treatment'.)

Stage IA or IB disease — For women with early-stage serous carcinoma with myometrial invasion (stage IA

or IB), we suggest adjuvant chemotherapy plus RT [3,6-9], although the evidence for use of RT is not as strong

as the evidence for the use of chemotherapy. The largest dataset supporting the adjuvant use of chemotherapy

in stage I serous carcinomas comes from the Uterine Papillary Serous Carcinoma Consortium study that

included 142 women with stage I serous cancers [6]. Following surgery, 23 percent received no further treatment,

while 14 and 63 percent were treated with adjuvant RT alone or adjuvant chemotherapy, respectively. Of those

receiving chemotherapy (primarily carboplatin and paclitaxel administered for three or more cycles), 37 percent

also received RT. Adjuvant chemotherapy was associated with:

● Patients who are 70 years or older with at least one factor

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As with most retrospective studies, there is the possibility of bias in the selection of treatments and particularly, in

who did or did not receive chemotherapy.

Stage II disease — For women with stage II serous carcinoma, we suggest adjuvant chemotherapy plus RT.

The largest report on outcomes for women with stage II serous carcinoma comes from the Uterine Papillary

Serous Carcinoma Consortium and included 55 women (20 and 35 with stage IIA and IIB disease, respectively)

[10]. Of these, 10 (18 percent) underwent observation following surgery, 19 (34.5 percent) were treated with

chemotherapy (18 of whom were treated with carboplatin plus paclitaxel), and 26 (47.3 percent) underwent RT

(though it is unclear if pelvic and/or VBT was administered). Of those treated with chemotherapy (n = 19), the

median number of cycles was five (range, three to six). Of the 38 total patients treated with RT (with or without

chemotherapy), 34, 50, and 16 percent were treated with VBT, whole-pelvic RT plus VBT, and whole-abdominal

RT (alone or in combination with pelvic RT or VBT), respectively.

Patients who received adjuvant chemotherapy (with or without RT) had:

This recommendation is supported by a report from the Canadian high-risk endometrial cancer consortium

(CHREC) [11]. They analyzed data on patients treated between 2000 and 2012 from seven centers. A

multivariable analysis including only surgically staged stage I and II serous carcinoma showed that the use of

chemotherapy was associated with an improvement in OS, while the use of adjuvant radiotherapy was not.

Clear cell carcinoma — There are no prospective data to help define the optimal management of women with

clear cell carcinoma. In the absence of high-quality data, some UpToDate contributors favor treating clear cell

carcinomas with chemotherapy and radiation, along the lines of serous carcinoma. If such an approach is

adopted, it is preferable to treat clear cell carcinoma initially with chemoradiation followed by chemotherapy,

given that this histology is likely to be more chemoresistant than other histologies. Other UpToDate contributors

utilize radiation alone for clear cell carcinoma (vaginal brachytherapy, with or without pelvic RT), given that the

limited data that exist support an improvement in survival with radiation but not chemotherapy. In a study by the

CHREC, among patients with stage I to III clear cell carcinoma, adjuvant radiotherapy was associated with an

improvement in overall survival, while adjuvant chemotherapy was not [11].

A statistically significant reduction in the recurrence rate (11 versus 30 and 25 percent with surgery alone or

surgery followed by RT, respectively).

A statistically significant improvement in five-year progression-free survival (PFS, 82, 64, and 65 percent,

respectively).

An improvement in five-year cancer-specific survival (88, 60, and 70 percent, respectively) that was

statistically nonsignificant.

A statistically significant reduction in the recurrence rate compared with those not treated with chemotherapy

(10 versus 50 percent, respectively).

● A statistically significant improvement in PFS at five years (86 versus 41 percent, respectively).

● An improvement in overall survival (OS, 88 versus 64 percent), although it was not statistically significant.

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Stage III disease, regardless of histology — Patients with extrauterine disease confined to the pelvis or vagina

(stage III) are treated with chemotherapy. Adjuvant chemotherapy is associated with improvement in both PFS

and OS, regardless of whether RT is used. Although there are more prospective randomized data supporting the

use of chemotherapy than exist for radiotherapy in stage III disease, we agree with the current American Society

for Radiation Oncology (ASTRO) guidelines and suggest use of radiotherapy in addition to chemotherapy,

particularly in women with a good performance status. (See 'Timing of radiation with chemotherapy' below.)

As a possible exception to this approach, some UpToDate contributors treat clear cell carcinoma as well as

grade 1 endometrioid carcinomas with limited nodal involvement (1 to 2 nodes) with radiation alone, although

others also utilize chemotherapy, as for other histologies. (See 'Clear cell carcinoma' above.)

The benefit of adjuvant chemotherapy for women with stage III endometrial cancer is supported by a 2013 metaanalysis

(updated in May 2014) that included the data from two Gynecologic Oncology Group (GOG) randomized

trials (n = 620) [12]:

Compared with RT, the administration of platinum-based combination chemotherapy resulted in:

While prospective randomized data of chemotherapy versus chemotherapy and radiation are not yet available, a

phase 2 study of combined-modality treatment suggested favorable outcomes compared with historic results of

chemotherapy only. In the Radiation Therapy Oncology Group (RTOG) 9708 phase 2 trial of pelvic radiation with

concurrent cisplatin followed by four cycles of paclitaxel and cisplatin, the pelvic failure rate was 2 percent [13],

whereas it was 18 percent among patients treated with chemotherapy only in GOG 122 [14]. Retrospective data

of patients with optimally resected stage IIIC disease also suggest improved outcomes with chemotherapy and

radiation compared with chemotherapy alone [15,16]. For example, in a registry study including over 21,000

patients with stage III endometrial cancer, patients receiving adjuvant chemoradiotherapy experienced a

decreased risk of death on multivariate analysis relative to those receiving adjuvant RT or chemotherapy only

(HR 0.62, 95% CI 0.56-0.70) [16]. Retrospective data also specifically support the use of RT in stage IIIC serous

carcinomas [17].

We await reporting of GOG 258, a prospective trial in which women with stage III disease were randomly

assigned to chemotherapy alone or chemotherapy with pelvic radiotherapy, to further inform our approach.

Choice of chemotherapy regimen — For most women with high-risk endometrial cancer, we suggest

carboplatin and paclitaxel in the adjuvant setting. This is based on the results of GOG 209, which were presented

at the 2012 Society of Gynecologic Oncology Annual Meeting [18]. This trial compared carboplatin plus paclitaxel

GOG 122 – A comparison of whole-abdominal RT versus chemotherapy (doxorubicin plus cisplatin) in

women with cytoreduced stage III or IV endometrial cancer.

GOG 184 – A comparison of two different chemotherapy regimens (doxorubicin plus cisplatin [AP] with or

without paclitaxel [TAP]) among women with stage III or IV endometrial cancer, all of whom were also

treated with RT.

● Significant improvement in OS (hazard ratio [HR] 0.75, 95% CI 0.57-0.99)

● Significant improvement in PFS (HR 0.74, 95% CI 0.59-0.92)

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with TAP in 1300 women with chemotherapy-naïve advanced endometrial cancer, including women with stage III

disease, and demonstrated that carboplatin and paclitaxel results in an equivalent overall response rate, similar

PFS, and is also less toxic. The results of GOG 209 are discussed separately. (See "Treatment of recurrent or

metastatic endometrial cancer", section on 'First-line chemotherapy' and "Treatment protocols for gynecologic

malignancies", section on 'Carboplatin plus paclitaxel'.)

Timing of radiation with chemotherapy — For those in whom radiation is indicated, acceptable approaches

include giving radiation after completion of six cycles of chemotherapy, "sandwiched" in between three cycles of

chemotherapy before and after radiation treatment, or concurrently, per RTOG 9708. Radiation adds toxicity to

chemotherapy but has been shown to be feasible in multiple studies. (See "Treatment-related toxicity from the

use of radiation therapy for gynecologic malignancies".)

Is there a role for adjuvant endocrine therapy? — For women with high-risk endometrial adenocarcinoma, we

recommend not using endocrine therapy as adjuvant treatment. (See "Treatment of low-risk endometrial cancer",

section on 'Progestin therapy'.).

CLINICAL TRIALS — Whenever possible, we prefer that women with high-risk endometrial cancer participate in

clinical trials [19].

A trial that has completed accrual and should clarify the standard of care in endometrial cancer is the

Postoperative Radiation Therapy for Endometrial Cancer 3 (PORTEC 3) trial, which included women with highrisk

stage I (including women with serous or clear cell cancers), stage II, and III endometrial cancers. Patients

were randomly assigned to treatment with adjuvant pelvic radiation therapy (RT) alone or to pelvic RT with

concomitant cisplatin followed by four cycles of chemotherapy (carboplatin plus paclitaxel).

Another study, Gynecologic Oncology Group (GOG 258), enrolled women with stage I or II serous or clear cell

cancer with positive peritoneal cytology or women with optimally resected (ie, residual tumor after surgery at any

one site ≤2 cm) stage III or IVA endometrial cancer, all of whom were randomly assigned to adjuvant

chemotherapy alone (six cycles of carboplatin plus paclitaxel) or to concomitant chemoradiation followed by four

cycles of adjuvant carboplatin plus paclitaxel.

SPECIAL CONSIDERATIONS

Newly diagnosed stage IV disease — For women with metastatic endometrial cancer extending to the bladder

or rectum (stage IVA) or to the abdominal cavity or other visceral organs (ie, liver or lung, stage IVB), the fiveyear

overall survival rate is approximately 25 percent [2]. Women with disease limited to the pelvis or abdominal

carcinomatosis may be candidates for surgical cytoreduction based on retrospective series showing superior

outcomes with optimal surgical debulking, regardless of histologic subtype [20-23]. (See "Endometrial carcinoma:

Pretreatment evaluation, staging, and surgical treatment", section on 'Cytoreduction'.)

However, upfront surgery may be challenging, particularly in women with bulky upper abdominal disease, and

there is no high-quality evidence regarding surgery prior to chemotherapy for women with metastatic endometrial

cancer. (See "Treatment of recurrent or metastatic endometrial cancer".)

Older women — Older age has been associated with higher rates of clinical failure, but whether age represents

an independent prognostic factor is controversial. Women over the age of 65 more frequently have deep

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myometrial invasion, high tumor grade, and advanced tumor stage. Furthermore, less aggressive therapy could

also account for some of the poor outcomes seen in older patients. (See "Approach to adjuvant treatment of

endometrial cancer", section on 'Older age'.)

Because organ function declines and the number of comorbidities increases as women become older, the risks

of chemotherapy are potentially magnified. As such, it becomes less clear if women will live long enough to

experience potential survival benefits of treatment to justify the expected risks of chemotherapy. Therefore, we

suggest older women undergo comprehensive geriatric assessment to aid in decisions regarding adjuvant

chemotherapy. (See "Systemic chemotherapy for cancer in elderly persons" and "Comprehensive geriatric

assessment for patients with cancer".)

Obese women — Endometrial cancer is associated with obesity, and morbid obesity is common among

endometrial cancer patients. Although clinical practice varies, overweight or obese women often receive

intentionally reduced chemotherapy doses based upon ideal rather than actual body weight. However, there are

no data to support this practice. We agree with guidelines from the American Society of Clinical Oncology and

suggest full weight-based cytotoxic chemotherapy dosing in the adjuvant setting [24]. (See "Dosing of anticancer

agents in adults", section on 'Overweight/obese patients'.)

Approach to lymph node dissection in such patients is discussed elsewhere. (See "Pelvic and paraaortic

lymphadenectomy in gynecologic cancers", section on 'Lymphadenectomy procedure'.)

PROGNOSIS — Women with high-risk endometrial cancer are at an increased risk of disease progression and

death from their disease, even when detected at an early stage. Beyond histologic subtype, prognosis is highly

dependent on both stage and tumor grade. For example, in a Surveillance, Epidemiology, and End Results

(SEER) study of over 44,000 women, five-year survival was 97, 80, 60, and 25 percent for stage I, II, III, or IV

disease [2]. Among women with stage III disease, five-year relative survival is 83, 68, and 48 percent for grade 1,

2, or 3 adenocarcinomas, respectively [2]. (See "Overview of endometrial carcinoma", section on 'Prognosis'.)

POSTTREATMENT SURVEILLANCE — The majority of recurrences occur within three years of treatment.

Approximately 70 percent of patients develop symptoms at the time of recurrence (eg, vaginal bleeding,

abdominal pain, cough, weight loss). While posttreatment surveillance protocols may vary by institution, we

suggest clinical exam (including symptom review, symptom-directed physical exam, and pelvic exam) at threemonth

intervals for two years, then every six months or annually. Detecting isolated vaginal occurrences early is

of particular importance as they may sometimes be cured by radiotherapy, or in patients with prior radiotherapy,

surgery. While CA-125 is used by some clinicians as part of routine surveillance, there is no high-quality

evidence that CA-125 surveillance improves outcomes. (See "Treatment of recurrent or metastatic endometrial

cancer", section on 'Isolated vaginal recurrence' and "Overview of endometrial carcinoma", section on

'Posttreatment surveillance'.)

SUMMARY AND RECOMMENDATIONS

Patients are classified as having high-risk endometrial cancer if they have serous or clear cell

adenocarcinoma (any stage) or pathologic stage III disease (table 1). Some experts also include the earlystage

tumors with specific risk factors for cancer (ie, deep myometrial invasion, grade 3 disease, tumor

lymphovascular space invasion [LVSI]) in this group. (See 'Definition of high risk' above.)

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REFERENCES

1. Cancer Genome Atlas Research Network, Kandoth C, Schultz N, et al. Integrated genomic characterization

of endometrial carcinoma. Nature 2013; 497:67.

2. Kosary C. Cancer of the Corpus Uteri. In SEER Survival Monograph: Cancer Survival Among Adults: U.S.

SEER Program, 1988-2001, Patient and Tumor Characteristics. NCI, SEER Program, National Cancer

Institute; Bethesda, MD 2007.

3. Havrilesky LJ, Secord AA, Bae-Jump V, et al. Outcomes in surgical stage I uterine papillary serous

carcinoma. Gynecol Oncol 2007; 105:677.

4. Liang LW, Perez AR, Cangemi NA, et al. An Assessment of Prognostic Factors, Adjuvant Treatment, and

Outcomes of Stage IA Polyp-Limited Versus Endometrium-Limited Type II Endometrial Carcinoma. Int J

Gynecol Cancer 2016; 26:497.

5. Mahdi H, Elshaikh MA, DeBenardo R, et al. Impact of adjuvant chemotherapy and pelvic radiation on

pattern of recurrence and outcome in stage I non-invasive uterine papillary serous carcinoma. A multiinstitution

study. Gynecol Oncol 2015; 137:239.

6. Fader AN, Starks D, Gehrig PA, et al. An updated clinicopathologic study of early-stage uterine papillary

serous carcinoma (UPSC). Gynecol Oncol 2009; 115:244.

7. Kelly MG, O'malley DM, Hui P, et al. Improved survival in surgical stage I patients with uterine papillary

serous carcinoma (UPSC) treated with adjuvant platinum-based chemotherapy. Gynecol Oncol 2005;

98:353.

8. Elit L, Kwon J, Bentley J, et al. Optimal management for surgically Stage 1 serous cancer of the uterus.

Gynecol Oncol 2004; 92:240.

9. Huh WK, Powell M, Leath CA 3rd, et al. Uterine papillary serous carcinoma: comparisons of outcomes in

For women with stage IA serous or clear cell carcinoma without myometrial invasion, we suggest adjuvant

vaginal brachytherapy (VBT) (Grade 2C). However, given the overall low risk of recurrence, observation

may be a reasonable alternative. (See 'Stage IA disease without myometrial invasion' above.)

For women with stage IA (with myometrial invasion), IB, and II serous carcinoma, we suggest adjuvant

chemotherapy plus VBT (Grade 2C). We suggest carboplatin plus paclitaxel rather than other platinumbased

combination regimens (Grade 2C). (See 'Stage IA or IB disease' above and 'Stage II disease' above

and 'Choice of chemotherapy regimen' above.)

For women with stage I/II clear cell cancer, we suggest adjuvant radiation therapy (RT) alone rather than

chemotherapy plus RT (Grade 2C). Some clinicians prefer to administer adjuvant chemotherapy, and in the

absence of high-quality data, this is a reasonable option. (See 'Clear cell carcinoma' above.)

For women with stage III endometrial cancer, we recommend adjuvant chemotherapy (Grade 1B). We

suggest carboplatin and paclitaxel rather than other combinations (Grade 2C). For women with good

performance status, we also suggest combining chemotherapy with directed RT in order to reduce the risk of

both local and distant recurrence (Grade 2C). Women with clear cell carcinomas or grade 1 tumors with

limited nodal involvement may reasonably be treated with RT alone. (See 'Stage III disease, regardless of

histology' above.)

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surgical Stage I patients with and without adjuvant therapy. Gynecol Oncol 2003; 91:470.

10. Fader AN, Nagel C, Axtell AE, et al. Stage II uterine papillary serous carcinoma: Carboplatin/paclitaxel

chemotherapy improves recurrence and survival outcomes. Gynecol Oncol 2009; 112:558.

11. Bernardini MQ, Gien LT, Lau S, et al. Treatment related outcomes in high-risk endometrial carcinoma:

Canadian high risk endometrial cancer consortium (CHREC). Gynecol Oncol 2016; 141:148.

12. Galaal K, Al Moundhri M, Bryant A, et al. Adjuvant chemotherapy for advanced endometrial cancer.

Cochrane Database Syst Rev 2014; :CD010681.

13. Greven K, Winter K, Underhill K, et al. Final analysis of RTOG 9708: adjuvant postoperative irradiation

combined with cisplatin/paclitaxel chemotherapy following surgery for patients with high-risk endometrial

cancer. Gynecol Oncol 2006; 103:155.

14. Randall ME, Filiaci VL, Muss H, et al. Randomized phase III trial of whole-abdominal irradiation versus

doxorubicin and cisplatin chemotherapy in advanced endometrial carcinoma: a Gynecologic Oncology

Group Study. J Clin Oncol 2006; 24:36.

15. Secord AA, Geller MA, Broadwater G, et al. A multicenter evaluation of adjuvant therapy in women with

optimally resected stage IIIC endometrial cancer. Gynecol Oncol 2013; 128:65.

16. Boothe D, Orton A, Odei B, et al. Chemoradiation versus chemotherapy or radiation alone in stage III

endometrial cancer: Patterns of care and impact on overall survival. Gynecol Oncol 2016; 141:421.

17. Lin JF, Muñiz K, Sukumvanich P, et al. Survival advantage associated with multimodal therapy in women

with node-positive (stage-IIIC) uterine papillary serous carcinoma: a National Cancer Database study.

BJOG 2016; 123:1846.

18. Miller DS, Filiaci G, Mannel R, et al. Randomized Phase III Noninferiority Trial of First Line Chemotherapy

for Metastatic or Recurrent Endometrial Carcinoma: A Gynecologic Oncology Group Study. LBA2.

Presented at the 2012 Society of Gynecologic Oncology Annual Meeting, Austin, TX.

19. NCCN Clinical Practice Guidelines in Oncology- Uterine Neoplasms (Version 2.2012)

http://www.nccn.org/professionals/physician_gls/pdf/uterine.pdf (Accessed on March 07, 2012).

20. Patsavas K, Woessner J, Gielda B, et al. Optimal surgical debulking in uterine papillary serous carcinoma

affects survival. Gynecol Oncol 2011; 121:581.

21. Rauh-Hain JA, Growdon WB, Schorge JO, et al. Prognostic determinants in patients with stage IIIC and IV

uterine papillary serous carcinoma. Gynecol Oncol 2010; 119:299.

22. Shih KK, Yun E, Gardner GJ, et al. Surgical cytoreduction in stage IV endometrioid endometrial carcinoma.

Gynecol Oncol 2011; 122:608.

23. Bristow RE, Zerbe MJ, Rosenshein NB, et al. Stage IVB endometrial carcinoma: the role of cytoreductive

surgery and determinants of survival. Gynecol Oncol 2000; 78:85.

24. Griggs JJ, Mangu PB, Anderson H, et al. Appropriate chemotherapy dosing for obese adult patients with

cancer: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol 2012; 30:1553.

Topic 16721 Version 14.0

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GRAPHICS

Staging uterine carcinoma* (TNM and International Federation of Gynecology and

Obstetrics [FIGO])

Primary tumor (T) (surgical-pathologic findings)

TNM

categories

FIGO

stages

Definition

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 one-half of the myometrium

T1b IB Tumor invades one-half or more of the myometrium

T2 II Tumor invades stromal connective tissue of the cervix but does not extend beyond uterus

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

categories

FIGO

stages

Definition

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 para-aortic lymph nodes, with or without positive

pelvic lymph nodes

Distant metastasis (M)

TNM

categories

FIGO

stages

Definition

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 para-aortic lymph nodes, vagina, pelvic

serosa, or adnexa.)

Anatomic stage/prognostic groups

Carcinomas*

Stage 0 Tis N0 M0

Stage I T1 N0 M0

Δ

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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 T1-T3 N1 M0

Stage IIIC2 T1-T3 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.

Graphic 51307 Version 14.0

Adjuvant treatment of high-risk endometrial cancers - UpToDate 3/17/17, 10:04 AM

https://www.uptodate.com/contents/adjuvant-treatment-of-high-risk-endometrial-cancers/print?source=see_link Page 12 of 12

Contributor Disclosures

Gini Fleming, MD Nothing to disclose Paul A DiSilvestro, MD Nothing to disclose Barbara Goff,

MD Consultant/Advisory Boards: Roche Diagnostics [Biomarkers for ovarian cancer (HE4)]. Employment

(Spouse): Lilly [General oncology (Gemcitabine, pemetrexed)] - No relevant conflict on topics. Don S Dizon,

MD, FACP Consultant/Advisory Boards: Pfizer [Chemotherapy (Biosimilars)]. Sadhna R Vora, MD Nothing to

disclose

Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are

addressed by vetting through a multi-level review process, and through requirements for references to be

provided to support the content. Appropriately referenced content is required of all authors and must conform

to UpToDate standards of evidence.

 

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