This article appears in the following Annals of Oncology issue: ESMO Clinical Recommendations [View the issue table of contents]
ESMO clinical recommendations |
Endometrial carcinoma: ESMO Clinical Recommendations for diagnosis, treatment and follow-up
1 Department of Gynecological Oncology, The Norwegian Radium Hospital, Oslo, Norway
2 Institute of Social and Preventive Medicine (ISPM), University of Geneva, Geneva, Switzerland
* Correspondence to: ESMO Guidelines Working Group, ESMO Head Office, Via L. Taddei 4, CH-6962 Viganello-Lugano, Switzerland; E-mail: clinicalrecommendations{at}esmo.org
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incidence |
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 Top incidence diagnosisstaging and risk assessmenttreatment planfollow-upnotereferences |
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The crude incidence of endometrial carcinoma in the European Union is 16 cases/100 000 women/year (range 13–24). The mortality is 4–5 cases/100 000/year. The lifetime risk of developing endometrial carcinoma is
1.7–2%, and age-standardized incidence rates continue to rise in most developed countries. |
diagnosis |
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Topincidencediagnosisstaging and risk assessmenttreatment planfollow-upnotereferences |
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The diagnosis of endometrial carcinoma requires histopathological confirmation. This diagnosis is made according to the WHO pathological classification. About 80% of endometrial carcinomas are of endometrioid type. Serous (5–10%), clear cell (1–5%), mucinous, mixed, squamous cell, transitional cell and undifferentiated carcinomas are other established subtypes. Endometrial carcinosarcoma is now considered a special, poor-prognosis subtype of endometrial carcinoma.
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staging and risk assessment |
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Topincidencediagnosisstaging and risk assessmenttreatment planfollow-upnotereferences |
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Endometrial carcinoma is a surgically staged disease. The minimal procedure should include the acquisition of peritoneal fluid or washings, a thorough exploration of the abdominal cavity and pelvic and para-aortic nodal areas, and a total hysterectomy with bilateral salpingo-oophorectomy. In high-risk cases retroperitoneal lymph node dissection and omentectomy (for serous carcinomas) are often recommended, though the effect of these procedures on survival is debated [III, B].
The most widely used staging system is the one endorsed by the Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) as given in Table 1.
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degree of differentiation:
Cases of endometrial carcinoma should be graded according to their degree of histological differentiation, as follows:
- G1, a non-squamous, non-morula solid growth pattern comprises
5% of the tumor;
- G2, a non-squamous, non-morula solid growth pattern comprises 5–50% of the tumor;
- G3, a non-squamous, non-morula solid growth pattern comprises >50% of the tumor.
- G2, a non-squamous, non-morula solid growth pattern comprises 5–50% of the tumor;
• Notable nuclear atypia, inappropriate for the architectural grade, raises the grade of a grade 1 or 2 tumor by one.
• Before surgery, patients should have a chest X-ray, clinical and gynecological examination including transvaginal ultrasound, blood counts, liver and renal function profiles. A CT scan of the abdomen and retroperitoneal nodes may be helpful in determining extra-uterine spread. Contrast-enhanced dynamic MRI is the best way to assess the uterine and locoregional pelvic extension of the disease [I, A]. There is, however, no fully reliable method to assess an individual patient's risk category either pre- or intra-operatively (frozen section). The preoperative histological diagnosis (type and grade) based on any type of endometrial sampling is changed at final histological evaluation in up to 25% of cases.
• Established, independent prognostic factors are FIGO surgical stage, histological grade, depth of myometrial invasion, histological type, tumor diameter, lymph–vascular space involvement, endocervical stromal invasion and patient age.
• About 75% of patients present with stage I disease and can be subdivided into three risk categories with regard to disease relapse and survival:
(i) low risk
• stage Ia/Ib, grade 1 or 2, endometrioid histology
(ii) intermediate risk
• stage Ic, grade 1 or 2, endometrioid histology
• stage Ia/Ib, grade 3, endometrioid histology
(iii) high risk
• stage Ic, grade 3, endometrioid histology
• stage Ia or Ib or Ic, serous, clear cell, small cell or undifferentiated histology.
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treatment plan |
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Topincidencediagnosisstaging and risk assessmenttreatment planfollow-upnotereferences |
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The type of surgery and postoperative therapy depends on the stage and other clinicopathological risk factors.
stage I
(i) low-risk group: no adjuvant therapy.
(ii) intermediate-risk group: adjuvant pelvic radiotherapy significantly reduces the risk of pelvic/vaginal relapses, but has no impact on overall survival (OS) [I, A]. Within the intermediate-risk group, in patients aged 
60 years, with deeply invasive G1 or G2 or superficially invasive G3 tumors, the loco-regional relapse rate is >15%, and adjuvant radiotherapy is recommended [II, B].
(iii) high-risk group: pelvic radiotherapy is recommended in order to increase loco-regional control. Adjuvant, platinum-based chemotherapy gives a significantly improved OS and progression-free survival (PFS) compared with adjuvant radiotherapy [I, A].
stage II
• Stage IIa: treated as stage I.
• Stage IIb: extended radical hysterectomy, bilateral salpingo-oophorectomy and lymph node dissection. Patients who had an extrafascial hysterectomy, or who have high-risk disease (according to definitions given for stage I) are recommended to have adjuvant pelvic (with or without intravaginal) radiotherapy.
• The adjuvant administration of progestational agents in low-stage endometrial cancer does not increase survival and is not recommended [I, A].
stages III and IV
• Maximal surgical cytoreduction is considered in patients with good performance status [III, B].
• Patients with stage III disease solely on the basis of positive peritoneal cyology are treated as patients with stage I or II disease, based on the other clinicopathological data.
• Pelvic control is increased with pelvic radiotherapy.
• Cisplatin, carboplatin, anthracyclines and paclitaxel have single-agent objective response rates.
• The combination of doxorubicin with cisplatin and paclitaxel (with bone marrow support) significantly improves PFS and OS compared with cisplatin and doxorubicin, but at the cost of higher toxicity, making it less attractive in this patient population [I, A].
• Cisplatin and doxorubicin significantly improved PFS and OS in patients with low residual stage III and IV disease compared with whole abdominal radiation therapy with pelvic boost [I, A].
• Because of toxicity considerations, an alternative option may be the combination of carboplatin and paclitaxel [III, B].
• Dosages, number of chemotherapy courses and response evaluation as recommended for advanced-stage ovarian cancer.
• Progestational agents, e.g. medroxyprogesterone acetate 200 mg daily, are active in steroid receptor-positive tumors (mostly G1 and G2 lesions) [III, B].
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follow-up |
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Topincidencediagnosisstaging and risk assessmenttreatment planfollow-upnotereferences |
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Most recurrences will occur within the first 3 years after treatment, and 3- to 4-montly evaluations with history, physical and gynecological examination are usually recommended. Follow-up intervals of 6 months are recommended during the fourth and fifth years, and annually thereafter. No impact on survival of a routine follow-up strategy has been demonstrated. However, since a significant number of relapses occur isolated in the vagina or pelvis, early detection and possibly curative treatment of these should be the main focus of follow-up. Routine technical examinations such as PAP smears or imaging studies are of unproven benefit.
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note |
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Topincidencediagnosisstaging and risk assessmenttreatment planfollow-upnotereferences |
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Levels of evidence [I–V] and grades of recommendations [A–D] as used by the American Society of Clinical Oncology are given in square brackets. Statements without grading were considered justified clinical practice by the experts and the ESMO faculty.
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footnotes |
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Approved by the ESMO Guidelines Working Group: October 2007, last update October 2008. This publication supercedes the previously published version—Ann Oncol 2008; 19 (Suppl 2):ii19–ii20.
Conflict of interest: the authors have reported no conflicts of interest.
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references |
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1. Kinkel K, Kaji Y, Yu KK, et al. Radiologic staging in patients with endometrial cancer: a meta-analysis. Radiology (1999) 212:711–718.
2. Chan JK, Wu H, Cheung MK, et al. The outcomes of 27 063 women with unstaged endometrioid uterine cancer. Gynecol Oncol (2007) 106:282–288.[CrossRef][Web of Science][Medline]
3. Frumovitz M, Singh DK, Meyer L, et al. Predictors of final histology in patients with endometrial cancer. Gynecol Oncol (2004) 95:463–468.[CrossRef][Web of Science][Medline]
4. Chan JK, Urban R, Cheung MK, et al. Lymphadenectomy in endometrioid uterine cancer staging: how many lymph nodes are enough? A study of 11 433 patients. Cancer (2007) 109:2454–2460.[CrossRef][Web of Science][Medline]
5. Mariani A, Webb MJ, Keeney GL, et al. Low-risk corpus cancer: is lymphadenectomy or radiotherapy necessary? Am J Obstet Gynecol (2000) 182:1506–1519.[CrossRef][Web of Science][Medline]
6. Scholten AN, van Putten WLJ, Beerman H, et al. Postoperative radiotherapy for stage 1 endometrial carcinoma: long-term outcome of the randomized PORTEC trial with central pathology review. Int J Radiation Oncology Biol Phys (2005) 63:834–838.[Web of Science][Medline]
7. Lukka H, Chambers A, Fyles A, et al. Adjuvant radiotherapy in women with stage I endometrial cancer: a systematic review. Gynecol Oncol (2006) 102:361–368.[CrossRef][Web of Science][Medline]
8. Høgberg T, Rosenberg P, Kristensen G, et al. A randomized phase III study on adjuvant treatment with radiation ± chemotherapy in early stage high-risk endometrial cancer (NSGO-EC-9501/EORTC 55991). J Clin Oncol (2007) 25(18S). Abstr 5503.
9. Martin-Hirsch PPL, Jarvis GG, Kitchener HC. Lilford. Progestagens for endometrial cancer (Cochrane review). Cochrane Database Syst Rev (1999) (Issue 4); CD001040.
10. Lambrou NC, Gómez-Marín O, Mirhashemi R, et al. Optimal surgical cytoreduction in patients with stage III and stage IV endometrial carcinoma: a study of morbidity and survival. Gynecol Oncol (2004) 93:653–658.[CrossRef][Web of Science][Medline]
11. Aapro MS, van Wijk FH, Bolis G, et al. Doxorubicin versus doxorubicin and cisplatin in endometrial carcinoma: definitive results of a randomised study (55872) by the EORTC Gynaecological Cancer Group. Ann Oncol (2003) 14:441–448.
12. Fleming GF, Brunetto VL, Cella D, et al. Phase III trial of doxorubicin plus cisplatin with or without paclitaxel plus filgastrim in advanced endometrial carcinoma: a Gynecologic Oncology Group study. J Clin Oncol (2004) 22:2159–2166.
13. Randall ME, Brunetto G, Muss HB, et al. Whole abdominal radiotherapy versus combination doxorubicin–cisplatin chemotherapy in advanced endometrial carcinoma: a randomized phase III trial of the Gynecologic Oncology Group. J Clin Oncol (2006) 24:36–44.
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