eMedicine Specialties > Obstetrics and Gynecology > Gynecologic Oncology
Uterine Cancer: Workup
Updated: Jun 4, 2009
Workup
Laboratory Studies
Although no laboratory tests aid in the diagnosis of uterine cancer, CA-125 has been used in surveillance of advanced endometrial cancer. In those patients who have increased CA-125 values pretreatment, this test might prove useful in post treatment surveillance. Elevated preoperative levels of CA-125 may also be useful in predicting who might need comprehensive surgical staging.
Imaging Studies
Because performance of an endometrial biopsy in the office is relatively easy and cost-effective, most physicians choose to perform this test in lieu of ultrasonography. Ultrasonography, nonetheless, helps exclude other pelvic pathology that might contribute to postmenopausal (PMP) bleeding. Endometrial stripe thickness also helps in determining which women with negative findings on office endometrial biopsy samples should have a formal curettage.
If cancer is diagnosed, appropriate laboratory and radiologic studies can be obtained based on individual risk factors. Chest imaging should be obtained in all patients to rule out lung metastases prior to treatment. Chest radiography is adequate for grade 1, clinically early-stage cancers. A CT of the chest, abdomen, and pelvis may be helpful for high-grade cancers or when examination findings or symptoms suggest advanced-stage disease. CT scan and/or MRI are typically not necessary in the workup of apparent early-stage endometrial cancer or uterine sarcomas because the first-line therapy for the vast majority of these patients includes exploratory surgery. Local extension and metastatic disease, requiring comprehensive staging, can be predicted using clinical evidence, including obvious cervical disease and high tumor grade on the endometrial biopsy specimen.
Other Tests
Currently, no screening regimens are recommended for asymptomatic women, including those who take tamoxifen or have hereditary nonpolyposis colorectal cancer (HNPCC) syndrome. The early detection, presenting symptoms, and higher survival rate make it unlikely that screening (eg, endometrial biopsy or transvaginal ultrasonography/endometrial stripe) can have a successful impact on earlier detection and increased survival rates.
Diagnostic Procedures
A workup should be completed for any postmenopausal vaginal discharge or bleeding and cancer or hyperplasia ruled out. Additionally, any woman older than 35 years and any woman younger than 35 years with risk factors for endometrial cancer, as outlined below, should have a workup for any irregular, heavy, or inter-menstrual bleeding.
The easiest way is to obtain tissue by performing an endometrial biopsy in the office. The use of office biopsies has proven cost-effective by reducing the number of women who need a curettage under general anesthesia. If the patient’s cervix is very stenotic, an alternative method of initial workup can be ultrasonographic assessment of the endometrial stripe. If the stripe is ≤4 mm, the risk of endometrial pathology is <5.5%.13 However if the stripe is >4 mm, or bleeding is persistent, tissue biopsy is still required. Up to 17% of type II endometrial cancers will have a thin stripe as these cancers develop in a background of atrophy.14
Transvaginal ultrasonography demonstrating an enlarged endometrial stripe (EMS = 2.4 cm).
The technique of dilatation and curettage (D&C) remains an important option for the diagnosis of endometrial cancer. If the office biopsy findings are negative, inadequate, or not possible; if the endometrial thickness by ultrasonography is greater than 4 mm; or if a high degree of suspicion exists, further thorough investigation with diagnostic hysteroscopy with D&C for site-directed biopsies is warranted. Concern exists regarding transtubal intraperitoneal expulsion of cancer cells, which can lead to controversies in treatment and prognosis.
Atypical glandular cells (AGC) reported on Papanicolaou test result is associated with cancer 3-17% of the time. The cancers can be of the cervix, endometrium, ovary, or fallopian tube. Therefore, along with cervical assessment, endometrial biopsy is crucial for women older than 35 years, as well as younger women at risk for endometrial pathology. Similarly, the presence of any endometrial cells in a postmenopausal woman’s Papanicolaou test result, any atypical endometrial cells, or any endometrial cells out of sync with menses in women older than 40 years requires endometrial biopsy to rule out pathology.15
Staging
Knowledge of the surgicopathologic, as well as clinical, staging of cancer of the uterine corpus16 is crucial in developing an appropriate management plan for endometrial cancer and uterine sarcomas. The staging classification is described below (see Pathophysiology for a discussion of grading classification):
Table 2. Staging of Cancer of the Uterine Corpus
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Table
| Stage | Characteristics | |
| Stage I (grade 1, 2, or 3) | IA | Limited to the endometrium |
| IB | Invasion of less than one half of the myometrium | |
| IC | Invasion of one half or more than one half of the myometrium | |
| Stage II (grade 1, 2, or 3) | IIA | Endocervical glandular involvement only |
| IIB | Cervical stromal invasion | |
| Stage III (grade 1, 2, or 3) | IIIA | Invades serosa and/or adnexa and/or positive peritoneal cytology |
| IIIB | Vaginal metastases | |
| IIIC | Metastases to pelvic and/or para-aortic lymph nodes | |
| Stage IV (grade 1, 2, or 3) | IVA | Invasion of bladder and/or bowel mucosa |
| IVB | Distant metastases, including intra-abdominal metastases and/or inguinal lymph nodes | |
| Stage | Characteristics | |
| Stage I (grade 1, 2, or 3) | IA | Limited to the endometrium |
| IB | Invasion of less than one half of the myometrium | |
| IC | Invasion of one half or more than one half of the myometrium | |
| Stage II (grade 1, 2, or 3) | IIA | Endocervical glandular involvement only |
| IIB | Cervical stromal invasion | |
| Stage III (grade 1, 2, or 3) | IIIA | Invades serosa and/or adnexa and/or positive peritoneal cytology |
| IIIB | Vaginal metastases | |
| IIIC | Metastases to pelvic and/or para-aortic lymph nodes | |
| Stage IV (grade 1, 2, or 3) | IVA | Invasion of bladder and/or bowel mucosa |
| IVB | Distant metastases, including intra-abdominal metastases and/or inguinal lymph nodes | |
Endometrial carcinoma FIGO stages.
More on Uterine Cancer |
| Overview: Uterine Cancer |
 Workup: Uterine Cancer |
| Treatment: Uterine Cancer |
| Follow-up: Uterine Cancer |
| Multimedia: Uterine Cancer |
| References |
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References
Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2008. CA Cancer J Clin. Mar-Apr 2008;58(2):71-96. [Medline].
Soliman PT, Oh JC, Schmeler KM, et al. Risk factors for young premenopausal women with endometrial cancer. Obstet Gynecol. Mar 2005;105(3):575-80. [Medline].
Walsh C, Holschneider C, Hoang Y, Tieu K, Karlan B, Cass I. Coexisting ovarian malignancy in young women with endometrial cancer. Obstet Gynecol. Oct 2005;106(4):693-9. [Medline].
Lu KH, Schorge JO, Rodabaugh KJ, et al. Prospective determination of prevalence of lynch syndrome in young women with endometrial cancer. J Clin Oncol. Nov 20 2007;25(33):5158-64. [Medline].
Lu KH, Dinh M, Kohlmann W, et al. Gynecologic cancer as a "sentinel cancer" for women with hereditary nonpolyposis colorectal cancer syndrome. Obstet Gynecol. Mar 2005;105(3):569-74. [Medline].
[Best Evidence] Renehan AG, Tyson M, Egger M, Heller RF, Zwahlen M. Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet. Feb 16 2008;371(9612):569-78. [Medline].
The Cancer and Steroid Hormone Study of the Centers for disease Control and the National Institute of Child Health and Human Development. Combination oral contraceptive use and the risk of endometrial cancer. The Cancer and Steroid Hormone Study of the Centers for Disease Control and the National Institute of Child Health and Human Development. JAMA. Feb 13 1987;257(6):796-800. [Medline].
Doherty JA, Cushing-Haugen KL, Saltzman BS, et al. Long-term use of postmenopausal estrogen and progestin hormone therapies and the risk of endometrial cancer. Am J Obstet Gynecol. Aug 2007;197(2):139.e1-7. [Medline].
Ramirez PT, Frumovitz M, Bodurka DC, Sun CC, Levenback C. Hormonal therapy for the management of grade 1 endometrial adenocarcinoma: a literature review. Gynecol Oncol. Oct 2004;95(1):133-8. [Medline].
Ushijima K, Yahata H, Yoshikawa H, et al. Multicenter phase II study of fertility-sparing treatment with medroxyprogesterone acetate for endometrial carcinoma and atypical hyperplasia in young women. J Clin Oncol. Jul 1 2007;25(19):2798-803. [Medline].
Lee TS, Jung JY, Kim JW, et al. Feasibility of ovarian preservation in patients with early stage endometrial carcinoma. Gynecol Oncol. Jan 2007;104(1):52-7. [Medline].
Grigsby PW, Kuske RR, Perez CA, Walz BJ, Camel MH, Kao MS, et al. Medically inoperable stage I adenocarcinoma of the endometrium treated with radiotherapy alone. Int J Radiat Oncol Biol Phys. Apr 1987;13(4):483-8. [Medline].
Karlsson B, Granberg S, Wikland M, et al. Transvaginal ultrasonography of the endometrium in women with postmenopausal bleeding--a Nordic multicenter study. Am J Obstet Gynecol. May 1995;172(5):1488-94. [Medline].
Wang J, Wieslander C, Hansen G, Cass I, Vasilev S, Holschneider CH. Thin endometrial echo complex on ultrasound does not reliably exclude type 2 endometrial cancers. Gynecol Oncol. Apr 2006;101(1):120-5. [Medline].
ACOG Practice Bulletin #99. Management of abnormal cervical cytology and histology. December 2008.
Creasman WT, Odicino F, Maisonnueve P. FIGO Annual Report on the Results of Treatment in Gynaecological Cancer: Carcinoma of the corpus uteri. J Epidemiol Biostat. 1998;23(1):35-61.
Case AS, Rocconi RP, Straughn JM Jr, et al. A prospective blinded evaluation of the accuracy of frozen section for the surgical management of endometrial cancer. Obstet Gynecol. Dec 2006;108(6):1375-9. [Medline].
Chan JK, Cheung MK, Huh WK, et al. Therapeutic role of lymph node resection in endometrioid corpus cancer: a study of 12,333 patients. Cancer. Oct 15 2006;107(8):1823-30. [Medline].
Palomba S, Falbo A, Mocciaro R, Russo T, Zullo F. Laparoscopic treatment for endometrial cancer: a meta-analysis of randomized controlled trials (RCTs). Gynecol Oncol. Feb 2009;112(2):415-21. [Medline].
Havrilesky LJ, Cragun JM, Calingaert B, et al. The prognostic significance of positive peritoneal cytology and adnexal/serosal metastasis in stage IIIA endometrial cancer. Gynecol Oncol. Feb 2007;104(2):401-5. [Medline].
Bristow RE, Zerbe MJ, Rosenshein NB, Grumbine FC, Montz FJ. Stage IVB endometrial carcinoma: the role of cytoreductive surgery and determinants of survival. Gynecol Oncol. Aug 2000;78(2):85-91. [Medline].
Morrow CP, Bundy BN, Kurman RJ, et al. Relationship between surgical-pathological risk factors and outcome in clinical stage I and II carcinoma of the endometrium: a Gynecologic Oncology Group study. Gynecol Oncol. Jan 1991;40(1):55-65. [Medline].
Creutzberg CL, van Putten WL, Koper PC, Lybeert ML, Jobsen JJ, Warlam-Rodenhuis CC, et al. Surgery and postoperative radiotherapy versus surgery alone for patients with stage-1 endometrial carcinoma: multicentre randomised trial. PORTEC Study Group. Post Operative Radiation Therapy in Endometrial Carcinoma. Lancet. Apr 22 2000;355(9213):1404-11. [Medline].
Scholten AN, van Putten WL, 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 Radiat Oncol Biol Phys. Nov 1 2005;63(3):834-8. [Medline].
Keys HM, Roberts JA, Brunetto VL, et al. A phase III trial of surgery with or without adjunctive external pelvic radiation therapy in intermediate risk endometrial adenocarcinoma: a Gynecologic Oncology Group study. Gynecol Oncol. Mar 2004;92(3):744-51. [Medline].
Blake P, Swart AM, Orton J, et al. Adjuvant external beam radiotherapy in the treatment of endometrial cancer (MRC ASTEC and NCIC CTG EN.5 randomised trials): pooled trial results, systematic review, and meta-analysis. Lancet. Jan 10 2009;373(9658):137-46. [Medline].
[Best Evidence] 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. Jan 1 2006;24(1):36-44. [Medline].
Fleming GF, Brunetto VL, Cella D, et al. Phase III trial of doxorubicin plus cisplatin with or without paclitaxel plus filgrastim in advanced endometrial carcinoma: a Gynecologic Oncology Group Study. J Clin Oncol. Jun 1 2004;22(11):2159-66. [Medline].
Sovak MA, Hensley ML, Dupont J, et al. Paclitaxel and carboplatin in the adjuvant treatment of patients with high-risk stage III and IV endometrial cancer: a retrospective study. Gynecol Oncol. Nov 2006;103(2):451-7. [Medline].
Lupe K, Kwon J, D'Souza D, et al. Adjuvant paclitaxel and carboplatin chemotherapy with involved field radiation in advanced endometrial cancer: a sequential approach. Int J Radiat Oncol Biol Phys. Jan 1 2007;67(1):110-6. [Medline].
Fung-Kee-Fung M, Dodge J, Elit L, Lukka H, Chambers A, Oliver T. Follow-up after primary therapy for endometrial cancer: a systematic review. Gynecol Oncol. Jun 2006;101(3):520-9. [Medline].
Bloss JD, Berman ML, Bloss LP, Buller RE. Use of vaginal hysterectomy for the management of stage I endometrial cancer in the medically compromised patient. Gynecol Oncol. Jan 1991;40(1):74-7. [Medline].
Chi DS, Curtin JP. Gynecologic cancer and laparoscopy. Obstet Gynecol Clin North Am. Mar 1999;26(1):201-15. [Medline].
Christopherson WM, Alberhasky RC, Connelly PJ. Carcinoma of the endometrium. II. Papillary adenocarcinoma: a clinical pathological study, 46 cases. Am J Clin Pathol. May 1982;77(5):534-40. [Medline].
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. Oct 15 1987;60(8 Suppl):2035-41. [Medline].
DiSaia PJ, Creasman WT, Boronow RC, Blessing JA. Risk factors and recurrent patterns in Stage I endometrial cancer. Am J Obstet Gynecol. Apr 15 1985;151(8):1009-15. [Medline].
Efange SM, Michelson RH, Knusel B, et al. Synthesis and biological evaluation of radioiodinated N-2-(4-piperidyl)ethyl benzamides. Nucl Med Biol. May 1993;20(4):527-38. [Medline].
Egarter C, Krestan C, Kurz C. Abdominal dissemination of malignant cells with hysteroscopy. Gynecol Oncol. Oct 1996;63(1):143-4. [Medline].
Gemignani ML, Curtin JP, Zelmanovich J, Patel DA, Venkatraman E, Barakat RR. Laparoscopic-assisted vaginal hysterectomy for endometrial cancer: clinical outcomes and hospital charges. Gynecol Oncol. Apr 1999;73(1):5-11. [Medline].
Granberg S, Wikland M, Karlsson B, Norstrom A, Friberg LG. Endometrial thickness as measured by endovaginal ultrasonography for identifying endometrial abnormality. Am J Obstet Gynecol. Jan 1991;164(1 Pt 1):47-52. [Medline].
Harlow BL, Weiss NS, Lofton S. The epidemiology of sarcomas of the uterus. J Natl Cancer Inst. Mar 1986;76(3):399-402. [Medline].
Hawwa ZM, Nahhas WA, Copenhaver EH. Postmenopausal bleeding. Lahey Clin Found Bull. Apr-Jun 1970;19(2):61-70. [Medline].
Hensley ML, Maki R, Venkatraman E, et al. Gemcitabine and docetaxel in patients with unresectable leiomyosarcoma: results of a phase II trial. J Clin Oncol. Jun 15 2002;20(12):2824-31. [Medline].
International Federation of Gynecology and Obstetrics. Annual report on the results of treatment in gynecologic cancer. Int J Gynecol Obstet. 1989;28:189.
Jemal A, Murray T, Ward E, et al. Cancer statistics, 2005. CA Cancer J Clin. Jan-Feb 2005;55(1):10-30. [Medline].
Kauppila A. Progestin therapy of endometrial, breast and ovarian carcinoma. A review of clinical observations. Acta Obstet Gynecol Scand. 1984;63(5):441-50. [Medline].
Kempson RL, Bari W. Uterine sarcomas. Classification, diagnosis, and prognosis. Hum Pathol. Sep 1970;1(3):331-49. [Medline].
Kurman RJ, Kaminski PF, Norris HJ. The behavior of endometrial hyperplasia. A long-term study of "untreated" hyperplasia in 170 patients. Cancer. Jul 15 1985;56(2):403-12. [Medline].
Lehoczky O, Bosze P, Ungar L, Tottossy B. Stage I endometrial carcinoma: treatment of nonoperable patients with intracavitary radiation therapy alone. Gynecol Oncol. Dec 1991;43(3):211-6. [Medline].
Leibsohn S, d'Ablaing G, Mishell DR Jr, Schlaerth JB. Leiomyosarcoma in a series of hysterectomies performed for presumed uterine leiomyomas. Am J Obstet Gynecol. Apr 1990;162(4):968-74; discussion 974-6. [Medline].
Liu JH. American College of Obstetricians and Gynecologists: Hormone Replacement Therapy. Educational Bulletin # 247.
Loeffler JS, Rosen EM, Niloff JM, Howes AE, Knapp RC. Whole abdominal irradiation for tumors of the uterine corpus. Cancer. Apr 1 1988;61(7):1332-5. [Medline].
Mackillop WJ, Pringle JF. Stage III endometrial carcinoma. A review of 90 cases. Cancer. Nov 15 1985;56(10):2519-23. [Medline].
Major FJ, Blessing JA, Silverberg SG, et al. Prognostic factors in early-stage uterine sarcoma. A Gynecologic Oncology Group study. Cancer. Feb 15 1993;71(4 Suppl):1702-9. [Medline].
Mariani A, Webb MJ, Keeney GL, Aletti G, Podratz KC. Assessment of prognostic factors in stage IIIA endometrial cancer. Gynecol Oncol. Jul 2002;86(1):38-44. [Medline].
Massi G, Savino L, Susini T. Vaginal hysterectomy versus abdominal hysterectomy for the treatment of stage I endometrial adenocarcinoma. Am J Obstet Gynecol. Apr 1996;174(4):1320-6. [Medline].
Milosevic MF, Dembo AJ, Thomas GM. The clinical significance of malignant peritoneal cytology in stage I endometrial carcinoma. Int J Gynecol Cancer. Sep 1992;2(5):225-235. [Medline].
Moore DH, Fowler WC Jr, Walton LA, Droegemueller W. Morbidity of lymph node sampling in cancers of the uterine corpus and cervix. Obstet Gynecol. Aug 1989;74(2):180-4. [Medline].
Moore TD, Phillips PH, Nerenstone SR, Cheson BD. Systemic treatment of advanced and recurrent endometrial carcinoma: current status and future directions. J Clin Oncol. Jun 1991;9(6):1071-88. [Medline].
Omura GA, Blessing JA, Major F, et al. A randomized clinical trial of adjuvant adriamycin in uterine sarcomas: a Gynecologic Oncology Group Study. J Clin Oncol. Sep 1985;3(9):1240-5. [Medline].
Orr JW Jr, Holloway RW, Orr PF, Holimon JL. Surgical staging of uterine cancer: an analysis of perioperative morbidity. Gynecol Oncol. Sep 1991;42(3):209-16. [Medline].
Parazzini F, La Vecchia C, Bocciolone L, Franceschi S. The epidemiology of endometrial cancer. Gynecol Oncol. Apr 1991;41(1):1-16. [Medline].
Peters WA 3rd, Andersen WA, Thornton WN Jr, Morley GW. The selective use of vaginal hysterectomy in the management of adenocarcinoma of the endometrium. Am J Obstet Gynecol. Jun 1 1983;146(3):285-9. [Medline].
Quinn MA, Campbell JJ. Tamoxifen therapy in advanced/recurrent endometrial carcinoma. Gynecol Oncol. Jan 1989;32(1):1-3. [Medline].
Reddoch JM, Burke TW, Morris M, Tornos C, Levenback C, Gershenson DM. Surveillance for recurrent endometrial carcinoma: development of a follow-up scheme. Gynecol Oncol. Nov 1995;59(2):221-5. [Medline].
Runowicz CD, Nuchtern LM, Braunstein JD, Jones JG. Heterogeneity in hormone receptor status in primary and metastatic endometrial cancer. Gynecol Oncol. Sep 1990;38(3):437-41. [Medline].
Schwartz SM, Weiss NS, Daling JR, et al. Incidence of histologic types of uterine sarcoma in relation to menstrual and reproductive history. Int J Cancer. Sep 30 1991;49(3):362-7. [Medline].
Silverberg SG, Major FJ, Blessing JA, et al. Carcinosarcoma (malignant mixed mesodermal tumor) of the uterus. A Gynecologic Oncology Group pathologic study of 203 cases. Int J Gynecol Pathol. 1990;9(1):1-19. [Medline].
Soper JT, Creasman WT, Clarke-Pearson DL, Sullivan DC, Vergadoro F, Johnston WW. Intraperitoneal chromic phosphate P 32 suspension therapy of malignant peritoneal cytology in endometrial carcinoma. Am J Obstet Gynecol. Sep 15 1985;153(2):191-6. [Medline].
Further Reading
Keywords
uterine cancer, uterus, endometrial cancer, postmenopausal vaginal bleeding, signs, symptoms, treatment, adenocarcinoma, adenosquamous carcinoma, cancer of the uterus, clear cell carcinoma, uterine papillary serous carcinoma, UPSC, leiomyosarcoma, uterine sarcoma, MMT, mixed mullerian tumors, endometrial stromal sarcoma, carcinosarcoma
