Changing Concepts in the Management of Endometrial Cancer

In their comprehensive review of changing concepts in the managementof endometrial cancer, Drs. Karasek and Faul highlight the contemporaryapproach to the management of patients with endometrial adenocarcinoma.The authors stress the evolution of treatment of endometrial cancerfrom preoperative radiation therapy followed by surgery to thecurrent practice of tailoring postoperative radiotherapy to varioussurgicopathologically defined risk factors.

The operative procedure for endometrial cancer is usually performedthrough an adequate abdominal incision that allows for thoroughintra-abdominal exploration and retroperitoneal lymph node removal,if necessary. An alternative method of surgically staging patientswith clinical stage I endometrial cancer is gaining in popularity.This approach combines laparoscopically assisted vaginal hysterectomywith laparoscopic lymphadenectomy. Although the laparoscopic approachmay decrease morbidity and length of hospital stay, its use shouldbe limited to experienced practitioners. Long-term follow-up ofpatients undergoing laparoscopy will be required to document theequivalence of this approach to conventional laparotomy.

Total abdominal hysterectomy and bilateral salpingo-oophorectomyare the standard operative procedures for carcinoma of the endometrium.The plane of excision lies outside the pubocervical fascia anddoes not require unroofing of the ureters. The ovarian and fallopiantubes are removed en bloc with the uterus. In some cases, pelviclymph node sampling is indicated. This consists of a sample oflymph nodes taken from the distal common iliac and superior iliacartery and vein. A third sample of lymphatics is obtained fromthe group of nodes that lie along the obturator nerve. In a lymphnode sampling procedure, it is important to achieve an adequatesample of nodes from each anatomic site, but no attempt is madeto perform a complete lymphadenectomy.

Which Patients Require Selective Lymphadenectomy?

Since lymph node sampling is not routinely performed by the generalgynecologist, it is important to identify the subset of patientswho will benefit from selective lymphadenectomy, which may requirethe further surgical expertise of a gynecologic oncologist. Ifthere is no gross intraperitoneal tumor noted at the time of laparotomy,pelvic and para-aortic lymph nodes should be sampled for the followingindications: (1) myometrial invasion of greater than one-half(outer half of myometrium); (2) regardless of tumor grade, tumorpresence in the isthmus-cervix or adnexal or other extrauterinemetastases; (3) presence of serous, clear cell, undifferentiated,or squamous types; and (4) lymph nodes that are visibly or palpablyenlarged.

In patients in whom para-aortic node sampling is indicated, samplingcan be performed through a mid-line peritoneal incision over thecommon iliac arteries and aorta. Node sampling can also be performedon the right by mobilizing the right colon medially and on theleft by mobilizing the left colon medially. In each case, a sampleof lymphatics and lymph nodes is resected along the upper commoniliac vessels on either side, and from the lower portion of theaorta and vena cava. On the left side, the lymph nodes and lymphaticsare slightly posterior to the aorta; on the right side, they lieprimarily in the vena caval fat bed. After these procedures, thepatient is surgically staged according to the 1988 InternationalFederation of Gynecology and Obstetrics (FIGO) criteria. The overallsurgical complication rate after this type of staging is approximately20%. The serious complication rate is 6% [1].

In a Gynecologic Oncology Group (GOG) study, 46% of the positivepara-aortic lymph nodes were enlarged, and 98% of the cases withaortic node metastases came from patients with positive pelvicnodes, adnexal or intra-abdominal metastases, or outer-one-thirdmyometrial invasion [1]. These risk factors affected only 25%of the patients, and yet they yielded most of the patients withpositive para-aortic nodes. Overall, 5% to 6% of patients withclinical stage I and II (occult) endometrial carcinoma have tumorspread to these lymph nodes [2].

Postoperative irradiation to the pelvis and aortic area appearsto be effective in patients with para-aortic node metastasis.In the GOG study [1], 37 of 48 patients with positive para-aorticnodes received postoperative irradiation, and 36% remain tumor-freeat 5 years. Potish and others [3] report a 5-year survival rateof 47% in a smaller group of patients who were also treated withpostoperative irradiation. Although patients with metastatic spreadto the para-aortic nodes account for only 5% to 6% of those withearly-stage endometrial cancer, it is important that these patientsbe identified, as approximately 40% will be salvaged with extended-fieldradiotherapy.

About Lymph Node Sampling

Regardless of grade, lymph nodes need not be sampled for patientswith tumor limited to the endometrium, as less than 1% of thesepatients have disease spread to pelvic or para-aortic lymph nodes[1,2]. A gray zone in deciding about lymph node sampling is representedby patients whose only risk factor is inner-one-half myometrialinvasion, particularly if the grade is 2 or 3. This group hasa 5% or less chance of node positivity [1]. Lymph node samplingshould be performed in these individuals if there is any questionabout the degree of myometrial invasion. This includes invasionthat approaches one-half of the myometrial thickness in patientswho are medically fit to undergo the sampling procedures.

The depth of myometrial invasion can be assessed easily at thetime of surgery. The excised uterus is opened, preferably awayfrom the operating table, and the depth of myometrial penetrationand presence or absence of endocervical involvement is determinedby clinical observation or by microscopic frozen section [4].In a 148-patient study, Doering and others [5] reported a 91%accuracy rate of gross visual examination of the cut uterine surfacefor determining the depth of myometrial invasion.

In patients with endometrial carcinoma, 9% have positive pelviclymph nodes (stage IIIC) [2]. The incidence is increased to 51%,32%, and 25%, respectively, in patients with extrauterine metastases,adnexal involvement, and deep myometrial invasion [1]. Patientswith pelvic lymph node metastases as their only high-risk factorshould be treated with postoperative whole-pelvic irradiation.In the GOG study, 13 (72%) of 18 patients with positive pelvicnodes are disease free 5 years after treatment. Potish and others[3] report a 5-year survival rate of 67% in a smaller series ofsimilarly treated patients.

Summary

In summary, the key to the surgical management of patients withendometrial cancer is identifying patients at risk for retroperitonealnodal metastases, since approximately 70% of patients with pelvicnodal metastases and 40% with aortic disease can be salvaged withadjuvant radiotherapy.

References:

1. Morrow CP, Bundy BN, Kumar RJ, et al: Relationship betweensurgical-pathological risk factors and outcome in clinical stagesI and II carcinoma of the endometrium: A Gynecologic OncologyGroup study. Gynecol Oncol 40:55, 1991.

2. Creasman WT, Morrow CP, Bundy BN, et al: Surgical pathologicspread patterns of endometrial cancer (a Gynecologic OncologyGroup study). Cancer 60:2035, 1987.

3. Potish RA, Twiggs LB, Adcock LL, et al: Para-aortic lymph noderadiotherapy in cancer of the uterine corpus. Obstet Gynecol654:251, 1985.

4. Malviya VK, Deppe G, Malone JM Jr, et al: Reliability of frozensection examination in identifying poor prognostic indicatorsin stage I endometrial adenocarcinoma. Gynecol Oncol 34:299,1989.

5. Doering DL, Barnhill DR, Weiser EB, et al: Intraoperative evaluationof depth of myometrial invasion in stage I endometrial adenocarcinoma.Obstet Gynecol 74:930, 1989.