Changing Concepts in the Management of Endometrial Cancer
Changing Concepts in the Management of Endometrial Cancer
In their comprehensive review of changing concepts in the management of endometrial cancer, Drs. Karasek and Faul highlight the contemporary approach to the management of patients with endometrial adenocarcinoma. The authors stress the evolution of treatment of endometrial cancer from preoperative radiation therapy followed by surgery to the current practice of tailoring postoperative radiotherapy to various surgicopathologically defined risk factors.
The operative procedure for endometrial cancer is usually performed through an adequate abdominal incision that allows for thorough intra-abdominal exploration and retroperitoneal lymph node removal, if necessary. An alternative method of surgically staging patients with clinical stage I endometrial cancer is gaining in popularity. This approach combines laparoscopically assisted vaginal hysterectomy with laparoscopic lymphadenectomy. Although the laparoscopic approach may decrease morbidity and length of hospital stay, its use should be limited to experienced practitioners. Long-term follow-up of patients undergoing laparoscopy will be required to document the equivalence of this approach to conventional laparotomy.
Total abdominal hysterectomy and bilateral salpingo-oophorectomy are the standard operative procedures for carcinoma of the endometrium. The plane of excision lies outside the pubocervical fascia and does not require unroofing of the ureters. The ovarian and fallopian tubes are removed en bloc with the uterus. In some cases, pelvic lymph node sampling is indicated. This consists of a sample of lymph nodes taken from the distal common iliac and superior iliac artery and vein. A third sample of lymphatics is obtained from the group of nodes that lie along the obturator nerve. In a lymph node sampling procedure, it is important to achieve an adequate sample of nodes from each anatomic site, but no attempt is made to perform a complete lymphadenectomy.
Which Patients Require Selective Lymphadenectomy?
Since lymph node sampling is not routinely performed by the general gynecologist, it is important to identify the subset of patients who will benefit from selective lymphadenectomy, which may require the further surgical expertise of a gynecologic oncologist. If there is no gross intraperitoneal tumor noted at the time of laparotomy, pelvic and para-aortic lymph nodes should be sampled for the following indications: (1) myometrial invasion of greater than one-half (outer half of myometrium); (2) regardless of tumor grade, tumor presence in the isthmus-cervix or adnexal or other extrauterine metastases; (3) presence of serous, clear cell, undifferentiated, or squamous types; and (4) lymph nodes that are visibly or palpably enlarged.
In patients in whom para-aortic node sampling is indicated, sampling can be performed through a mid-line peritoneal incision over the common iliac arteries and aorta. Node sampling can also be performed on the right by mobilizing the right colon medially and on the left by mobilizing the left colon medially. In each case, a sample of lymphatics and lymph nodes is resected along the upper common iliac vessels on either side, and from the lower portion of the aorta and vena cava. On the left side, the lymph nodes and lymphatics are slightly posterior to the aorta; on the right side, they lie primarily in the vena caval fat bed. After these procedures, the patient is surgically staged according to the 1988 International Federation of Gynecology and Obstetrics (FIGO) criteria. The overall surgical complication rate after this type of staging is approximately 20%. The serious complication rate is 6% .
In a Gynecologic Oncology Group (GOG) study, 46% of the positive para-aortic lymph nodes were enlarged, and 98% of the cases with aortic node metastases came from patients with positive pelvic nodes, adnexal or intra-abdominal metastases, or outer-one-third myometrial invasion . These risk factors affected only 25% of the patients, and yet they yielded most of the patients with positive para-aortic nodes. Overall, 5% to 6% of patients with clinical stage I and II (occult) endometrial carcinoma have tumor spread to these lymph nodes .
Postoperative irradiation to the pelvis and aortic area appears to be effective in patients with para-aortic node metastasis. In the GOG study , 37 of 48 patients with positive para-aortic nodes received postoperative irradiation, and 36% remain tumor-free at 5 years. Potish and others  report a 5-year survival rate of 47% in a smaller group of patients who were also treated with postoperative irradiation. Although patients with metastatic spread to the para-aortic nodes account for only 5% to 6% of those with early-stage endometrial cancer, it is important that these patients be identified, as approximately 40% will be salvaged with extended-field radiotherapy.
About Lymph Node Sampling
Regardless of grade, lymph nodes need not be sampled for patients with tumor limited to the endometrium, as less than 1% of these patients have disease spread to pelvic or para-aortic lymph nodes [1,2]. A gray zone in deciding about lymph node sampling is represented by patients whose only risk factor is inner-one-half myometrial invasion, particularly if the grade is 2 or 3. This group has a 5% or less chance of node positivity . Lymph node sampling should be performed in these individuals if there is any question about the degree of myometrial invasion. This includes invasion that approaches one-half of the myometrial thickness in patients who are medically fit to undergo the sampling procedures.
The depth of myometrial invasion can be assessed easily at the time of surgery. The excised uterus is opened, preferably away from the operating table, and the depth of myometrial penetration and presence or absence of endocervical involvement is determined by clinical observation or by microscopic frozen section . In a 148-patient study, Doering and others  reported a 91% accuracy rate of gross visual examination of the cut uterine surface for determining the depth of myometrial invasion.
In patients with endometrial carcinoma, 9% have positive pelvic lymph nodes (stage IIIC) . The incidence is increased to 51%, 32%, and 25%, respectively, in patients with extrauterine metastases, adnexal involvement, and deep myometrial invasion . Patients with pelvic lymph node metastases as their only high-risk factor should be treated with postoperative whole-pelvic irradiation. In the GOG study, 13 (72%) of 18 patients with positive pelvic nodes are disease free 5 years after treatment. Potish and others  report a 5-year survival rate of 67% in a smaller series of similarly treated patients.
In summary, the key to the surgical management of patients with endometrial cancer is identifying patients at risk for retroperitoneal nodal metastases, since approximately 70% of patients with pelvic nodal metastases and 40% with aortic disease can be salvaged with adjuvant radiotherapy.
1. Morrow CP, Bundy BN, Kumar RJ, et al: Relationship between surgical-pathological risk factors and outcome in clinical stages I and II carcinoma of the endometrium: A Gynecologic Oncology Group study. Gynecol Oncol 40:55, 1991.
2. Creasman WT, Morrow CP, Bundy BN, et al: Surgical pathologic spread patterns of endometrial cancer (a Gynecologic Oncology Group study). Cancer 60:2035, 1987.
3. Potish RA, Twiggs LB, Adcock LL, et al: Para-aortic lymph node radiotherapy in cancer of the uterine corpus. Obstet Gynecol 654:251, 1985.
4. Malviya VK, Deppe G, Malone JM Jr, et al: Reliability of frozen section examination in identifying poor prognostic indicators in stage I endometrial adenocarcinoma. Gynecol Oncol 34:299, 1989.
5. Doering DL, Barnhill DR, Weiser EB, et al: Intraoperative evaluation of depth of myometrial invasion in stage I endometrial adenocarcinoma. Obstet Gynecol 74:930, 1989.