Current management of early-stage endometrial cancer

Areas of controversy

The major areas of controversy in the management of early-stage endometrial cancer include the extent of lymph-node sampling, the appropriate adjuvant therapy, and the use of laparoscopy in the surgical management of malignancy.

Lymph-node sampling. While the prognostic importance of lymph-node metastases is not a matter of debate, the indications for lymph-node sampling and the extent of dissection are highly contested issues. The surgical staging procedure includes lymph-node sampling, but the protocol does not clearly state which patients should undergo sampling, nor does it describe the extent of the sampling required. The answers to these matters are still evolving and will ultimately depend on a better understanding of the appropriate role of adjuvant therapy.

The evidence supporting lymph-node sampling originally came from Gynecologic Oncology Group (GOG) study 33.⁴ In this study, the incidence of pelvic and para-aortic lymph-node metastases was greater for patients with high-grade and deeply invasive tumors (TABLE 3). The risk of lymph-node metastases in patients with tumor limited to the endometrium has been reported to be 4% or less.⁷ Thus, patients with grade 1 tumors limited to the endometrium or with only superficial invasion may not require lymph-node sampling. In higher-grade tumors or those with deep myometrial invasion, the risk of lymph-node metastases warrants surgical sampling of nodal basins.

To determine the depth of myometrial invasion, the uterine specimen should be analyzed intraoperatively by either visual inspection or pathologic evaluation using frozen sectioning. Both techniques have a 5% to 10% inaccuracy rate for depth of myometrial invasion and tumor grade.^8-11

In addition, because tumor grade may be incorrectly assessed in 30% to 50% of specimens when it is based on preoperative biopsy, it should be confirmed intraoperatively.¹² Intraoperative palpation of the retroperitoneal nodes has been found to be inaccurate in several series, with discrepancy rates of up to 30%.¹³ Over one third of lymph-node metastases may be only microscopic, less than 2 mm in diameter.¹⁴

Adjuvant therapy. Current postoperative treatment is tailored to the individual patient’s risk of recurrence, based on numerous pathologic factors including tumor grade, depth of myometrial invasion, lymph-node metastases, vascular space invasion, and histologic subtype. While radiation is the most common mode of adjuvant therapy, chemotherapy is given in selected cases. For example, uterine serous carcinoma behaves similarly to ovarian cancer in its histologic appearance, patterns of spread, and high frequency of advanced and recurrent disease. Therefore, in cases of serous carcinoma, cytotoxic chemotherapy has been used in the adjuvant setting to reduce the risk of recurrence.^15,16 However, the usefulness of this treatment is not yet established and is the subject of ongoing research.

Adjuvant radiation therapy aims to reduce the risk of recurrence with minimal toxicity without compromising efficacy. An early report from Aalders et al found that patients with early-stage endometrial cancer who were treated with postoperative vaginal and pelvic radiation had a lower incidence of pelvic recurrences and a higher incidence of distant metastases than patients treated with vaginal radiation alone.¹⁷ However, survival rates did not differ between the 2 groups. In a 1987 study by Fanning et al of low-risk patients with grade 2 tumors that invaded less than one third of the myometrium, postoperative radiation therapy was not found to increase survival when compared with surgery alone. These findings suggest that, for favorable tumors, adjuvant treatment can be avoided.¹⁸

Larson et al reported 4 vaginal and 4 distant recurrences in 105 patients with grade 2 or grade 3 tumors or more than 50% myometrial invasion who were treated with comprehensive surgical staging and no adjuvant therapy.¹⁹ All 4 vaginal recurrences were successfully salvaged with pelvic radiation therapy. In a 1996 study of 22 patients with high-risk tumors due to deep myometrial invasion, cervical involvement, positive peritoneal cytology, or high-grade histology, Fanning et al found 1 recurrence (in the lung) with vaginal brachytherapy alone after a median follow-up of 3 years.²⁰

A GOG study (GOG 99), reported recently in abstract form, randomized patients with intermediate-risk, early-stage endometrial cancer to adjuvant pelvic radiation therapy or no further treatment.²¹ Patients receiving pelvic radiation therapy had a lower incidence of recurrent disease, but there was no difference in overall survival.

These data suggest that pelvic radiation therapy probably can be eliminated from adjuvant therapy for intermediate-risk disease confined to the uterus in the setting of comprehensive surgical staging. Further, providing adjuvant vaginal brachytherapy to intermediate-risk patients should improve local control. Neither pelvic radiation nor adjuvant vaginal brachytherapy will successfully treat the portion of patients destined for distant metastasis; these patients account for about half of all treatment failures.