When lymphadenectomy may (or may not) be necessary
After prospectively studying more than 300 endometrial cancer patients treated at the Mayo Clinic between 1984 and 1996,5 Mariani and colleagues launched a new study to assess a novel pattern of surgical management that aims to reduce the number of low-risk patients receiving lymphadenectomy. According to this pattern, the following types of women were able to bypass lymphadenectomy:
- those who had type-I, grades-1 and -2 tumors
- those with myometrial invasion ≤50%
- those with a primary tumor ≤2 cm in diameter.
Women who had endometrial cancer that did not meet these criteria underwent complete lymphadenectomy to the level of the renal vessels. Histologic assessment of the uterus to determine grade, depth of invasion, and primary tumor diameter was performed by frozen-section analysis in all cases.
The study included 422 women from January 2004 to December 2006. According to the guidelines of the study, 112 patients did not require lymphadenectomy. However, 22 (20%) women in this group did undergo the procedure because of palpable lymphadenopathy, initiation of dissection before the frozen-section report was received, or physician preference. All nodes were negative in these patients.
Of the women who met criteria for lymphadenectomy, 29 (9%) did not undergo dissection; among the reasons were disseminated disease, comorbid conditions, and advanced age. Of the women defined as at-risk who did undergo lymphadenectomy, 22% had lymph-node metastases.
Most positive para-aortic nodes lay above the inferior mesenteric artery
Information regarding the anatomic location of para-aortic nodal metastases was available for a small subset of women in the study. Seventy-seven percent of these women had para-aortic nodal metastasis above the inferior mesenteric artery. In addition, 71% of these patients had ipsilateral pelvic nodes that were free of disease. However, these patients had a poorer prognosis, and many would have received adjuvant therapy based on their hysterectomy specimen alone.
Recommendation for practice
This study suggests that there is a subset of patients who have endometrial cancer that is very low in risk and, because of this, they may forego lymph-node dissection without harm. In addition, a significant number of periaortic nodal metastases occur above the inferior mesenteric artery and in the absence of pelvic node involvement.
One of the limitations of this study is the need for intraoperative uterine assessment by frozen section by an expert pathologist—a service that is not widely available.
Taken together, these data suggest that, if the uterus can be assessed by frozen section at the time of surgery, a subset of clinical stage-I patients can be spared lymphadenectomy and its attendant risks.
Patients undergoing lymphatic assessment should undergo full systematic lymphnode dissection, not sampling. The dissection should include the region above the inferior mesenteric artery.
Removal of lymph nodes in endometrial cancer remains complex and controversial, a fact that strengthens the argument that an experienced gynecologic oncologist should be involved in the care of patients who have this disease.
Chemotherapy is warranted in advanced or recurrent disease
Homesley H, Filiaci V, Gibbons S, et al. Randomized phase III trial in advanced endometrial carcinoma of surgery and volume-directed radiation followed by cisplatin and doxorubicin with or without paclitaxel: a Gynecologic Oncology Group study. Abstract presented at the Society of Gynecologic Oncologists, March 2008.
Adjuvant therapy for advanced-stage endometrial cancer has varied considerably over the years, and treatment of these patients remains somewhat controversial. Clinical trials comparing chemotherapy with radiation, and chemotherapy regimens with each other, have led to an era in which chemotherapy is used to treat more women than ever before.
In 2006, the Gynecologic Oncology Group (GOG) published the results of a prospective randomized study (GOG 122) that compared whole-abdomen radiation to doxorubicin and cisplatin in stage-III or -IV endometrial cancer. The investigators determined that chemotherapy was superior to whole-abdomen radiation in this trial.6
This finding was quickly followed by another trial (GOG 177) in which doxorubicin plus cisplatin was compared with a regimen of doxorubicin, cisplatin, and paclitaxel. Women in this trial had stage-III or -IV or recurrent disease. A history of radiation treatment did not disqualify patients from the study, and the treatment groups were well balanced in randomization. The doxorubicin–cisplatin–paclitaxel arm improved progression-free and overall survival, making this combination the preferred treatment.7
After volume-directed radiation, paclitaxel does not add benefit
Several retrospective analyses of radiation versus chemotherapy have shown improvement with radiation or combination therapy.8 Most recently, the GOG released data from a trial comparing chemotherapy regimens after radiation treatment. GOG 184 evaluated surgically debulked, stage-III or -IV patients who had received volume-directed radiation; subjects were randomized into either of two chemotherapy regimens: