In both surgical groups (with and without lymphadenectomy), approximately 80% of patients had disease confined to the uterus. Nodes were harvested in 91% of the patients in the lymphadenectomy group, compared with 5% of patients in the traditional-surgery group. Nine percent of women in the lymphadenectomy group had positive nodes.
The authors observe that more women had deeply invasive disease and adverse histologic types in the group that underwent lymphadenectomy. There were no differences between the two groups in overall survival; disease-specific survival; recurrence-free survival; or recurrence-free, disease-specific survival, after adjustment for baseline differences. Subgroup analysis for low-risk, high-risk, and advanced disease also failed to demonstrate differences in overall survival and recurrence-free survival.
Study from Italy produces similar findings
An independent randomized, controlled trial examining survival outcomes for endometrial cancer patients with and without lymphadenectomy was released by the Italian group in late 2008. In this study, 537 patients who had histologically confirmed endometrial carcinoma believed to be confined to the uterus were randomized to total abdominal hysterectomy and bilateral salpingo-oophorectomy with or without pelvic lymphadenectomy.
Anatomic boundaries of the pelvic lymph-node dissection were clearly defined, and a minimum lymph-node count of 20 was specified for inclusion. Intraoperative frozen section was utilized to exclude patients who had grade-1 disease that was less than 50% invasive. The option of para-aortic lymph-node dissection or sampling was left to the discretion of the surgeon. If pelvic nodes were larger than 1 cm, they were removed or sampled regardless of randomization.
Unlike the ASTEC trial, this study did not attempt to control adjuvant treatment. Patients were treated according to the discretion of the physician. Most patients received no further therapy; only 20% underwent radiation therapy, and 7% received chemotherapy.
WHAT THIS EVIDENCE MEANS FOR PRACTICE
Given the findings of these two, large, multi-institutional trials with strikingly similar results but major problems, what is a gynecologist to do? Can lymphadenectomy be avoided in patients whose disease is believed to be confined to the uterus?
For now, the answer is a tentative “No.”
There appears to be no survival advantage to removal of lymph nodes when disease is confined to the uterus, but that is not to say there is no benefit to systematic lymphadenectomy—just that there is no survival benefit afforded by the procedure. Benefits of lymphadenectomy, which include more precise definition of the extent of disease, minimization of over- or undertreatment, and a reduction in overall treatment and cost, still remain. The concept of surgical debulking put forward by Bristow and coworkers still has merit, and any gross disease should be removed, if feasible.2
Lymphadenectomy in endometrial cancer remains controversial and complex, especially as we lack a precise method for determining which patients will have nodal disease. Our practice remains to remove the lymph nodes whenever possible to better tailor any adjuvant treatment.—DAVID G. MUTCH, MD; B. J. RIMEL, MD
Women in the lymphadenectomy group were more likely to have stage-IIIC disease, which is directly attributable to histologic evaluation of the lymph nodes in this group. The authors point out that these patients had more accurate assessment of their prognosis, allowing for the tailoring of adjuvant treatment.
The overall survival and disease-free survival curves for the two experimental groups were similar, consistent with data from the ASTEC trial. This proved to be true for both the intention-to-treat and according-to-protocol groups. The authors note that their results are similar to those of the ASTEC trial, despite the significant difference in the number of nodes removed in each trial.
Some aspects of the trials hamper interpretation and comparison
Outcomes are improved when surgery is performed by a trained gynecologic oncologist. In the ASTEC trial, each lymphadenectomy was performed by a specialized gynecologic surgeon who was “skilled in the procedure.” In the Italian study, the type of surgeon was not specified, but the specific anatomic boundaries of the dissection and the minimum node count were. More specific data are needed before any conclusions can be drawn about the effect of surgical skill on outcome in these trials.
In the ASTEC trial, 9% of patients in the lymphadenectomy group had no nodes removed, and more than 60% of patients would not have met criteria for inclusion in the lymphadenectomy arm of the Italian study—suggesting that the majority of women in the ASTEC trial had inadequate lymphadenectomy. Para-aortic lymphadenectomy was left to the discretion of the attending surgeon, and some patients did have resection of these nodes. The data do not include information about whether these patients were treated in the para-aortic region based on the histology of these nodes.