November 25, 2008 — Systematic pelvic lymphadenectomy does not improve disease-free or overall survival in patients with early-stage endometrial cancer, according to a report by Italian researchers published online November 25 in the Journal of the National Cancer Institute.
In this first direct and fully reported survival comparison of systematic pelvic lymphadenectomy and no lymphadenectomy after conventional surgery in patients with stage I endometrial carcinoma, no differences were seen in survival.
The 5-year disease-free survival rates were 81% among patients who underwent lymphadenectomy and 81.7% among patients who did not undergo lymphadenectomy. Similarly, overall survival rates were 85.9% in the lymphadenectomy group and 90.0% in the no-lymphadenectomy group. The median time to relapse was similar in both groups: 14 months in the lymphadenectomy group and 13 months in the no-lymphadenectomy group.
However, although there was no survival benefit, the authors note that lymphadenectomy is still important in determining prognosis and tailoring adjuvant therapies.
The findings from this study are consistent with those from an earlier randomized controlled trial that found no survival benefit associated with pelvic lymphadenectomy in early-stage endometrial cancer (Gynecol Oncol. 2006:101:S21–S22), according to an accompanying editorial.
"Lymphadenectomy does not appear to improve overall survival," lead author Pierluigi Benedetti Panici, MD, chair of the Department of Obstetrics and Gynecology at La Sapienza University, in Rome, Italy, told Medscape Oncology. "The study conclusion is that lymphadenectomy maintains its role for staging."
"This is particularly important because patients who are not completely 'staged' are addressed to adjuvant treatment," Dr. Panici added. "As a result of overtreatment — usually with radiotherapy — women suffer from long-term side effects."
Endometrial cancer care is rapidly evolving toward more personalized treatment recommendations, improving outcome and minimizing toxicity and cost, write Christine Walsh, MD, and Beth Karlan, MD, from the Cedars-Sinai Medical Center, in Los Angeles, California. But they also question whether these new findings "obviate the need for lymph-node assessment in early-stage endometrial cancer."
The answer to that question comes down, in part, to one's personal philosophy, the editorialists write. "We have level I evidence demonstrating that neither pelvic lymphadenectomy nor adjuvant radiation therapy confers any survival benefit in early-stage endometrial cancer. These results bust the myth that is based on previous retrospective studies, that lymphadenectomy, in and of itself, provides therapeutic benefit and survival advantage in endometrial cancer."
"Yet, this trial continues to support the notion that lymphadenectomy can provide important prognostic information and can help guide adjuvant treatment recommendations," they conclude.
No Differences Noted in Survival
Pelvic lymph nodes are the most common site of extrauterine tumor spread in early-stage endometrial cancer, but to date, definitive results from well-designed randomized trials comparing outcomes of pelvic lymphadenectomy with standard hysterectomy and bilateral adnexectomy alone have not been forthcoming. In this study, Dr. Panici and colleagues conducted a randomized controlled trial in which women with stage I endometrial cancer were assigned to have a standard hysterectomy and ovary removal with or without lymphadenectomy.
The authors randomized 514 patients with preoperative stage I endometrial carcinoma to undergo pelvic systematic lymphadenectomy (n = 264) or no lymphadenectomy (n = 250). Adjuvant therapy could be administered after surgery at the discretion of the treating physician.
The primary outcome was overall survival, defined as the time from randomization to death from any cause, and secondary end points were disease-free survival and surgical morbidity.
In the lymphadenectomy group, the overall median number of lymph nodes removed was 30 (interquartile range, 22 - 42), whereas none were removed in the no-lymphadenectomy group (P < .001). At a median follow-up of 49 months, 67 patients (13%) experienced a recurrence of endometrial cancer. Of these patients, 34 (12.9%) were in the lymphadenectomy group and 33 (13.2%) were in the no-lymphadenectomy group. During this time period, there were 53 deaths: 42 (8.2%) from endometrial cancer and 11 (2.1%) from other causes, without evidence of relapse.
The sites of first disease recurrences were similar between the 2 patient groups.
Sites of Disease Recurrence
| Recurrence site | Lymphadenectomy group, n (%) | No-lymphadenectomy group, n (%) |
| No recurrence | 231 (87.5) | 217 (86.8) |
| Lung | 8 (3) | 8 (3.2) |
| Intraperitoneum | 8 (3) | 7 (2.8) |
| Vagina | 7 (2.6) | 6 (2.4) |
| Lymph node | 4 (1.5) | 4 (1.6) |
| Bone | 4 (1.5) | 3 (1.2) |
| Liver | 2 (0.7) | 3 (1.2) |
| Missing data | 3 (1.1) | 3 (1.2) |
The researchers also observed a statistically significantly higher rate of early- and late-postoperative complications in patients who had undergone pelvic systematic lymphadenectomy (81 vs. 34 patients).
However, surgical staging of the disease was improved with the systematic use of lymphadenectomy, and statistically significantly more patients with lymph-node metastases were found in the lymphadenectomy group than in the no-lymphadenectomy group (13.3% vs 3.2%; difference, 10.1%)
"Pelvic systematic lymphadenectomy did not change the natural history of the disease, as can be inferred from the pattern of disease recurrence, which was similar between the 2 groups," write the authors. "However, pelvic lymphadenectomy did allow for an accurate prognosis on the basis of a pathological lymph-node assessment and, in our trial, provided for approximately 10% of the upstaging to surgical stage IIIC."
Therefore, they conclude, "lymphadenectomy maintained its importance in determining a patient's prognosis and in tailoring adjuvant therapies."
The study was partially funded by grants from Università di Roma La Sapienza and the Mario Negri Institute, in Milan, Italy.
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