Systematic lymphadenectomy did not improve survival in endometrial carcinoma

Compared with standard surgery, pelvic lymphadenectomy did not improve overall or recurrence-free survival in women with early endometrial cancer, according to data published in The Lancet.

Researchers in Europe conducted A Study in the Treatment of Endometrial Cancer (ASTEC), a two-part trial designed to address the efficacy of surgical and radiological therapies in women with endometrial cancer.

The data reported herein are from the surgical portion of the trial, which aimed to determine whether pelvic lymphadenectomy could improve survival among this patient population. The randomized, controlled trial was conducted from July 1998 to March 2005 at 85 centers in four countries.

The study included 1,408 women at a median age of 63 years with endometrial carcinoma initially thought to be confined to corpus uteri. Patients were randomly assigned to standard surgery defined as hysterectomy with bilateral salpingo-oophorectomy, peritoneal washings and palpation of para-aortic nodes (n=704) or standard surgery plus lymphadenectomy.

Of patients in the lymphadenectomy group, 72 women had between one and four lymph nodes removed and 396 had ≥10 nodes removed. In the standard surgery group, 35 women had nodes removed. The median count was two and four women had ≥10 nodes removed.

After a median follow-up of 37 months, 191 women had died; overall survival curves indicated no differences between the two groups. The researchers classified four women in the standard surgery group and nine in the lymphadenectomy group as having treatment-related or disease- and treatment-related deaths. One-third of the deaths in both groups were not related to disease or treatment.

Disease recurred in 75 women in the standard surgery group and 98 women in the lymphadenectomy group. At the time of analysis, death or disease recurrence occurred in 107 patients from the standard surgery group and 144 patients from the lymphadenectomy group.

No benefit to OS, recurrence-free survival

The researchers combined Kaplan-Meier curves for OS and recurrence-free survival with model curves that fit the Royston-Parmar parametric model and the absolute difference between the treatment groups over time. According to these curves, five-year OS was 81% (95% CI, 77%-85%) for standard surgery and 80% (95% CI, 76%-84%) for lymphadenectomy.

Similarly, five-year recurrence-free survival favored standard surgery by 6%. Rates were 79% (95% CI, 75%-83%) for standard surgery and 73% (95% CI, 69%-77%) for lymphadenectomy. According to the researchers, throughout the study period the absolute difference in OS was near zero, while the absolute difference in recurrence-free survival increased.

“This large, randomized trial suggests that unless surgical staging will directly affect adjuvant therapy, routine systematic pelvic lymphadenectomy cannot be recommended in women undergoing primary surgery for stage I endometrial cancer outside of clinical trials,” the researchers wrote.

According to the researchers, differences in pretreatment characteristics suggested that women in the standard surgery group may have been at a lower risk for recurrence compared with women in the lymphadenectomy group. After adjusting for such differences, the researchers reported an HR close to 1.0 for OS and recurrence-free survival. Lymphadenectomy was not associated with benefit to OS (HR=1.04; 95% CI, 0.74-1.45) or recurrence-free survival (HR=1.25; 95% CI, 0.93-1.6).

Lancet. 2008;doi:10.1016/S0140-6736(08)61766-3.