Systematic pelvic lymphadenectomy vs. no lymphadenectomy in early-stage endometrial carcinoma: randomized clinical trial.
BACKGROUND
Pelvic lymph nodes are the most common site of extrauterine tumor spread in early-stage endometrial cancer, but the clinical impact of lymphadenectomy has not been addressed in randomized studies. We conducted a randomized clinical trial to determine whether the addition of pelvic systematic lymphadenectomy to standard hysterectomy with bilateral salpingo-oophorectomy improves overall and disease-free survival.


METHODS
From October 1, 1996, through March 31, 2006, 514 eligible patients with preoperative International Federation of Gynecology and Obstetrics stage I endometrial carcinoma were randomly assigned to undergo pelvic systematic lymphadenectomy (n = 264) or no lymphadenectomy (n = 250). Patients' clinical data, pathological tumor characteristics, and operative and early postoperative data were recorded at discharge from hospital. Late postoperative complications, adjuvant therapy, and follow-up data were collected 6 months after surgery. Survival was analyzed by use of the log-rank test and a Cox multivariable regression analysis. All statistical tests were two-sided.


RESULTS
The median number of lymph nodes removed was 30 (interquartile range = 22-42) in the pelvic systematic lymphadenectomy arm and 0 (interquartile range = 0-0) in the no-lymphadenectomy arm (P < .001). Both early and late postoperative complications occurred statistically significantly more frequently in patients who had received pelvic systematic lymphadenectomy (81 patients in the lymphadenectomy arm and 34 patients in the no-lymphadenectomy arm, P = .001). Pelvic systematic lymphadenectomy improved surgical staging as statistically significantly more patients with lymph node metastases were found in the lymphadenectomy arm than in the no-lymphadenectomy arm (13.3% vs 3.2%, difference = 10.1%, 95% confidence interval [CI] = 5.3% to 14.9%, P < .001). At a median follow-up of 49 months, 78 events (ie, recurrence or death) had been observed and 53 patients had died. The unadjusted risks for first event and death were similar between the two arms (hazard ratio [HR] for first event = 1.10, 95% CI = 0.70 to 1.71, P = .68, and HR for death = 1.20, 95% CI = 0.70 to 2.07, P = .50). The 5-year disease-free and overall survival rates in an intention-to-treat analysis were similar between arms (81.0% and 85.9% in the lymphadenectomy arm and 81.7% and 90.0% in the no-lymphadenectomy arm, respectively).


CONCLUSIONS
Although systematic pelvic lymphadenectomy statistically significantly improved surgical staging, it did not improve disease-free or overall survival.
Benedetti Panici
Pierluigi
P
Department of Obstetrics and Gynecology, La Sapienza University of Rome, Rome, Italy. pierluigi.benedettipanici@uniroma1.it
Basile
Stefano
S
Maneschi
Francesco
F
Alberto Lissoni
Andrea
A
Signorelli
Mauro
M
Scambia
Giovanni
G
Angioli
Roberto
R
Tateo
Saverio
S
Mangili
Giorgia
G
Katsaros
Dionyssios
D
Garozzo
Gaetano
G
Campagnutta
Elio
E
Donadello
Nicoletta
N
Greggi
Stefano
S
Melpignano
Mauro
M
Raspagliesi
Francesco
F
Ragni
Nicola
N
Cormio
Gennaro
G
Grassi
Roberto
R
Franchi
Massimo
M
Giannarelli
Diana
D
Fossati
Roldano
R
Torri
Valter
V
Amoroso
Mariangela
M
Crocè
Clara
C
Mangioni
Costantino
C
D018262:Adenocarcinoma, Clear Cell / Q000401:mortality / Q000473:pathology; D000231:Adenocarcinoma, Papillary / Q000401:mortality / Q000473:pathology; D000368:Aged; D018269:Carcinoma, Endometrioid / Q000401:mortality / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D018284:Cystadenocarcinoma, Serous / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D016889:Endometrial Neoplasms / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology* / Q000532:radiotherapy / Q000601:surgery; D005260:Female; D006801:Humans; D007044:Hysterectomy; D053208:Kaplan-Meier Estimate; D008197:Lymph Node Excision; D008875:Middle Aged; D018200:Mixed Tumor, Mullerian / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D010052:Ovariectomy / Q000379:methods; D018579:Patient Selection; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018714:Radiotherapy, Adjuvant; D012107:Research Design