Journal of the National Cancer Institute Advance Access published online on November 25, 2008
JNCI Journal of the National Cancer Institute, doi:10.1093/jnci/djn397
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© The Author 2008. Published by Oxford University Press.
ARTICLES |
Systematic Pelvic Lymphadenectomy vs No Lymphadenectomy in Early-Stage Endometrial Carcinoma: Randomized Clinical Trial
Affiliations of authors: Department of Obstetrics and Gynecology, La Sapienza University, Rome, Italy (PBP, SB, MA); S. Maria Goretti Hospital, Latina, Italy (FM); S. Gerardo Hospital, Monza, Italy (AAL, MS, CM); Gemelli Hospital, Rome, Italy (GS); Department of Obstetrics and Gynecology, Campus Biomedico University, Rome, Italy (RA); Fondazione Policlinico S. Matteo di Pavia, Pavia, Italy (ST); S. Raffaele Hospital, Milan, Italy (GM); S. Anna Hospital, Turin, Italy (DK); Department of Obstetrics and Gynecology, Catania University, Catania, Italy (GG); Aviano Hospital, Aviano, Italy (EC); Department of Obstetrics and Gynecology, University of Varese, Varese, Italy (ND); Istituto Nazionale Tumori, Fondazione G. Pascale, Naples, Italy (SG); Department of Obstetrics and Gynecology, Parma University, Parma, Italy (MM); INT, Milan, Italy (FR); Department of Obstetrics and Gynecology, Genova University, Genova, Italy (NR); Department of Obstetrics and Gynecology, University of Bari, Bari, Italy (GC); Treviglio Hospital, Treviglio, Italy (RG); Department of Obstetrics and Gynecology, University of Verona, Verona, Italy (MF); IFO-Istituto Regina Elena, Rome, Italy (DG); Mario Negri Institute, Milan, Italy (RF, VT); Jackson Memorial Hospital, Miami, FL (CC)
Correspondence to: Pierluigi Benedetti Panici, Professor, Department of Obstetrics and Gynecology, La Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy (e-mail: pierluigi.benedettipanici{at}uniroma1.it).
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).
Conclusion: Although systematic pelvic lymphadenectomy statistically significantly improved surgical staging, it did not improve disease-free or overall survival.
| CONTEXT AND CAVEATS Prior knowledge The most common site for the spread of early-stage endometrial cancer is the pelvic lymph nodes, but randomized trials have not assessed the impact of pelvic systematic lymphadenectomy in addition to standard hysterectomy with bilateral salpingo-oophorectomy on overall and disease-free survival. Study design Phase 3 randomized trial among patients with early-stage endometrial carcinoma who were randomly assigned to standard surgery for endometrial cancer with or without lymphadenectomy. Contribution Systematic pelvic lymphadenectomy did not improve disease-free or overall survival of patients with early-stage endometrial cancer, but the added information obtained from the pelvic lymph nodes removed during lymphadenectomy helped to more accurately determine the stage of the disease. Implications Lymph node status of patients with early-stage endometrial cancer was confirmed to be of prognostic value that only partly overlaps with other prognostic factors for endometrial cancer and may be of value in tailoring adjuvant therapies. However, it had no discernible therapeutic impact. Limitations The lymphadenectomy used did not systematically include some types of lymph nodes. The protocol lacked strict criteria for adjuvant therapies. From the Editors
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Manuscript received March 29, 2008; revised September 9, 2008; accepted October 6, 2008.
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J Natl Cancer Inst 2008 100: 1657.
J Natl Cancer Inst 2008 100: 1657.
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