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Lymphadenectomy in endometrial cancer: what's the right question?

Published:February 10, 2012DOI:https://doi.org/10.1016/j.ajog.2012.01.041
      To the Editors:
      We read, with great interest, the article by Sharma et al,
      • Sharma C.
      • Deutsch I.
      • Lewin S.N.
      • et al.
      Lymphadenectomy influences the utilization of adjuvant radiation treatment for endometrial cancer.
      in which, in a large retrospective study on data from the National Cancer Institute's Surveillance, Epidemiology, and End Results database, the authors analyzed women with stages I-II endometrioid adenocarcinomas of the uterine corpus treated between 1988 and 2006. Findings suggest that, especially among women with high- to intermediate-risk tumors, patients who undergo lymphadenectomy are less likely to receive external-beam radiation. According to the authors, data support lymphadenectomy for the majority of women with endometrial carcinoma, thus sparing radiation-related morbidity and costs.
      The debate concerning the proper indications for additional surgical procedures like lymphadenectomy, as well as postoperative treatments, is longstanding.
      Both prospective randomized trials evaluating hysterectomy, with or without lymph node dissection, showed pelvic lymphadenectomy does not influence survival, with findings subsequently confirmed by a metaanalysis.
      • May K.
      • Bryant A.
      • Dickinson H.O.
      • et al.
      Lymphadenectomy for the management of endometrial cancer.
      Likewise, in spite of variegated retrospective analyses of selected groups of patients, aortic lymphadenectomy failed to demonstrate survival benefit in any prospective trials.
      • Benedetti Panici P.
      • Basile S.
      • Maneschi F.
      • et al.
      Systematic pelvic lymphadenectomy vs. no lymphadenectomy in early-stage endometrial carcinoma: randomized clinical trial.
      As to adjuvant therapies, we agree with the authors that an optimal treatment is still unknown. Many trials demonstrated that radiation may improve local control without any impact on overall survival for patients affected by uterine-confined disease.
      • Nout R.A.
      • Smit V.T.
      • Putter H.
      • et al.
      Vaginal brachytherapy versus pelvic external beam radiotherapy for patients with endometrial cancer of high-intermediate risk (PORTEC-2): an open-label, non-inferiority, randomised trial.
      In our opinion, the question should not be whether lymphadenectomy alters adjuvant radiation rate but rather whether nodal resection could have an impact on the natural history of endometrial carcinoma.
      Data seem to suggest nodal status may represent a collateral marker of biological disease aggressiveness, without providing definitive indications on cancer spread.
      • Benedetti Panici P.
      • Basile S.
      • Maneschi F.
      • et al.
      Systematic pelvic lymphadenectomy vs. no lymphadenectomy in early-stage endometrial carcinoma: randomized clinical trial.
      To date, there is no reliable marker to identify high-risk patients, needing strict follow-up, with or without adjuvant treatments.
      In a randomized trial of women with apparent stages I-IIA endometrial cancer (Post-Operative Radiation Therapy for Endometrial Carcinoma-2), vaginal brachytherapy resulted not inferior to pelvic radiation in preventing locoregional relapse.
      • Nout R.A.
      • Smit V.T.
      • Putter H.
      • et al.
      Vaginal brachytherapy versus pelvic external beam radiotherapy for patients with endometrial cancer of high-intermediate risk (PORTEC-2): an open-label, non-inferiority, randomised trial.
      So, are we going down the wrong road?
      It appears illogical to avoid a treatment jeopardized by considerable morbidity and costs without survival benefit (ie, radiotherapy) by choosing another procedure (ie, lymphadenectomy), this too blighted by costs and morbidity, with no proven survival benefit.
      Until we have reliable biomolecular markers, brachytherapy seems a reasonable choice when aiming for locoregional control, especially for nonsexually active women, or else chemotherapy treatment could be used to control a suspected systemic spread of disease.
      In these cases, without pelvic radiotherapy, salvage lymphadenectomy could be safely performed in the case of nodal relapse.

      References

        • Sharma C.
        • Deutsch I.
        • Lewin S.N.
        • et al.
        Lymphadenectomy influences the utilization of adjuvant radiation treatment for endometrial cancer.
        Am J Obstet Gynecol. 2011; 205: 562.e1-562.e9
        • May K.
        • Bryant A.
        • Dickinson H.O.
        • et al.
        Lymphadenectomy for the management of endometrial cancer.
        Cochrane Database Syst Rev. 2010; (CD007585)
        • Benedetti Panici P.
        • Basile S.
        • Maneschi F.
        • et al.
        Systematic pelvic lymphadenectomy vs. no lymphadenectomy in early-stage endometrial carcinoma: randomized clinical trial.
        J Natl Cancer Inst. 2008; 100: 1707-1716
        • Nout R.A.
        • Smit V.T.
        • Putter H.
        • et al.
        Vaginal brachytherapy versus pelvic external beam radiotherapy for patients with endometrial cancer of high-intermediate risk (PORTEC-2): an open-label, non-inferiority, randomised trial.
        Lancet. 2010; 375: 816-823

      Linked Article

      • Lymphadenectomy influences the utilization of adjuvant radiation treatment for endometrial cancer
        American Journal of Obstetrics & GynecologyVol. 205Issue 6
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          We analyzed the effect of lymphadenectomy on the use of adjuvant radiation treatment for women with stage I-II endometrial cancer.
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        American Journal of Obstetrics & GynecologyVol. 206Issue 5
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          We appreciate the interest of Dr Basile and his colleagues in our work. Utilizing a large population-based database of patients with endometrial cancer treated from 1988 to 2006, we noted that those women who underwent lymphadenectomy were less likely to receive adjuvant external beam radiotherapy than those who did not undergo nodal evaluation. The association between lymphadenectomy and avoidance of radiation was strongest for women with intermediate risk tumors (Fédération Internationale de Gynécologie et d'Obstétrique 1988 stage IB grades 2 and 3 and stage IC grades 1 and 2).
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