Research Article| Volume 43, ISSUE 12, P2270-2276, December 2017

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Could lymphadenectomy be avoided in locally advanced cervical cancer patients administered preoperative chemoradiation? A large-scale retrospective study

Published:September 23, 2017DOI:



      To identify a subset of cervical cancer (CC) patients administered chemoradiation (CT/RT) plus radical surgery (RS), who can be spared lymphadenectomy, and complications.

      Patients and methods

      430 Stage IB2-IIB patients without LN involvement at imaging were accrued (March 1996–December 2015) at Gynecologic Oncology Unit of the Catholic University of Rome/Campobasso. CT/RT consisted of pelvic irradiation plus cisplatin based chemotherapy. Objective response was evaluated according to RECIST criteria; radical hysterectomy and pelvic ± aortic lymphadenectomy was attempted in patients achieving response or stable disease. Surgical morbidity was classified according to the Chassagne grading system.


      421 cases underwent RS; metastatic pelvic and aortic LNs were documented in 10.7%, and 8.8% of cases, respectively. In patients without residual tumor in the cervix, there was only 1 case (0.53%) with positive pelvic LNs, and 1 case (2.3%) with metastatic aortic LNs. Analysis of patients according to pre- and post-CT/RT imaging was able to select cases without any metastatic LNs: in patients with negative pelvic LNs at pre- and post-CT/RT imaging, none of cases without residual disease in the cervix had metastatic pelvic or aortic LNs. Of 149 early complications, 76 (51.0%) were lymphovascular. The most frequent late complications were lymphovascular (N = 25/61, 41.0%).


      Lymphadenectomy could be avoided in stage IB2-IIB CC patients undergoing preoperative CT/RT, when a careful evaluation of pre- and post-CT/RT imaging and histological assessment of no residual disease in the cervix is made. This approach may avoid lymphadenectomy in 40% of patients with a favourable impact on lymphovascular morbidity.


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        • McNeil C.
        New standard of care for cervical cancer sets stage for next questions.
        J Natl Cancer Inst. 1999; 91: 500-501
        • Chemoradiotherapy for Cervical Cancer Meta-analysis Collaboration (CCCMAC)
        Reducing uncertainties about the effect of chemoradiotherapy for cervical cancer: individual patient data meta-analysis.
        Cochrane Database Syst Rev. 2010 Jan; 20 (CD008285)
        • Benedetti-Panici P.
        • Greggi S.
        • Colombo A.
        • Amoroso M.
        • Smaniotto D.
        • Giannarelli D.
        • et al.
        Neoadjuvant chemotherapy and radical surgery versus exclusive radiotherapy in locally advanced squamous cell cervical cancer: results from the Italian multicenter randomized study.
        J Clin Oncol. 2002; 20: 179-188
        • Neoadjuvant Chemotherapy for Locally Advanced Cervical Cancer Meta-analysis Collaboration
        Neoadjuvant chemotherapy for locally advanced cervical cancer: a systematic review and meta-analysis of individual patient data from 21 randomised trials.
        Eur J Cancer. 2003; 39: 2470-2486
        • Keys H.M.
        • Bundy B.N.
        • Stehman F.B.
        • Okagaki T.
        • Gallup D.G.
        • Burnett A.F.
        • et al.
        Gynecologic Oncology Group. Radiation therapy with and without extrafascial hysterectomy for bulky stage IB cervical carcinoma: a randomized trial of the Gynecologic Oncology Group.
        Gynecol Oncol. 2003; 89: 343-353
        • Ferrandina G.
        • Margariti P.A.
        • Smaniotto D.
        • Petrillo M.
        • Salerno M.G.
        • Fagotti A.
        • et al.
        Long-term analysis of clinical outcome and complications in locally advanced cervical cancer patients administered concomitant chemoradiation followed by radical surgery.
        Gynecol Oncol. 2010; 119: 404-410
        • Classe J.M.
        • Rauch P.
        • Rodier J.F.
        • Morice P.
        • Stoeckle E.
        • Lasry S.
        • et al.
        • Groupe des Chirurgiens de Centre de Lutte Contre le Cancer
        Surgery after concurrent chemoradiotherapy and brachytherapy for the treatment of advanced cervical cancer: morbidity and outcome: results of a multicenter study of the GCCLCC (Groupe des Chirurgiens de Centre de Lutte Contre le Cancer).
        Gynecol Oncol. 2006; 102: 523-529
        • Castelnau-Marchand P.
        • Chargari C.
        • Bouaita R.
        • Dumas I.
        • Farha G.
        • Kamsu-Kom L.
        • et al.
        What to expect from immediate salvage hysterectomy following concomitant chemoradiation and image-guided adaptive brachytherapy in locally advanced cervical cancer.
        Cancer Radiother. 2015; 19: 710-717
        • Morice P.
        • Rouanet P.
        • Rey A.
        • Romestaing P.
        • Houvenaeghel G.
        • Boulanger J.C.
        • et al.
        Results of the GYNECO 02 study, an FNCLCC Phase III trial comparing hysterectomy with no hysterectomy in patients with a (clinical and radiological) complete response after chemoradiation therapy for stage IB” or II cervical cancer.
        Oncologist. 2012; 17: 64-71
        • Cetina L.
        • González-Enciso A.
        • Cantú D.
        • Coronel J.
        • Pérez-Montiel D.
        • Hinojosa J.
        • et al.
        Brachytherapy versus radical hysterectomy after external beam chemoradiation with gemcitabine plus cisplatin: a randomized, phase III study in IB2-IIB cervical cancer patients.
        Ann Oncol. 2013; 24: 2043-2047
        • Eifel P.J.
        • Winter K.
        • Morris M.
        • Levenback C.
        • Grigsby P.W.
        • Cooper J.
        • et al.
        Pelvic irradiation with concurrent chemotherapy versus pelvic and para-aortic irradiation for high-risk cervical cancer: an update of radiation therapy oncology group trial (RTOG) 90–01.
        J Clin Oncol. 2004; 22: 872-880
        • Jones B.
        Toxicity after cervical cancer treatment using radiotherapy and chemotherapy.
        Clin Oncol. 2009; 21: 56-63
        • Gondi V.
        • Bentzen S.M.
        • Sklenar K.L.
        • Dunn E.F.
        • Petereit D.G.
        • Tannehill S.P.
        • et al.
        Severe late toxicities following concomitant chemoradiotherapy compared to radiotherapy alone in cervical cancer: an inter-era analysis.
        Int J Radiat Oncol Biol Phys. 2012; 84: 973-982
        • Ferrandina G.
        • Ercoli A.
        • Fagotti A.
        • Fanfani F.
        • Gallotta V.
        • Margariti A.P.
        • et al.
        Completion surgery after concomitant chemoradiation in locally advanced cervical cancer: a comprehensive analysis of Pattern of Postoperative Complications.
        Ann Surg Oncol. 2014; 21: 1692-1699
        • Motton S.
        • Houvenaeghel G.
        • Delannes M.
        • Querleu D.
        • Soulé-Tholy M.
        • Hoff J.
        • et al.
        Results of surgery after concurrent chemoradiotherapy in advanced cervical cancer: comparison of extended hysterectomy and extrafascial hysterectomy.
        Int J Gynecol Cancer. 2010; 20: 268-275
        • Touboul C.
        • Uzan C.
        • Mauguen A.
        • Gouy S.
        • Rey A.
        • Pautier P.
        • et al.
        Prognostic factors and morbidities after completion surgery in patients undergoing initial chemoradiation therapy for locally advanced cervical cancer.
        Oncologist. 2010; 15: 405-415
        • Houvenaeghel G.
        • Buttarelli M.
        • de Troyer J.
        • Carcopino X.
        • Lelièvre L.
        • Tallet A.
        • et al.
        Surgical resection after chemotherapy for advanced cervical carcinoma.
        Cancer Radiother. 2006; 10: 471-476
        • Ferrandina G.
        • Petrillo M.
        • Restaino G.
        • Rufini V.
        • Macchia G.
        • Carbone A.
        • et al.
        Can radicality of surgery be safely modulated on the basis of MRI and PET/CT imaging in locally advanced cervical cancer patients administered preoperative treatment?.
        Cancer. 2012; 118: 392-403
        • Ferrandina G.
        • Legge F.
        • Fagotti A.
        • Fanfani F.
        • Distefano M.
        • Morganti A.
        • et al.
        Preoperative concomitant chemoradiotherapy in locally advanced cervical cancer: safety, outcome, and prognostic measures.
        Gynecol Oncol. 2007; 107: S127-S132
        • Macchia G.
        • Ferrandina G.
        • Legge F.
        • Deodato F.
        • Ruggieri V.
        • Lorusso D.
        • et al.
        Prolonged chemoradiation in locally advanced carcinoma of the uterine cervix: final results of a phase II study (ESTER-1).
        Am J Clin Oncol. 2010; 33: 577-582
        • Macchia G.
        • Morganti A.G.
        • Deodato F.
        • Cilla S.
        • Lucidi A.
        • Massaccesi M.
        • et al.
        Concomitant boost plus large-field preoperative chemoradiation in locally advanced uterine cervix carcinoma: phase II clinical trial final results (LARA-CC-1).
        Gynecol Oncol. 2012; 125: 594-599
        • Ferrandina G.
        • Gambacorta A.
        • Gallotta V.
        • Smaniotto D.
        • Fagotti A.
        • Tagliaferri L.
        • et al.
        Chemoradiation with concomitant boosts followed by radical surgery in locally advanced cervical cancer: long-term results of the ROMA-2 prospective phase 2 study.
        Int J Radiat Oncol Biol Phys. 2014; 90 (15): 778-785
        • Therasse P.
        • Arbuck S.G.
        • Eisenhauer E.A.
        • Wanders J.
        • Kaplan R.S.
        • Rubinstein L.
        • et al.
        New guidelines to evaluate the response to treatment in solid tumors: european organization for research and treatment of cancer, national cancer institute of the United States, national cancer institute of Canada.
        J Natl Cancer Inst. 2000; 92: 205-216
        • Piver M.S.
        • Rutledge F.
        • Smith J.P.
        Five classes of extended hysterectomy for women with cervical cancer.
        Obstet Gynecol. 1974; 44: 265-272
        • Chassagne D.
        • Sismondi P.
        • Horiot J.C.
        • Sinistrero G.
        • Bey P.
        • Zola P.
        • et al.
        A glossary for reporting complications of treatment in gynecological cancers.
        Radiother Oncol. 1993; 26: 195-202
        • Kaplan F.L.
        • Meier P.
        Non parametric estimation from incomplete observations.
        Am J Stat Assoc. 1958; 53: 457-481
        • Mantel N.
        Evaluation of survival data and two new rank order statistics arising in its consideration.
        Cancer Chemother Rep. 1966; 50: 163-170
        • Todo Y.
        • Yamamoto R.
        • Minobe S.
        • Suzuki Y.
        • Takeshi U.
        • Nakatani M.
        • et al.
        Risk factors for postoperative lower-extremity lymphedema in endometrial cancer survivors who had treatment including lymphadenectomy.
        Gynecol Oncol. 2010; 119: 60-64
        • Ferrandina G.
        • Mantegna G.
        • Petrillo M.
        • Fuoco G.
        • Venditti L.
        • Terzano S.
        • et al.
        Quality of life and emotional distress in early stage and locally advanced cervical cancer patients: a prospective, longitudinal study.
        Gynecol Oncol. 2012; 124: 389-394
        • Mantegna G.
        • Petrillo M.
        • Fuoco G.
        • Venditti L.
        • Terzano S.
        • Anchora L.P.
        • et al.
        Long-term prospective longitudinal evaluation of emotional distress and quality of life in cervical cancer patients who remained disease-free 2-years from diagnosis.
        BMC Cancer. 2013; 13: 127
        • Beesley V.L.
        • Rowlands I.J.
        • Hayes S.C.
        • Janda M.
        • O'Rourke P.
        • Marquart L.
        • et al.
        Australian National Endometrial Cancer Study Group. Incidence, risk factors and estimates of a woman's risk of developing secondary lower limb lymphedema and lymphedema-specific supportive care needs in women treated for endometrial cancer.
        Gynecol Oncol. 2015; 136: 87-93
        • Ferrandina G.
        • Distefano M.
        • Ludovisi M.
        • Morganti A.
        • Smaniotto D.
        • D'Agostino G.
        • et al.
        Lymph node involvement in locally advanced cervical cancer patients administered preoperative chemoradiation versus chemotherapy.
        Ann Surg Oncol. 2007; 14: 1129-1135
        • Fanfani F.
        • Fagotti A.
        • Gagliardi M.L.
        • Ferrandina G.
        • Monterossi G.
        • Gallotta V.
        • et al.
        Pre-hysterectomy cone biopsy is able to predict response in locally advanced cervical cancer patients submitted to neo-adjuvant chemoradiation.
        Eur J Surg Oncol. 2013; 39: 1025-1029
        • Battaglia A.
        • Buzzonetti A.
        • Martinelli E.
        • Fanelli M.
        • Petrillo M.
        • Ferrandina G.
        • et al.
        Selective changes in the immune profile of tumor-draining lymph nodes after different neoadjuvant chemoradiation regimens for locally advanced cervical cancer.
        Int J Radiat Oncol Biol Phys. 2010; 76: 1546-1553
        • Santin A.D.
        Lymph node metastases: the importance of the microenvironment.
        Cancer. 2000; 88: 175-179
        • Gallotta V.
        • Ferrandina G.
        • Chiantera V.
        • et al.
        Laparoscopic radical hysterectomy after concomitant chemoradiation in locally advanced cervical cancer: a prospective phase II study.
        J Minim Invasive Gynecol. 2015; 22: 877-883
        • Gallotta V.
        • Chiantera V.
        • Conte C.
        • Vizzielli G.
        • Fagotti A.
        • Nero C.
        • et al.
        Robotic radical hysterectomy after concomitant chemoradiation in locally advanced cervical cancer: a prospective phase II study.
        J Minim Invasive Gynecol. 2016; (S1553–4650): 31045-31047