Michael Höckel1, Benjamin Wolf2, Katja Schmidt3, Meinhard Mende4, Bahriye Aktas2, Rainer Kimmig5, Nadja Dornhöfer2, Lars-Christian Horn6. 1. Leipzig School of Radical Pelvic Surgery, University of Leipzig, Leipzig, Germany; Department of Gynecology and Obstetrics, University of Essen, Essen, Germany; Department of Gynecology and Obstetrics, Technical University of Munich, Munich, Germany. Electronic address: michael.hoeckel@uniklinik-leipzig.de. 2. Department of Gynecology and Obstetrics, University of Leipzig, Leipzig, Germany. 3. Institute of Anatomy, University of Leipzig, Leipzig, Germany. 4. Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany. 5. Department of Gynecology and Obstetrics, University of Essen, Essen, Germany. 6. Division of Breast, Gynecological and Perinatal Pathology, University of Leipzig, Leipzig, Germany.
Abstract
BACKGROUND: Previous findings from our centre suggest that carcinoma of the cervix propagates within ontogenetic cancer fields, tissue compartments defined by staged morphogenesis. We aimed to determine whether surgical treatment that accounts for stage-associated, ontogenetic cancer fields and their associated lymphoid tissues results in locoregional tumour control without the need for adjuvant radiotherapy. METHODS: We did the final clinical and histopathological evaluation of data from, the single-centre, observational, cohort study, the Leipzig School Mesometrial Resection Study. Patients of any age with stage IB1, IB2, IIA1, IIA2, or IIB cervical cancer (according to 2009 International Federation of Gynecology and Obstetrics [FIGO]) had total mesometrial resection or extended mesometrial resection and therapeutic lymph node dissection, done on the basis of ontogenetic cancer fields. We defined sentinel node, first-line, second-line, and third-line lymph node regions as progressive regional cancer fields. Primary outcomes were disease-specific survival and recurrence-free survival, and treatment-related morbidity (assessed with the Franco-Italian glossary). Applying Cox proportional hazard models, ontogenetic local (T) and regional (N) tumour staging was compared with pathological T and N staging. This trial is registered with the German Clinical Trials Register, number DRKS00015171. FINDINGS: Between Oct 16, 1999, and June 27, 2017, 523 patients were treated per protocol and followed up for a median of 61·8 months (IQR 49·3-94·8). In 495 patients with cervical cancer treated with cancer field surgery, 5-year disease-specific survival was 89·4% (95% CI 86·5-92·4) and recurrence-free survival was 83·1% (79·7-86·6). In the per-protocol population of 523 patients, treatment-related morbidity comprised 112 (21%) grade 2 and 15 (3%) grade 3 complications. The most common moderate and severe treatment-related complications and sequelae were wound dehiscence (17 [3%]), hydronephrosis (17 [3%]), bowel obstruction (26 [5%]), and lymph oedema (33 [6%]). One patient (<1%), who received total mesometrial resection, died from postoperative brain infarction. INTERPRETATION: Total or extended mesometrial resection with therapeutic lymph node dissection based on ontogenetic cancer fields results in good survival outcomes of patients with cervical cancer in our institution, but needs to be investigated further in multicentre trials. FUNDING: Leipzig School of Radical Pelvic Surgery, University of Leipzig Medical School, and the Gynecologic Oncology Research Foundation.
BACKGROUND: Previous findings from our centre suggest that carcinoma of the cervix propagates within ontogenetic cancer fields, tissue compartments defined by staged morphogenesis. We aimed to determine whether surgical treatment that accounts for stage-associated, ontogenetic cancer fields and their associated lymphoid tissues results in locoregional tumour control without the need for adjuvant radiotherapy. METHODS: We did the final clinical and histopathological evaluation of data from, the single-centre, observational, cohort study, the Leipzig School Mesometrial Resection Study. Patients of any age with stage IB1, IB2, IIA1, IIA2, or IIB cervical cancer (according to 2009 International Federation of Gynecology and Obstetrics [FIGO]) had total mesometrial resection or extended mesometrial resection and therapeutic lymph node dissection, done on the basis of ontogenetic cancer fields. We defined sentinel node, first-line, second-line, and third-line lymph node regions as progressive regional cancer fields. Primary outcomes were disease-specific survival and recurrence-free survival, and treatment-related morbidity (assessed with the Franco-Italian glossary). Applying Cox proportional hazard models, ontogenetic local (T) and regional (N) tumour staging was compared with pathological T and N staging. This trial is registered with the German Clinical Trials Register, number DRKS00015171. FINDINGS: Between Oct 16, 1999, and June 27, 2017, 523 patients were treated per protocol and followed up for a median of 61·8 months (IQR 49·3-94·8). In 495 patients with cervical cancer treated with cancer field surgery, 5-year disease-specific survival was 89·4% (95% CI 86·5-92·4) and recurrence-free survival was 83·1% (79·7-86·6). In the per-protocol population of 523 patients, treatment-related morbidity comprised 112 (21%) grade 2 and 15 (3%) grade 3 complications. The most common moderate and severe treatment-related complications and sequelae were wound dehiscence (17 [3%]), hydronephrosis (17 [3%]), bowel obstruction (26 [5%]), and lymph oedema (33 [6%]). One patient (<1%), who received total mesometrial resection, died from postoperative brain infarction. INTERPRETATION: Total or extended mesometrial resection with therapeutic lymph node dissection based on ontogenetic cancer fields results in good survival outcomes of patients with cervical cancer in our institution, but needs to be investigated further in multicentre trials. FUNDING: Leipzig School of Radical Pelvic Surgery, University of Leipzig Medical School, and the Gynecologic Oncology Research Foundation.
Authors: Mirko Griesel; Tobias P Seraphin; Nikolaus C S Mezger; Lucia Hämmerl; Jana Feuchtner; Walburga Yvonne Joko-Fru; Mazvita Sengayi-Muchengeti; Biying Liu; Samukeliso Vuma; Anne Korir; Gladys C Chesumbai; Sarah Nambooze; Cesaltina F Lorenzoni; Marie-Thérèse Akele-Akpo; Amalado Ayemou; Cheick B Traoré; Tigeneh Wondemagegnehu; Andreas Wienke; Christoph Thomssen; Donald M Parkin; Ahmedin Jemal; Eva J Kantelhardt Journal: Oncologist Date: 2021-03-10