Surgical resection based on ontogenetic cancer field theory for cervical cancer: 10-year updated results of the MMR study

5539 Background: Previously published findings from our center suggest that carcinoma of the cervix propagates within ontogenetic cancer fields, tissue compartments defined by staged morphogenesis. In the MMR study we aimed to determine whether surgical treatment that accounts for stage-associated, ontogenetic cancer fields and their associated lymphoid tissues results in locoregional tumor control without the need for adjuvant radiotherapy. Methods: The Leipzig School Mesometrial Resection Study (MMR study) is an ongoing, prospective, single-center, observational cohort study including patients with primary cervical cancer. All study participants undergo either total or extended mesometrial resection (TMMR or EMMR) and therapeutic lymph node dissection. Because this treatment strategy enables surgical removal of all locoregional at-risk tissues, no adjuvant radiotherapy is necessary, even in the presence of established risk factors. The trial is registered at the German Clinical Trials Register, number DRKS00015171. For this updated analysis, we identified patients in our institutional study database with primary cervical cancer staged IB1 – IIA2 according to the 2009 International Federation of Gynecology and Obstetrics staging system. Using the Kaplan-Meier estimator, we calculated recurrence free and overall survival. Results: Between October 16, 1999, and December 16, 2020, 420 patients were treated per protocol and followed up for a median of 136 months (IQR 77-190). The median age was 42 years (IQR 36-51). 329 patients (78.3%) had stage IB1, 58 (13.8%) stage IB2, 24 (5.7%) stage IIA1 and 9 (2.1%) stage IIA2 disease. Patients had either squamous cell (n = 297, 70.7%), adenocarcinoma (n = 104, 24.8%), adenosquamous (n = 18, 4.3%) or other (n = 1, 0.24%) histology. The nodal status was pN0 in 349 (83.1%) patients and pN1 in 71 (16.9%) of the cases. Clinically occult parametrial involvement was present in 47 (11.2%) patients. 10-year overall survival was 90.2% (95% confidence interval [CI] 87.1-93.4) and recurrence-free survival was 90.6% (95% CI 87.8-93.6). Stratified for lymph node status 10-year overall survival was 91.7% (95% confidence interval [CI] 88.5-95) for pN0 and 83.2% (95% confidence interval [CI] 74.6-92.9) for pN1. Recurrence-free survival was 93.8% (95% CI 91.2-96.5) for pN0 and 75.4% (95% CI 65.9-86.3) for pN1. Conclusions: Despite dispense of adjuvant radiotherapy, patients treated with total or extended mesometrial resection with therapeutic lymph node dissection have excellent survival outcomes. Additional multicenter studies are needed to further investigate and confirm our results. Clinical trial information: DRKS00015171 .