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Mismatch repair status and surgical approach in apparent early-stage endometrial cancer
    1. 1Queensland Centre for Gynaecological Cancer Research, Faculty of Medicine, Centre for Clinical Research, Brisbane, Queensland, Australia
    2. 2Gynaecological Cancer Group, Population Health Program, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia
    3. 3Population Health Program, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia
    4. 4School of Public Health, University of Queensland, Brisbane, Queensland, Australia
    5. 5Department of Gynaecological Oncology, Chris O'Brien Lifehouse, Sydney, New South Wales, Australia
    6. 6Faculty of Medicine, University of Sydney, Sydney, New South Wales, Australia
    1. Correspondence to Dr Rhett Morton, Queensland Centre for Gynaecological Cancer Research, University of Queensland, Brisbane, Queensland, Australia; rhett.morton{at}uq.edu.au

    Abstract

    Objective To test the hypothesis that mismatch repair (MMR) status (as an accurate surrogate marker for microsatellite stability) modifies the effect of surgical approach on oncological outcome for apparent early-stage endometrial cancer.

    Methods Observational data from a large prospective population study on endometrial cancer were analyzed using target trial methodology and doubly robust methods, including propensity score matching and adjusted regression analyses. Laparoscopy was compared with laparotomy, stratified by MMR status on outcomes of recurrence and site, and recurrence-free, overall, and disease-specific survival.

    Results After matching, there were 400 patients for analysis, with 200 in each treatment group. The mean age was 62 years and mean body mass index was 32 kg/m2. Most patients had early-stage disease (stage I n=362 (90%)) and endometrioid histology (n=363 (91%)). Adjuvant pelvic radiation was administered to 11%, adjuvant vaginal brachytherapy to 13% and adjuvant chemotherapy to 5% of patients. Five-year recurrence-free survival did not differ significantly between modes of surgery across the cohort (p=0.7) or within MMR strata (MMR-proficient p=0.9, MMR-deficient p=0.6). Similarly, there was no significant difference in overall or disease-specific survival by mode of surgery across the cohort or within MMR strata. There was no significant difference in the HR for recurrence for those treated with laparoscopy stratified by MMR status (MMR-proficient HR=0.99 (95% CI 0.28 to 3.58); MMR-deficient HR=0.83 (95% CI 0.24 to 2.87)), even when restricted to endometrioid subtype.

    Conclusion In this study, there was no evidence of a difference in survival outcomes according to mode of surgery and MMR status.

    • Endometrial Neoplasms

    Data availability statement

    Data are available upon reasonable request. In accordance with the journal’s guidelines, we will provide our data for the reproducibility of this study in other centers if such is requested.

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    Data availability statement

    Data are available upon reasonable request. In accordance with the journal’s guidelines, we will provide our data for the reproducibility of this study in other centers if such is requested.

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    Footnotes

    • Contributors RM: conceptualisation, statistical methodology, data curation, statistical analysis, writing-original draft preparation and editing. PMW, RN: statistical methodology, writing-reviewing and editing. AO: writing-reviewing and editing. RF: conceptualisation, writing-reviewing and editing, research supervision. All authors have approved the final submitted manuscript. RM is responsible for the overall content as guarantor.

    • Funding The Australian National Endometrial Cancer Study (ANECS) was supported by project grants from the National Health and Medical Research Council (NHMRC) of Australia (grant No. 339435); The Cancer Council Queensland (grant No. 4196615); Cancer Council Tasmania (grant No. 403031 and grant No. 457636); and Cancer Australia (grant No. 1010859). The present study was conducted without additional funding.

    • Competing interests None declared.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.