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Endometrial cancer
2022-RA-568-ESGO Prognostic Relevance of FIGO grading is Limited to NSMP Endometrial Cancers
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  1. Lisa Vermij1,
  2. Jan Jobsen2,
  3. Mariel Brinkhuis3,
  4. Suzan Roothaan3,
  5. Alicia Leon-Castillo1,
  6. Naveena Singh4,
  7. Linda Mileshkin5,
  8. Melanie Powell6,
  9. Prafull Ghatage7,
  10. Meg McLachlin8,
  11. Alexandra Leary9,
  12. Catherine Genestie10,
  13. Hans Nijman11,
  14. Ina Jürgenliemk-Schulz12,
  15. Remi Nout13,
  16. Vincent Smit1,
  17. Stephanie de Boer13,
  18. Carien Creutzberg13,
  19. Nanda Horeweg13 and
  20. Tjalling Bosse1
  1. 1Pathology, Leiden University Medical Center, Leiden, Netherlands
  2. 2Radiation Oncology, Medisch Spectrum Twente, Enschede, Netherlands
  3. 3Pathology, Laboratorium Pathologie Oost-Nederland, Hengelo, Netherlands
  4. 4Pathology, Barts Health NHS Trust, London, UK
  5. 5Cancer Medicine, Peter MacCallum Cancer Centre, Melbourne, Australia
  6. 6Clinical Oncology, Barts Health NHS Trust, London, UK
  7. 7Gynecological Oncology, Tom Baker Cancer Centre, Calgary, AB, Canada
  8. 8Pathology and Laboratory Medicine, Western University, London, ON, Canada
  9. 9Medical Oncology, Gustave Roussy, Villejuif, France
  10. 10Pathology, Gustave Roussy, Villejuif, France
  11. 11Gynaecology, University Medical Center Groningen, Groningen, Netherlands
  12. 12Radiation Oncology, University Medical Center Utrecht, Utrecht, Netherlands
  13. 13Radiation Oncology, Leiden University Medical Center, Leiden, Netherlands

Abstract

Introduction/Background FIGO grading of endometrioid-type endometrial cancers (EEC) is standard clinical practice. Upon the incorporation of the molecular classification in the risk-assessment of EC patients, the role of grading is debated. Here, we assessed the prognostic value of grading in molecularly classified high-risk EC (HREC).

Methodology A total of 670 HREC patients from the PORTEC-3 clinical trial (n=424), and a prospective clinical cohort from Medisch Spectrum Twente in the Netherlands (n=246), were used for this study. Cases were molecularly classified following the 2020 WHO diagnostic algorithm (POLE-mutated [POLEmut], mismatch repair deficient [MMRd], no specific molecular profile [NSMP] and p53-abnormal [p53abn] EC). The Kaplan-Meier method, log-rank test and prespecified multivariable Cox proportional-hazard models were used for the assessment of time-to-overall-recurrence by molecular subgroup and grade.

Results In total, 433 EEC were identified, including 254 (58.7%) low-grade and 179 (41.3%) high-grade EEC. POLEmut and p53abn EEC were predominantly high-grade (n=40/45, 88.9% and n=38/46, 82.6%, respectively), while NSMP EC were mostly low-grade (n=153/180, 85.0%). Within MMRd EEC there was an equal distribution between low- and high-grade (n=88/162, 54.3% and n=74/162, 45.7%, respectively). 5-year overall recurrence was significantly lower for patients with high-grade NSMP EEC (82.7% versus 51.9%; p=0.002; figure 1A). High-grade MMRd EEC had a slightly lower risk of recurrence than low-grade MMRd EEC, but this did not reach statistical significance (figure 1B). No significant differences in risk of recurrence was observed in POLEmut and p53abn EEC. Multivariable analysis confirmed independent unfavorable prognostic impact of high-grade within NSMP EEC, but not in MMRd EEC (table 1).

View this table:
Abstract 2022-RA-568-ESGO Table 1

Multivariable analysis including risk factors for recurrence in NSMP and MMRd high-risk EEC

Abstract 2022-RA-568-ESGO Figure 1
Abstract 2022-RA-568-ESGO Figure 1

Kaplan-Meier survival analysis demonstrating the time to recurrence for FIGO grading in high-risk endometrioid endometrial cancers (EC) molecularly classified as no specific molecular profile (NSMP) and mismatch repair deficient (MMRd)

Conclusion FIGO grading showed independent prognostic value in high-risk NSMP EEC, but not in POLEmut, MMRd or p53abn EEC. Our findings suggest that prognostic value of grading in EEC is limited to the NSMP molecular subgroup. Future studies should clarify whether this holds up in (low-)intermediate-risk EEC.

https://doi.org/10.1136/ijgc-2022-ESGO.214

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