Potential competing risk of death in older high-risk endometrial carcinoma patients: Results from a multicentric retrospective cohort

Violaine Gorgeu; Bruno Borghese; Meriem Koual; Pierre-Alexandre Just; Marie-Aude Lefrere Belda; Nicolas Delanoy; Catherine Durdux; Charles Chapron; François Goldwasser; Claire Gervais; Helene Blons; Benoit Terris; Cécile Badoual; Valerie Taly; Pierre Laurent-Puig; Anne-Sophie Bats; Jérôme Alexandre; Guillaume Beinse

doi:10.1016/j.ygyno.2022.05.016

Potential competing risk of death in older high-risk endometrial carcinoma patients: Results from a multicentric retrospective cohort

Gynecol Oncol. 2022 Aug;166(2):269-276. doi: 10.1016/j.ygyno.2022.05.016. Epub 2022 May 26.

Authors

Violaine Gorgeu¹, Bruno Borghese², Meriem Koual³, Pierre-Alexandre Just⁴, Marie-Aude Lefrere Belda⁵, Nicolas Delanoy⁶, Catherine Durdux⁷, Charles Chapron⁸, François Goldwasser¹, Claire Gervais⁶, Helene Blons⁹, Benoit Terris⁴, Cécile Badoual⁵, Valerie Taly¹⁰, Pierre Laurent-Puig⁹, Anne-Sophie Bats¹¹, Jérôme Alexandre¹², Guillaume Beinse¹³

Affiliations

¹ Université de Paris, Institut du Cancer Paris CARPEM, F-75006 Paris, France; Department of medical oncology, APHP.Centre, Hopital Cochin, Paris, France.
² Université de Paris, Institut du Cancer Paris CARPEM, F-75006 Paris, France; Department of gynecological surgery, APHP.Centre, Hopital Cochin, Paris, France; Centre de Recherche des Cordeliers, « Equipe labélisée Ligue Contre le Cancer », Sorbonne Université, Université de Paris, INSERM UMR1138, Paris, France.
³ Université de Paris, Institut du Cancer Paris CARPEM, F-75006 Paris, France; Department of gynecological surgery, APHP.Centre, Hopital Européen Georges Pompidou, Paris, France.
⁴ Université de Paris, Institut du Cancer Paris CARPEM, F-75006 Paris, France; Department of pathology, APHP.Centre, Hopital Cochin, Paris, France.
⁵ Université de Paris, Institut du Cancer Paris CARPEM, F-75006 Paris, France; Department of pathology, APHP.Centre, Hopital Européen Georges Pompidou, Paris, France.
⁶ Université de Paris, Institut du Cancer Paris CARPEM, F-75006 Paris, France; Department of medical oncology, APHP.Centre, Hopital Européen Georges Pompidou, Paris, France.
⁷ Université de Paris, Institut du Cancer Paris CARPEM, F-75006 Paris, France; Department of radiotherapy, APHP.Centre, Hopital Européen Georges Pompidou, Paris, France.
⁸ Université de Paris, Institut du Cancer Paris CARPEM, F-75006 Paris, France; Department of gynecological surgery, APHP.Centre, Hopital Cochin, Paris, France.
⁹ Université de Paris, Institut du Cancer Paris CARPEM, F-75006 Paris, France; Centre de Recherche des Cordeliers, « Equipe labélisée Ligue Contre le Cancer », Sorbonne Université, Université de Paris, INSERM UMR1138, Paris, France; Department of Biology, APHP.Centre, Hopital Européen Georges Pompidou, Paris, France.
¹⁰ Centre de Recherche des Cordeliers, « Equipe labélisée Ligue Contre le Cancer », Sorbonne Université, Université de Paris, INSERM UMR1138, Paris, France.
¹¹ Université de Paris, Institut du Cancer Paris CARPEM, F-75006 Paris, France; Centre de Recherche des Cordeliers, « Equipe labélisée Ligue Contre le Cancer », Sorbonne Université, Université de Paris, INSERM UMR1138, Paris, France; Department of gynecological surgery, APHP.Centre, Hopital Européen Georges Pompidou, Paris, France.
¹² Université de Paris, Institut du Cancer Paris CARPEM, F-75006 Paris, France; Department of medical oncology, APHP.Centre, Hopital Cochin, Paris, France; Centre de Recherche des Cordeliers, « Equipe labélisée Ligue Contre le Cancer », Sorbonne Université, Université de Paris, INSERM UMR1138, Paris, France. Electronic address: jerome.alexandre@aphp.fr.
¹³ Université de Paris, Institut du Cancer Paris CARPEM, F-75006 Paris, France; Department of medical oncology, APHP.Centre, Hopital Cochin, Paris, France; Centre de Recherche des Cordeliers, « Equipe labélisée Ligue Contre le Cancer », Sorbonne Université, Université de Paris, INSERM UMR1138, Paris, France.

PMID: 35643579
DOI: 10.1016/j.ygyno.2022.05.016

Abstract

Introduction: Adjuvant therapeutic decisions in older endometrial carcinoma (EC) patients are challenged by a balance between more frequent aggressive EC and comorbidities. We assessed whether EC and comorbidities are competing or cumulative risks in older EC patients.

Methods: All consecutive patients treated for FIGO stage I-IV EC in two University Hospitals in Paris between 2010 and 2017 were retrospectively included. Patients were categorized as: <70 years (y), >70y without comorbidity (fit), and > 70y with a Charlson comorbidity index>3 (comorbid). Association between high-risk EC (2021-ESGO-ETRO-ESP) or comorbidity, and disease-specific-survival (DSS), was evaluated using Cox model (estimation of cause-specific hazard ratio (CSHR), and Fine-Gray model (subdistribution HR) to account for competing events (death unrelated with EC).

Results: Overall, 253 patients were included (median age = 67y, IQR[59-77], median follow-up = 61.5 months, [44.4-76.8]). Among them, 109 (43%) were categorized at high-risk (proportion independent of age), including 67 (26%) who had TP53-mutated tumors. Comorbidity and high-risk group were both associated with all-cause mortality (HR = 4.09, 95%CI[2.29; 7.32] and HR = 3.21, 95%CI [1.69; 6.09], respectively). By multivariate analysis, patients with high-risk EC exhibited poorer DSS, regardless of age/comorbidity (Adjusted-CSHR = 6.62, 95%CI[2.53;17.3]; adjusted-SHR = 6.62 95%CI[2.50;17.5]). Patients>70y-comorbid with high-risk EC had 5-years cumulative incidences of EC-related and EC-unrelated death of 29% and 19%, respectively. In patients <70y, 5-years cumulative incidence of EC-related and EC-unrelated death were 25% and < 1% (one event), respectively.

Conclusion: High-risk EC patients are exposed to poorer DSS regardless of age/comorbidities, comorbidities and cancer being two cumulative rather than competing risks. Our results suggest that age/comorbidity alone should not lead to underestimate EC-specific survival.

Keywords: Comorbidity; Competing risk; EC; Molecular characterization; Prognostic stratification.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Cohort Studies
Comorbidity
Endometrial Neoplasms* / pathology
Female
Humans
Proportional Hazards Models
Retrospective Studies
Risk Factors