Abstract
BackgroundThe Cancer Genome Atlas (TCGA) project shed light on the vital role of tumor molecular features in predicting endometrial cancer patients’ prognosis. This study aims to investigate the survival impact of surgical approaches on patients with different genetic alterations.Methods473 endometrial cancer patients from TCGA database were selected. To analyze the prognostic impact of surgical approach, survival analyses were conducted in patients with different molecular features. Finally, a simplified molecular stratification model was established to select patients suitable for open or minimally invasive surgery (MIS).ResultsIn our cohort, 291 patients received open surgery and 182 received MIS. Molecular features influenced patients’ survival after different surgical approaches. Based on survival analyses, three molecular subtypes were generated, with subtype 1 harboring POLE mutation (POLEmt), microsatellite-instability high (MSI-H), homologous recombination repair (HRR) pathway mutation or MUC16 mutation (MUC16mt); subtype 3 carrying TP53 mutation; and subtype 2 without specific molecular feature. The survival influence of molecular subtypes depended on surgical approaches. In the open surgery cohort, three subtypes showed similar survival outcome, while in the MIS cohort, prognosis varied significantly among three subtypes, with subtype 1 the best and subtype 3 the worst. In stepwise Cox regression, molecular subtype was an independent predictor of recurrence-free survival in patients receiving MIS (p < 0.001).ConclusionThe molecular features of endometrial cancer are associated with patients’ prognosis after different surgical approaches. MIS should be recommended in patients with POLEmt, MSI-H, HRR pathway mutation or MUC16mt, while for patients with TP53 mutation, open surgery is better concerning oncological safety.
Highlights
Endometrial cancer is one of the most common gynecologic malignancies both in western countries and around the world [1, 2]
The advantages of minimally invasive surgery (MIS) over open surgery have been proved in two large trials, LAP2 and the Laparoscopic Approach to Cancer of the Endometrium (LACE) trial [3, 4, 9, 10]
In 2013, the Cancer Genome Atlas (TCGA) research network proposed four molecular subtypes of endometrial cancer based on multiomics analysis [12], which linked molecular features to endometrial cancer patients’ survival outcomes
Summary
Endometrial cancer is one of the most common gynecologic malignancies both in western countries and around the world [1, 2]. In 2013, the Cancer Genome Atlas (TCGA) research network proposed four molecular subtypes of endometrial cancer based on multiomics analysis [12], which linked molecular features to endometrial cancer patients’ survival outcomes. In the currently ongoing PORTEC-4a trial, researchers are trying to decide radiotherapy strategy based on patients’ molecular risk profile in stage I endometrial cancer [13]. These lead us to reconsider the possible survival influence of surgical approaches (open surgery vs MIS) on patients with distinct molecular features. This study aims to investigate the survival impact of surgical approaches on patients with different genetic alterations
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