| Resum: |
Is tumor molecular profile associated with outcomes among patients with low-grade endometrial cancer? In this retrospective multicenter cohort study of 393 patients, outcomes for patients with low-grade endometrial cancer were not associated with molecular subgroup. These findings do not support routine molecular profiling in patients with low-grade endometrial cancer. This cohort study assesses the association of molecular profiling with disease-specific survival among patients with low-grade endometrial cancer. Patients with low-grade (ie, grade 1-2) endometrial cancer (EC) are characterized by their favorable prognosis compared with patients with high-grade (ie, grade 3) EC. With the implementation of molecular profiling, the prognostic relevance of tumor grading might lose attention. As most patients present with low-grade EC and have an excellent outcome, the value of molecular profiling for these patients is unclear. To determine the association of molecular profiling with outcomes among patients with low-grade EC. This retrospective cohort study included a multicenter international European cohort of patients diagnosed with EC between 1994 and 2018, with a median follow-up of 5. 9 years. Molecular subgroups were determined by next-generation sequencing using single-molecule molecular inversion probes and by immunohistochemistry. Subsequently, tumors were classified as polymerase epsilon (POLE)- altered, microsatellite instable (MSI), tumor protein p53 (TP53)- altered, or no specific molecular profile (NSMP). Patients diagnosed with any histological subtypes and FIGO (International Federation of Gynecology and Obstetrics) stages of EC were included, but patients with early-stage EC (FIGO I-II) were only included if they had known lymph node status. Data were analyzed February 20 to June 16, 2022. Molecular testing of the 4 molecular subgroups. The main outcome was disease-specific survival (DSS) within the molecular subgroups. A total of 393 patients with EC were included, with a median (range) age of 64. 0 (31. 0-86. 0) years and median (range) body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) of 29. 1 (18. 0-58. 3). Most patients presented with early-stage (290 patients [73. 8%]) and low-grade (209 patients [53. 2%]) disease. Of all patients, 33 (8. 4%) had POLE- altered EC, 78 (19. 8%) had MSI EC, 72 (18. 3%) had TP53 -altered EC, and 210 (53. 4%) had NSMP EC. Across all molecular subgroups, patients with low-grade EC had superior 5-year DSS compared with those with high-grade EC, varying between 90% to 100% vs 41% to 90% (P < . 001). Multivariable analysis in the entire cohort including age, tumor grade, FIGO stage, lymphovascular space invasion, and the molecular subgroups as covariates found that only high-grade (hazard ratio [HR], 4. 29; 95% CI, 2. 15-8. 53; P < . 001), TP53 -altered (HR, 1. 76; 95% CI, 1. 04-2. 95; P = . 03), and FIGO stage III or IV (HR, 4. 26; 95% CI, 2. 50-7. 26; P < . 001) disease were independently associated with reduced DSS. This cohort study found that patients with low-grade EC had an excellent prognosis independent of molecular subgroup. These findings do not support routine molecular profiling in patients with low-grade EC, and they demonstrate the importance of primary diagnostic tumor grading and selective profiling in low-grade EC to increase cost-effectiveness. |
visitant ::
identificació
(University of Turku)
