Impact of molecular profiling in patients with endometrial cancer: real world experience from India

The introduction of The Cancer Genome Atlas (TCGA) had made a paradigm shift towards molecular based classification that impacted the treatment of endometrial cancer (EC). Here we aim to share our initial experience with the implementation of molecular testing into daily clinical practice of endometrial cancer.

This is an ambispective cohort study on prospectively collected data of 350 endometrial cancer patients who underwent primary surgery between 2020 and 2024 at our institution. Clinical, radiological, pathological and treatment related data were obtained through hospital management systems (HMS).

The median age of our cohort was 59 years. Most of the patients had endometrioid histology (267, 76.3%) and early-stage disease (288, 82.3%). Effectively 64 patients had p53 mutation if 8 double classifiers with p53 abnormality were excluded.115 patients had mismatch repair deficient (MMRd) tumors. Out of 350 patients POLE mutation was tested in 110 (31.4%). 5 patients out of these 110 (4.5%) had pathogenic POLE mutations and one had POLE variant of unknown significance (VUS). None of the patients with POLE ultra-mutated tumors received any adjuvant treatment or developed any recurrences. All of 11/64 p53 mutant patients (17.2%) developed systemic metastatic recurrences. At a median follow-up of 33 months, 3-year overall survival (OS) of POLE ultra-mutated and p53abn subgroups were 100% and 87% respectively. MMRd and nonspecific molecular pattern (NSMP) subgroups achieved OS of 97% and 96% respectively.

Assessment of the molecular profile is currently a standard investigation for evaluation of EC at our institution. This study represents a real-world experience of routine molecular marker testing among patients with EC from a tertiary care center of India.

We aim to share our initial experience with the implementation of molecular testing into daily clinical practice of endometrial cancer. Phase wise implementation of molecular testing started at our institute in 2015.It became routine in 2023. POLE ultra-mutated tumors have shown excellent prognosis. None of those patients developed any recurrences even without any adjuvant treatment. p53 abnormal tumors have the worst prognosis, with systemic recurrence being the predominant pattern of failure. MMRd and NSMP subset of patients performed moderately in between POLE mutant and p53 abnormal tumors.Molecular profiling is the most important futuristic step towards optimized adjuvant treatment for endometrial cancer in a developing country like India.