Impact of Molecular Classification on Multidisciplinary Treatment Decision Making in Early-Stage Endometrial Cancer: A Prospective Real-World Study From India.
TL;DR
Integration of molecular classification modified adjuvant treatment in approximately one fifth of patients, supporting the feasibility and clinical utility of molecularly integrated MDT decision making in early-stage endometrial cancer even in resource-constrained settings.
Abstract
Purpose
Molecular classification has refined risk stratification in endometrial cancer and is now incorporated into the 2023 International Federation of Gynecology and Obstetrics (FIGO) staging system. However, prospective real-world data on its impact on multidisciplinary tumor board (MDT) decision making remain limited. We evaluated the impact of molecular information on adjuvant treatment recommendations in stage I to II endometrial cancer.
Methods
This prospective observational study included patients with surgically treated FIGO 2023 stage I to II endometrial carcinoma discussed at MDT between February 2024 and December 2025. Clinicopathologic risk stratification was performed using the ESGO-ESTRO-ESP 2016 criteria. Molecular classification was determined using POLE sequencing and immunohistochemistry for mismatch repair (MMR) and TP53. Estrogen receptor status was not assessed, as no specific molecular profile (NSMP) subclassification was part of the operative framework during the study period. MDT recommendations were recorded before and after the integration of molecular results.
Results
A total of 122 patients were included. Molecular subtypes were NSMP in 55 (45.1%), MMR-deficient in 41 (33.6%), TP53-abnormal in 24 (19.7%), and POLE-mutated in two (1.6%). Integration of molecular classification changed MDT recommendations in 25 cases (20.5%), with escalation in 15 (12.3%) and de-escalation in 10 (8.2%). Therapy modification was most frequent in TP53-abnormal tumors (62.5%) compared with other subgroups (10.2%; odds ratio, 14.7 [95% CI, 5.1 to 42.1]; P < .001). No treatment changes were observed in NSMP or POLE-mutated tumors. The net incremental treatment cost was ₹11.8 lakh across the cohort; including molecular testing, the overall incremental cost was ₹34,672 per patient (∼$418 US dollars).
Conclusion
Integration of molecular classification modified adjuvant treatment in approximately one fifth of patients. Changes were biologically consistent, supporting the feasibility and clinical utility of molecularly integrated MDT decision making in early-stage endometrial cancer even in resource-constrained settings.