Variation in practice in endometrial cancer and potential for improved care and equity through molecular classification

Improving Risk Assessment for Metastatic Disease in Endometrioid Endometrial Cancer Patients Using Molecular and Clinical Features: An NRG Oncology/Gynecologic Oncology Group Study

“…In addition, information from an MS7-like test in un-staged cases referred to a specialist would contribute to a more personalized approach when deciding between surveillance, interval surgical staging, and empiric radiotherapy. Unfortunately, variations in practice patterns among gynecologists and subspecialty gynecologic oncologists highlight the need for biomarkers to incrementally enhance conventional pathologic features for risk assessment [ 47 , 48 ]. We were reassured by the improved sensitivity and the high NPV of the MS7 risk score, especially when combined with MI, compared with that indicated by G3 disease, which is currently used by many gynecologists to make clinical decisions regarding referral.…”

Molecular classification in endometrial cancer: Opportunities for precision oncology in a changing landscape

“…Molecular features have now been integrated into the most recent ESGO/ESTRO/ESP risk stratification and subsequent adjuvant treatment recommendations according to risk group assignment (https://ijgc.bmj.com/content/31/1/12). 24 In retrospective series looking at this 2020 system of classification, approximately 10% of cases were reassigned to higher or lower risk groups, respectively 35,36 . Jamieson et al 36 reported that ~33% of patients with POLE mutations were likely overtreated by receiving adjuvant radiation with or without chemotherapy with an unclear clinical benefit, and 42% of patients who were retrospectively recognized to have p53abn ECs had less therapy than current guidelines would have recommended, which may have contributed to adverse outcomes.…”

“…Because of the abundance of data on the proven value of molecular classification in EC, the focus now needs to be on strategies for implementation of/access to molecular classification for all patients with EC, ideally at the time of their initial diagnosis. Access to testing and to the downstream surgical and treatment opportunities that come with the knowledge of the molecular subtype may begin to reduce the tremendous disparities in EC cancer care that we currently observe 36,44,45 . A shift in mentality is needed to support the upfront investment of a few hundred dollars for molecular subtyping (with valuable information for hereditary cancer implications, disease prognosis, and directing treatment) rather than the high investment of complex molecular profiling at EC recurrence, which may direct a palliative treatment benefit of 3–6 months.…”

“…Access to testing and to the downstream surgical and treatment opportunities that come with the knowledge of the molecular subtype may begin to reduce the tremendous disparities in EC cancer care that we currently observe. 36,44,45 A shift in mentality is needed to support the upfront investment of a few hundred dollars for molecular subtyping (with valuable information for hereditary cancer implications, disease prognosis, and directing treatment) rather than the high investment of complex molecular profiling at EC recurrence, which may direct a palliative treatment benefit of 3-6 months. Some of the upfront costs could be tempered by the discontinuation of what in current practice is a tremendous volume of immunohistochemistry testing of unclear clinical relevance unrelated to molecular subtypes.…”

Therapeutic Benefit of Systematic Lymphadenectomy in Node-Negative Uterine-Confined Endometrioid Endometrial Carcinoma: Omission of Adjuvant Therapy

“…Similarly to chemotherapy, surgical therapy should be individualized based on the molecular profiles of the tumor [ 169 , 170 ]. Patients with POLE exonuclease domain mutation (EDM) may not need to undergo lymphadenectomy, as none of the POLE EDM tumors had extrauterine disease [ 171 ].…”