Integration of molecular classification in the 2023 FIGO staging forprognostic refinement in endometrial cancer

Since the publication of the last International Federation of Gynecology and Obstetrics (FIGO) staging system for endometrial cancer in 2009, a substantial amount of new evidence has been acquired regarding tumor biology and the prognostic significance of molecular subgroups.1 The Cancer Genome Atlas (TCGA)  has classified endometrial carcinomas into four molecular subgroups, namely POLE ultramutated (POLEmut), mismatch repair  deficient (MMRd), p53 abnormal (p53abn), and “no specific molecular profile” (NSMP), which have been shown by multiple studies to be highly prognostic.1 Molecular classification is thus encouraged for all endometrial carcinomas in the European guidelines, including the guidelines jointly published by ESGO, the European Society for Radiotherapy and Oncology and the European Society of  Pathology (the ESGO-ESTRO-ESP guidelines) and the European Society for Medical Oncology (ESMO) guidelines.1 During the ESGO Congress 2024, Professor Nicole Concin, president of ESGO, presented the key updates in the 2023 FIGO staging system, focusing on the integration of molecular classification.1

The updated FIGO staging system aims to integrate the current level of evidence for higher prognostic precision and identification of treatment-relevant subgroups.1 The integration of molecular markers remains optional but is highly recommended if available to increase prognostic precision in the 2023 FIGO staging system, which is otherwise primarily based on surgical/anatomical and histological findings.1 In most situations, molecular classification is recorded but does not change the FIGO stage, except in early endometrial cancer patients (stage I and II)  with POLEmut endometrial carcinoma confined to the uterine corpus (stage IAmPOLEmut), or with p53abn endometrial carcinoma with myometrial invasion (stage IICmp53abn).1

Patients with POLEmut endometrial carcinoma have been shown to have excellent clinical outcomes and remain recurrence-free even without adjuvant treatment.1 Treatment de-escalation and omission of adjuvant treatment may thus be considered as no additional benefit is observed with adjuvant chemotherapy for these low-risk patients.1 On the other hand, patients with p53abn endometrial carcinoma were shown to have a poor clinical outcome, even if staged by lymphadenectomy as  stage I.1 These patients are also more likely to benefit from platinum-based chemotherapy as approximately half of these cancers are homologous recombination deficient.1 The recommended treatment for these high-risk patients is thus external bean radiation therapy (EBRT) with concurrent or sequential adjuvant chemotherapy, while chemotherapy alone is an alternative option.1

In summary, the new 2023 FIGO staging system integrates molecular classification if known, leading to higher prognostic precision compared to the 2009 staging system as demonstrated in five validation studies to date.1 The molecular subtype changes the FIGO stage in 2 distinct situations in early-stage disease and should be recorded in all other circumstances if available.1 It is not only prognostic but treatment-relevant as well.1 Integrating molecular classification into international guidelines and FIGO staging will thus benefit patients with endometrial cancer.1

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