GENERAL DISCUSSION 187 8 Surgical approach In patients with increased risk for LNM, additional LN surgery is recommended to guide tailored adjuvant therapy. Full LND is associated with substantial surgical morbidity. SLN mapping has emerged as a feasible, safe and accurate alternative to full LND in EC.44, 45 The introduction of SLN has many advantages over full LND, however there remain few challenges. A recent review shows a bilateral detection rate of only 60%, when using a cervical injection with indocyanine green.44 Patients with failure of bilateral SLN mapping, still require side specific LND.46, 47 Proper preoperative non-invasive risk stratification of truly low-risk patients for LNM reduces unnecessary referrals to oncology centers, operating time and ultra-staging, hence decreasing health care costs and surgical related morbidity. Postoperative risk stratification For decades, tumor grading, histological subtype and surgical FIGO staging have been used to guide adjuvant treatment choices.48 In the presence of LNM, adjuvant therapy results in a 5-year survival rate of 65% compared to 5-10% if LNM remain undetected and untreated.49-54 In 2014, the first joint European Society for Medical Oncology (ESMO), European SocieTy for Radiotherapy & Oncology (ESTRO) and European Society of Gynaecological Oncology (ESGO) consensus conference was held, resulting in the ESMO-ESGO-ESTRO 2016 risk classification groups (low / intermediate/ high-intermediate / high / advanced / metastatic). Hormonal biomarkers, p53, and L1CAM, being reported as having prognostic value in observational studies, were not incorporated in the 2016 ESMO-ESGO-ESTRO risk classification groups. However, in this thesis (chapter 5) it is demonstrated that the IHC biomarkers p53, L1CAM and ER/PR are prognostically relevant in the ESMO-ESGOESTRO 2016 risk classification groups and in addition to LN status. This is in accordance with multiple other studies which have investigated IHC markers in relation to LNM, outcome and the latest ESGO/ESTRO/ESP 2020 classification in EC.15-17, 55, 56 In the latest ESGO/ESTRO/ESP 2020 guideline the molecular subgroups are incorporated into risk classification groups for guidance of adjuvant treatment. However, some critical notes remain, the predictive relevance of molecular subgroups is mainly extracted from retrospective studies, hampering translation to the current clinical context and its costbenefit. Furthermore, the guideline did not include hormonal biomarkers or L1CAM expression, which are shown prognostic highly relevant in the NSMP subgroup.18, 56-59 Within the molecular subgroups the historical histopathological subtypes according to Bokhman (type 1 and type 2) are present.38, 60 Type 1, EEC histology with mostly positive ER/PR expression, is mainly represented by the POLEmut, MSI and NSMP subgroup. Type 2, NEEC histology with generally negative ER/PR expression, is mainly represented by the TP53mut subgroup.60 In Chapter 6 it is illustrated that hormonal biomarkers remain prognostically
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