Background: A recently published staging of endometrial cancer has described 12 separate clusters. LVSI has been incorporated in stage 1 and 2 LVSI has been considered in G1 and G2 histology and has been ignored in grade 3, clear and serous histology. Stage 3 is divided in 4 categories based on disease extent and nodal metastasis, ignoring both the LVSI and histology.
The aim of this analysis was to distribute endometrial cancer patients according to new stages and based on the patters of failure investigate the inter-group prognostic homogeneity and intra-group heterogeneity. Following which propose a simplified prognostic groupings supported by patterns of failure and survival data.
Methods: Patients with intermediate, intermediate-high- and high-risk endometrial cancer treated with primary surgery and staged as (old) 1 to 3C, presented for adjuvant radiotherapy treatment sequentially between 1996 – 2014 were selected. Observation cut-off date was Dec 2018. Histology included was endometrioid/mucinous, clear cell and serous. OS and DFS as well as patterns of failure were analyzed. Distinct prognostic clusters were identified based on recurrence-free and overall survival (OS) using Cox proportional hazard models and Kaplan–Meier technique
Results: Mean Age of the patient was 64 (24-95 years.) Median survival and relapse free survival of the entire cohort was 5.46 and 5.87 years respectively. Kaplan-Meier survivor function at 5 years by FIGO staging 2023 was 93, 92, 96, 100, 91, 90, 82, 67, 80, 72 and 59% respectively for stage 1A1, 1A2, 1B, 1C, 2A, 2B, 2C, 3A2, 3B, 3C1 and 3C2. As can be seen many of these groups are iso-prognostic. Many stages showed intragroup heterogeneity such as 2C1 (serous histology, LVSI negative) had 5yrs OS 74% whereas, 2C1 (G3, Clear cell, LVSI negative) had 5 yrs OS 89%. Similarly, stage 3A2 had 2 groups with survival of 84% and 56% and 3C1 with survival of 86% and 54%! Based on patterns of failure a 3-tiered staging system could be fashioned that had low-risk n=528, intermediate-risk n=409 and high-risk n=220 with 5 yrs OS of 92%, 83% and 65% respectively. A detailed analysis will be presented.
Discussion: The new staging system is largely based on ESMO/ESGO/ESTRO classification. In this scheme, LVSI has been treated as a binary value, focal and no LVSI as one group and substantial LVSI as another group. The definition of substantial LVSI was 4.8% of patients from a pooled analysis of PORTEC-1 (n=714) & PORTEC 2 (n=427) early-stage endometrial cancer studies. However, prognostic significance of LVSI has a graded effect. A study by Restaino et al. reported that recurrence rates in LVSI-negative, focal-LVSI and diffuse-LVSI cases were 6.6%, 14.7% and 24.9%. Similarly, Pifer et al reported Among patients who underwent surgical LN assessment (n = 347), LNs were involved in 3.3% without LVSI, 7.5% with focal LVSI (OR 2.4), and 15.2% with substantial LVSI (OR 5.3) (p = .005), In our patient population (n=1187) the LVSI rate (present or absent) was 47% and its presence affected the survival in all stages and histology. The present staging system does not include the role of LVSI in advanced stage while more emphasis have been focused on molecular markers. A recently published review by Raffone A et al, has shown that LVSI has a prognostic value for worse oncological outcome independent of the molecular classification. In absence of LVSI and lymph-nodes, histology, grade, myometrial invasion (MI) and tumour size had no prognostic significance, except in serous histology. LVSI was related to histology grade and lymph-node metastasis. The ratio for LVSI to LN was 3:1 except for serous histology where it was 2:1. Based on patterns of failure three prognostic clusters emerged with 5 yrs OS of 92%, 83% and 65% and distant relapse rate of 6.5%, 11.2% and 35.2% respectively.
Conclusions: It is not clear as to the aim of new staging of endometrial cancer. It does not lead to prognostic clustering. Looking at the heterogeneity of disease extent within the same group it also does not facilitate the application of loco-regional adjuvant radiotherapy. Whilst endometrial cancer patients can be stratified in three distinct prognostic group based on histology, LVSI and nodal status irrespective of the extent of the disease. For loco-regional control of disease and providing good quality of life the anatomical extent of the disease should form the basis of adjuvant treatment.