SENECA 研究：基于分子分类进行子宫内膜癌分期。

SENECA study: staging endometrial cancer based on molecular classification.

机构信息

Department of Gynecologic Oncology, Universidad de Navarra, Pamplona, Navarra, Spain

Hospital Universitario Nuestra Senora de la Candelaria, Santa Cruz de Tenerife, Spain.

出版信息

Int J Gynecol Cancer. 2024 Sep 2;34(9):1313-1321. doi: 10.1136/ijgc-2024-005711.

DOI:10.1136/ijgc-2024-005711

PMID:39153831

Abstract

OBJECTIVE

Management of endometrial cancer is advancing, with accurate staging crucial for guiding treatment decisions. Understanding sentinel lymph node (SLN) involvement rates across molecular subgroups is essential. To evaluate SLN involvement in early-stage (International Federation of Gynecology and Obstetrics 2009 I-II) endometrial cancer, considering molecular subtypes and new European Society of Gynaecological Oncology (ESGO) risk classification.

METHODS

The SENECA study retrospectively reviewed data from 2139 women with stage I-II endometrial cancer across 66 centers in 16 countries. Patients underwent surgery with SLN assessment following ESGO guidelines between January 2021 and December 2022. Molecular analysis was performed on pre-operative biopsies or hysterectomy specimens.

RESULTS

Among the 2139 patients, the molecular subgroups were as follows: 272 (12.7%) p53 abnormal (p53abn, 1191 (55.7%) non-specific molecular profile (NSMP), 581 (27.2%) mismatch repair deficient (MMRd), 95 (4.4%) POLE mutated (POLE-mut). Tracer diffusion was detected in, at least one side, in 97.2% of the cases; with a bilateral diffusion observed in 82.7% of the cases. By ultrastaging (90.7% of the cases) or one-step nucleic acid amplification (198 (9.3%) of the cases), 205 patients were identified with affected sentinel lymph nodes, representing 9.6% of the sample. Of these, 139 (67.8%) had low-volume metastases (including micrometastases, 42.9%; and isolated tumor cells, 24.9%) while 66 (32.2%) had macrometastases. Significant differences in SLN involvement were observed between molecular subtypes, with p53abn and MMRd groups having the highest rates (12.50% and 12.40%, respectively) compared with NSMP (7.80%) and POLE-mut (6.30%), (p=0.004); (p53abn, OR=1.69 (95% CI 1.11 to 2.56), p=0.014; MMRd, OR=1.67 (95% CI 1.21 to 2.31), p=0.002). Differences were also noted among ESGO risk groups (2.84% for low-risk patients, 6.62% for intermediate-risk patients, 21.63% for high-intermediate risk patients, and 22.51% for high-risk patients; p<0.001).

CONCLUSIONS

Our study reveals significant differences in SLN involvement among patients with early-stage endometrial cancer based on molecular subtypes. This underscores the importance of considering molecular characteristics for accurate staging and optimal management decisions.

摘要

目的

子宫内膜癌的治疗方法在不断发展，准确分期对于指导治疗决策至关重要。了解不同分子亚型中前哨淋巴结（sentinel lymph node，SLN）受累的情况非常重要。本研究旨在评估早期（国际妇产科联合会 2009 年 I-II 期）子宫内膜癌中 SLN 受累情况，同时考虑分子亚型和新的欧洲妇科肿瘤学会（European Society of Gynaecological Oncology，ESGO）风险分类。

方法

SENECA 研究回顾性分析了 2021 年 1 月至 2022 年 12 月期间，66 个中心的 16 个国家的 2139 例 I-II 期子宫内膜癌患者的数据。患者按照 ESGO 指南接受手术，并进行 SLN 评估。术前活检或子宫切除术标本进行分子分析。

结果

在 2139 例患者中，分子亚组如下：p53 异常（p53abn）272 例（12.7%），非特异性分子谱（non-specific molecular profile，NSMP）1191 例（55.7%），错配修复缺陷（mismatch repair deficient，MMRd）581 例（27.2%），POLE 突变（POLE-mut）95 例（4.4%）。97.2%的病例至少一侧检测到示踪剂扩散，82.7%的病例观察到双侧扩散。通过超分期（90.7%的病例）或一步法核酸扩增（198 例[9.3%]），205 例患者被确定为 SLN 受累，占样本的 9.6%。其中，139 例（67.8%）为低容量转移（包括微转移[42.9%]和孤立肿瘤细胞[24.9%]），66 例（32.2%）为大体积转移。分子亚型之间 SLN 受累的差异具有统计学意义，p53abn 和 MMRd 亚组的发生率最高（分别为 12.50%和 12.40%），与 NSMP（7.80%）和 POLE-mut（6.30%）相比差异具有统计学意义（p=0.004）；（p53abn，OR=1.69（95% CI 1.11-2.56），p=0.014；MMRd，OR=1.67（95% CI 1.21-2.31），p=0.002）。ESGO 风险组之间也存在差异（低危患者为 2.84%，中危患者为 6.62%，中高危患者为 21.63%，高危患者为 22.51%；p<0.001）。