Jamieson Amy, Huvila Jutta, Thompson Emily F, Leung Samuel, Chiu Derek, Lum Amy, McConechy Melissa, Grondin Katherine, Aguirre-Hernandez Rosalia, Salvador Shannon, Kean Sarah, Samouelian Vanessa, Gougeon Francois, Azordegan Nazila, Lytwyn Alice, Parra-Herran Carlos, Offman Saul, Gotlieb Walter, Irving Julie, Kinloch Mary, Helpman Limor, Scott Stephanie A, Vicus Danielle, Plante Marie, Huntsman David G, Gilks C Blake, Talhouk Aline, McAlpine Jessica N
Department of Gynecology and Obstetrics, Division of Gynecologic Oncology, University of British Columbia, Vancouver, Canada.
Department of Pathology, University of Turku, Turku University Hospital, Turku, Finland; Department of Molecular Oncology, University of British Columbia, Vancouver, Canada.
Gynecol Oncol. 2022 May;165(2):201-214. doi: 10.1016/j.ygyno.2022.02.001. Epub 2022 Mar 1.
We measured the variation in practice across all aspects of endometrial cancer (EC) management and assessed the potential impact of implementation of molecular classification.
Centers from across Canada provided representative tumor samples and clinical data, including preoperative workup, operative management, hereditary cancer program (HCP) referrals, adjuvant therapy, surveillance and outcomes, for all EC patients diagnosed in 2016. Tumors were classified into the four ProMisE molecular subtypes.
A total of 1336 fully evaluable EC patients were identified from 10 tertiary cancer centers (TC; n = 1022) and 19 community centers (CC; n = 314). Variation of surgical practice across TCs was profound (14-100%) for lymphadenectomy (LND) (mean 57% Gr1/2, 82% Gr3) and omental sampling (20% Gr1/2, 79% Gr3). Preoperative CT scans were inconsistently obtained (mean 32% Gr1/2, 51% Gr3) and use of adjuvant chemo or chemoRT in high risk EC ranged from 0-55% and 64-100%, respectively. Molecular subtyping was performed retrospectively and identified 6% POLEmut, 28% MMRd, 48% NSMP and 18% p53abn ECs, and was significantly associated with survival. Within patients retrospectively diagnosed with MMRd EC only 22% had been referred to HCP. Of patients with p53abn EC, LND and omental sampling was not performed in 21% and 23% respectively, and 41% received no chemotherapy. Comparison of management in 2016 with current 2020 ESGO/ESTRO/ESP guidelines identified at least 26 and 95 patients that would have been directed to less or more adjuvant therapy, respectively (10% of cohort).
Molecular classification has the potential to mitigate the profound variation in practice demonstrated in current EC care, enabling reproducible risk assessment, guiding treatment and reducing health care disparities.
我们测量了子宫内膜癌(EC)管理各方面的实践差异,并评估了分子分类实施的潜在影响。
加拿大各地的中心提供了2016年确诊的所有EC患者的代表性肿瘤样本和临床数据,包括术前检查、手术管理、遗传性癌症项目(HCP)转诊、辅助治疗、监测和结果。肿瘤被分为四种ProMisE分子亚型。
从10个三级癌症中心(TC;n = 1022)和19个社区中心(CC;n = 314)共识别出1336例可完全评估的EC患者。各TC之间手术实践的差异在淋巴结清扫术(LND)方面很大(14 - 100%)(平均57%为1/2级,82%为3级),大网膜取样方面差异也很大(20%为1/2级,79%为3级)。术前CT扫描的获取情况不一致(平均32%为1/2级,51%为3级),高危EC患者辅助化疗或放化疗的使用范围分别为0 - 55%和64 - 100%。分子亚型分类是回顾性进行的,识别出6%的POLE突变型、28%的错配修复缺陷型(MMRd)、48%的非特异性分子谱型(NSMP)和18%的p53异常型EC,且与生存显著相关。在回顾性诊断为MMRd EC的患者中,只有22%被转诊至HCP。在p53异常型EC患者中,分别有21%和23%未进行LND和大网膜取样,41%未接受化疗。将2016年的管理情况与当前2020年ESGO/ESTRO/ESP指南进行比较,发现分别至少有26例和95例患者本应接受更少或更多的辅助治疗(占队列的10%)。
分子分类有可能减轻当前EC治疗中所显示的实践差异,实现可重复的风险评估,指导治疗并减少医疗保健差异。