全子宫筋膜切除术（TMMR）或依据当前国际指南治疗的子宫颈癌FIGO（2009）IB1-IIB期的肿瘤学结果：一项观察队列研究

根据国际指南，早期子宫颈癌（CC）采用治愈性目的的标准治疗（ST）包括根治性子宫切除伴盆腔淋巴结清扫（FIGO 2009 期IB1、IIA1），在最终病理风险因素的基础上推荐辅助化放疗。局部晚期阶段（FIGO 2009 期IB2、IIA2、IIB）推荐根治性放化疗。在此背景下，全子宫筋膜切除术（TMMR）结合治疗性淋巴结清扫（tLND）且未进行辅助放疗，已成为一种前景看好的治疗方式。本文比较TMMR+tLND与ST的肿瘤学结局。在这项观察队列研究中，从瑞典的基于人群的登记资料中识别采用国际指南治疗的女性患者，以及从莱比锡子宫筋膜切除研究数据库（DRKS 0001517）中识别接受TMMR的患者（2011-2020）。提取相关临床和肿瘤相关变量。采用log-rank检验、累积发生率函数和比例风险回归分析，计算调整后风险比（HR）及其95%置信区间（CI），校正潜在混杂因素。2011年至2020年，共纳入1007例患者：其中733例接受ST治疗，274例接受TMMR。五年无复发生存率（RFS）为77.9%（95% CI 74.3-81.1）对比82.6%（95% CI 77.2-86.9），p=0.053。在早期子宫颈癌中，TMMR组的RFS显著优于ST组，91.2%对81.8%（p=0.002）。调整分析显示，TMMR组复发风险较低（HR 0.39；95% CI 0.22-0.69）以及死亡风险较低（HR 0.42；95% CI 0.21-0.86），与ST相比。5年复发风险的绝对差异为9.4%（95% CI 3.2-15.7），有利于TMMR。在局部晚期子宫颈癌中，RFS和OS未见显著差异。与ST相比，无放疗的TMMR在早期子宫颈癌患者中具有优越的肿瘤学结果，而在晚期患者中未观察到差异。我们的结果结合之前的证据提示，TMMR可能应作为局限于子宫韧带区的早期和局部晚期子宫颈癌的首选治疗方案。本研究由瑞典临床研究中心和斯德哥尔摩地区提供资金支持。

According to international guidelines, standard treatment (ST) with curative intent in cervical cancer (CC) comprises radical hysterectomy and pelvic lymphadenectomy in early stages (International Federation of Gynecology and Obstetrics (FIGO) 2009 IB1, IIA1), adjuvant chemoradiation is recommended based on risk factors upon final pathology. Definitive chemoradiation is recommended in locally advanced stages (FIGO 2009 IB2, IIA2, IIB). Total mesometrial resection (TMMR) with therapeutic lymph node dissection (tLND) without adjuvant radiation has emerged as a promising treatment. Here we compare oncologic outcome by TMMR + tLND or ST.In this observational cohort study, women treated according to international guidelines were identified in the population-based registries from Sweden and women treated with TMMR were identified in the Leipzig Mesometrial Resection (MMR) Study Database (DRKS 0001517) 2011-2020. Relevant clinical and tumour related variables were extracted. Recurrence-free survival (RFS) and overall survival (OS) by ST or TMMR was analysed with log-rank test, cumulative incidence function and proportional hazard regression yielding hazard ratios (HR) with 95% confidence intervals (CI), adjusted for relevant confounders.Between 2011 and 2020, 1007 women were included in the final analysis. 733 women were treated according to ST and 274 with TMMR. RFS at five years was 77.9% (95% CI 74.3-81.1) and 82.6% (95% CI 77.2-86.9) for the ST and TMMR cohorts respectively (p = 0.053). In early-stage CC, RFS was higher after TMMR as compared to ST, 91.2% vs 81.8% (p = 0.002). In the adjusted analysis, TMMR was associated with a lower hazard of recurrence (HR 0.39; 95% CI 0.22-0.69) and death (HR 0.42; 95% CI 0.21-0.86) compared to ST. The absolute difference in risk of recurrence at 5 years was 9.4% (95% CI 3.2-15.7) in favor of TMMR. In locally advanced CC, no significant differences in RFS or OS was observed.Compared to ST, TMMR without radiation therapy was associated with superior oncologic outcomes in women with early-stage cervical cancer whereas no difference was observed in locally advanced disease. Our findings together with previous evidence suggest that TMMR may be considered the primary option for both early-stage and locally advanced cervical cancer confined to the Müllerian compartment.This study was supported by grants from Centre for Clinical Research Sörmland (Sweden) and Region Stockholm (Sweden).