Ⅱ期至Ⅲ期食管癌的生存状况与治疗模式

现有临床试验倾向于采用新辅助放化疗（NCRT）联合手术作为局部晚期食管癌（EC）的首选方案，及围手术期化疗作为食管腺癌（EAC）的优先治疗方式。然而，目前尚不清楚这些试验结果是否在临床实际治疗中得到体现，并影响患者的生存结局。本文旨在研究不同治疗方式在临床环境中对食管癌患者生存的影响。本回顾性队列研究利用美国外科医师协会维护的国家癌症数据库，筛选2006年1月至2020年12月间接受三模态治疗（NCRT后行食管切除术）、确切放化疗（DCRT）、单一放疗（RT）或围手术期化疗的Ⅱ期至Ⅲ期食管癌患者，排除贲门癌患者。分析时间为2023年12月至2024年8月。研究中，围手术期化疗、三模态治疗、DCRT和单一放疗作为比较对象。在整个队列中，采用Cox比例风险模型比较不同治疗组的总生存期（OS），并在患者中根据鳞状细胞癌或腺癌、年龄超过65岁的患者进行亚组分析。为减少生存偏倚，还进行6个月标志性生存分析。研究共纳入57,116名患者（中位年龄64岁，IQR 57-72；男性45,410人，占79.5%）；其中21,619人（37.9%）接受三模态治疗，32,493人（57.1%）接受DCRT，2,692人（4.7%）接受单一放疗，312人（0.5%）接受围手术期化疗。在总体人群中，37,698人（66.0%）为EAC，接受围手术期化疗的312人中，有283人（90.7%）为EAC。调整后生存分析显示，围手术期化疗（AHR，0.33；95% CI，0.28-0.39；P<.001）和三模态治疗（AHR，0.45；95% CI，0.44-0.46；P<.001）均优于DCRT。相比之下，单一放疗的结果较差（AHR，1.37；95% CI，1.30-1.45；P<.001）。围手术期化疗的中位OS为66.2个月（95% CI，43.1-111.9），显著长于仅DCRT的18.1个月（95% CI，17.8-18.4；P<.001）。三模态治疗的中位OS为43.9个月（95% CI，42.8-45.5），虽然短于围手术期化疗，但优于DCRT和单一放疗的中位OS（13.5个月，95% CI，12.8-14.0；P<.001）。在超过65岁患者亚组中，接受围手术期化疗的患者中位OS更长（56.7个月；95% CI，36.4-115.2；P<.001），而接受其他治疗的患者中位OS较短（如三模态：40.1个月；95% CI，38.1-42.0；P<.001）。仅接受放疗的患者生存最差（13.6个月；95% CI，12.8-14.4；P<.001）。综上，在Ⅱ至Ⅲ期食管癌患者中，三模态治疗与DCRT或单一放疗相比，能显著改善局部晚期食管癌的总体生存；围手术期化疗则显著改善腺癌患者的生存预后。

Existing clinical trials favor neoadjuvant chemoradiation therapy (NCRT) followed by surgery alone for locally advanced esophageal cancer (EC) and perioperative chemotherapy as the preferred modality for esophageal adenocarcinoma (EAC). However, it is unclear whether these trial findings are reflected in the patterns of care and survival outcomes among patients in the clinical setting.To investigate survival outcomes in the clinical setting among patients with EC after various treatment modalities.This retrospective cohort study examined data from the National Cancer Database maintained by the American College of Surgeons and focused on patients with clinical stage II or III EC, excluding those with gastroesophageal junction cancer, who underwent trimodality therapy (NCRT followed by esophagectomy), definitive chemoradiation therapy (DCRT), radiotherapy (RT) alone, or perioperative chemotherapy from January 2006 to December 2020. Analyses were conducted from December 2023 to August 2024.Perioperative chemotherapy, trimodality therapy, DCRT, and single-modality RT.A Cox proportional hazards regression model was used to compare overall survival (OS) between treatment groups in the entire cohort, among patients with squamous cell carcinoma or adenocarcinoma, and among those older than 65 years. Landmark survival analysis at 6 months was performed to reduce survivorship bias.The study included 57 116 patients (median age, 64 [IQR, 57-72] years; 45 410 [79.5%] male); 21 619 patients (37.9%) received trimodality therapy, 32 493 (57.1%) received DCRT, 2692 (4.7%) received single-modality RT, and 312 (0.5%) received perioperative chemotherapy. In the overall study population, 37 698 patients (66.0%) had EAC, and of the 312 patients that received perioperative chemotherapy, 283 (90.7%) had EAC. In adjusted survival analysis, perioperative chemotherapy (adjusted hazard ratio [AHR], 0.33; 95% CI, 0.28-0.39; P <.001) and trimodality therapy (AHR, 0.45; 95% CI, 0.44-0.46; P < .001) were associated with improved OS compared with DCRT. In contrast, RT alone was associated with worse outcomes compared with DCRT (AHR, 1.37; 95% CI, 1.30-1.45; P < .001). The median OS for perioperative chemotherapy of 66.2 months (95% CI, 43.1-111.9 months; P < .001) was longer compared with that for DCRT alone (18.1 months; 95% CI, 17.8-18.4 months; P < .001). Trimodality therapy was associated with a median OS of 43.9 months (95% CI, 42.8-45.5 months; P < .001), which was shorter than that for perioperative chemotherapy but improved compared with DCRT and RT alone, which was associated with a median OS of 13.5 months (95% CI, 12.8-14.0 months; P < .001). In the subgroup of patients older than 65 years, those who received perioperative chemotherapy had longer median OS (56.7 months; 95% CI, 36.4-115.2 months; P < .001) compared with those receiving other treatment modalities (eg, trimodality therapy: 40.1 months; 95% CI, 38.1-42.0 months; P < .001). Patients who received RT alone had the worst median OS (13.6 months; 95% CI, 12.8-14.4 months; P < .001).In this cohort study of patients with stage II to III EC, trimodality therapy was associated with improved OS compared with DCRT or RT alone for locally advanced EC and perioperative chemotherapy was associated with improved OS for adenocarcinoma.