既往研究表明，42%至50%的局部晚期肝细胞癌（HCC）患者在联合局部治疗（LRT）加免疫治疗（IO）后达到完全缓解（CR）。然而，缺乏关于 CR 预测因素以及无需手术和停止 IO 后长期临床结果的数据。为了评估 LRT-IO 后达到 CR 并进行观察的不可切除 HCC 患者的长期临床结果，该队列研究包括 2018 年 1 月至 2022 年 12 月期间在 2 项前瞻性研究中 LRT-IO 后达到 CR 的不可切除 HCC 患者。数据截止时间为 2023 年 6 月。放射学 CR 是根据修订后的疗效评估标准定义的实体瘤。所有患者在 CR 后均接受密切监测，无需手术干预，并停止 IO。所有患者均接受立体定向全身放疗，随后接受抗程序性细胞死亡蛋白 1 或抗程序性死亡配体 1 治疗。 49 名患者在立体定向放射治疗前接受了一剂经动脉化疗栓塞治疗。主要结局是 3 年总生存 (OS) 率。次要结局包括 3 年进展时间、3 年局部控制率和复发模式。使用多变量分析对与 CR 相关的因素进行分析。 共有 63 名患者入组（58 名男性 [92.1%]；中位年龄，69 岁[范围，18-90 岁]）； 38例（60.3%）患者有大血管侵犯，肿瘤中位直径为10 cm（范围3.8-31.1 cm）。中位随访时间为 34.7 个月（95% CI，6.5-64.6 个月）。 29 例患者 (46.0%) 达到 CR。达到 CR 的患者的 3 年 OS 率明显优于未达到 CR 的患者（75.5% [95% CI, 58.2%-98.3%] vs 28.1% [95% CI, 7.4%-29.4%]；P < 。 001）。 29例CR患者中，3年疾病进展率为58.7%（95% CI，38.7%-79.1%），3年局部控制率为90.5%（95% CI，78.2%- 100%）。 10 名患者（34.5%）出现复发；其中，孤立性肝内疾病复发6例（60.0%）接受了根治性手术治疗。不存在肿瘤血管侵犯（比值比，0.30；95% CI，0.10-0.89）和最大病变直径总和为 8 cm 或更小（比值比，0.26；95% CI，0.07-0.98）与CR. 这项 LRT-IO 队列研究及长期随访数据发现，局部晚期不可切除 HCC 患者有持久缓解。放射学 CR 患者可以获得长期生存。有必要进行进一步的随机临床试验。

Previous studies showed that 42% to 50% of patients with locally advanced hepatocellular carcinoma (HCC) achieved complete remission (CR) after combined locoregional therapy (LRT) plus immunotherapy (IO). However, data on predictors of CR and long-term clinical outcomes without surgery and after discontinuation of IO are lacking.To assess the long-term clinical outcomes among patients with unresectable HCC who achieved CR after LRT-IO and were placed on a watch-and-wait protocol.This cohort study included patients with unresectable HCC who achieved CR after LRT-IO in 2 prospective studies between January 2018 and December 2022. The time of data cutoff was June 2023. Radiologic CR was defined per modified Response Evaluation Criteria in Solid Tumors. All patients underwent close surveillance after CR without surgical interventions, and IO was discontinued.All patients had received stereotactic body radiotherapy followed by anti-programmed cell death protein 1 or anti-programmed death ligand 1 therapy. Forty-nine patients had received a dose of transarterial chemoembolization before stereotactic body radiotherapy.The primary outcome was the 3-year overall survival (OS) rate. Secondary outcomes included the 3-year time-to-progression rate, 3-year local control rate, and relapse pattern. Factors associated with CR were analyzed using multivariate analyses.A total of 63 patients were enrolled (58 male [92.1%]; median age, 69 years [range, 18-90 years]); 38 patients (60.3%) had macrovascular invasion, and the median tumor diameter was 10 cm (range, 3.8-31.1 cm). The median follow-up time was 34.7 months (95% CI, 6.5-64.6 months). Twenty-nine patients (46.0%) achieved CR. The patients achieving CR had a significantly better 3-year OS rate than patients not achieving CR (75.5% [95% CI, 58.2%-98.3%] vs 28.1% [95% CI, 7.4%-29.4%]; P < .001). Among the 29 patients with CR, the 3-year time-to-progression rate was 58.7% (95% CI, 38.7%-79.1%) and the 3-year local control rate was 90.5% (95% CI, 78.2%-100%). Ten patients (34.5%) developed recurrence; among them, 6 (60.0%) with solitary intrahepatic disease relapse underwent curative surgical treatment. The absence of tumor vascular invasion (odds ratio, 0.30; 95% CI, 0.10-0.89) and the sum of the largest lesion diameters of 8 cm or less (odds ratio, 0.26; 95% CI, 0.07-0.98) were associated with CR.This cohort study of LRT-IO with long-term follow-up data found a durable response in patients with locally advanced unresectable HCC. Long-term survival was attainable in patients with radiologic CR. Further randomized clinical trials are warranted.