直肠癌患者发生局部复发和/或远处转移后的肿瘤学结局仍缺乏研究。 分析德国直肠癌研究组连续三项 2 期或 3 期试验中直肠癌患者治疗失败后的总体生存趋势该队列研究是对 3 项随机 2 期或 3 期试验（CAO/ARO/AIO-94、-04 和 -12 试验，在德国进行）的事后分析，其中包括 1948 名局部晚期直肠腺癌患者。 CAO/ARO/AIO-94试验在1995年2月至2002年9月期间招募患者，CAO/ARO/AIO-04试验在2006年7月至2010年2月期间招募患者，CAO/ARO/AIO-12试验在6月期间招募患者2015年和2018年1月。统计分析于2022年9月至2023年3月期间进行。CAO/ARO/AIO-94试验A组391例患者中共有119例，CAO/ARO/AIO-04试验1236例患者中共有295例，CAO/ARO/AIO-12 试验中的 306 例患者中有 69 例经历了治疗失败（R2 切除或局部复发或远处转移），并被纳入进一步分析。在所有 3 个试验队列中评估了治疗失败和总体生存的特征。在 3 项试验中接受治疗的 1948 名患者中，有 15 名因数据缺失而被排除。其余 1933 名局部晚期直肠腺癌（cT3 或 4 或 cN）患者（中位年龄 62.5 岁 [范围 19-84 岁]；1363 名男性 [71%] 和 570 名女性 [29%]）在 3 个连续治疗期内接受治疗临床试验中，483 例治疗失败并进行了分析。对所有患者进行中位随访 36 个月（IQR，24-51 个月）后，CAO/ARO/AIO-04 试验中治疗失败后的总生存率显着提高（3 年时，44% [IQR，37] %-51%]；风险比 [HR]，0.61 [95% CI，0.47-0.79]）并在 CAO/ARO/AIO-12 试验中进一步改善（3 年时，73% [IQR，60%-87] %]；HR，0.32 [95% CI，0.18-0.54]）与 CAO/ARO/AIO-94 试验（3 年时，30% [IQR，22%-39%]）相比（均 P < .001 ）。远处转移是整个 5 年随访期间治疗失败的主要原因（范围为 67%-87%），并且在所有 3 项试验中，前 18 个月治疗失败的相对风险最高。 ypTNM 分期与治疗失败的风险和时间间隔显着相关。治疗失败后总生存期的改善与性别无关。这项队列研究表明，过去几十年挽救策略的进步可能改善了经历治疗失败的直肠癌患者的总生存期。

Oncologic outcomes among patients with rectal cancer after developing local recurrence and/or distant metastases remain poorly studied.To analyze the trend of overall survival after treatment failure for patients with rectal cancer within three consecutive phase 2 or 3 trials of the German Rectal Cancer Study Group.This cohort study is a post hoc analysis of 3 randomized phase 2 or 3 trials (CAO/ARO/AIO-94, -04, and -12 trials, conducted in Germany) that included 1948 patients with locally advanced rectal adenocarcinoma. The CAO/ARO/AIO-94 trial recruited patients between February 1995 and September 2002, the CAO/ARO/AIO-04 trial recruited patients between July 2006 and February 2010, and the CAO/ARO/AIO-12 trial recruited patients between June 2015 and January 2018. Statistical analysis was conducted between September 2022 and March 2023.A total of 119 of 391 patients in the CAO/ARO/AIO-94 trial group A, 295 of 1236 patients in the CAO/ARO/AIO-04 trial, and 69 of 306 in the CAO/ARO/AIO-12 trial experienced treatment failure (R2 resection or local recurrence or distant metastases) and were included in further analyses.Characteristics of treatment failure and overall survival were assessed in all 3 trial cohorts.Of the 1948 patients treated in the 3 trials, 15 were excluded because of missing data. Of the remaining 1933 patients (median age, 62.5 years [range, 19-84 years]; 1363 men [71%] and 570 women [29%]) with locally advanced rectal adenocarcinoma (cT3 or 4 or cN+) treated within 3 consecutive clinical trials, 483 experienced treatment failure and were analyzed. After a median follow-up of 36 months (IQR, 24-51 months) for all patients, overall survival after treatment failure was significantly improved in the CAO/ARO/AIO-04 trial (at 3 years, 44% [IQR, 37%-51%]; hazard ratio [HR], 0.61 [95% CI, 0.47-0.79]) and further improved in the CAO/ARO/AIO-12 trial (at 3 years, 73% [IQR, 60%-87%]; HR, 0.32 [95% CI, 0.18-0.54]) compared with the CAO/ARO/AIO-94 trial (at 3 years, 30% [IQR, 22%-39%]) (both P < .001). Distant metastasis was the main reason for treatment failure throughout a 5-year follow-up (range, 67%-87%), and the relative risk for treatment failure was highest in the first 18 months in all 3 trials. ypTNM stage was significantly associated with the risk and time interval to treatment failure. Improvement in overall survival after treatment failure was independent of sex.This cohort study suggests that advancements in salvage strategies during the past decades have likely improved overall survival among patients with rectal cancer who experienced treatment failure.