ImportanceThe timing of adjuvant chemotherapy after surgery for colorectal cancer and its association with long-term outcomes have been investigated in national cohort studies, with no consensus on the optimal time from surgery to adjuvant chemotherapy.ObjectiveTo analyze the association between the timing of adjuvant chemotherapy after surgery for colorectal cancer and disease-free survival.Design, Setting, and ParticipantsThis is a post hoc analysis of the phase 3 SCOT randomized clinical trial, from 244 centers in 6 countries, investigating the noninferiority of 3 vs 6 months of adjuvant chemotherapy. Patients with high-risk stage II or stage III nonmetastatic colorectal cancer who underwent curative-intended surgery were randomized to either 3 or 6 months of adjuvant chemotherapy consisting of fluoropyrimidine and oxaliplatin regimens. Those with complete information on the date of surgery, treatment type, and long-term follow-up were investigated for the primary and secondary end points. Data were analyzed from May 2022 to February 2024.InterventionIn the post hoc analysis, patients were grouped according to the start of adjuvant chemotherapy being less than 6 weeks vs greater than 6 weeks after surgery.Main Outcomes and MeasuresThe primary end point was disease-free survival. The secondary end points were adverse events in the total treatment period or the first cycle of adjuvant chemotherapy.ResultsA total of 5719 patients (2251 [39.4%] female; mean [SD] age, 63.4 [9.3] years) were included in the primary analysis after data curation; among them, 914 were in the early-start group and 4805 were in the late-start group. Median (IQR) follow-up was 72.0 (47.3-88.1) months, with a median (IQR) of 56 (41-66) days from surgery to chemotherapy. Five-year disease-free survival was 78.0% (95% CI, 75.3%-80.8%) in the early-start group and 73.2% (95% CI, 72.0%-74.5%) in the late-start group. In an adjusted Cox regression analysis, the start of adjuvant chemotherapy greater than 6 weeks after surgery was associated with worse disease-free survival (hazard ratio, 1.24; 95% CI, 1.06-1.46; P = .01). In adjusted logistic regression models, there was no association with adverse events in the total treatment period (odds ratio, 0.82; 95% CI, 0.65-1.04; P = .09) or adverse events in the first cycle of treatment (odds ratio, 0.77; 95% CI, 0.56-1.09; P = .13).Conclusions and RelevanceIn this international population of patients with high-risk stage II and stage III colorectal cancer, starting adjuvant chemotherapy more than 6 weeks after surgery was associated with worse disease-free survival, with no difference in adverse events between the groups.Trial Registrationisrctn.org Identifier: ISRCTN59757862

中文翻译：

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从结直肠癌手术到辅助化疗的时间


结直肠癌术后辅助化疗时机及其与长期预后的关系已在全国队列研究中进行了探讨，但对于手术至辅助化疗的最佳时间尚未达成共识。 目的分析结直肠癌术后辅助化疗时机与长期预后的关系。设计、设置和参与者这是对来自 6 个国家 244 个中心的 3 期 SCOT 随机临床试验的事后分析，调查了 3 个月与 6 个月辅助化疗的非劣效性。接受治疗性手术的高危 II 期或 III 期非转移性结直肠癌患者被随机接受 3 或 6 个月的辅助化疗，包括氟嘧啶和奥沙利铂方案。对那些拥有手术日期、治疗类型和长期随访完整信息的患者进行了主要和次要终点的调查。数据分析时间为 2022 年 5 月至 2024 年 2 月。干预在事后分析中，根据术后开始辅助化疗时间少于 6 周与超过 6 周对患者进行分组。主要结果和措施主要终点为无病生存。次要终点是总治疗期间或第一个辅助化疗周期中的不良事件。 结果 总共 5719 名患者（2251 [39.4%] 女性；平均 [SD] 年龄，63.4 [9.3] 岁）被纳入主要研究终点。数据整理后进行分析；其中，早起步组914人，晚起步组4805人。中位随访时间 (IQR) 为 72.0 (47.3-88.1) 个月，从手术到化疗的中位随访时间 (IQR) 为 56 (41-66) 天。 早期开始组的五年无病生存率为 78.0%（95% CI，75.3%-80.8%），晚期开始组为 73.2%（95% CI，72.0%-74.5%）。在调整后的 Cox 回归分析中，术后 6 周以上开始辅助化疗与较差的无病生存率相关（风险比，1.24；95% CI，1.06-1.46；磷= .01)。在调整后的逻辑回归模型中，与总治疗期间的不良事件没有关联（比值比，0.82；95% CI，0.65-1.04；磷= .09）或第一个治疗周期中的不良事件（比值比，0.77；95% CI，0.56-1.09；磷= .13). 结论和相关性在国际 II 期和 III 期结直肠癌高危患者群体中，术后 6 周以上开始辅助化疗与较差的无病生存率相关，且不良事件发生率没有差异团体。试用注册isrctn。组织标识符： ISRCTN59757862