Bong Jun Woo, Lee Hwamin, Jeong Seogsong, Kang Sanghee
Department of Surgery, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Republic of Korea.
Department of Biomedical Informatics, Korea University College of Medicine, Seoul, Republic of Korea.
JAMA Netw Open. 2025 Aug 1;8(8):e2525660. doi: 10.1001/jamanetworkopen.2025.25660.
IMPORTANCE: Colorectal cancer is a leading cause of cancer mortality, with increasing incidence in older adults. Oxaliplatin-based adjuvant chemotherapy is standard for stage II to III colorectal cancer, but its benefit in older patients remains unclear. OBJECTIVE: To investigate whether there is an optimal age threshold for a survival benefit of adding oxaliplatin to fluoropyrimidine-based adjuvant chemotherapy in older patients with stage II to III colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS: This population-based, retrospective cohort study using data from the Korea Health Insurance Review and Assessment Service included patients who underwent curative resection for stage II to III colorectal cancer and received adjuvant chemotherapy between January 2014 and December 2016. Participants were followed up until date of death or April 30, 2024, whichever occurred earlier. EXPOSURES: Oxaliplatin-based adjuvant chemotherapy compared with fluoropyrimidine-only chemotherapy. MAIN OUTCOMES AND MEASURES: The primary outcome was overall survival, analyzed using Cox proportional hazards regression and propensity score matching. Age thresholds from 60 to 80 years were systematically assessed to identify the optimal cutoff for oxaliplatin benefit. The association between chemotherapy discontinuation and oxaliplatin use was evaluated using multivariate regression analysis. RESULTS: Among a total of 53 147 patients, 8561 (mean [SD] age, 63.2 [11.2] years; 5084 [59.4%] male) were included in this study (stage II: 2913 [34.0%]; stage III: 5648 [65.9%]). Oxaliplatin was not associated with improved survival among patients with stage II disease across all age thresholds (adjusted hazard ratios [AHRs] ranged from 0.71 [95% CI, 0.34-1.50] to 1.09 [95% CI, 0.73-1.64]). In patients with stage III disease, oxaliplatin was associated with significantly improved survival up to age 70 years (AHR, 0.59; 95% CI, 0.46-0.77; P < .001), with a 5-year overall survival rate of 84.8% in the oxaliplatin group and 78.1% in the nonoxaliplatin group (P = .003). In patients older than 70 years, oxaliplatin was not associated with survival (AHR, 0.85; 95% CI, 0.67-1.07; P = .18). Multivariate regression analysis showed that oxaliplatin use was significantly associated with chemotherapy discontinuation in patients older than 70 years with stage III disease (adjusted odds ratio [AOR], 1.55; 95% CI, 1.19-2.03; P = .001), whereas no such association was observed in patients aged 70 years or younger (AOR, 1.22; 95% CI, 0.93-1.62; P = .16). CONCLUSIONS AND RELEVANCE: In this population-based cohort study, oxaliplatin addition was associated with significantly improved survival among patients with stage III colorectal cancer aged 70 years or younger but not in those older than 70 years. There was no association with improved survival among patients with stage II disease regardless of age. Moreover, in patients older than 70 years with stage III disease, oxaliplatin use was significantly associated with chemotherapy discontinuation.
重要性:结直肠癌是癌症死亡的主要原因之一,在老年人中的发病率呈上升趋势。以奥沙利铂为基础的辅助化疗是II期至III期结直肠癌的标准治疗方案,但其在老年患者中的获益仍不明确。 目的:探讨在II期至III期老年结直肠癌患者中,在基于氟嘧啶的辅助化疗基础上加用奥沙利铂是否存在生存获益的最佳年龄阈值。 设计、地点和参与者:这项基于人群的回顾性队列研究使用了韩国健康保险审查和评估服务的数据,纳入了2014年1月至2016年12月期间接受II期至III期结直肠癌根治性切除并接受辅助化疗的患者。对参与者进行随访,直至死亡日期或2024年4月30日,以先发生者为准。 暴露因素:以奥沙利铂为基础的辅助化疗与单纯氟嘧啶化疗的比较。 主要结局和测量指标:主要结局为总生存期,采用Cox比例风险回归和倾向得分匹配进行分析。系统评估了60至80岁的年龄阈值,以确定奥沙利铂获益的最佳临界值。使用多变量回归分析评估化疗中断与奥沙利铂使用之间的关联。 结果:在总共53147例患者中,本研究纳入了8561例(平均[标准差]年龄,63.2[11.2]岁;5084例[59.4%]为男性)(II期:2913例[34.0%];III期:5648例[65.9%])。在所有年龄阈值下,奥沙利铂与II期疾病患者的生存期改善无关(调整后风险比[AHRs]范围为0.71[95%CI,0.34 - 1.50]至1.09[95%CI,0.73 - 1.64])。在III期疾病患者中,奥沙利铂与70岁及以下患者的生存期显著改善相关(AHR,0.59;95%CI,0.46 - 0.77;P < 0.001),奥沙利铂组的5年总生存率为84.8%,非奥沙利铂组为78.1%(P = 0.003)。在70岁以上的患者中,奥沙利铂与生存期无关(AHR,0.85;95%CI,0.67 - 1.07;P = 0.18)。多变量回归分析显示,在70岁以上的III期疾病患者中,使用奥沙利铂与化疗中断显著相关(调整后优势比[AOR],1.55;95%CI,1.19 - 2.03;P = 0.001),而在70岁及以下的患者中未观察到这种关联(AOR,1.22;95%CI,0.93 - 1.62;P = 0.16)。 结论和相关性:在这项基于人群的队列研究中,加用奥沙利铂与70岁及以下的III期结直肠癌患者的生存期显著改善相关,但与70岁以上的患者无关。无论年龄如何,奥沙利铂与II期疾病患者的生存期改善均无关联。此外,在70岁以上的III期疾病患者中,使用奥沙利铂与化疗中断显著相关。
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