Purpose To estimate the causal effect of surgery vs chemotherapy on survival in patients with T1-3NxM0 pancreatic cancer in a rigorous framework addressing selection bias and immortal time bias. Methods We used population-based Danish healthcare registries to conduct a cohort study emulating a hypothetical randomized trial to estimate the absolute difference in survival, comparing surgery with chemotherapy. We included pancreatic cancer patients diagnosed during 2008-2021. Exposure was surgery or chemotherapy initiated within a 16-week grace period after diagnosis. At the time of diagnosis, data of each patient was duplicated; one copy was assigned to the surgery protocol and one copy to the chemotherapy protocol of the hypothetical trial. Copies were censored when the assigned treatment deviated from the observed treatment. To account for informative censoring, uncensored patients were weighted according to confounders. For comparison, we also applied a more conventional analysis using propensity score-based inverse probability weighting. Results We included 1,744 patients with a median age of 68 years; 73.6% underwent surgery and 18.6% had chemotherapy without surgery. 7.8% received no treatment. The 3-year survival was 39.7% (95% CI 36.7% to 42.6%) after surgery and 22.7% (95% CI: 17.7% to 28.4%) after chemotherapy, corresponding to an absolute difference of 17.0% (95% CI: 10.8% to 23.1%). In the conventional survival analysis, this difference was 23.0% (95% CI: 17.0% to 29.0%). Conclusion Surgery was superior to chemotherapy in achieving long-term survival for pancreatic cancer. The difference comparing surgery and chemotherapy was substantially smaller when using the clone-censor-weight approach than conventional survival analysis.

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手术与化疗对胰腺癌患者的影响：目标试验模拟

目的 在解决选择偏倚和永生时间偏倚的严格框架内评估手术与化疗对 T1-3NxM0 胰腺癌患者生存的因果影响。方法 我们使用基于人口的丹麦医疗保健登记处进行了一项队列研究，模拟一项假设的随机试验，以估计生存率的绝对差异，比较手术与化疗。我们纳入了 2008 年至 2021 年诊断的胰腺癌患者。暴露是在诊断后 16 周宽限期内开始的手术或化疗。诊断时，每个患者的数据都是重复的；一份用于假设试验的手术方案，一份用于化疗方案。当指定的治疗偏离观察到的治疗时，副本就会被审查。为了解释信息审查，根据混杂因素对未经审查的患者进行加权。为了进行比较，我们还应用了更传统的分析，即基于倾向得分的逆概率加权。结果 我们纳入了 1,744 名患者，中位年龄为 68 岁； 73.6% 接受了手术，18.6% 接受了化疗但未进行手术。 7.8% 未接受治疗。手术后 3 年生存率为 39.7%（95% CI 36.7% - 42.6%），化疗后 3 年生存率为 22.7%（95% CI：17.7% - 28.4%），绝对差异为 17.0%（95% CI：17.7% - 28.4%）。 10.8% 至 23.1%）。在常规生存分析中，这一差异为 23.0%（95% CI：17.0% 至 29.0%）。结论 在实现胰腺癌长期生存方面，手术优于化疗。使用克隆审查权重方法时，手术和化疗之间的差异比传统的生存分析要小得多。