Patients with localized pancreatic ductal adenocarcinoma (PDAC) are best treated with surgical resection of the primary tumour and systemic chemotherapy, which provides considerably longer overall survival (OS) durations than either modality alone. Regardless, most patients will have disease relapse owing to micrometastatic disease. Although currently a matter of some debate, considerable research interest has been focused on the role of neoadjuvant therapy for all forms of resectable PDAC. Whilst adjuvant combination chemotherapy remains the standard of care for patients with resectable PDAC, neoadjuvant chemotherapy seems to improve OS without necessarily increasing the resection rate in those with borderline-resectable disease. Furthermore, around 20% of patients with unresectable non-metastatic PDAC might undergo resection following 4–6 months of induction combination chemotherapy with or without radiotherapy, even in the absence of a clear radiological response, leading to improved OS outcomes in this group. Distinct molecular and biological responses to different types of therapies need to be better understood in order to enable the optimal sequencing of specific treatment modalities to further improve OS. In this Review, we describe current treatment strategies for the various clinical stages of PDAC and discuss developments that are likely to determine the optimal sequence of multimodality therapies by integrating the fundamental clinical and molecular features of the cancer.

局限性胰腺导管腺癌 （PDAC） 患者最好通过手术切除原发肿瘤和全身化疗进行治疗，与单独使用任何一种方式相比，这可提供更长的总生存期 （OS） 持续时间。无论如何，大多数患者会因微转移性疾病而复发。尽管目前存在一些争论，但相当大的研究兴趣集中在新辅助治疗对所有形式的可切除 PDAC 的作用上。虽然辅助联合化疗仍然是可切除 PDAC 患者的标准治疗，但新辅助化疗似乎可以改善 OS，而不一定会增加临界可切除疾病患者的切除率。此外，大约 20% 的不可切除非转移性 PDAC 患者在诱导联合化疗联合或不联合放疗 4-6 个月后可能会接受切除，即使没有明确的放射学反应，从而改善该组的 OS 结局。需要更好地了解对不同类型疗法的不同分子和生物学反应，以便能够对特定治疗方式进行最佳排序，从而进一步改善 OS。在本综述中，我们描述了 PDAC 各个临床阶段的当前治疗策略，并讨论了通过整合癌症的基本临床和分子特征可能确定多模式治疗最佳顺序的发展。