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Invited Commentary
June 20, 2024

The Sequencing Conundrum in Localized Pancreatic Adenocarcinoma—Progress or Passive Acceptance?

Author Affiliations
  • 1Division of Hematology-Oncology, Massachusetts General Hospital, Boston
  • 2Division of Hematology/Oncology, University of Arizona Cancer Center, Tucson
JAMA Oncol. 2024;10(8):1036-1037. doi:10.1001/jamaoncol.2024.0870

Despite years of surgical and therapeutic advances, pancreatic ductal adenocarcinoma (PDAC) remains a deadly disease with dismal long-term outcomes. Multimodality treatment with systemic chemotherapy in localized PDAC has shown incremental improvements in survival; however, many questions linger, with the most pressing being what is the correct sequencing in perioperative therapy? Neoadjuvant therapy is preferred in borderline resectable disease given improved R0 resection rates and overall survival (OS).1 However, in upfront resectable disease, there are conflicting schools of thought and varying institutional practices. Adjuvant chemotherapy with modified fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) has shown superiority over single-agent gemcitabine and is the recommended treatment per National Comprehensive Cancer Network guidelines after upfront pancreatectomy.2 However, given the aggressive nature of PDAC, upfront chemotherapy first could potentially eradicate micrometastases early and also help ascertain the biology of the cancer, sparing a futile surgical procedure if there is development of metastasis during initial systemic therapy.

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