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Impact of Neoadjuvant Approach and Tumor Response on Survival in Pancreatic Adenocarcinoma
Journal article   Open access   Peer reviewed

Impact of Neoadjuvant Approach and Tumor Response on Survival in Pancreatic Adenocarcinoma

Mohammed O Suraju, Brian Longbottom, Jasmine A Peterson, Terry Hayes, Kiers Brevik, Sean Y Kim, Paolo Goffredo, Imran Hassan, Hassan Aziz and Carlos H F Chan
Journal of surgical oncology, Vol.134(5), pp.631-638
09/03/2026
DOI: 10.1002/jso.70329
PMCID: PMC13619096
PMID: 42693621
Appears in  UI Libraries Support Open Access
url
https://doi.org/10.1002/jso.70329View
Published (Version of record) Open Access

Abstract

Neoadjuvant therapy for pancreatic adenocarcinoma (PDAC) has evolved from single-agent to multi-agent approaches, largely informed by metastatic disease studies demonstrating improved survival; albeit at the price of increased toxicity. It remains unclear how response to varied neoadjuvant regimens impact survival. We hypothesized that tumor response to different neoadjuvant approaches reflects underlying tumor biology, and achieving a pathologic complete response (pCR) with single-agent neoadjuvant may signal favorable biology. Adult PDAC patients (2010-2021) who received neoadjuvant therapy were identified in the National Cancer Database. Tumor response was categorized as pCR (pT0N0), moderate (≥ 2 T-stage reduction), or minimal/no response (≤ 1 T-stage reduction). Patients with stage IV disease, margin positive, or nodal involvement on final pathology were excluded; sensitivity analyses including these patients were performed. Neoadjuvant regimens were classified as single-agent, multi-agent, or multi-agent therapy plus adjuvant chemotherapy. Of 1923 patients, 9.8% achieved pCR, 19.1% had moderate response and 71.1% had minimal/no response. The 3-year overall survival (OS) was 74% [68-81] for pCR, 56% [51-62] for moderate, and 50% [47-52] for minimal/no response. Notably, 11% of pCR patients received single-agent therapy and had a 3-year OS comparable to those who received more intensive regimens, even after adjusting for confounders. Conversely, single-agent therapy in moderate or minimal/no responders was associated with significantly worse survival. Sensitivity analyses including patients with nodal metastasis and positive margins demonstrated consistent trends. Most PDAC patients benefit from multi-agent neoadjuvant, although a small subset achieve pCR with single-agent therapy and experience excellent outcomes. Response to varied neoadjuvant approaches merits further investigation in biomarker-driven studies and may inform opportunities for therapy personalization in appropriately selected PDAC patients.
 multi‐agent pancreatic adenocarcinoma pathologic complete response neoadjuvant single‐agent survival UIOWA OA Agreement

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