Evidence map›Paper›PMID 42154110›Full record

ArticleAnnals of surgical oncology2026

Re-evaluating the Role of Neoadjuvant Chemotherapy in Early-Stage Pancreatic Ductal Adenocarcinoma: Unveiling the Impact of Immortal Time Bias on Survival.

Amir Ashraf Ganjouei, Jane Wang, Sophia Hernandez, Laleh Foroutani, Fernanda Romero Hernandez, Kenzo Hirose, Eric Nakakura, Carlos Corvera, Adnan Alseidi, Mohamed Abdelgadir Adam

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Article in Annals of surgical oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

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10 authors.

Amir Ashraf GanjoueiDepartment of Surgery, University of California, San Francisco, San Francisco, CA, USA.
Jane WangDepartment of Surgery, University of California, San Francisco, San Francisco, CA, USA.
Sophia HernandezDepartment of Surgery, University of California, San Francisco, San Francisco, CA, USA.
Laleh ForoutaniDepartment of Surgery, University of California, San Francisco, San Francisco, CA, USA.
Fernanda Romero HernandezDepartment of Surgery, University of California, San Francisco, San Francisco, CA, USA.
Kenzo HiroseDepartment of Surgery, University of California, San Francisco, San Francisco, CA, USA.
Eric NakakuraDepartment of Surgery, University of California, San Francisco, San Francisco, CA, USA.
Carlos CorveraDepartment of Surgery, University of California, San Francisco, San Francisco, CA, USA.
Adnan AlseidiDepartment of Surgery, University of California, San Francisco, San Francisco, CA, USA.
Mohamed Abdelgadir AdamDepartment of Surgery, University of California, San Francisco, San Francisco, CA, USA. Mohamed.Adam@ucsf.edu.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe survival benefit of neoadjuvant chemotherapy (NAC) in early-stage pancreatic ductal adenocarcinoma (PDAC) remains uncertain. Although retrospective studies often suggest improved outcomes, these findings may be confounded by immortal time bias (ITB), the interval between diagnosis and treatment during which patients must survive to receive therapy, potentially inflating survival estimates. This study applied multiple bias-adjusted analytic methods to re-evaluate the association between NAC and overall survival in early-stage PDAC.

methodsUsing the National Cancer Database (2012-2017), we identified adults with resectable clinical T1 and T2 PDAC who underwent pancreatectomy. Overall survival was compared between multiagent NAC and upfront surgery by using Kaplan-Meier and multivariable Cox models. We used three statistical approaches to adjust for immortal time bias: 1) a 9-month landmark analysis; 2) a time-varying Cox regression model; and 3) a propensity-matched time-varying Cox model.

resultsAmong 13,466 patients, 15.8% received NAC. Before bias adjustment, NAC was associated with longer median survival (33.4 vs. 25.7 months; HR 0.78, p < 0.001). However, after correcting for immortal time bias, this apparent survival advantage disappeared: landmark analysis (HR 0.94, p = 0.072), time-varying model (HR 1.06, p = 0.2), and matched cohort (HR 0.94, p = 0.2).

conclusionsThis study shows that ITB significantly influences survival estimates in retrospective analyses of NAC for early-stage resectable PDAC. When appropriately adjusted, NAC was not associated with a survival advantage compared to upfront surgery. These findings underscore the need for methodological rigor in retrospective studies and caution against overinterpreting unadjusted survival advantages.

Indexed as

Antineoplastic Combined Chemotherapy ProtocolsCarcinoma, Pancreatic DuctalNeoadjuvant TherapyPancreatectomyPancreatic NeoplasmsAgedBiasChemotherapy, AdjuvantFemaleFollow-Up StudiesHumansMaleMiddle AgedNeoplasm StagingPrognosisRetrospective StudiesImmortal time biasNCDBNeoadjuvant chemotherapyPancreatic ductal adenocarcinomaSurvival analysisUpfront surgery

Identifiers

PMID42154110

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.