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Time-varying impact of established prognostic factors in resected pancreatic ductal adenocarcinoma

Prognostic factors in resected pancreatic ductal adenocarcinoma (PDAC) have been determined under the assumption that hazard ratios (HRs) remain static. However, PDAC is a dynamic disease with evolving conditional survival. The aim of this study was to determine if the impact of prognostic factors i...

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Main Authors: Javed, Ammar A. (Author) , Fatimi, Asad Saulat (Author) , Rompen, Ingmar F. (Author) , Mahmud, Omar (Author) , van Goor, Iris W J M (Author) , Habib, Joseph R (Author) , Andel, Paul (Author) , Campbell, Brady A (Author) , Schouten, Thijs J (Author) , Bagante, Fabio (Author) , Mughal, Nabiha A (Author) , Stoop, Thomas F (Author) , Lafaro, Kelly J (Author) , Burkhart, Richard A (Author) , Burns, William R (Author) , Hewitt, Brock (Author) , Sacks, Greg D (Author) , van Santvoort, Hjalmar C (Author) , den Dulk, Marcel (Author) , Daams, Freek (Author) , Mieog, J Sven D (Author) , Stommel, Martijn W J (Author) , Patijn, Gijs A (Author) , de Hingh, Ignace (Author) , Festen, Sebastiaan (Author) , Nijkamp, Maarten W (Author) , Klaase, Joost M (Author) , Lips, Daan J (Author) , Wijsman, Jan H (Author) , van der Harst, Erwin (Author) , Manusama, Eric (Author) , van Eijck, Casper H J (Author) , Koerkamp, Bas Groot (Author) , Kazemier, Geert (Author) , Busch, Olivier R (Author) , Molenaar, Izaak Quintus (Author) , Daamen, Lois A (Author) , Besselink, Marc G (Author) , He, Jin (Author) , Wolfgang, Christopher L (Author)
Format: Article (Journal)
Language:English
Published: 03 September 2025
In: Journal of the National Cancer Institute
Year: 2025, Volume: 117, Issue: 12, Pages: 2526-2534
ISSN:1460-2105
DOI:10.1093/jnci/djaf196
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1093/jnci/djaf196
Verlag, lizenzpflichtig, Volltext: https://academic.oup.com/jnci/article/117/12/2526/8246817
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Author Notes:Ammar A Javed, Asad Saulat Fatimi, Ingmar F Rompen, Omar Mahmud, Iris WJM van Goor, Joseph R Habib, Paul Andel, Brady A Campbell, Thijs J Schouten, Fabio Bagante, Nabiha A Mughal, Thomas F Stoop, Kelly J Lafaro, Richard A Burkhart, William R Burns, Brock Hewitt, Greg D Sacks, Hjalmar C van Santvoort, Marcel den Dulk, Freek Daams, J Sven D Mieog, Martijn WJ Stommel, Gijs A Patijn, Ignace de Hingh, Sebastiaan Festen, Maarten W Nijkamp, Joost M Klaase, Daan J Lips, Jan H Wijsman, Erwin van der Harst, Eric Manusama, Casper HJ van Eijck, Bas Groot Koerkamp, Geert Kazemier, Olivier R Busch, Izaak Quintus Molenaar, Lois A Daamen, Marc G Besselink, Jin He, Christopher L Wolfgang, Dutch Pancreatic Cancer Group and the PANC-PALS Consortium
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Summary:Prognostic factors in resected pancreatic ductal adenocarcinoma (PDAC) have been determined under the assumption that hazard ratios (HRs) remain static. However, PDAC is a dynamic disease with evolving conditional survival. The aim of this study was to determine if the impact of prognostic factors in PDAC is time-varying.This was a multicenter, retrospective cohort study of the prospectively maintained Dutch Pancreatic Cancer Recurrence Database and New York University and Johns Hopkins Hospital Institutional Databases. Patients with complete macroscopic resection of histopathologically proven PDAC between 2014 and 2019 and available follow-up data were included. The time-varying impact of prognostic factors identified by univariable Cox regression was modeled using Aalen’s Additive Regression Models (Aalen’s models) and visualized as plots of cumulative hazard.In total, 3104 patients were included, of whom 938 (30.2%) received neoadjuvant therapy (NAT), whereas the rest underwent upfront surgery (US). A total of 201 (6.5%) patients achieved observed long-term survival (>5 years). Aalen’s models showed that lymphovascular invasion, perineural invasion, and nodal disease were prognostic up to 2 years postoperatively. At varying points thereafter, these variables lost their impact in the NAT but not US patients. Similarly, during the fourth year of follow-up, American Society of Anesthesiology scores became impactful in the NAT but not in the US patients.The impact of prognostic factors in resected PDAC across NAT and US patients is time-varying. Our results suggest that aggressive disease drives early mortality but, after NAT, tumor-biological factors lose prognostic importance to frailty and comorbidities over time.
Item Description:Gesehen am 04.03.2026
Physical Description:Online Resource
ISSN:1460-2105
DOI:10.1093/jnci/djaf196

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