• Leonard W F Seelen, Deesje Doppenberg, Thomas F Stoop, Anne Nagelhout, Lilly J H Brada, Koop Bosscha, Olivier R Busch, Geert A Cirkel, Marcel den Dulk, Freek Daams, Susan van Dieren, van EijckCasper H JCHJDepartment of Surgery, Erasmus MC Cancer Institute, Rotterdam, The Netherlands., Sebastiaan Festen, Bas Groot Koerkamp, Nadia Haj Mohammad, de HinghIgnace H J TIHJTDepartment of Surgery, Catharina Hospital, Eindhoven, The Netherlands., Daan J Lips, Maartje Los, Vincent E de Meijer, Gijs A Patijn, Marco B Polée, StommelMartijn W JMWJDepartment of Surgery, Radboud University Medical Center, Nijmegen, The Netherlands., Marieke S Walma, Roeland F de Wilde, Johanna W Wilmink, I Quintus Molenaar, Hjalmar C van Santvoort, Marc G Besselink, and Dutch Pancreatic Cancer Group.
• Department of Surgery, UMC Utrecht Cancer Center and St Antonius Hospital Nieuwegein: Regional Academic Cancer Center Utrecht, Utrecht, The Netherlands.
• Ann. Surg. 2024 May 1; 279 (5): 832841832-841.

ObjectiveThis nationwide multicenter study aimed to define clinically relevant thresholds of relative serum CA19-9 response after 2 months of induction chemotherapy in patients with locally advanced pancreatic cancer (LAPC).BackgroundCA19-9 is seen as leading biomarker for response evaluation in patients with LAPC, but early clinically useful cut-offs are lacking.MethodsAll consecutive patients with LAPC after 4 cycles (m)FOLFIRINOX or 2 cycles gemcitabine-nab-paclitaxel induction chemotherapy (±radiotherapy) with CA19-9 ≥5 U/mL at baseline were analyzed (2015-2019). The association of CA19-9 response with median OS (mOS) was evaluated for different CA19-9 cut-off points. Minimum and optimal CA19-9 response were established via log-rank test. Predictors for OS were analyzed using COX regression analysis.ResultsOverall, 212 patients were included, of whom 42 (19.8%) underwent resection. Minimum CA19-9 response demonstrating a clinically significant median OS difference (12.7 vs. 19.6 months) was seen at ≥40% CA19-9 decrease. The optimal cutoff for CA19-9 response was ≥60% decrease (21.7 vs. 14.0 mo, P =0.021). Only for patients with elevated CA19-9 levels at baseline (n=184), CA19-9 decrease ≥60% [hazard ratio (HR)=0.59, 95% CI, 0.36-0.98, P =0.042] was independently associated with prolonged OS, as were SBRT (HR=0.42, 95% CI, 0.25-0.70; P =0.001), and resection (HR=0.25, 95% CI, 0.14-0.46, P <0.001), and duration of chemotherapy (HR=0.75, 95% CI, 0.69-0.82, P <0.001).ConclusionsCA19-9 decrease of ≥60% following induction chemotherapy as optimal response cut-off in patients with LAPC is an independent predictor for OS when CA19-9 is increased at baseline. Furthermore, ≥40% is the minimum cut-off demonstrating survival benefit. These cut-offs may be used when discussing treatment strategies during early response evaluation.Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.

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