Carbohydrate Antigen 19-9 (CA19-9) Response After Induction FOLFIRINOX for Locally Advanced Pancreatic Cancer Identifies Patients Who May Benefit from Surgical Exploration: Multicentre, Observational Cohort Study

Medicine Oncology
Locally Advanced Pancreatic Cancer CA19-9 FOLFIRINOX Surgical Exploration Prognostic Factors Survival Rate

Pancreatic cancer is a highly malignant tumor with an extremely low five-year survival rate, especially for patients with locally advanced pancreatic cancer (LAPC), who have limited treatment options and poor prognosis. LAPC is defined based on the degree of tumor contact with adjacent blood vessels and is often considered “unresectable” at diagnosis. Currently, induction chemotherapy (such as the FOLFIRINOX regimen) has become one of the standard treatments for LAPC. However, although induction therapy can shrink tumors to some extent, it remains controversial which patients may benefit from surgery after induction therapy.

To address this question, researchers aimed to predict which LAPC patients might achieve longer survival after surgical exploration by analyzing changes in CA19-9 (carbohydrate antigen 19-9) levels after induction therapy and the patient’s performance status. CA19-9 is a commonly used biomarker in pancreatic cancer, but its relationship with surgical prognosis after induction therapy remains unclear. Therefore, this study sought to determine the independent predictive value of post-induction CA19-9 levels, the extent of CA19-9 decrease, and performance status on overall survival (OS) after surgical exploration through a multicenter retrospective cohort study.

Source of the Paper

This study was conducted by the Trans-Atlantic Pancreatic Surgery (TAPS) Consortium, involving multiple internationally renowned institutions. The primary authors include Esther N. Dekker and Bas Groot Koerkamp from the Erasmus MC Cancer Institute in the Netherlands, as well as experts from institutions such as the Memorial Sloan Kettering Cancer Center and the University of Texas MD Anderson Cancer Center in the United States. The paper was published in 2025 in the BJS (British Journal of Surgery) under the title “Carbohydrate antigen 19-9 (CA19-9) response after induction FOLFIRINOX for locally advanced pancreatic cancer identifies patients who may benefit from surgical exploration: multicentre, observational cohort study.”

Study Process and Results

Study Design

This study was a multicenter retrospective cohort study that included 958 LAPC patients who received FOLFIRINOX induction therapy within the TAPS consortium between 2012 and 2019. The primary objective was to identify factors that independently predict overall survival in patients undergoing surgical exploration after induction therapy. The study was conducted in the following steps:

  1. Patient Screening and Grouping: All patients received FOLFIRINOX induction therapy and underwent restaging after treatment. Based on restaging results, patients were divided into three groups: metastatic disease (M1), non-metastatic disease (M0) without surgical exploration, and non-metastatic disease (M0) with surgical exploration.
  2. Data Analysis: Multivariable Cox proportional hazards models were used to assess the impact of CA19-9 levels, the extent of CA19-9 decrease, and performance status on survival after surgical exploration.
  3. Survival Prediction Model: Based on the above independent predictors, a prediction model for 3-year overall survival after surgical exploration was constructed and visualized using contour plots.

Study Results

  1. Patient Characteristics: Among the 958 patients, 221 (23.1%) had metastatic disease (M1) at restaging, while 724 (75.6%) had non-metastatic disease (M0). Of these, 234 (24.4%) M0 patients underwent surgical exploration, and 490 (51.1%) M0 patients did not. In the surgical exploration group, 213 patients had baseline CA19-9 levels ≥5 U/ml, excluding 21 CA19-9 non-producers.
  2. Survival Analysis: The median overall survival in the surgical exploration group was 29.5 months, compared to 11.5 months in M0 patients who did not undergo surgical exploration. Multivariable analysis identified independent predictors of overall survival after surgical exploration, including post-induction CA19-9 levels (HR 1.14, 95% CI 1.01-1.29), the extent of CA19-9 decrease (HR 0.89, 95% CI 0.79-0.99), and a performance status ≥1 (HR 1.71, 95% CI 1.21-2.42). Baseline CA19-9 levels had no significant impact on survival after surgical exploration.
  3. Survival Prediction Model: Based on these factors, a prediction model for 3-year overall survival after surgical exploration was developed. The results showed that patients with a CA19-9 decrease >80% and post-induction CA19-9 levels <50 U/ml, particularly those with a performance status of 0, had the highest 3-year survival rates.

Study Conclusion

This study demonstrated that post-induction CA19-9 levels, the extent of CA19-9 decrease, and performance status are independent predictors of overall survival in LAPC patients after surgical exploration. For patients with a performance status of 0, a CA19-9 decrease >80%, and post-induction CA19-9 levels <50 U/ml, surgical exploration may significantly improve survival. These findings provide important evidence for clinical decision-making, helping physicians better identify patients who may benefit from surgery.

Highlights and Significance

  1. Key Findings: This study is the first to systematically evaluate the relationship between changes in CA19-9 after induction therapy and survival after surgical exploration, clarifying the predictive value of the extent of CA19-9 decrease and post-induction CA19-9 levels.
  2. Clinical Significance: The results provide a scientific basis for treatment decisions in LAPC patients, helping physicians better assess the potential benefits of surgery after induction therapy and optimize treatment strategies.
  3. Methodological Innovation: The study used multivariable analysis and a survival prediction model, combined with contour plot visualization, to provide clinicians with intuitive tools for individualized treatment decisions.
  4. Multicenter Collaboration: This study was conducted through collaboration among multiple internationally renowned institutions, with a broad data source and high external validity of the results.

Other Valuable Information

The limitations of this study include its retrospective design, missing data for some variables, and variations in treatment protocols across centers. Future large-scale prospective studies are needed to validate these findings. Additionally, the study did not include data on patients’ quality of life, and future research could further explore the impact of surgery on patients’ quality of life.

This study provides important scientific evidence for the treatment of LAPC patients and has significant clinical application value.