Although staging has historically been determined based on anatomic criteria alone, the international cohort study demonstrates that anatomic staging of patients with localised pancreatic ductal adenocarcinoma (PDAC) can be improved by evaluating two readily available clinical characteristics. Biology, reflected by baseline CA 19-9, and patient condition, reflected by performance status (PS), are equally important prognostic factors for patients with localised PDAC treated with induction (m)FOLFIRINOX regimen.
In addition to anatomic factors (A: borderline resectable or locally advanced), tumour biology (B: CA 19-9 >500) and patient condition (C: WHO PS ≥1) were important independent poor prognostic factors. Together these ABC factors constitute a clinical staging system with predicted 5-year survival that ranged from 4.8% to 47.0%. The findings are published by Dr. Bas Groot Koerkamp of the Department of Surgery, Erasmus MC Cancer Institute in Rotterdam, the Netherlands, and colleagues from the Trans-Atlantic Pancreatic Surgery (TAPS) Consortium on 5 February 2024 in the JCO.
The authors wrote in the background that conventional TNM staging for PDAC depends on tumour size, nodal status, and the presence of distant metastatic disease. It is best used for pathologic staging after surgical resection rather than clinical staging at diagnosis. However, nodal status is typically unknown at clinical staging because imaging is inaccurate for nodal status. Moreover, tumour size was not shown as an independent poor prognostic factor which severely hampers TNM staging of patients with PDAC.
Patients with localised PDAC have traditionally been clinically staged at presentation by evaluating the relationship of the primary tumour to the hepatic and mesenteric vasculature. At multidisciplinary team meetings, tumours are routinely categorised as potentially resectable, borderline resectable, and locally advanced PDAC reflecting primarily the technical feasibility of performing a margin-negative resection.
In 2008, researchers from The University of Texas MD Anderson Cancer Center created the ABC classification to account for clinical factors beyond anatomy. It was conceived to characterise patients with localised PDAC with a particularly poor prognosis: those with radiographic findings suspicious but not diagnostic for extrapancreatic metastases (e.g. indeterminate liver or lung lesions), confirmed N1 disease, elevated serum CA 19-9, or suboptimal PS. These higher-risk patients were hypothesised to benefit from neoadjuvant therapy to treat micrometastatic disease, clarify tumour biology, and optimise comorbidities and condition before surgery.
The latest study published in the JCO hypothesised that serum CA 19-9 and PS may improve clinical staging for all patients presenting with localised PDAC. The first aim of the study was to investigate whether the components of the ABC classification are independent prognostic risk factors in patients with localised PDAC who received (m)FOLFIRINOX as initial treatment. The second aim was to investigate the combined prognostic value of the ABC factors in a new clinical staging system.
It was a retrospective cohort study conducted at 5 high-volume centres in the US and the Netherlands from 2012 to 2019. Multivariable Cox proportional hazards analysis was used to investigate the impact of the ABC factors for overall survival (OS).
Overall, 1,835 patients with localised PDAC were included. Tumour stage at diagnosis was potentially resectable in 346 patinets (18.9%), borderline resectable in 531 patients (28.9%), and locally advanced in 958 patients (52.2%). The baseline CA 19-9 was >500 U/mL in 559 patients (32.5%). PS was ≥1 in 1,110 patients (60.7%).
Independent poor prognostic factors for OS were borderline resectable disease (hazard ratio [HR] 1.26, 95% confidence interval [CI] 1.06 to 1.50]), locally advanced disease (HR 1.71, 95% CI 1.45 to 2.02), CA 19-9 >500 U/mL (HR 1.36, 95% CI 1.21 to 1.52]), and WHO PS ≥1 (HR 1.31, 95% CI 1.16 to 1.47).
Patients were assigned 1 point for each poor ABC factor and 2 points for locally advanced disease. The median OS for patients with score 0-4 was 49.7, 29.9, 22.0, 19.1, and 14.9 months with corresponding 5-year OS rates of 47.0%, 28.9%, 19.2%, 9.3%, and 4.8%, respectively.
The ABC staging system allows for staging of all patients presenting with localised PDAC into prognostic groups with 0 to 4 points. It can be used to inform patients and physicians about prognosis. The ABC staging can also be used as a stratification factor in clinical trials. In the ongoing PREOPANC-3 study, randomly assigning patients with potentially resectable PDAC between neoadjuvant mFOLFIRINOX and up-front surgery, patients are stratified by serum CA 19-9 level and PS.
In an accompanied editorial, Dr. Michele Milella of the Section of Innovation Biomedicine—Oncology Area, Department of Engineering for Innovation Medicine, University of Verona in Verona, Italy wrote that overall, these data importantly add to our knowledge. However, understanding of which population of patients with pancreatic cancer this approach would best be applied, particularly since emerging data are challenging FOLFIRINOX as a universal standard for neoadjuvant treatment of localised PDAC, would require further analysis of the data and extensive external validation, across the entire disease spectrum.
The study was previously presented in part at the Alpine Liver and Pancreatic Surgery meeting in Madonna Di Campiglio, Italy on 4 February 2023 and at the E-AHPBA Congress in Lyon, France on 9 June 2023.
The study was supported by the Dutch Cancer Society and ZonMw.
References
- Dekker EN, van Dam JL, Janssen QP, et al. for the Trans-Atlantic Pancreatic Surgery (TAPS) Consortium. Improved Clinical Staging System for Localized Pancreatic Cancer Using the ABC Factors: A TAPS Consortium Study. JCO; Published online 5 February 2024. DOI: https://doi.org/10.1200/JCO.23.01311
- Milella M. Stage Classification and Prognosis Assessment in Localized Pancreatic Cancer: It Takes Two to Tango. JCO; Published online 5 February 2024. DOI: https://doi.org/10.1200/JCO.23.02494