Favorable tumor biology in locally advanced pancreatic cancer—beyond CA19-9

Abstract

Patients with pancreatic ductal adenocarcinoma (PDAC) are frequently staged as unresectable locally advanced pancreatic cancer (LAPC) at the time of diagnosis. Recently, the administration of multi-agent induction chemotherapy has resulted in treatment response in up to 60% of these patients rendering their tumors technically resectable. Operative strategies have evolved to allow for successful oncologic resection of LAPC. These technically complex procedures involving vascular resections and reconstructions are now being performed with increasing safety at high-volume centers. However, even after induction therapy and successful resection, disease recurrence sometimes occurs early on, limiting the benefit of resecting the local tumor.Therefore, selection of surgical candidates should factor in each patient's tumor biology which could result in accurate treatment guidance to improve patient outcomes while avoiding overtreatment. Well-informed patient selection is critical to improve outcomes in LAPC. Multidisciplinary teams have to determine the appropriate care for LAPC patients at the time of reevaluation after administration of induction chemotherapy. At this point the concept of favorable vs. unfavorable tumor biology becomes highly relevant and having access to biomarkers that are predictive of tumor behavior are of paramount importance. Currently, CA19-9 remains the only clinically utilized biomarker for PDAC, however, its use is limited by factors discussed in this review.While CA19-9 holds value in patient assessment, additional biomarkers are required that could supplement and improve the current ability to classify tumor biology and predict behavior in individual patients. Recent investigations on the use of circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs) using liquid biopsies, as well as patient-derived organoids to characterize tumor biology have shown promise in achieving precise tumor biology-based patient stratification. Serial assessment of these biomarkers throughout therapy could supplement or even replace the anatomic criteria for resectability in the future.

Improved Clinical Staging System for Localized Pancreatic Cancer Using the ABC Factors: A TAPS Consortium Study

“…Future studies should search for additional biomarkers reflecting tumor behavior, such as circulating tumor DNA, to further improve staging. 21,22 Moreover, a decrease in standardized uptake value of PDAC on positron emission tomography scans after neoadjuvant treatment is a promising prognostic factor, especially in patients who are nonsecretors of CA 19-9. [23][24][25][26] Several smaller studies found that a poor performance status of ≥2 was a poor prognostic factor for OS for patients with PDAC.…”

Minimum and Optimal CA19-9 Response After Two Months Induction Chemotherapy in Patients with Locally Advanced Pancreatic Cancer

“…13 Several alternative serum biomarkers are recently described, such as carcinoma embryonic antigen (CEA), 45 DUPAN-2, 46 and circulating tumor cells/DNA. 47 Besides serological tumor markers, FDG-PET combined with either CT or magnetic resonance imaging may be a valuable tool to assess the biological disease response during/after chemo (radio) therapy, especially in patients with non-elevated CA19-9. 48 This is underlined by the 2021 Japanese Society of Hepato-Biliary-Pancreatic Surgery guideline, which proposed the implementation of the metabolic tumor activity on fluorodeoxyglucose positron emission tomography as biological parameter in the A-B-C resectability criteria from Isaji and colleagues.…”

“…Second, there remains a proportion of patients with non-elevated baseline CA19-9, and patients without CA19-9 due to a Lewis antigen negative phenotype for whom other indicators for tumor biology should be used 13 . Several alternative serum biomarkers are recently described, such as carcinoma embryonic antigen (CEA), 45 DUPAN-2, 46 and circulating tumor cells/DNA 47 . Besides serological tumor markers, FDG-PET combined with either CT or magnetic resonance imaging may be a valuable tool to assess the biological disease response during/after chemo (radio) therapy, especially in patients with non-elevated CA19-9 48 .…”

Impact of preoperative CA19-9 and histology grade on prognosis of pancreatic ductal adenocarcinoma and its value in TNM stage

“…Tumor biology shows signi cant impact on the prognosis of patients with malignancy and has been incorporated into the staging system to improve the accuracy of prognostic prediction [10,11] . Since both tumor burden and malignant degree could re ect the characteristics of tumor biology [12,13] , we supposed that combination of the factors which represent tumor burden and malignant degree would provide a full understanding of tumor biology on prognosis of cancer, and incorporating factors associated with tumor biology into staging system could improve the accuracy of the TNM staging system in predicting prognosis. Carbohydrate antigen 19 − 9 (CA19-9) is associated with the tumor burden 14] and histology grade is associated with the degree of malignancy [15,16] .…”