Tailoring Adjuvant Chemotherapy to Biologic Response Following Neoadjuvant Chemotherapy Impacts Overall Survival in Pancreatic Cancer

J Gastrointest Surg. 2023 Apr;27(4):691-700. doi: 10.1007/s11605-022-05476-w. Epub 2022 Oct 24.

Abstract

Background: The role of postoperative chemotherapy in patients with resected pancreatic cancer who receive neoadjuvant treatment is unknown. Clinicians use changes in CA19-9 and histopathologic scores to assess treatment response. We sought to investigate if CA19-9 normalization in response to NAT can help guide the need for postoperative treatment.

Methods: Patients with elevated baseline CA19-9 (CA19-9 > 37U/mL) who received NAT followed by surgery between 2011 and 2019 were retrospectively reviewed. Treatment response was determined by CA19-9 normalization following NAT and histopathologic scoring. The role of postoperative chemotherapy was analyzed in light of CA19-9 normalization and histopathologic response.

Results: We identified and included 345 patients. Following NAT, CA19-9 normalization was observed in 125 patients (36.2%). CA19-9 normalization was associated with a favorable histopathologic response (41.6% vs 23.2%, p < 0.001) and a lower ypT (p < 0.001) and ypN stage (p = 0.003). Receipt of adjuvant chemotherapy was associated with improved overall survival in patients in whom CA19-9 did not normalize following NAT (26.8 vs 16.4 months, p = 0.008). In patients who received 5FU-based NAT and in whom CA19-9 did not normalize, receipt of 5FU-based adjuvant chemotherapy was associated with improved OS (p = 0.014).

Conclusion: CA19-9 normalization in response to NAT was associated with favorable outcomes and can serve as a biomarker for treatment response. In patients where CA19-9 did not normalize, receipt of postoperative chemotherapy was associated with improved OS. These patients also benefited from additional 5FU-based postoperative chemotherapy following 5FU-based NAT.

Keywords: Biologic response; Neoadjuvant chemotherapy; Pancreatic ductal adenocarcinoma; Pathologic response.

MeSH terms

  • Biological Products* / therapeutic use
  • CA-19-9 Antigen
  • Chemotherapy, Adjuvant
  • Fluorouracil / therapeutic use
  • Humans
  • Neoadjuvant Therapy
  • Pancreatic Neoplasms* / drug therapy
  • Pancreatic Neoplasms* / pathology
  • Retrospective Studies

Substances

  • CA-19-9 Antigen
  • Fluorouracil
  • Biological Products