Decreased serum carbohydrate antigen 19-9 levels after neoadjuvant therapy predict a better prognosis for patients with pancreatic adenocarcinoma: a multicenter case-control study of 240 patients

BMC Cancer. 2019 Mar 21;19(1):252. doi: 10.1186/s12885-019-5460-4.

Abstract

Background: Carbohydrate antigen (CA) 19-9 levels after resection are considered to predict prognosis; however, the significance of decreased CA19-9 levels after neoadjuvant therapy has not been clarified. This study aimed to define the prognostic significance of decreased CA19-9 levels after neoadjuvant therapy in patients with pancreatic adenocarcinoma.

Methods: Between 2001 and 2012, 240 consecutive patients received neoadjuvant therapy and subsequent resection at seven high-volume institutions in Japan. These patients were divided into three groups: Normal group (no elevation [≤37 U/ml] before and after neoadjuvant therapy), Responder group (elevated levels [> 37 U/ml] before neoadjuvant therapy but decreased levels [≤37 U/ml] afterwards), and Non-responder group (elevated levels [> 37 U/ml] after neoadjuvant therapy). Analyses of overall survival and recurrence patterns were performed. Uni- and multivariate analyses were performed to clarify the clinicopathological factors influencing overall survival. The initial metastasis sites were also evaluated in these groups.

Results: The Responder group received a better prognosis than the Non-responder group (3-year overall survival: 50.6 and 41.6%, respectively, P = 0.026), but the prognosis was comparable to the Normal group (3-year overall survival: 54.2%, P = 0.934). According to the analysis of the receiver operating characteristic curve, the CA19-9 cut-off level defined as no elevation after neoadjuvant therapy was ≤103 U/ml. The multivariate analysis revealed that a CA19-9 level ≤ 103 U/ml, (P = 0.010, hazard ratio: 1.711; 95% confidence interval: 1.133-2.639), tumor size ≤27 mm (P = 0.040, 1.517; (1.018-2.278)), a lack of lymph node metastasis (P = 0.002, 1.905; (1.276-2.875)), and R0 status (P = 0.045, 1.659; 1.012-2.627) were significant predictors of overall survival. Moreover, the Responder group showed a lower risk of hepatic recurrence (18%) compared to the Non-responder group (31%), though no significant difference in loco-regional, peritoneal or other distant recurrence were observed between groups (P = 0.058, P = 0.700 and P = 0.350, respectively).

Conclusions: Decreased CA19-9 levels after neoadjuvant therapy predicts a better prognosis, with low incidence of hepatic recurrence after surgery.

Keywords: Carbohydrate antigen 19–9; Neoadjuvant therapy; Pancreatic cancer.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • CA-19-9 Antigen / blood*
  • Carcinoma, Pancreatic Ductal / epidemiology*
  • Carcinoma, Pancreatic Ductal / secondary
  • Case-Control Studies
  • Female
  • Humans
  • Incidence
  • Liver Neoplasms / epidemiology*
  • Liver Neoplasms / secondary
  • Male
  • Middle Aged
  • Neoadjuvant Therapy / methods
  • Neoplasm Recurrence, Local / epidemiology*
  • Neoplasm Recurrence, Local / pathology
  • Pancreatectomy
  • Pancreatic Neoplasms / blood
  • Pancreatic Neoplasms / mortality*
  • Pancreatic Neoplasms / pathology
  • Pancreatic Neoplasms / therapy
  • Prognosis
  • Response Evaluation Criteria in Solid Tumors
  • Survival Analysis

Substances

  • CA-19-9 Antigen