Decreased serum CA19-9 levels after neoadjuvant therapy predict a low incidence of hepatic recurrence after surgery and a better prognosis for patients with pancreatic adenocarcinoma: A multicenter case-control study of 240 patients

Abstract

Introduction: Neoadjuvant therapy (NAT) is considered a potential approach to improve long-term survival for patients with pancreatic adenocarcinoma (PDAC) (ASCO-GI 2019). However, surrogate markers that predict prognostic significance in the resection after NAT have been still unclear. This study aimed to define the impact of decreased CA19-9 levels after NAT in terms of survival and recurrence patterns. Method: Between 2001 and 2012, 240 consecutive patients received NAT 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 NAT), Responder group (elevated levels [>37 U/ml] before NAT but decreased levels [<37 U/ml] afterwards), and Non-responder group (elevated levels after NAT). Overall survival (OS) and uni- and multivariate analyses were performed to clarify the clinicopathological factors influencing OS. The initial metastasis sites were also evaluated in these groups. Result: The Responder group received a better prognosis than the Non-responder group (3-year OS: 50.6% and 41.6%, respectively, P=0.026), but the prognosis was comparable to the Normal group (3-year OS: 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 NAT was <103 U/ml. The multivariate analysis revealed that a CA19-9 level<103 U/ml, (P=0.010, HR: 1.711), tumor size <27 mm (P=0.040, 1.517), a lack of lymph node metastasis (P=0.002, 1.905), and R0 status (P=0.045, 1.659) were significant predictors of OS. Moreover, the Respondergroup 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). Conclusion: Decreased CA19-9 levels after NAT is a therapeutic indicator for the effects against hepatic micrometastases. The decreased CA19-9 values indicate the optical timing for subsequent surgery and predict better prognosis after surgery.