Hs-CRP, albumin and CA19-9 after neoadjuvant therapy predict postoperative survival in borderline resectable pancreatic ductal adenocarcinoma

Abstract

Background: Systemic inflammation and tumor markers have shown prognostic value in resectable pancreatic ductal adenocarcinoma (PDAC). This study aimed at assessing preoperative laboratory values as prognostic factors in borderline resectable patients treated with neoadjuvant therapy (NAT). Methods: Between 2000 and 2015, 399 consecutive PDAC patients underwent surgery at Helsinki University Hospital. Borderline resectable patients (n=94) received NAT. Resectable propensity scored patients (n=182) underwent upfront surgery (US). NAT included folfirinox, single gemcitabine or combined with cisplatin, capecitabine or nab-paclitaxel with or without radiation. Preoperative high-sensitivity CRP (hs-CRP, mg/l), leukocytes (E9/l), albumin (g/l), bilirubin (g/l), platelets (E9/l), CA19-9 (kU/l)and CEA (μg/l) were assessed. Survival was estimated with Kaplan-Meier and Cox Regression. Results: In both NAT and US patients, hs-CRP <3 presented with longer survival than hs-CRP =3 (NAT 49 vs. 24 months, p<0.001; US 30 vs. 23 months, p=0.032). Additionally, albumin =35 (33 vs. 17 months, p=0.002) and CA19-9 =37 (43 vs. 18 months, p<0.001) associated with survival. Combining hs-CRP and CA19-9 together predicted survival better than either one alone: those with hs-CRP <3 and CA19-9 =37 had a median survival of 54 months compared to those with either hs-CRP or CA19-9 over the reference limit (27 months) and those with both values over the reference limit (16 months, p<0.001). In NAT patients, those recurring within one year after surgery had higher hs-CRP (4.2 vs. 1.9, p=0.038) and CA19-9 (209 vs. 22, p<0.001) and lower albumin (36.5 vs. 38.8, p=0.005) than not recurred patients. Both Hs-CRP =3 and CA19-9 >37 predicted worse survival (HR 5.52, p=0.007) and adjuvant therapy better survival (HR 0.40, p=0.006) in multivariate analysis in NAT patients. Only one NAT patient with hs-CRP =3 (total n=52) survived more than five years (hs-CRP=3.93). Conclusion: Hs-CRP, albumin and CA19-9 after NAT predicted postoperative survival in borderline resectable PDAC patients.