Histological tumor necrosis in pancreatic cancer after neoadjuvant therapy

The pathological prognostic factors in pancreatic cancer patients who have received neoadjuvant therapy (NAT) are still elusive. The aim of the present study was to investigate the prognostic potential of histological tumor necrosis (HTN) in patients who received NAT and to evaluate tumor changes after NAT. HTN was studied in 44 pancreatic cancer patients who received NAT followed by surgery (NAT group) compared with 263 patients who received upfront surgery (UFS group). The prognostic factors in the NAT group were analyzed, and carbonic anhydrase 9 (CA-9) expression was compared between the NAT and USF group to evaluate the hypoxic microenvironment changes during NAT. HTN was found in 15 of 44 patients in the NAT group, and its frequency was lower than that in the UFS group (34 vs. 51%, P=0.04). Cox proportional hazards models identified HTN as an independent risk factor for relapse-free survival in the NAT group [risk ratio (RR), 5.60; 95% confidence interval (CI): 2.27-14.26, P<0.01]. Significant correlations were found between HTN and CA-9 expression both in the NAT and UFS groups (P<0.01 for both). CA-9 expression was significantly upregulated in the NAT group overall, although this upregulation was specifically induced in patients without HTN. In conclusion, HTN was a poor prognostic factor in pancreatic cancer patients receiving NAT followed by surgery, and the present study suggests a close association between HTN and tumor hypoxia. Increased hypoxia after NAT may support the thesis for re-engineering the hypoxia-alleviating tumor microenvironment in NAT regimens for pancreatic cancer.