The Prep-02/JSAP05 trial, a phase II/III study, evaluated preoperative chemotherapy versus surgery-first in patients with resectable pancreatic ductal adenocarcinoma. A total of 364 patients were enrolled: one group received two cycles of gemcitabine plus S-1 before surgery, while the other underwent immediate surgery. Both groups were advised to complete six months of postoperative S-1.
Results showed a significant survival benefit for the preoperative chemotherapy group. Median overall survival increased from 26.6 to 37.0 months, and the three-year survival rate rose from 36.6% to 50.2%. Relapse-free survival improved, and liver recurrence decreased. Preoperative treatment did not reduce surgical rates, and lymph node involvement was lower, indicating better control of hidden metastases.
While chemotherapy caused notable side effects, it did not increase surgical complications or deaths. Early progression during treatment also helped identify aggressive tumors, avoiding unnecessary surgery. These findings establish neoadjuvant gemcitabine plus S-1 as a new standard for resectable pancreatic cancer.