The predictors and patterns of the early recurrence of pancreatic ductal adenocarcinoma after pancreatectomy: the influence of pre- and post- operative adjuvant therapy: a single-center and retrospective analysis
The perioperative factors predicting or influencing early pancreatic ductal adenocarcinoma (PDAC) recurrence are unclear. This study attempted to identify the predictive factors for early PDAC recurrence post-pancreatectomy and the influence of pre-and post-operative adjuvant therapy. Methods One hundred and fifteen patients undergoing curative resection for PDAC between 2000 and 2016 at our institution were retrospectively analyzed. Patients were divided into two groups: those who did and did
... se who did and did not experience PDAC recurrence within 6 months postoperatively. Results Thirty-four (30%) patients experienced early recurrence. Multivariate analyses demonstrated postoperative carbohydrate antigen 19-9 (CA19-9) de-normalization, no postoperative adjuvant chemotherapy (ACT), and serosal invasion were independent risk factors for early recurrence (P<0.001, P=0.001, and P=0.010, respectively). A subgroup analysis showed patients with (n=51) and without (n=64) preoperative chemoradiotherapy (CRT) had different predictors. Although postoperative ACT was not a significant indicator in patients with preoperative CRT, CA19-9 denormalization and no postoperative ACT were significant indicators in patients without preoperative CRT. Preoperative CRT strongly prevented early local recurrence while postoperative ACT prevented early distant recurrence. Conclusions CA19-9 de-normalization was an important predictor of early recurrence of PDAC. Although postoperative ACT was an important preventive measure against early recurrence, particularly for distant recurrence, preoperative CRT might compensate for a lack of postoperative ACT. Preoperative CRT could strongly prevent the early local recurrence of PDAC. These perioperative adjuvant therapies could have a complementary relationship. Background Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis; only 3% of patients survive at 5 years after diagnosis [1,2]. Only 20% of patients with PDAC are eligible to undergo radical resection . Although surgical resection provides the only chance for a cure, it is associated with a median overall survival (OS) period of 11 to 23 months, with a 5-year OS rate of about 20% [4,5]. 4 The early recurrence of PDAC postoperatively is a frequently observed, serious problem, even after macroscopically curative resection is performed. La Torre et al. reported that 60% of patients experience local or systemic recurrence within the first 12 months after curative resection . Some reports suggested that the preoperative factors that are associated with the survival time after surgery were tumor size , preoperative lymph node metastasis , the preoperative serum carbohydrate antigen 19-9 (CA19-9) level [3,4,6,7], histological grades [4,7], duration of symptoms , and the preoperative modified Glasgow Prognostic Score . These might be predictors of the early recurrence of PDAC postoperatively. Neoadjuvant therapy was not actually recommended for patients with R-PDAC in the 2016 NCCN guideline , but neoadjuvant chemotherapy or chemoradiotherapy (CRT) may reduce the early recurrence of PDAC. Upfront surgery might be a predictor of the early recurrence of PDAC, even for those with R-PDAC. The aim of this study was to identify the predictive factors for the early recurrence of PDAC and to detect the influence of preoperative CRT, as well as adjuvant chemotherapy (ACT), on the early recurrence of PDAC after surgery. Material And Methods This study was approved by the institutional review board of Kagawa University. A total of 142 consecutive patients undergoing pancreatectomy for PDAC between January 2000 and May 2016 were retrospectively examined. Informed consent was obtained from all patients according to the institutional protocol of our hospital. All 142 patients had a PDAC that was histologically examined by at least two pathologists. Of the 142 patients, 27 patients were excluded. Ten patients were censored within 6 months, 10 were classified as unresectable category based on the 2016 NCCN guideline , 5 had unclear recurrence timing, 1 underwent R2 resection, and 1 had perioperative mortality. The data from the remaining 115 patients were retrospectively analyzed. The patients were diagnosed with resectable ([R], n=86) or borderline resectable ([BR], n=29) PDAC according to the 2016 NCCN guidelines  . All surgical procedures were divided into the following three types: classic, pylorus-preserving, or subtotal stomach-preserving pancreaticoduodenectomy recurrence of PDAC, particularly for distant recurrence. Preoperative CRT had a strong potential to prevent the early local recurrence of PDAC. In addition, preoperative CRT might compensate for the lack of postoperative ACT. In patients who are not expected to be capable of receiving postoperative ACT, preoperative CRT should be considered.