A population-based study of synchronous distant metastases and prognosis in patients with PDAC at initial diagnosis

OBJECTIVE: Cancer of the pancreas is a life-threatening condition and has a high distant metastasis (DM) rate of over 50% at diagnosis. Therefore, this study aimed to determine whether patterns of distant metastases correlated with prognosis in pancreatic ductal adenocarcinoma (PDAC) with metastatic spread, and build a novel nomogram capable of predicting the 6, 12, 18-month survival rate with high accuracy. METHODS: We analyzed data from the Surveillance, Epidemiology, and End Results (SEER) database for cases of PDAC with DM. Kaplan-Meier analysis, log-rank tests and Cox-regression proportional hazards model were used to assess the impact of site and number of DM on the cancer-specific survival (CSS) and over survival (OS). A total of 2709 patients with DM were randomly assigned to the training group and validation group in a 7:3 ratio. A nomogram was constructed by the dependent risk factors which were determined by multivariate Cox-regression analysis. An assessment of the discrimination and ability of the prediction model was made by measuring AUC, C-index, calibration curve and decision curve analysis (DCA). In addition, we collected 98 patients with distant metastases at the time of initial diagnosis from Ningbo University Affiliated LiHuili Hospital to verify the efficacy of the prediction model. RESULTS: There was a highest incidence of liver metastases from pancreatic cancer (2387,74.36%), followed by lung (625,19.47%), bone (190,5.92%), and brain (8,0.25%). The prognosis of liver metastases differed from that of lung metastases, and the presence of multiple organ metastases was associated with poorer prognosis. According to univariate and multivariate Cox-regression analyses, seven factors (i.e., diagnosis age, tumor location, grade of tumor differentiation, T-stage, receipt of surgery, receipt of chemotherapy status, presence of multiple organ metastases) were included in our nomogram model. In internal and external validation, the ROC curves, C-index, calibration curves and DCA were calculated, which confirmed that this nomogram can precisely predict prognosis of PDAC with DM. CONCLUSION: Metastatic PDAC patients with liver metastases tended to have a worse prognosis than those with lung metastases. The number of DM had significant effect on the overall survival rate of metastatic PDAC. This study had a high prediction accuracy, which was helpful clinicians to analyze the prognosis of PDAC with DM and implement individualized diagnosis and treatment.