Clinical significance of site-specific metastases in pancreatic cancer: a study based on both clinical trial and real-world data

Background: There is limited consensus on whether metastatic patterns are correlated with prognosis and treatment efficacy in pancreatic cancer. A better understanding of clinical implication of the metastatic patterns is pivotal for therapeutic decision-making and drug development. Methods: This study included 977 patients with metastatic pancreatic cancer (MPC) in three cohorts. The training cohort included 273 patients from clinical trial NCT00574275 and 367 patients from clinical trial NCT01124786. As the validation cohort, 337 patients from Changzhou No.2 People's Hospital and Shanghai General Hospital were enrolled. The correlations between different patterns of metastases and clinicopathological characteristics were investigated with the Pearson Chi-Square test. Kaplan-Meier analysis and log-rank test were applied to analyze the survival outcomes among groups with different metastatic patterns. The prognostic value of the number of metastatic sites and other variables was evaluated using the Cox regression model. Results: MPC patients aged ≥65 years had a higher rate of lung metastasis and those with liver metastasis were prone to have a high level of carbohydrate antigen 19-9 (CA19-9). Additionally, patients with isolated lung metastasis had much better overall survival (OS) than those with isolated liver or peritoneum metastasis. Cox regression analyses showed that the number of metastatic sites was an independent prognostic factor for OS in patients with MPC. Furthermore, for patients with one-site or two-site metastasis, there was a significant difference in OS among patients receiving no chemotherapy, monotherapy and combination therapy. However, for patients with more than two metastatic sites, receiving combination therapy or monotherapy showed limited superiority in OS over receiving no chemotherapy. Conclusion: MPC patients with isolated lung metastasis had better OS than those with isolated liver or peritoneum metastasis. Moreover, the number of metastatic sites showed prognostic and predictive value in patients with MPC.