Patterns of disease dissemination and survival in patients with synchronous and metachronous metastatic pancreatic adenocarcinoma: Nationwide population-based study

Abstract

Aim: Despite advances in understanding pancreatic adenocarcinoma, evidence on its metastatic patterns and impact on patient survival remains limited. This study aims to identify patterns of disease dissemination in synchronous versus metachronous metastatic pancreatic adenocarcinoma (mPAC) and their association with overall survival (OS). Methods: Patients diagnosed with synchronous- or metachronous-mPAC were selected from the Netherlands Cancer Registry (2015–2021). Patient, tumor, and treatment characteristics were compared using Chi-squared tests. Survival data, calculated from detection of metastatic disease (OS-M), were analyzed using Kaplan-Meier and Log-rank tests. Results: Overall, 10,788 patients with synchronous- and 508 with metachronous-mPAC were included. Median time to first metastasis in metachronous-mPAC was 13.2 months (IQR 9–23), varying significantly by metastatic site (liver-only 11.5; lung-only 28.0 months). Compared to synchronous-mPAC, patients with metachronous-mPAC had less liver metastases (48 % versus 75 %, p < 0.001), but more lung (29 % versus 21 %, p < 0.001) and peritoneal (35 % versus 25 %, p < 0.001) metastases. Synchronous metastases to liver-only, lung-only, lymph node-only, or multiple sites at first diagnosis had a median OS-M that was (nearly) half compared to metachronous metastases to the same sites. Bone-only or peritoneum-only metastases in synchronous-mPAC showed a median OS-M comparable to metachronous-mPAC. Conclusion: This nationwide population-based study reveals that metachronous-mPAC less commonly presents with liver metastases and more often metastasizes to lung, peritoneum or other atypical sites compared to synchronous-mPAC. These distinct metastatic patterns and their differences in survival may help enhance the prognostic estimation for individual patients from the detection of metastatic disease and warrants further research into the biology underlying metastasis development.