Prognostic factors and sites of metastasis in unresectable locally advanced pancreatic cancer

Abstract

Due to differences in natural history and therapy, clinical trials of patients with advanced pancreatic cancer have recently been subdivided into unresectable locally advanced pancreatic cancer (LAPC) and metastatic disease. We aimed to evaluate prognostic factors in LAPC patients who were treated with first-line chemotherapy and describe patterns of disease progression. Patients with LAPC who initiated first-line palliative chemotherapy, 2001-2011 at the BC Cancer Agency were included. A retrospective chart review was conducted to identify clinicopathologic variables, treatment, and subsequent sites of metastasis. Kaplan-Meier and Cox-regression survival analyses were performed. A total of 244 patients were included in this study. For the majority of patients (94.3%), first-line therapy was single-agent gemcitabine. About 144 (59%) patients developed distant metastatic disease and the most frequent metastatic sites included peritoneum/omentum (42.3%), liver (41%), lungs (13.9%), and distant lymph nodes (9%). Median overall survival (OS) for the entire cohort was 11.7 months (95% CI, 10.6-12.8). Development of distant metastases was associated with significantly inferior survival (HR 3.56, 95% CI 2.57-4.93), as was ECOG 2/3 versus 0/1 (HR 1.69, 95% CI 1.28-2.23), CA 19.9 > 1000 versus ≤ 1000 (HR 1.59, 95% CI 1.19-2.14) and female gender, (HR 1.57, 95% CI 1.19-2.08). In this population-based study, 41% of LAPC patients treated with first-line chemotherapy died without evidence of distant metastases. Prognostic factors for LAPC were baseline performance status, elevated CA 19.9, gender, and development of distant metastasis. Results highlight the heterogeneity of LAPC and the importance of locoregional tumor control.

Keywords: CA 19.9; LAPC; PDAC; liver metastasis; locally advanced pancreatic cancer; metastatic sites; pancreatic ductal adenocarcinoma; prognostic factors; survival.

Figure 1

Overall survival by ECOG performance status. Kaplan–Meier curve of LAPC patients with ECOG PS 0–1 (n = 146) versus ECOG PS 2–3 (n = 98). P = 0.0002, HR 1.69 (95% CI 1.28–2.23).

Figure 2

Overall survival by CA 19.9 levels. Kaplan–Meier curve of LAPC patients with CA 19.9 < 1000 (n = 150) versus CA 19.9 > 1000 (n = 73). P-value, 0.0018, HR 1.59 (95% CI 1.19–2.14).