Failure of normalization of CA19-9 following resection for pancreatic cancer is tantamount to metastatic disease

Background: Multidisciplinary therapy for pancreatic cancer involves radical resection followed by gemcitabinebased chemotherapy. Carbohydrate antigen 19-9 (CA19-9), when elevated preoperatively, is a useful marker to monitor disease status following resection. However, little has been reported on outcomes of patients in whom CA19-9 never normalizes. We hypothesize that failure of CA19-9 normalization within 6 months is prognostically equivalent to metastatic disease. Methods: From our pancreatectomy database, we identified 93 patients with pancreatic adenocarcinoma and elevated CA19-9 prior to resection with levels recorded postoperatively. Patients were grouped based on normalization or persistent elevation of CA19-9 at 6 months after resection. CA19-9 levels normalized (≤35 u/ml) after resection in 38 (41%) and remained elevated in 55 (59%). Clinicopathologic characteristics were compared using Student's t-test and contingency table analyses. Survival curves were constructed using Kaplan-Meier method and compared by log-rank analysis. Cox regression was used to determine predictors of survival. Results: The two groups had comparable clinicopathologic characteristics except for nodal status and perineural invasion, which were higher in patients with persistently elevated CA19-9. Persistent CA19-9 conferred shorter median overall survival of 10.8 months compared with 23.8 months in patients with normalization (p<0.001), which persisted when controlling for nodal status. Multivariate analysis demonstrated persistently elevated CA19-9 as the sole statistically significant negative predictor of survival [hazard ratio (HR) 2.20, p = 0.002]. Conclusions: Persistent CA19-9 elevation after pancreatectomy correlates with shorter survival analogous to unresected or metastatic disease and should be regarded as persistent disease regardless of radiographic findings. These patients should be considered for accrual to clinical trials or initiation of alternative therapy.