Defining the optimal timing of adjuvant therapy for resected pancreatic cancer: A statewide cancer registry analysis.

Abstract

406 Background: Recent long-term results from the ESPAC-3 trial suggest that while completing adjuvant therapy (AT) is necessary after resection of pancreatic adenocarcinoma (PDAC), early initiation of AT before 8 weeks may not be associated with improved overall survival (OS). The primary aim of this study was to evaluate the impact of early vs. late AT initiation on OS in a statewide population-based analysis. Methods: Among all patients with stage I-III PDAC in the Surveillance Epidemiology and End Results (SEER) - Kentucky Cancer Registry (KCR) from 2004-2012, those undergoing pancreatectomy were stratified by postoperative chemotherapy/radiotherapy delivery and timing. Patients with preoperative therapy, no AT, or postoperative therapy beyond 16 weeks, were excluded. Remaining patients were stratified into 2 groups defined as “early” (<8 weeks) and “late” AT (8-16 weeks). A Cox regression model was created to analyze the impact of AT timing, adjusting for clinicopathologic variables. Results: Of the 4,882 total patients with PDAC, 1,193 (24%) underwent pancreatectomy. Of these, only 364 (30%) received AT within 16 weeks. With median age 65 years (range 20-101), 86% patients were stage II and 76% were node-positive. Median time to AT initiation was 52 days (range 5-111). Timing of AT did not affect OS (median OS: early AT, 19.5 vs. 19.7 mo, late AT, p=0.63). Median OS for stages I, II, and III were 46.1, 19.3, and 8.6 mo, respectively (p<0.001). Poorly/undifferentiated tumors were associated with worse median OS 17.6 vs. 21.3 mo for well/moderately differentiated tumors (p<0.001). Lymph node positivity was associated with worse median OS 18.1 vs. 25.8 mo for node negativity (p<0.001). On multivariate analysis, factors that affected OS included stage (II, HR 2.54, p=0.022; III, HR 5.16, p<0.001), node positivity (HR 1.57, p=0.008), poorly/undifferentiated grade (HR 1.50; p=0.002), but not AT timing. Conclusions: In this SEER-KCR analysis, there was no difference in OS between early and late AT initiation. Despite its proven value, the ideal window for AT initiation remains unknown as tumor biology continues to trump current treatment regimens.