Adjuvant chemoradiation therapy for pancreatic adenocarcinoma: who really benefits?

Abstract

Background: The role of adjuvant chemoradiation therapy (CRT) in pancreatic cancer remains controversial. The primary aim of this study was to determine if CRT improved survival in patients with resected pancreatic cancer in a large, multiinstitutional cohort of patients.

Study design: Patients undergoing resection for pancreatic adenocarcinoma from seven academic medical institutions were included. Exclusion criteria included patients with T4 or M1 disease, R2 resection margin, preoperative therapy, chemotherapy alone, or if adjuvant therapy status was unknown.

Results: There were 747 patients included in the initial evaluation. Primary analysis was performed between patients that had surgery alone (n=374) and those receiving adjuvant CRT (n=299). Median followup time was 12.2 months and 14.5 months for survivors. Median overall survival for patients receiving adjuvant CRT was significantly longer than for those undergoing operation alone (20.0 months versus 14.5 months, p=0.001). On subset and multivariate analysis, adjuvant CRT demonstrated a significant survival advantage only among patients who had lymph node (LN)-positive disease (hazard ratio 0.477, 95% CI 0.357 to 0.638) and not for LN-negative patients (hazard ratio 0.810, 95% CI 0.556 to 1.181). Disease-free survival in patients with LN-negative disease who received adjuvant CRT was significantly worse than in patients who had surgery alone (14.5 months versus 18.6 months, p=0.034).

Conclusions: This large multiinstitutional study emphasizes the importance of analyzing subsets of patients with pancreas adenocarcinoma who have LN metastasis. Benefit of adjuvant CRT is seen only in patients with LN-positive disease, regardless of resection margin status. CRT in patients with LN-negative disease may contribute to reduced disease-free survival.

Figure 1

Kaplan-Meier survival curves for overall survival by treatment group. Two and 5-year overall survivals for patients receiving adjuvant chemoradiation therapy (n = 299) were 43.2% (95% CI, 37.2% to 50.2%) and 15.6% (95% CI, 10.0% to 24.4%), respectively, and for those undergoing surgery alone (n = 374) were 33.5% (95% CI, 28.5% to 39.5%) and 19.0% (95% CI, 14.3% to 25.4%), respectively. Overall survival with chemoradiation therapy versus surgery, p = 0.001 by log rank analysis.

Figure 2

Kaplan-Meier survival curves for overall survival for treatment groups stratified by resection margin and lymph node (LN) status. (A) Patients with either R0 or R1 resection margin benefitted significantly from adjuvant chemoradiation therapy (CRT) compared with those undergoing surgery alone (R0 CRT [n = 200] versus R0 surgery [n = 298], p = 0.001; R1 CRT [n = 99] versus R1 surgery [n = 76], p = 0.003). (B) Only patients with LN-positive disease benefitted from adjuvant CRT compared with patients undergoing surgery alone; LN-negative patients showed no benefit with adjuvant CRT (LN+ CRT [n = 193] versus LN+ surgery [n = 208], p < 0.001; LN− CRT [n = 106] versus LN𢈒 surgery [n = 164], p = 0.774).

Figure 3

Kaplan-Meier survival curve for disease-free survival by treatment group. Two- and 5-year disease-free survivals for patients receiving adjuvant CRT (n = 299) were 25.2% (95% CI, 20.3% to 31.2%) and 10.3% (95% CI, 6.6% to 16.0%), respectively, and for those undergoing surgery alone (n = 374) were 28.7% (95% CI, 24.1% to 34.3%) and 15.9% (95% CI, 11.7% to 21.6%), respectively. Disease-free survival with chemoradiation therapy versus surgery, p = 0.552 by log rank analysis.

Figure 4

Kaplan-Meier survival curves for disease-free survival for treatment groups stratified by resection margin and lymph node (LN) status. (A) Patients with either R0 or R1 resection margin showed no differences in disease-free survival with adjuvant chemoradiation therapy (CRT) compared with those undergoing surgery alone (R0 CRT [n = 200] versus R0 surgery [n = 298]), p = 0.429; R1 CRT [n = 99] versus R1 surgery [n = 76], p = 0.156. (B) Patients with LN-negative disease who received adjuvant CRT had significantly worse disease-free survival compared with patients undergoing surgery alone (LN− CRT [n = 106] versus LN− surgery [n = 164], p = 0.034). For LN-positive patients, a significant benefit was seen with adjuvant CRT compared with patients undergoing surgery alone (LN+ CRT [n = 193] versus LN+ surgery [n = 208], p < 0.001).