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Adjuvant Therapy After Pancreatic Cancer Resection

Adjuvant chemotherapy adds a significant survival benefit compared with the deleterious effect of adjuvant chemoradiotherapy after surgical resection for pancreatic cancer.

Some data suggest that adjuvant therapy after surgical resection for pancreatic cancer may improve long-term survival, but it is not used routinely because evidence from randomized studies is inconclusive. The European Study Group for Pancreatic Cancer randomly assigned 289 patients who had undergone complete macroscopic resection of histologically proven pancreatic ductal adenocarcinoma to receive postoperative chemoradiotherapy alone, chemotherapy alone, combination chemoradiotherapy and chemotherapy, or neither treatment (observation). Clinical features and characteristics of the tumors were similar among groups.

After a median follow-up of 47 months, 237 patients (82%) had died. Median survival times were 17 months in the observation group, 14 months in the chemoradiotherapy alone group, 22 months in the chemotherapy alone group, and 20 months in the combination group. Median survival among all patients who received chemoradiotherapy was 16 months, compared with 18 months among all patients who did not receive chemoradiotherapy (P=0.05). Estimated 2- and 5-year survival rates were 29% and 10%, respectively, among patients who received chemoradiotherapy versus 41% and 20%, respectively, among those who did not receive chemoradiotherapy.

Median survival was 20 months for all patients who received chemotherapy versus 15.5 months for those who did not receive chemotherapy (P=0.009). Estimated 2- and 5-year survival rates were 40% and 21%, respectively, among patients who received chemotherapy, and 30% and 8%, respectively, among those who did not receive chemotherapy.

The adjusted hazard ratio for death was 1.47 with the use of chemoradiotherapy and 0.77 with the use of chemotherapy. The median time to tumor recurrence was 10.7 months among patients who received chemoradiotherapy and 15.2 months for those who did not receive chemoradiotherapy (P=0.04). Time to recurrence in patients who received chemotherapy was significantly longer than that in patients who did not receive chemotherapy (15.3 months vs. 9.4 months). Observed quality of life did not differ significantly between patients who received chemotherapy and those who did not, or between patients who received chemoradiotherapy and those who did not.

Comment: This study is the largest randomized trial of adjuvant therapy for pancreatic cancer reported to date. The data show that adjuvant chemotherapy adds a significant survival benefit and that adjuvant chemoradiotherapy has a deleterious effect. An editorialist suggests that the latter effect likely results from treatment-related toxicity. Regardless of the interpretation of the data, two glaring conclusions are that patients with pancreatic cancer have poor prognoses and that new adjuvant therapies need to be developed and tested. The benefit of an additional few months of survival offered by adjuvant chemotherapy was complicated by adverse events in 20% of patients.

— Stuart Sherman, MD

Published in Journal Watch Gastroenterology July 27, 2004

Citation(s):

Neoptolemos JP et al. A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med 2004 Mar 18; 350:1200-10.

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• Medline abstract (Free)

Choti MA. Adjuvant therapy for pancreatic cancer -- The debate continues. N Engl J Med 2004 Mar 18; 350:1249-51.

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• Medline abstract (Free)