Evolving trends in combined modality therapy for pancreatic cancer

Only 5%-15% of patients with pancreatic adenocarcinoma undergo potentially curative resection. Evidence that postoperative adjuvant therapy improves outcome is limited to a single randomized trial utilizing split-course chemoradiation. More aggressive regimens have developed and are associated with, at best, a modest improvement in patient outcome. The potentially significant morbidity associated with pancreaticoduodenectomy, which can compromise the delivery of postoperative chemoradiation, has led to the investigations of preoperative regimens. Although such an approach is feasible, its ultimate impact warrants further evaluation. Among the 4% of patients who present with unresectable or locally advanced disease, combined modality therapy has produced the most promising results. However, only modest improvements in survival have so far been achieved. Combined modality therapy with radioisotope implantation appears to have the greatest potential for improving local control and survival in these patients. Intraoperative radiation therapy (IORT) may be associated with lower morbidity than radioisotope implantation, but its impact may be limited by radiobiological disadvantage associated with single-dose boost therapy. The problem of distant metastasis remains significant. New chemotherapeutic agents have the potential to produce better results than those achieved with 5-fluorouracil. Continued advances in surgery, radiation, and systemic therapy should lead to the increased use of modern combined modality interventions with an associated further improvement in patient outcome.