Combined modality therapy of rectal cancer

In 2005, 40,340 new cases of rectal cancer were diagnosed in the United States [1]. The mainstay of therapy of this malignancy was surgery [2]. For patients with early stage tumors (lesions confined to the rectal wall without lymph node metastases), 5 year survival is excellent with recent series reporting 80% or greater cure rates [3]. In contrast, local and systemic failures pose significant challenges to patients undergoing potentially curative resection for more advanced staged tumors [4]. Treatment strategies of preoperative or postoperative chemotherapy and radiation therapy have been employed to prevent local and systemic failure and improve survival for these patients. Over the past 15 years, randomized trials have demonstrated statistically significant improvements in local control, freedom from distant metastases, and survival with radiation therapy and concurrent and maintenance 5-fluorouracil (5-FU)-based chemotherapy [5-12]. In a large Intergroup trial, the 7 year disease-free survival of 1695 patients with stage II and III rectal cancer undergoing resection and postoperative radiation therapy with concurrent and maintenance 5-FU-based chemotherapy was only 50% [11]. Despite the best contemporary adjuvant therapy, local recurrence and systemic failure remain important challenges, particularly in the treatment of patients with more advanced tumors. Innovative therapies should be pursued to improve on these outcomes.