Locally Advanced Rectal Cancer: What Does the Local Treatment Response Tell Us About the Global Picture?

Abstract

Historically, both local as well as distant failure rates were unsatisfactory for locally advanced rectal tumors after surgery alone (1). Significant progress has been made on the local front with the introduction of mesorectal excision as well as neoadjuvant short-course radiation therapy or long-course chemoradiotherapy. In the German CAO/ARO/ AIO-94 trial, patients with clinical stage II or III rectal carcinoma treated with neoadjuvant radiation therapy and infusional 5-fluorouracil (5-FU), surgery, and 4 cycles of adjuvant bolus 5-FU had a 7.1% rate of localeregional failure at 10 years (2). The long-term control result from this trial provides an important benchmark for patients with clinical stage II and III rectal cancer going forward. The CAO/ARO/AIO-94 study also provides another important and concerning benchmark statistic: nearly 30% of the patients treated with neoadjuvant therapy developed distant metastatic disease by 10 years (2). Thus, locally advanced rectal adenocarcinoma would seem to be a prime candidate for true multimodality therapy, with a calling for effective systemic therapy above and beyond what is delivered as a radiosensitizer concurrently with radiation therapy during neoadjuvant therapy. The integration of localeradiation and surgeryetherapies and systemic therapy is founded on the principle of spatial cooperation and is the basis for many common cancer treatment algorithms (3). Adjuvant chemotherapy for resected rectal cancer would seem all the more natural given the data from