Treatment of locally advanced rectal cancer: controversies and questions

Rectal cancers extending through the rectal wall, or involving locoregional lymph nodes (T3/4 or N1/2), have been more difficult to cure. The confines of the bony pelvis and the necessity of preserving the autonomic nerves makes surgical extirpation challenging, which accounts for the high rates of local and distant relapse in this setting. Combined multimodality treatment for rectal cancer stage II and III was recommended from National Institute of Health consensus. Neoadjuvant chemoradiation using fluoropyrimidine-based regimen prior to surgical resection has emerged as the standard of care in the United States. Optimal time of surgery after neoadjuvant treatment remained unclear and prospective randomized controlled trial is ongoing. Traditionally, 6-8 wk waiting period was commonly used. The accuracy of studies attempting to determine tumor complete response remains problematic. Currently, surgery remains the standard of care for rectal cancer patients following neoadjuvant chemoradiation, whereas observational management is still investigational. In this article, we outline trends and controversies associated with optimal pre-treatment staging, neoadjuvant therapies, surgery, and adjuvant therapy.