Commentary: Rectal Cancer—An Evolution of Treatment

The treatment of rectal cancer has evolved substantially over the past two decades. In the past, rectal cancer was frequently treated with surgery alone, which resulted in high rates of local failure, with significant patient morbidity and mortality. Sentinel trials in the 1980s to early 1990s demonstrated that adjuvant chemoradiotherapy resulted in lower rates of local failure and superior survival versus resection alone [1, 2]. This observation led to the adoption of adjuvant chemoradiotherapy as standard treatment for patients with stage II–III disease. Subsequently, proponents of total mesorectal excision (TME) reported that local regional failure rates were 10% with this approach, bringing the role of radiation therapy into question. However, a large, randomized Dutch trial comparing neoadjuvant radiation therapy alone followed by TME with TME alone showed that despite the superior surgical technique, radiation therapy resulted in a significantly lower rate of local failure. The 2-year local failure rate was 2.4% for patients undergoing preoperative radiation therapy and TME versus 8.2% for patients undergoing TME only (p .001) [3]. The sequencing of radiation therapy relative to surgery has been controversial for several decades. Advocates of preoperative therapy argued that this approach had many benefits, including higher rates of sphincter preservation and better radiation tolerance. In Germany, a large randomized trial (CAO/ARO/AIO-94) comparing preoperative with postoperative chemoradiotherapy confirmed that a preoperative approach resulted in superior treatment compliance, less acute and late toxicity, and a significantly higher rate of local regional control, again simply by altering the sequence of chemoradiotherapy in relationship to surgery [4]. This has led to a new standard of care in the U.S. and Europe in the treatment of stage II–III and selected stage IV rectal cancer patients. The primary disadvantage of preoperative chemoradiotherapy is the potential to irradiate patients with stage I (T1-2 N0) disease. When treated with TME alone, these patients have low rates of local recurrence and any benefit of radiation therapy is limited. Therefore, meticulous pretreatment staging with endoscopic ultrasound (EUS) and/or magnetic resonance imaging (MRI) is important. Despite this, there is still the potential to “upstage” patients who have early-stage disease. This is exemplified in the adjuvant arm of the German rectal trial where 18% of patients staged to have stage II or greater disease by EUS preoperatively were found to have pathologic stage I disease [4]. The integration of thin-section MRI into the pretherapy evaluation of rectal cancer patients likely represents a further refinement in staging accuracy and may potentially spare stage I patients from neoadjuvant therapy. In the hands of experienced endoscopists and radiologists, preoperative EUS and MRI appear to strongly correlate with pathologic stage. As discussed by Drs. Glynne-Jones and Harrison [5], contemporary randomized trials have demonstrated that neoadjuvant chemoradiotherapy produces superior tumor downstaging, pathologic complete response rates, and local control relative to preoperative radiation therapy alone. Therefore, it is logical to assume that, in patients with lowlying rectal cancers, sphincter preservation through downstaging may be achieved in some patients with neoadjuvant therapy, particularly with the knowledge that “historically” large distal margins may not be necessary to obtain durable