0011) (16). Although plane of surgery was an independent predictor of local recurrence, there was no evidence that the benefit of radiation was dependent on the plane of surgery (P=0.3 for trend). The effects of optimal mesorectal resection and radiation were additive, with 3 year local recurrence rate of 1% in patients who had short course preoperative radiotherapy and mesorectal plane of resection. Radiation reduced

local recurrence by greater than 50% regardless of plane of resection. CRM status remains Inhibitors,research,lifescience,medical an important indicator of local control in the era of TME, as recognized in NCI consensus guidelines (17). CRM of >2mm is preferable, though the risk of recurrence Inhibitors,research,lifescience,medical is likely a continuum, with larger margins at lower risk of recurrence. The presence of close CRM is one factor influencing the decision of whether or not to employ adjuvant radiation therapy, though the MRC CR07

trial suggests that radiation decreases local recurrence even in the setting of CRM >1mm (Table 1). Part of the challenge for treating physicians is deciding on whether the degree of benefit of local control justifies the potential toxicities, Inhibitors,research,lifescience,medical and the decision to use radiation will depend on a constellation of risk factors rather than margin status alone. MRI scan has been used as a tool to predict negative circumferential margin, with a meta-analysis reporting sensitivity of 94% and specificity of 85% (18). The use of MRI scan to identify patients more likely to benefit from radiation therapy, however, remains investigational. Inhibitors,research,lifescience,medical Location The anatomic definition of the proximal extent of the rectum is debated. The rectum is extraperitoneal on its posterior surface. The upper one-third of the rectum is covered by the peritoneum on the anterior and lateral surfaces, and the inferior two-thirds of the rectum is completely extraperitoneal.

The proximal extent of the Inhibitors,research,lifescience,medical rectum has classically been defined as the peritoneal reflection. The peritoneal reflection cannot be visualized by imaging Volasertib in vivo studies. Rather, it is defined at the time of operation. Therefore, whether or not a tumor is in the true rectum can be challenging to determine prior to surgery. In the adjuvant setting, randomized trials demonstrating a benefit to radiation in stage before II or III disease have variably defined the rectum as below the peritoneal reflection, below the sacral promontory, <12 cm from the anal verge on rigid proctoscopy, or <16 cm from the anal verge (1), (2), (15), (19), (20), (21), (22). Neoadjuvant trials do not allow for intraoperative evaluation of the peritoneal reflection, and have variably included patients with tumor from <12 cm to <16 cm from the anal verge (15), (21). Yun et al. reported that the average length of the posterior peritoneal reflection from the anal verge at the time of surgery was 14 cm in 46 patients, and it correlated with patient height (23).