Even if the tumor lies within the rectum, proximal rectal cancers have relatively lower benefit from radiation compared to distal. Prior to the advent of TME, the MRC working group identified location in the rectum as a prognostic factor in a selleck compound randomized trial of preoperative radiotherapy (3). Lesions less than 8 cm from the anal verge had Inhibitors,research,lifescience,medical a 5 year local disease free survival rate of 52%, vs. 62% for lesions greater

than 8 cm from the anal verge (P=0.008). This difference translated into an overall survival difference at 5 years of 35% for distal lesions compared to 48% for more proximal lesions (P<0.001). While distal tumors may represent a more challenging Inhibitors,research,lifescience,medical surgery, this trial showed no difference in the rate of gross total resection as assessed by the surgeon (62% with distal lesions and 65% with proximal lesions). Circumferential margins status, however, was not assessed.

Despite reductions in local recurrence in the TME era, distal lesions continue to carry a worse prognosis. The Dutch rectal cancer trial reported that increasing distance from the Inhibitors,research,lifescience,medical anal verge was associated with higher local control on multivariate analysis (P=0.02, Table 2) (11). On univariate analysis, the addition of radiation therapy to TME did not improve local control in tumors more than 10 cm from the anal verge. Multivariate tests, however, suggested that the favorable effects of radiation probably didn’t differ based on Inhibitors,research,lifescience,medical location in the rectum. This trial was not adequately powered to determine whether or not radiation has a small impact on local control in the proximal

rectum, but at a minimum this trial demonstrates that the absolute benefit of radiation in the proximal rectum, if present, is small. Table 2 Influence of location on margin status and local recurrence(14),(15) The Dutch trial revealed an increased incidence of positive margins in distal tumors within 5cm from the anal verge (Table 2) (14). Interestingly, lesions located between 5 and 10 cm from Inhibitors,research,lifescience,medical the anal verge Endonuclease had an incidence of positive margins similar to more proximal lesions but an intermediate local failure rate. This suggests that margin status alone is not sufficient for predicting local recurrence and tumor location is an important independent consideration. Similar to the results of the Dutch trial, the MRC CR07 trial comparing preoperative radiotherapy to selective adjuvant chemoradiotherapy demonstrated that tumor location influences local recurrence and CRM positivity (Table 2) (15). CRM was positive in 15% of patients with distal extent of tumor 0-5cm from the anal verge, versus 9% of patients with distal extend of tumor >10 cm from the anal verge (P=0.004) (16). Neoadjuvant radiotherapy was found to be superior to selective adjuvant chemoradiotherapy for all tumor locations (Table 2).