**6. Appropriate distal margins of resection in the era of neoadjuvant therapy**

Following resection of the rectum, current standard procedure is examination of the distal edge to ensure that the cells at this distal margin are free of any tumor characteristics. A positive distal margin is an unequivocal indication for additional treatment as it signifies that the resection has not been adequate.

This length from the tumor to the distal edge is of even greater importance when consider‐ ing those cancers occurring in the distal or lower portions of the rectum (close to the anal sphincters). In treating patients with lower rectal tumors, a balance of performing an oncologically free operation versus obtaining proper anal sphincter function must be maintained. There is no question that when it comes to patient's preference, an LAR is always preferred to an APR [39-41].

Prior to the era of CRT, substantially large margins of resections were thought to be necessary. A 5 cm margin was widely used, which emanated from studies showing this to result in acceptable outcomes compared to those with greater than 5 cm distal margins [4-10]. In an attempt to perform sphincter preservation operations, this number was rapidly challenged and reduced to the point in which margins less than 5 cm became acceptable [42-47].

With the current tri-modality management of rectal cancer, a 2 centimeter margin has been adopted with excellent oncologic outcomes [48-52]. In 2004, Habr-Gama published results of observing patient who achieved a clinical complete response (cCR) following neoadjuvant CRT [34]. This concept, in a way, challenged the need to obtain a large margin in patients with low rectal tumors who have responded well to pre-operative treatment. Studies have emerged that indicate that even a 1 cm distal margin is oncologically safe [40;48;49;52-58]. This has been considered oncologically acceptable in the literature. The vast majority of work that has examined the question of 1 cm margins has indicated that there is no statistically significant difference in regards to survival or recurrence between groups of patients with margins greater than 1 cm than those with margins less than or equal to 1 cm [40;48;49;52;54-58] Table 1.

More recently, the 1 cm margin has been challenged to be further reduced. Some surgeons have suggested that sub-centimeter margins as small as 2 mm or 5 mm margins are also safe [54].


A meta-analysis indicated a higher rate of anastomotic recurrence by only 1.6% in the <1cm margin groups, but this small observed difference was not statistically significant. A systematic review of the literature on sub-1 cm distal margins of resection found in only two papers a possible adverse outcome associated with this smaller margin [54]. However, in these two papers, the percentage of patients submitting to neoadjuvant CRT was less than 5% [59;60].

Distal margins of 8 mm or 5 mm have also been proposed [40;54;56;61], but there is currently not enough data to draw definitive conclusions at this time. The results so far seem to point to these margins also being oncologically safe. Published data on possible adverse oncologic outcomes with 8 mm margins has been documented, but this has occurred in the absence of neoadjuvant CRT [62]. In this case, margins below the 8 mm cutoff point were found to correlate with a significantly higher rate of recurrence and lower rate of long-term survival. However, when the same length of distal margin is evaluated within the context of neoadjuvant CRT, 8 mm margins have not been found to have adverse oncologic outcomes compared to patients having more than 8 mm margins. In this study, the authors did find a higher rate of mucosal recurrence in patients with less than 8 mm margins. They concluded that the probable cause of a higher rate of mucosal recurrence was tumor shedding into the anastomosis [40].

Another study evaluated patients who had received neoadjuvant therapy with margins less than or equal to 5 mm in regards to 5 year outcome and local recurrence [61]. There was no difference in local recurrence 5 years after surgical intervention. This finding was echoed by a number of similar studies [48;53;54;56] (Table 2). Additionally, a meta-analysis demonstrated a small non-significant rate of anastomotic recurrence by 1.7% in the 5mm group, but again this also was not statistically significant [54].


It is important to keep in mind that in all of these retrospective studies, there is a clear aspect of selection bias. Typically, patients that are selected for smaller margins are those that have tumors that are expected to have more favorable outcomes. Low tumors, which have less favorable predicted outcomes are usually treated with an abdominoperineal resection (APR), a procedure that renders the question of margins moot [54]. This makes it difficult to properly match patient populations being compared in these studies. It is also important to emphasize that there is a lack of consistent methodology of measuring the distal margin across all studies. Measurement of the distal margin is done in a variety of circumstances: pinned, unpinned, fixed, immediately after sectioning, etc [54;63;64]. A lack of standardization is disadvantageous to drawing a unified conclusion; however, the broad consensus that exists regardless of this wide range of measurement techniques suggests that the conclusion is nonetheless valid.

Furthermore, while the surgical donuts are oftentimes assessed for tumor cells, they are not included in measurement of the distal margin of resection and therefore the true margin is usually slightly larger than the distal margin of resection. Therefore, a margin reported and measured as 5 mm may in fact be significantly larger, which helps explain why some patients with low margins approaching 0 mm still seem to have acceptable oncologic outcomes.

In conclusion, in the era of neoadjuvant CRT, smaller distal margins are acceptable so long as the overall status of the patient is considered as well as the possible behavior of the tumor. Patients with well differentiated tumors who have achieved an excellent response to neoad‐ juvant CRT might only need negative margins. However, patients who have poorly differen‐ tiated tumors and no response to pre-operative CRT might need greater margins (greater or equal to 1 cm). The distal margin is one of the few that the surgeon can correct and monitor intra-operatively [40;64] and therefore ought to be a constant consideration for all surgeons when performing a rectal resection. This must be done by balancing the desire for sphincter preservation with the need to maintain an oncologically safe and thorough procedure.
