Optimal Time Intervals between Pre-Operative Radiotherapy or Chemoradiotherapy and Surgery in Rectal Cancer?

In rectal cancer therapy, radiotherapy or chemoradiotherapy (RT/CRT) is extensively used pre-operatively to (i) decrease local recurrence risks, (ii) allow radical surgery in non-resectable tumors, and (iii) increase the chances of sphincter-saving surgery or (iv) organ-preservation. There is a growing interest among clinicians and scientists to prolong the interval from the RT/CRT to surgery to achieve maximal tumor regression and to diminish complications during surgery.

The pros and cons of delaying surgery depending upon the aim of the pre-operative RT/CRT are critically evaluated.

Depending upon the clinical situation, the need for a time interval prior to surgery to allow tumor regression varies. In the first and most common situation (i), no regression is needed and any delay beyond what is needed for the acute radiation reaction in surrounding tissues to wash out can potentially only be deleterious. After short-course RT (5Gyx5) with immediate surgery, the ideal time between the last radiation fraction is 2-5 days, since a slightly longer interval appears to increase surgical complications. A delay beyond 4 weeks appears safe; it results in tumor regression including pathologic complete responses, but is not yet fully evaluated concerning oncologic outcome. Surgical complications do not appear to be influenced by the CRT-surgery interval within reasonable limits (about 4-12 weeks), but this has not been sufficiently explored. Maximum tumor regression may not be seen in rectal adenocarcinomas until after several months; thus, a longer than usual delay may be of benefit in well responding tumors if limited or no surgery is planned, as in (iii) or (iv), otherwise not.

A longer time interval after CRT is undoubtedly of benefit in some clinical situations but may be counterproductive in most situations. After short-course RT, long-term results from the clinical trials are not yet available to routinely recommend an interval longer than 2-5 days, unless the tumor is non-resectable at diagnosis.