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

Abstract

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

Timing of surgery following neoadjuvant chemoradiotherapy in locally advanced rectal cancer – A comparison of magnetic resonance imaging at two time points and histopathological responses

“…In these cases pre-operative MR may not only direct surgical dissection, but also alert the MDT to the need for further upfront systemic chemotherapy, contact radiotherapy or extended surgical resection. In this cohort of patients, the identification of an optimal time for surgery post-NACRT which coincides with maximal oncological down-staging is an urgent question [21,31]. This pilot study suggests that further volume reduction and down-staging occurs between Week 9 and Week 14 post-NACRT, with more favourable ymrT, ymrTRG and volume changes found at Week 14.…”

Pre- and Post-Surgery Treatments in Rectal Cancer: A Long-Term Single-Centre Experience

“…Similarly, in a study conducted with 1593 patients attending 92 Dutch hospitals who underwent preoperative ccrt, the highest chance of pathologic complete response was noted when the interval between ccrt and surgery was about 11 weeks, with no apparent further increase being noted beyond that time 14 . Prolongation of the interval to 6-8 weeks or more from 4-6 weeks to improve rates of local control or survival has been considered not to be reasonable in tumours considered upfront to be resectable 15 .…”

Remaining cancer cells within the fibrosis after neo-adjuvant treatment for locally advanced rectal cancer

“…Several studies have shown a higher degree of downsizing and downstaging 10e12 weeks after completion of CRT before surgery. 18,19 At the time of this study the general policy was to perform surgery after eight weeks. CK 20 is a well known stable biomarker for colorectal cancer.…”