Desley van Zoggel

Chapter 2 28 Discussion This study has demonstrated high pCR rates in patients with locally recurrent rectal carcinoma after a new sequential neoadjuvant regimen consisting of ICT followed by CRRT. This is comparable to pCR rates described after chemoradiotherapy in locally advancedprimary rectal cancer.18,19 Furthermore, pCRexhibiteda strong relationshipwith OS, LRFS and MFS. This is an important finding as the treatment options for this group of patients are limited. Thus, new treatment options should focus on increasing the pCR rate. To date, only case reports 20–22 have described pCR in locally recurrent rectal cancer. In subgroupanalyses of the ICTandCRRTgroups, thebenefit of apCRwas apparent only in the ICT group. This findingmight reflect a systemic effect, reducing the development of systemic micrometastasis and improving not only local, but also distant recurrence rates. These are, however, speculations, as these trends could not be demonstrated by survival differences in the two groups. This lack of statistical significance might be due to a power problem; hence, these data need to be interpreted with caution. Similar R0 margin rates were observed in patients who underwent ICT and those who had CRRT alone. However, there is a need to clarify why the ICT was initiated. ICT was formerly administered exclusively to patients with unresectable locally recurrent rectal cancer. In several cases, remarkable resultswere observed: many lesions became resectable, and some patients even had a pCR. After observing favourable results in this poor category of patients, this regimenwas expanded to patients with locally recurrent rectal cancer and better prognostic features. The ICT group thus consisted of surgically unfavourable recurrent cases and could hamper any comparison. However, the finding that ICT results inmore pCRs and similar R0 resection rates in these unfavourable cases demonstrates that it has a definite role in intensifying the response of neoadjuvant treatment in previously irradiated patients with locally recurrent rectal cancer. Studies of ICT in recurrent rectal cancer are not available, but the findings here are in line with the results of studies on primary locally advanced rectal cancer, which demonstrated a higher response rate after ICT before chemoradiotherapy and also seemed to translate into a better outcome.23,24 Further radiological guidelines are required to enable categorization of ‘resectable’ versus ‘irresectable’ disease, such that similar groups of patients can be compared to demonstrate a difference in R0 resection rate. Amajor advantage of a neoadjuvant treatment regimen including ICT is the avoidance of possible overtreatment in patients with progressive systemic disease. This regimen enables the possibility of observing oncobiological behaviour of the recurrent disease, and unnecessary surgery might be prevented in patients with progressive distant