Pre-operative combined modality therapy in the management of locally advanced rectal cancer

Aims To review the use of pre-operative combined modality therapy (CMT, chemotherapy with radiotherapy) in the management of resectable rectal cancer. Methods A systematic search was performed on pre-operative CMT and rectal cancer. Additional information was retrieved from hand searching the literature and from relevant congress proceedings. We addressed the following issues: Phase II studies of pre-operative CMT, pre-operative radiotherapy (RT) alone vs pre-operative CMT, pre-operative vs post-operative CMT, functional outcome and pathologic downstaging after CMT, prediction and importance of complete response to CMT. Results Pre-operative CMT results in an average pathological complete response (pCR) rate of 18.5% in Phase II studies. Compared with pre-operative RT alone, the addition of CT significantly improves tumour response but not overall survival while acute toxicity increases and the effect on sphincter preservation is at present unclear. Pre-operative CMT has been proven to be superior to post-operative CMT in a German multicenter randomized trial. The scarce available data suggest that the addition of CT might worsen anorectal function compared to pre-operative RT alone. Although a significant pathological response is prognostically favourable, the clinical and imaging tools available at present do not allow to accurately predict pCR in clinical complete responders confirming the indication for surgery in this subgroup. Conclusions Pre-operative CMT enhances tumour response and could therefore, have a role in patients with possibly invaded resection margins or low lying cancers, although both acute toxicity and anorectal function are worse compared to RT alone. The final results of ongoing randomized trials will more accurately establish the role of pre-operative CMT in resectable rectal cancer patients.