Locally Advanced Rectal Cancer

Abstract

Traditionally, there has been a high local recurrence rate in rectal cancer and 10-40% of patients require a permanent stoma. Both short-course preoperative radiotherapy (SCPRT) and long-course preoperative chemoradiation (CRT) are used to reduce the risk of local recurrence and enable a curative resection. Total mesorectal excision has reduced the rate of local recurrence (even without radiotherapy) to below 10%, but has highlighted a high risk of metastatic disease in 30-40% of patients. Current trials suggest that in resectable cancers, where the preoperative magnetic resonance imaging (MRI) suggests the circumferential resection margin (CRM) is not potentially involved, then SCPRT and CRT are equivalent in terms of outcomes such as local recurrence, disease-free survival (DFS) and overall survival (OS). For patients with more advanced disease, where the CRM is breached or threatened according to the MRI, the integration of more active chemotherapy and biological agents into chemoradiation is an attractive strategy because of the high risk of metastases. However, in none of the trials published in the last decade has chemoradiation impacted on DFS or OS. We examine the strategies of neoadjuvant, concurrent, consolidation (after chemoradiation and before surgery) and postoperative adjuvant chemotherapy with cytotoxic agents, and the integration of biological agents for future potential strategies of treatment. We also compare the trials and compare the different strategies of long-course preoperative radiotherapy and SCPRT; the intensification of preoperative radiation and chemoradiation with dose escalation of external beam radiotherapy, using brachytherapy, intra-operative radiotherapy, hyperfractionation, and various available techniques such as intensity-modulated radiotherapy. We recommend examining dose escalation of radiotherapy to the primary tumour where MRI predicts a threatened CRM. Of the potential treatment strategies involving cytotoxic agents, such as neoadjuvant, concurrent, consolidation and postoperative adjuvant chemotherapy, the most promising would appear to be consolidation chemotherapy following chemoradiation in locally advanced disease, and neoadjuvant chemotherapy in MRI-selected patients who do not require radiation. Improvement in the quality of surgery is also an important future goal.