Long-term experience with oral fluoropyrimidines and oxaliplatin-based long-course chemoradiotherapy in locally advanced rectal cancer patients.

Abstract

e15159 Background: Neoadjuvant radiotherapy (RT) previous to surgery (S), both as short-course RT (SCRT) and as long-course RT with 5-FU-based chemotherapy (LCRCT), is used in locally advanced rectal cancer (LARC), with consistent benefits in the local relapse (LR) risk. However, survival benefits have been elusive to find, especially with the use of total mesorectal excision (TME). Concerns about over-treating patients (pts) and long-term side effects have also cast more doubts in a blanket approach of treating all pts with neoadjuvant RT, especially with LCRCT. Methods: Retrospective review of cT3-T4 and/or N+ rectal cancer pts (1999-2014) treated with LCRCT and oral 5-FU and oxaliplatin (65% of pts), followed by TME and 5-FU-based CT. Clinical, radiological and pathological prognostic factors for LR, distant metastases (DM), disease-free survival (DFS) and overall survival (OS) are shown. Results: 203 pts. 98.5% proceeded to S; TME done in 89.7%. Downstaging rate: 70.4% (mainly N staging); pathological complete responses: 14.9%. LR and DM rate was 8.3% and 27%. TNM pathological data (ypTN) were better prognostic factors than tumour regression grades. Prognostic factors (multivariate): circumferential margin (CRM) and perineural invasion. No benefit seen with the addition of oxaliplatin. Compliance to adjuvant CT was poor; < 50% received the full dose. 5- and 10-year DFS and OS: 71.4% and 54.9% and 75.4% and 62.4%. Elderly pts had a worse OS, due to higher unexpected toxicity and lower treatment compliance. Mucinous tumours showed a poor response to LCRCT. Prognostic factors (multivariate) for OS and DFS: older age, CRM invasion, an unsuccessful TME and a heavy lymph node burden. Conclusions: The identification of pts with a low risk of LR where RT could be avoided is based on the premise of an exquisite imaging staging and a surgical team specialized in TME. A free CRM and a successful TME are pivotal for success. Clinical lymph node staging is problematic. The role of adjuvant CT remains undefined, and compliance rates are poor. Neoadjuvant CT is an option, especially if there is a high risk of DM. Better tolerated options, such as SCRT, should be used in elderly or frail pts.