Induction chemotherapy followed by chemoradiotherapy and TME for high-risk locally advanced rectal cancer with and without synchronous resectable metastases.

Abstract

599 Background: Induction chemotherapy (ICT) followed by chemoradiation (CRT) may improve tumor downsizing and disease control among patients (pts) with locally advanced rectal cancer (LARC). We retrospectively assessed the safety and short-term efficacy of ICT followed by CRT and total mesorectal excision (TME) in pts with high-risk LARC with or without synchronous resectable metastases. Methods: We reviewed records of 44 consecutive stage III (n=23) or stage IV synchronous (n=27) pts with LARC treated with ICT followed by CRT between 12/06 – 12/10. Pts had high-risk primary tumors based on advanced T and/or N stage by endorectal ultrasound and/or MRI: T3 (n= 35), T4 (n=7) and N1 (N=18), N2 (n=19). Recurrence-free (RFS) and overall survival (OS) were estimated by Kaplan-Meier methods. Results: Median age was 52 yrs, 66% were female. Pts received a median of 6 cycles of 5-FU based ICT combined with oxaliplatin (n=44). CRT (median dose 50.4 Gy) was delivered with continuous infusion 5-FU; two pts did not complete the prescribed CRT. During induction CT, 10 (22.7%) pts experienced grade 3+ neutropenia. Grade 3+ neutropenia or GI toxicity occurred in 3 (6.8%) and 3 (6.8%) pts, respectively during CRT. Imaging or endoscopic assessment showed that 35 pts had disease regression after ICT, whereas 1 pt progressed and 2 had stable disease. Response to ICT was not assessed in 6 pts. 7 pts did not undergo surgery due to: progression of disease (n=2); comorbid disease (n=2); or pt refusal (n=3). 37 pts proceeded to TME including 17 with known distant metastasis, 16 of whom underwent metastasectomy. 17 pts had tumor response > 90% including 8 with pathologic CR. With a median follow-up of 29.4 mos, 1 pt who underwent TME developed local recurrence. Amongst the 9 pts who had distant recurrences, 7 had initial stage IV disease. The 3-yr RFS among the resected stage III pts was 95%; the 3-yr OS for stage III pts and stage IV pts were 100% and 80% respectively. Conclusions: In this retrospective series, ICT prior to CRT was associated with acceptable toxicity and a substantial incidence of tumor regression. OS and RFS appear promising in this high-risk group of patients.