Efficacy and safety of preoperative neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer : a clinical analysis of 291 patients

Abstract

Objective To evaluate the efficacy and safety of neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer (LARC) before surgery. Methods A total of 291 LARC patients who received preoperative chemoradiotherapy and surgery with or without postoperative adjuvant chemotherapy from March 2003 to May 2012 were included in the study. The radiotherapy delivered was two-dimensional conformal radiotherapy (2DRT) and three-dimensional conformal radiotherapy (3 DRT) , and the total dose ranged from 45 to 50 Gy in 23-25 fractions. All the patients received preoperative chemotherapy including FOLFOX6, XELOX, and Xeloda for 2- 4 cycles. Surgery following the principle of total mesorectal excision was performed 3-8 weeks after radiotherapy. Postoperative adjuvant chemotherapy was delivered to 134 patients. The overall survival (OS) , disease-free survival (DFS , relapse-free survival(RFS) , and distant metastasis-free survival (DMFS) were determined using the Kaplan-Meier method, and survival difference analysis and univariate prognostic analysis were performed using the log-rank test. Multivariate prognostic analysis was performed using the Cox proportional hazard model. Results All the patients completed the preoperative neoadjuvant chemoradiotherapy and surgery. The rate of radical resection(R0) was 98.9%, and the sphincter preservation rate was 53.6%. The downstaging rates in tumor (T)stage, node (N) stage, and clinical stage were 73.1%, 83.6%, and 79.4%, respectively. Pathologic complete response rate was 26.8%. Grade 3 adverse hematologic reactions, grade 3 diarrhea, and grade 3radiodermatitis were observed in 7.9%, 7.2% and 2.7% of total patients, respectively. Postoperative perineal pain and delayed wound healing were reported in 12.3% and 8.2% of total patients, respectively. The follow-up rate was 94.5% and the 5-year sample size was 95 patients. The 5-year OS, DFS, RFS, and DMFS were 76.6%, 72.1%, 88.8%, and 79.7%, respectively. The 5-year local recurrence rate and distant metastasis rate were 7.5% and 15.8%, respectively. Multivariate analysis revealed that the postoperative pathological staging was a prognostic influencing factor. Conclusions Preoperative neoadjuvant chemoradiotherapy increases the R0 and sphincter preservation rates, and results in significant tumor downstaging. Treatment-related adverse reactions are moderate and perioperative complications are not increased. The local recurrence rate is low and long-term survival rate is increased. Clinical application of preoperative neoadjuvant chemoradiotherapy as a standard treatment regimen for LARC is highly recommended. Key words: Rectal neoplasms, locally advanced/neoadjuvant chemoradiotherapy; Rectal neoplasms, locally advanced/surgery; Prognosis