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J Cancer 2017; 8(7):1179-1186. doi:10.7150/jca.18091 This issue Cite

Research Paper

The Role of Adjuvant Chemotherapy for Colorectal Liver Metastasectomy after Pre-Operative Chemotherapy: Is the Treatment Worthwhile?

Yun Wang^{1, 2*}, Zhi-qiang Wang^{1, 2*}, Feng-hua Wang^{1, 2}, Yun-fei Yuan^{1, 3}, Bin-kui Li^{1, 3}, Pei-rong Ding^{1, 4}, Gong Chen^{1, 4}, Xiao-jun Wu^{1, 4}, Zhen-hai Lu^{1, 4}, Zhi-zhong Pan^{1, 4}, De-sen Wan^{1, 4}, Peng Sun^{1, 5}, Shu-mei Yan^{1, 5}, Rui-hua Xu^{1, 2✉}, Yu-hong Li^{1, 2✉}

1. Sate key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, P.R. China;
2. Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China;
3. Department of hepatobiliary surgery, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China;
4. Department of colorectal surgery, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China;
5. Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China.
*These authors contributed equally to this work

✉ Corresponding authors: Professor Yu-Hong Li and Rui-hua Xu, Sate key Laboratory of Oncology in South China and Department of medical oncology, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, P.R. China; E-mail: liyhorg.cn; xurhorg.cn. More

Abstract

Peri-operative chemotherapy has been proposed to improve the survival of patients with colorectal cancer hepatic metastases (CRCHM). However, the role of the adjuvant chemotherapy post-metastasectomy for CRCHM patients who have undergone pre-operative chemotherapy is still undetermined. We retrospectively analyzed the role of adjuvant chemotherapy post-metastasectomy on relapse-free survival (RFS) and overall survival (OS) in 163 CRCHM patients who received pre-operative chemotherapy using a Kaplan-Meier curve and univariate/multiple Cox model. Ten patients with rapidly progressing disease were further excluded in a sensitivity analysis. Seven risk factors (metachronous/synchronous metastases, differentiated grade of the primary tumor, number of metastases, size of the max metastasis, duration of pre-operative chemotherapy, radiologic response and pathologic regression) were used to stratify patients and investigate the beneficial features of adjuvant chemotherapy post-metastasectomy. The results indicated that adjuvant chemotherapy post-metastasectomy prolonged both RFS (median RFS: 3.3 vs. 10.2 m, P = 0.002) and OS (median OS: 28.1 vs. 40.7 m, P = 0.005) in CRCHM patients who received pre-operative chemotherapy. After adjusting for other risk factors in a multiple Cox model, the adjuvant chemotherapy group was estimated to have a 54.0 % relapse-free survival (hazard ratio (HR) = 0.46, 95 % confidence interval (CI) 0.31 - 0.69, P < 0.001) and a 55.0 % overall survival (HR [95 % CI]: 0.45 [0.26 - 0.78], P = 0.005) advantage compared to patients without adjuvant chemotherapy. Additionally, the benefit of adjuvant chemotherapy post-liver resection remained in sensitivity analysis. After the risk stratification, patients with synchronous metastases, poor differentiation, ≥ 3 metastases per patient, size of the maximum metastasis >3 cm, a short duration of pre-operative chemotherapy, radiologic response and poor pathologic regression seem to benefit more from adjuvant chemotherapy. To sum up, adjuvant chemotherapy post-metastasectomy might be considered for CRCHM patients who have received preoperative chemotherapy, especially for those with high-risk factors.

Keywords: Colorectal cancer, Liver metastases, Adjuvant chemotherapy.

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