Nomogram to Predict Distant Metastasis Probability for Pathological Complete Response Rectal Cancer Patients After Neoadjuvant Chemoradiotherapy

Ting Jiang,1,* Shuang Liu,1,* Xiaojun Wu,2,* Xiaoqing Liu,3 Weizhan Li,4 Shanfei Yang,1 Peiqiang Cai,5 Shaoyan Xi,6 Zhifan Zeng,1 Yuanhong Gao,1 Gong Chen,2 Weiwei Xiao1 1Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China; 2Department of Colorectal Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China; 3Department of Radiation Oncology, Guangzhou Concord Cancer Center, Guangzhou, People’s Republic of China; 4Department of Radiation Oncology, Panyu Center Hospital, Guangzhou, People’s Republic of China; 5Department of Radiology, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China; 6Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Gong Chen; Weiwei Xiao Email chengong@sysucc.org.cn; xiaoww@sysucc.org.cnPurpose: This study aimed to predict the risks of distant metastasis (DM) of locally advanced rectal cancer (LARC) patients with pathological complete response (pCR) after neoadjuvant chemoradiotherapy (NACRT) and total mesorectal excision (TME), and to find the association between adjuvant chemotherapy (ACT) and their survival outcomes.Methods and Materials: A total of 242 patients with LARC achieving pCR after NACRT were enrolled in this retrospective study. We developed a nomogram model using logistic regression analyses for predicting risk of DM. The model performance was evaluated by the concordance index and calibration curve. Survival was determined using Kaplan–Meier survival curve.Results: Age, pre-operative CEA, pre-treatment CEA and distance of tumor to anal verge were identified as significantly associated variables that could be enrolled in the model to predict the risk of DM for pCR patients. The nomogram we created had a bootstrapped-concordance index of 0.731 (95% CI = 0.627 to 0.834) and was well calibrated. The high risk group was more likely to develop DM than low risk group (total score) (95% CI = 1.439 to 6.493, P = 0.0036). The 1-year, 3-year, and 5-year distant metastasis-free survival (DMFS) for the low and high risk groups (total score ≤ 90 vs > 90) was 97.8%, 94.2%, 94.2% and 91.3%, 83.4%, 81.8%, respectively (P = 0.0036). DM occurred within 1 and 2 years after TME surgery was 33.3% and 55.6% for the low risk group, and 47.3% and 84.2% for the high risk group. The value of ACT was assessed among the whole cohort, patients with cT3-4, with cN+ or with either DM risk group, but no significant difference was observed concerning DMFS whether ACT was given or not (all P > 0.05). Active treatment after DM was more beneficial than palliative treatment (P < 0.001).Conclusion: The nomogram model, including age, pre-operative CEA, pre-treatment CEA and distance to anal verge, predicted the probability of DM among LARC patients achieving pCR after NACRT. The effects of ACT were not seen in different subgroups, while closer clinical follow-up may have greater contribution to pCR patients in the first 2 years, especially for patients with relatively higher risk to develop DM. It is suggested that timely active treatment can bring survival benefit for pCR patients developing DM after NACRT.Keywords: locally advanced rectal cancer; LARC, pathological complete response; pCR, adjuvant chemotherapy; ACT, distant metastasis; DM