Abstract: Objective To compare the prognostic outcomes of KRAS mutation metastatic colorectal cancer treated by chemotherapy alone versus chemotherapy plus local therapy (surgery,radiofrequency ablation,radiotherapy,TACE,etc.). Methods Clinical data about 135 KRAS-mutated advanced colorectal cancer (ACRC) patients treated in the first medical center of Chinese PLA General Hospital from 2012 to 2019 were collected.There were 86 males (63.7%) and 49 females (36.3%),with the median age of onset of 53.5 years old.The patients were divided into chemotherapy group (n=57) and comprehensive treatment (including chemotherapy combined with targeted and local therapy) group (n=78).There was no significant difference in general data between the two groups. Results In the comprehensive treatment group,partial remission (PR) was achieved in 21 (26.9%) cases,stable disease (SD) in 53 (67.9%) cases,disease progression (PD) in 4 (5.1%) cases,and the overall objective response rate (ORR) was 26.9%,the disease control rate (DCR) was 94.9%,with the median progression-free survival (mPFS) of 11.1 months (95% CI:9.5-12.8).In the chemotherapy group,complete response (CR) was achieved in 1 (1.8%) case,PR in 19 (33.3%) cases,SD in 26 (45.6%) cases,PD in 11 (19.3%) cases;The ORR was 35.1%,DCR was 80.7%,and mPFS was 6.1 months (95% CI:4.1-8.1).There was no significant difference in ORR between the two groups,but the comprehensive treatment group had significant greater DCR (94.9% vs 80.7%,P=0.013) and mPFS (11.1 months vs 6.1 months,P=0.000). Conclusion For patients with KRAS gene-mutated metastatic colorectal cancer,comprehensive therapy has similar disease remission rate with chemotherapy.However,it has obvious advantages in DCR and PFS.On the basis of effective chemotherapy,early local therapy can be considered.