The Effect of Primary Tumor Site on Survival in Metastatic Colorectal Cancer Patients and their Relation to KRAS and Biological Therapy

Background: Depending on whether the primary tumor site is in the right or 
left colon, previous investigations have indicated differences in biology and 
prognosis for colorectal cancer. Further divisions into right, left and rectum or 
even exact primary site have also been analyzed. Possible differences in 
response to biological agents have also been reported based on primary tumor 
site.
Methods: We performed a retrospective analysis on 165 metastatic colorectal 
cancer (mCRC) patients treated in clinical oncology department, Assiut 
university hospital, Egypt from January 2015 to December 2019. Patients were 
divided according to their primary site into: right sided colon cancer, left sided 
colon cancer and rectal cancer. In this study the effect of primary site on 
survival and their relation to KRAS status and biological therapy were 
evaluated.
Results: 165 patients were analyzed, mean age was 42 years. Progression free 
survival (PFS) and overall survival (OS) of right sided tumors were less than 
survival in left sided tumors and rectum with significant P value for PFS 0.001 
and OS 0.01. As for patients who received biological therapy, right sided tumors 
were associated with decreased OS compared with left sided and rectal tumors 
with significant P-value; for Panitumumab (P value < 0.001), Cetuximab (P 
value 0.002), Bevacizumab with wild KRAS (P value 0.3) which was not 
significant and Bevacizumab with mutant KRAS (P value < 0.001). In right 
sided wild KRAS tumors, patients who received anti epidermal growth factor 
receptor (EGFR) therapy had worse OS than vascular endothelial growth factor 
(VEGF) monoclonal antibody, with OS of anti EGFR was 23 months for 
panitumumab and 21 months for cetuximab whereas in VEGF monoclonal 
antibody (Bevacizumab), OS was 30 months. In left sided and rectal wild KRAS 
tumors, patients who received anti EGFR therapy had better OS than VEGF 
monoclonal antibody, with OS for left sided and rectal cancer who received 
panitumumab was 43 and 42 months respectively and for cetuximab 46 and 43 
months respectively, whereas for Bevacizumab OS was 35 and 36 months 
respectively. 
Conclusion: Patients with right sided mCRC have worse survival than those 
with left sided and rectal tumors. In patients with wild type KRAS tumors 
treatment with anti EGFR therapy showed better survival than bevacizumab in 
patients with left sided and rectal tumors and was associated with worse survival 
among those with right sided tumors.