Factors	Coefficient	HR (95%CI)	p-value	Adjusted HR (95%CI)	p-value
Age	0.021	1 (0.987–1.06)	0.221	1.484 (0.6691–3.293)	0.331
Age > 65 years	0.17	1.2 (0.578–2.45)	0.637
Male	0.53	1.7 (0.775–3.7)	0.186
Colon cancer stage III	0.8	2.2 (0.957–5.2)	0.063	1.777 (0.6813–4.635)	0.239
N stage II–III	0.68	2 (0.962–4.05)	0.063	1.570 (0.6869–3.590)	0.285
Right side colon cancer	1	2.8 (1.38–5.8)	0.004	2.875 (1.3965–5.920)	0.004

Colon cancer is one of the top five most common types of cancer worldwide. The hypothesis of different embryological origins for the different sides of colon cancer is displayed in molecular and tumor genetics and might affect the survival outcomes. It was observed initially in metastatic settings from previous studies. Studies on advanced colorectal cancer revealed that left-sided colon cancer has better median survival than right-sided colon cancer with regorafenib treatment, even based on biomarkers with PFS durations of 2.6 months and 1.9 months, respectively (p = 0.04) [9]. Another study showed some differences in tumor genetic markers such as the BRAF mutation and microsatellite instability (MSI) of right-sided and left-sided colon cancer also affect the survival outcomes [10]; however, the median survival of advanced right-sided colon cancer was still lower than that of advanced left-sided colon cancer (13.2 vs. 20 months). Regarding the frontline treatment of the KRAS mutation in advanced colon cancer [11], it was shown that cetuximab treatment for KRAS wild-type, left-sided colon cancer was superior in terms of OS (35.8 months vs. 14.4 months; p = 0.031); however, no significant difference was found in the OS when treated with bevacizumab. However, there were two studies that showed no significant difference in the prognosis and OS outcome between right-sided and left-sided colon cancer [12, 13]. Recent population-based studies conducted in the Norwegian population that included all stages of colon cancer showed increasing survival trends with left-sided colon cancer over the past four decades [14]. In the adjuvant setting, a meta-analysis by Petrelli et al. that included colon cancer of different stages (stages I, II, and III) confirmed that the left-sided location of tumors was associated with better survival outcomes (HR 0.84; 95% CI, 0.79–0.89; p < 0.001) [15]. Several studies confirmed that the five-year OS of right-sided colon cancer after curative surgery is lower than of left-sided colon cancer (82.1% vs. 88.7%; p < 0.05) [2]. In Japan, a cancer registry-based study also showed that the anatomical side of the colon could be a prognostic factor, especially in advanced-stage colon cancer [16]. Our study also showed that patients with right-sided colon cancer had an average age of 64.07 years while the average age of patients with left-sided colon cancer was 61.44 years. Other previous studies showed that right-sided colon cancer has lower survival rates than left-sided colon cancer [17]. Regarding adjuvant chemotherapy, the combination of oxaliplatin and 5-fluorouracil (5FU), including oral 5FU derivatives such as capecitabine, is a standard adjuvant treatment. The MSI test becomes important in adjuvant settings, especially in stage II colon cancer [18]. Previous studies revealed that MSI-high, especially in stage II colon cancer, 5FU-based regimens may add only a little benefit to the treatment [19-21]; however, some patients with stage III colon cancer with MSI-high have better prognoses than microsatellite stability patients. Unlike fluorouracil, oxaliplatin does not affect the MSI status [18, 22]. Our findings confirmed that early-stage left-sided colon cancer has a five-year OS rate of 66.98% while right-sided colon cancer had a rate of 57.77%. We also found that left-sided colon cancer responds better to adjuvant chemotherapy than right-sided colon cancer. A poorly-differentiated morphology was also found in right-sided colon cancer more than in left-sided colon cancer in our study. Also, in line with the findings of other studies, the incidence of left-sided colon cancer is higher than that of right-sided colon cancer. However, our study had certain limitations. First, there was a paucity of data on tumor genetic mutations such as MSI and KRAS because genetic testing is not routine in our clinical practice. Second, this study was a retrospective, single-center study, and the data collected were based on medical records. Some important information was incomplete, which resulted in a decrease in the number of eligible cases and the amount of data that could be analyzed. Nevertheless, our results were still consistent with those of previous studies.

In conclusion, our study findings confirmed that left-sided colon cancer had a better prognosis in the early-stage. Prospective studies involving multicenter data and tumor genetic exploration for each side of the colon should be performed in the future. Future studies including optimal durations of oxaliplatin-based chemotherapy should be conducted based on the laterality of colon cancer and based on tumor genetic information. This will bring more precision to personalized treatment in the future.