A Belgian Population-Based Study Reveals Subgroups of Right-sided Colorectal Cancer with a Better Prognosis Compared to Left-sided Cancer

Abstract

Background: Patients with left-sided colorectal cancer (L-CRC) are known to have a significantly better prognosis than those with right-sided CRC (R-CRC). It has been hypothesized that RAS, BRAF mutations, or deficient mismatch repair status (MMR) might be responsible for the prognostic effect of primary tumor location (PTL). This study aims to evaluate the prognostic effect of PTL in the Belgian population and to determine the role of biomarkers (MMR, BRAF, and RAS status) in this effect.

Patients and methods: We performed a retrospective analysis of Belgian Cancer Registry data. First, we studied the prognostic effect of PTL on 5-year relative survival of 91,946 patients diagnosed with CRC (all stages) from 2004-2015. Second, we investigated the interaction between biomarkers and the prognostic effect of PTL in 1818 patients diagnosed with stage IV CRC in 2014-2015.

Results: L-CRC was associated with a significantly better 5-year relative survival compared to R-CRC in all stages and ages combined (68.4%, 95% CI, 67.7-69.1% vs 65.6%, 95% CI, 64.7-66.4%). Also, when stratified by age, sex, and stage, the prognosis of L-CRC was better compared to R-CRC in most subgroups. Only in stage II and certain subgroups of elderly patients, the opposite was observed. Furthermore, our data showed that none of the biomarkers had a significant interaction with the effect of PTL on survival.

Conclusion: This population-based study confirms that L-CRC is associated with significantly better relative survival compared to R-CRC, in all stages and ages combined. Furthermore, in stage IV L-CRC is associated with a longer survival than R-CRC, regardless of MMR, RAS, and BRAF status.

Keywords: colorectal neoplasms; population register; primary tumor location; survival; tumor biomarkers.

Figure 1.

Graphical representation of 5-year relative survival according to location and stage. Left-sided CRC was associated with a significantly better survival in stages I, III, and IV compared to right-sided CRC. Abbreviations: RC, right colon; LC, left colon; R, rectum; LCR, left colon and rectum.

Figure 2.

Odds ratios comparing right- to left-sided CRC according to age, stage, and sex. The odds ratio was defined as the odds to die of colorectal cancer during the 5 years follow-up in the non-reference category (right-sided CRC) versus the reference category (left-sided CRC). Five-year relative mortality in stage I, patients with left-sided colorectal cancer aged 0-59 year was used as reference survival (in each sex separately). In most subgroups, left-sided CRC is associated with a significantly better 5-year relative survival compared to right-sided CRC. Only in the subgroups of stage I ­>80-year-old males, stage II >70-year-old males and females, stage III >80-year-old females, and stage IV >80-year-old males, a significantly better survival in right-sided CRC was observed. Dots, females; triangles, males. Abbreviations: RC, right colon; LCR, left colon and rectum.

Figure 3.

Kaplan-Meier curves of overall survival according to primary tumor location. Kaplan-Meier curves of overall survival according to mutational status, mismatch repair status and primary tumor location. Dotted lines represent 95% CIs. (A) All patients with KRAS mutant tumors, (B) all patients with KRAS wild-type tumors, (C) all patients with NRAS mutant tumors, (D) all patients with NRAS wild-type tumors, (E) all patients with BRAF mutant tumors, (F) all patients with BRAF wild-type tumors, (G) all patients with tumors with deficient mismatch repair status, (H) all patients with tumors with proficient mismatch repair status. Abbreviations: MT, mutant type; WT, wild-type; LCR, left-sided colon cancer and rectal cancer; RC, right-sided colon cancer.