The occurrence of colon cancer on the right vs left side of the colon is a prognostic factor for all stages of the disease, according to a large meta-analysis published in JAMA Oncology. The left- vs right-sidedness of the primary tumor within the colon should be considered when deciding on intensity of treatment for metastatic disease and may be a way to stratify patients for adjuvant colon cancer studies.
The analysis, which included 1,437,846 patients, showed that primary colon tumors occurring on the left side were associated with an absolute 19% reduced risk of death (hazard ratio [HR], 0.82; P < .001). This result was independent of tumor stage, race, use of adjuvant chemotherapy, the year of study, or number of study participants.
Fausto Petrelli, MD, of ASST Bergamo Ovest, in Treviglio, Italy, and colleagues analyzed 66 studies in which patients were followed for a median of 65 months. The analysis included 59 retrospective and 7 prospective studies published between 1995 and 2016.
Analysis based on patient race led to the same conclusion of better survival for left-sided colon tumors (HR, 0.8 and 0.82 for Asian vs non-Asian race; P < .001). There were no differences in outcomes from prospective studies compared with retrospective studies (HR, 0.82 for both; P < .001). Results also did not differ between the studies published between 1995 and 2005 vs those published between 2006 and 2016.
Previous studies had suggested that the location of a colon tumor—the right-sided colon up to the splenic flexure or the left-sided colon including the descending, sigmoid, and/or rectosigmoid colon—may influence prognosis due to differing biological features that may impact clinical outcomes for patients; right- vs left-sided tumors typically have unique clinical and molecular features. Right-sided tumors are associated with a clinical presentation of iron deficiency anemia from occult blood loss and molecular features include defective mismatch repair genes, as well as mutations in the KRAS and BRAF oncogenes and in microRNA-31. Left-sided tumors are associated with CIN, p53, NRAS, microRNA-146a, microRNA-147b, and microRNA-1288, and typically present with hematochezia and change in bowel habits.
“Results from our analysis clearly demonstrate that primary tumor location has a critical role in determining colon cancer prognosis, being a surrogate of different and poor biology,” wrote the authors.
They noted that surgical technique, as well as a difference in sensitivity to chemotherapy, could account for the worse survival outcomes for patients with right-sided colon tumors.
“Based on the results of this study, the side of origin of colon cancer (left vs right) should be acknowledged as a criterion for establishing prognosis in both earlier and advanced stages of disease. Moreover, primary tumor location should be carefully considered when deciding treatment intensity in metastatic and locoregional settings, and should represent an important stratification factor for future adjuvant studies,” the authors concluded.