Survival Prognosis in Right vs Left Primary Side in Colon Cancer (note: Lynch Syndrome pts)

open access: Survival Prognosis in Right vs Left Primary Side in Colon Cancer JAMA Oncology 

 There are suggestions that localization of CC (right CC [RCC]^3,4 sided up to splenic flexure and left CC [LCC], including descending, and sigmoid and/or rectosigmoid cancers) potentially influences prognosis owing to differing biological features. Clinical presentation is also different: iron deficiency anemia from occult blood loss is more prevalent in patients with right-sided CCs; conversely, hematochezia and change in bowel habits is a more common presenting symptom for left-sided CCs.³ From a molecular point of view, RCC and LCC are 2 different entities, with RCC associated with defective mismatch repair (MMR) genes (Lynch Syndrome), mutations of KRAS and BRAF, and microRNA-31, whereas LCC is associated with CIN, p53, NRAS, microRNA-146a, microRNA-147b, and microRNA-1288.⁴

 In this systematic review and meta-analysis, we evaluated the independent prognostic value of site of primary tumor (left-sided vs right-sided primary location) in patients with cancer of the colon.

 Tumors arising on the right side of the colon, in fact, seem to follow different molecular pathways of oncogenesis. These RCCs more commonly are diploid and characterized by mucinous histology, high microsatellite instability, CpG island methylation, and BRAF mutations.^81- 85

 In stage II completely resected CC, the presence of MSI has been associated with a more favorable prognosis and a lack of benefit from fluorouracil-based adjuvant chemotherapy.⁸⁴ More recently, Sinicrope et al⁵ evaluated the prognostic impact of deficient DNA MMR in patients with stage III enrolled in a randomized trial of FOLFOX-based adjuvant chemotherapy and found that among deficient MMR cancers only proximal tumors had favorable outcome.

Conclusions

Based on the results of this study, the side of origin of CC (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.