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Left-sided tumor location reduces colon cancer mortality risk
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Patients diagnosed with left-sided colon cancer appeared to have nearly a 20% reduced risk for death compared with those with right-sided tumors, according to results of a systematic review and meta-analysis published in JAMA Oncology.
Thus, primary colon cancer tumor location of either the right or left side may influence prognosis because of differing biological features, according to the researchers.
“Based on the results of this study, the side of origin of colon cancer should be acknowledged as a criterion for establishing prognosis in both earlier and advanced stages of disease,” Fausto Petrelli, MD, of the oncology unit at ASST Bergamo Ovest in Treviglio, Italy, and colleagues wrote. “Moreover, primary tumor locations should be carefully considered when deciding treatment intensity in metastatic and locoregional settings, and should represent an important stratification factor for future adjuvant studies.”
Right-sided and left-sided colon cancer tumors have different biological features, clinical presentation and molecular abnormalities. To determine the prognostic role of primary tumor location, Petrelli and colleagues searched PubMed, EMBASE, The Cochrane Library, Web of Science and other databases to identify 66 studies conducted from 1995 to 2016 that reported on OS based on tumor location. The studies involved 1.4 million patients and had a median follow-up of 65 months. The proportion of patients with left-sided tumors in the studies ranges from 17.6% to 67%, and the proportion of right-sided tumors ranged from 10% to 71%.
Results of a multivariate analysis that adjusted for stage, race, adjuvant chemotherapy, year of study, number of participants, and quality of included studies indicated left-sided primary tumor location was associated with a significantly reduced risk for mortality (HR = 0.82; 95% CI, 0.79-0.84).
This effect appeared greater in studies that included fewer than 880 patients (HR = 0.7; 95% CI, 0.65-0.76) than in studies with more patients (HR = 0.84; 95% CI, 0.82-0.87).
Studies that exclusively included patients with stage IV disease (n = 20) compared with those that only included patients with stage I to stage III disease (n = 25) showed a significantly greater mortality reduction associated with left-sided colon cancer (HR = 0.73; 95% CI, 0.69-0.78 vs. HR = 0.84; 95% CI, 0.79-0.89).
Researchers reported an increasing amount of evidence showing that colon tumors proximal and distal to splenic flexure are distinct clinical and biological entities.
“It has been hypothesized that this could be the result of the delicate balance that immune cells have to maintain between immunogenicity against pathogens and tolerance for the commensal microbiota, which is much more represented in the distal colorectum,” the researchers wrote. “This observation could also explain the differences in immunological response to tumors developing in the proximal colon characterized by an increased immune activity and, in turn, reflect the specific differences in pathogenesis and outcome.”
Further, iron deficiency anemia from occult blood loss is more prevalent in patients with right-sided colon cancer, researchers wrote. Conversely, hematochezia and change in bowel habits is a more common symptom for left-sided colon cancer.
Further, right-sided colon cancer tumors more commonly are diploid and characterized by mucinous histology, high microsatellite instability, CpG island methylation and BRAF mutations. Conversely, left-sided colon cancer tumors frequently have p53 and KRAS mutations.
Researchers acknowledged significant differences for metastatic and locoregional populations, which may be a limitation to these findings. Further, they excluded 29 articles where primary tumor location was not significantly associated with OS, or HR data were not obtainable.
“Our work confirms and emphasizes previous reports indicating an increased importance of primary tumor location in clinical decision-making processes,” Petrelli and colleagues wrote. – by Chuck Gormley
Disclosure: The researchers report no relevant financial disclosures.
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