Date Published: June 12, 2019
Publisher: Public Library of Science
Author(s): Joseph Chung Yan Chan, Connie Irene Diakos, Alexander Engel, David Lok Hang Chan, Nick Pavlakis, Anthony Gill, Stephen John Clarke, Jason S. Gold.
Recent literature has suggested that tumor sidedness in colorectal cancer (CRC) is an independent prognostic and potentially predictive marker of survival. The aims of the study were to determine the prognostic significance of tumor sidedness in colorectal cancer patients undergoing primary tumor resection and to assess associated tumor biology.
A total of 3281 consecutive patients who underwent surgical resection of their primary CRC from January 1998 to December 2012 were analyzed for association with tumor biologic factors and with overall survival. Metastatic patients were excluded from analysis.
Left sided CRCs were associated with a number of additional key prognostic markers including BRAFV600E wildtype status (P<0.001), mismatch repair proficiency (p<0.001), absence of peritumoral lymphocytic response (p = 0.001), high lymphocyte-to-monocyte ratio (p<0.001) and low neutrophil-to-lymphocyte ratio (p<0.001). In primary analysis with 3067 patients, there was no statistical difference in sidedness in the univariate analysis (p = 0.291). Three further subgroup analyses were performed. In the first subgroup, only stage III patients were analyzed. In the second, patients with mismatch repair deficiency were removed. In the third, additional clinicopathologic variables known to be independently prognostic were added into analysis. In all three subgroup analyses tumor sidedness was not an independent prognostic marker. Tumor sidedness was not an independent prognostic marker of CRC. However, right sided CRCs were associated with several key independent prognostic markers supporting a hypothesis that tumor sidedness is a surrogate for other biomarkers.
Colorectal cancer (CRC) is one of the most commonly diagnosed cancers worldwide with data from the World Health Organization estimating that up to 1.4 million people are diagnosed annually . Survival rates from CRC in the Western world have improved particularly in the metastatic setting where targeted therapies, combined with advances in molecular testing, have been introduced . However, significant gaps in our knowledge of CRC and the lack of effective biomarkers for treatment and prognostic stratification remain problematic, especially in the post-operative adjuvant setting.
The current study successfully achieved the aims of investigating the association of primary CRC tumor sidedness with survival and the tumor biology of cancer sidedness. To date, this is one of the largest cohorts with the inclusion of mismatch repair status data to address CRC tumor sidedness.