Background

• Colorectal cancer (CRC) is a heterogeneous disease with different genetic alterations and clinical behavior
• CRC was recently classified into four consensus molecular subtypes (CMSs) with distinguishing features¹
• CMS 1-4 tumors have different carcinogenic pathways and genomic patterns
• Recent retrospective analysis of CALGB 80405 showed that left-sided colon tumors respond differently to biologics compared to right-sided colon tumors¹, likely due to molecular differences
• In the CALGB 80405 analysis, rectal cancers were included as part of the “left-sided” tumors
• However molecular variations between rectal and left-sided colon tumors are not well defined

Objective

• To identify the molecular variations among left-sided CRC tumors:
  • Rectal cancers
  • Sigmoid colon cancers
  • Descending colon cancers (plus splenic flexure)

Methods

• Retrospective analysis of 1,730 CRC tumors that were profiled by Caris Life Sciences between 2009 and 2016 was performed
• All samples were independently reviewed by at least one pathologist, in addition to the local pathologist
• Only primary tumors were included in the current analysis
• Tumors without clearly defined origins were excluded
• Chi-square test was used for comparison between groups (IBM SPSS Statistics, Version 23) and significance was defined as p < 0.05

Conclusions

• Rectal cancers have molecular features that are different from left-sided colon tumors
• Clinical trials should stratify patients based on the location of the primary tumor (right vs. left) as well as molecular features
• Better understanding of disease biology may help to identify therapeutic targets and advance precision medicine