The current literature on stage IV colorectal cancer (CRC) indicates a survival advantage for left-sided CRC. Still, the biological basis remains unclear. We assessed the interaction of cancer location with microsatellite instability (MSI) and KRAS mutation to elaborate how key molecular features modify the effect of cancer location on overall survival.
The 2010-2015 United States National Cancer Database was searched for stage IV colorectal adenocarcinomas. Overall survival (OS) was assessed via Cox models, implementing 2/3-way interaction terms.
A total of 73,685 patients were included, of which n = 11,720/n=25,433 had data on microsatellite and KRAS status. Left-sided CRC was an independent predictor of improved OS (vs. right: HR = 0.75, p < 0.001). Rectal cancer had highest OS (2/5-year OS: 43%/10%) compared to cancers of the rectosigmoid junction (HR = 1.07), sigmoid (HR = 1.12), descending colon (HR = 1.19), transverse colon (HR = 1.41), ascending colon (HR = 1.45) or cecum/appendix (HR = 1.45, p < 0.001 respectively). Patients with stable microsatellites (MSS) had improved OS versus MSI (HR = 0.93, p = 0.027); KRAS wildtype showed superior OS over KRAS mutation (HR = 0.88, p < 0.001). CRC location interacted with microsatellite status and KRAS mutation: the prognostic impact of MSS was more pronounced in rectal cancers versus other locations (interaction p < 0.001); the prognostic impact of KRAS wildtype was larger in rectal cancers (interaction p < 0.001). In a 3-way interaction model, the largest prognostic impact of MSS and KRAS wildtype was noted for rectal cancer (interaction term p < 0.05). The table summarizes 2/4-year OS rates.Table: 529P
Adjusted 2-year and 4-year OS rates by cancer location and mutational status
|Location / mutational status||Two year OS||Four year OS|
|rectal CRC, MSS, KRAS wildtype||68%||38%|
|rectal CRC, MSS, KRAS mutation||56%||29%|
|rectal CRC, MSI, KRAS wildtype||66%||39%|
|rectal CRC, MSI, KRAS mutation||43%||18%|
|other CRC, MSS, KRAS wildtype||60%||31%|
|other CRC, MSS, KRAS mutation||52%||24%|
|other CRC, MSI, KRAS wildtype||47%||25%|
|other CRC, MSI, KRAS mutation||48%||20%|
Survival for stage IV CRC shows marked variation depending on location, MSI and KRAS mutation. The prognostic effects of molecular features varies by CRC location, demonstrating largest impact in rectal cancers.
Clinical trial identification
Legal entity responsible for the study
Hyun S. Kim, MD.
Has not received any funding.
All authors have declared no conflicts of interest.