Primary tumour location, molecular alterations, treatments, and outcome in a population-based metastatic colorectal cancer cohort

Abstract

Primary tumour; Molecular alterations; Metastatic colorectal cancer

Tumor primari; Alteracions moleculars; Càncer colorectal metastàtic

Tumor primario; Alteraciones moleculares; Cáncer colorrectal metastásico

Background: Metastatic colorectal cancer (mCRC) patients in trials are selected. The aim was to study mCRC features population-based. Methods: All 765 mCRC patients in the Uppsala region, Sweden, 2010-2020 were identified and analysed for RAS (n = 356/708) and BRAF-V600E (n = 123/708) mutations (mt) and deficient mismatch repair (dMMR, n = 58/643). Results: Right colon primary tumours were associated with BRAF-V600Emt and dMMR and had worse median overall survival (mOS) than left colon or rectal mCRC. RAS&BRAF wildtype (wt) and proficient MMR were seen in 22%, 45%, and 31% of right colon, left colon, and rectum, respectively. Patients with right colon primaries received best supportive care only more often (34% vs 25% vs 24%) and metastasectomy less often (21% vs 31% vs 33%) than left colon and rectal primaries. In molecularly homogeneous subgroups (RAS&BRAFwt/RASmt/BRAF-V600Emt/dMMR) no difference in mOS were seen between right and left colon primaries, whereas rectal primaries had better mOS (26/15/8/9 vs 24/21/8/8 vs 32/23/6/NA months, respectively). This was also the case in homogenous treatment groups. Primary tumour location turned non-significant in multivariable OS analyses. Conclusions: The high variation of BRAF-V600Emt, RASmt, dMMR, and treatment allocation population-based per primary tumour location explain the poor outcome in right-sided cancers.

This work was funded by grants from the Swedish Cancer Society (22 2054 Pj 01H), Lions Cancerforskningsfond Mellansverige, and an unrestricted start-up grant from Amgen. The funders had no role in the design of the study, nor in the analyses of data or the writing of this report. Open access funding provided by Uppsala University.