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Background <p>Metastatic colorectal cancer (mCRC) patients in trials are selected. The aim was to study mCRC features population-based.</p> Methods <p>All 765 mCRC patients in the Uppsala region, Sweden, 2010–2020 were identified and analysed for RAS (<i>n</i> = 356/708) and <i>BRAF</i>-V600E (<i>n</i> = 123/708) mutations (mt) and deficient mismatch repair (dMMR, <i>n</i> = 58/643).</p> Results <p>Right colon primary tumours were associated with <i>BRAF</i>-V600Emt and dMMR and had worse median overall survival (mOS) than left colon or rectal mCRC. RAS&amp;<i>BRAF</i> 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&amp;<i>BRAF</i>wt/RASmt/<i>BRAF</i>-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.</p> Conclusions <p>The high variation of <i>BRAF</i>-V600Emt, RASmt, dMMR, and treatment allocation population-based per primary tumour location explain the poor outcome in right-sided cancers.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年5月28日

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  • Emerik Osterlund,
  • Klara Hammarström,
  • Luís Nunes,
  • Lucy Mathot,
  • Artur Mezheyeuski,
  • Tobias Sjöblom,
  • Bengt Glimelius

摘要

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.