Association Between Baseline Circulating Tumor Cells, Molecular Tumor Profiling, and Clinical Characteristics in a Large Cohort of Chemo-naïve Metastatic Colorectal Cancer Patients Prospectively Collected

Clin Colorectal Cancer. 2020 Sep;19(3):e110-e116. doi: 10.1016/j.clcc.2020.02.014. Epub 2020 Mar 6.


Background: Clinicopathologic characteristics and prognostic and predictive factors offer valuable guidance when selecting optimal first-line treatment in patients with metastatic colorectal cancer (CRC). The association between baseline circulating tumor cell (bCTC) count, molecular tumor profile, and clinicopathologic features was analyzed in a chemo-naïve metastatic CRC population.

Patients and methods: A total of 1202 patients from the Spanish VISNÚ-1 (FOLFIRINOX/bevacizumab vs. FOLFOX/bevacizumab) and VISNÚ-2 (FOLFIRI/bevacizumab vs. FOLFIRI/cetuximab; RAS-wildtype) studies were analyzed for mutational status and bCTC count. The association between clinicopathologic characteristics and bCTC count, mutational status, and microsatellite instability (MSI) was analyzed in 589 eligible patients.

Results: Interestingly, 41% of the population studied presented ≥3 bCTC count. bCTC count ≥3 was associated with worse performance status (according Eastern Cooperative Oncology Group scale), stage IV at diagnosis, at least 3 metastatic sites, and elevated carcinoembryonic antigen (CEA) levels; but not with RAS or BRAF mutations or high MSI. BRAFmut (BRAF mutated) tumors were associated with right-sided primary tumors, peritoneum, distant lymph node metastasis, and less frequent liver involvement. RASmut (RAS mutated) was associated with worse performance status; stage IV at diagnosis; right-sided primary tumors; liver, lung, and bone metastases; at least 3 metastatic sites; and elevated CEA, whereas PIK3CAmut (PIK3CA mutated) tumors were associated with right-sided primary tumors, high CEA serum levels, and older age. High MSI was associated with right-sided primary tumors, distant lymph nodes metastasis, and lower CEA levels.

Conclusions: In our study, elevated bCTCs and RASmut were associated with clinicopathologic features known to be associated with poor prognosis; whereas the poor prognosis of BRAFmut tumors in chemo-naïve metastatic CRC is not explained by associations with poor clinicopathologic prognostic factors, except right-sided primary tumors.

Trial registration number: VISNU 1 ID: NCT01640405/ VISNU 2 ID: NCT01640444.

Keywords: BRAF; CEA; Gene expression profiles; Microsatellite instability; Mutational status.

Publication types

  • Clinical Trial, Phase II
  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bevacizumab / therapeutic use
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / genetics*
  • Bone Neoplasms / drug therapy*
  • Bone Neoplasms / genetics
  • Bone Neoplasms / mortality
  • Bone Neoplasms / secondary
  • Camptothecin / analogs & derivatives
  • Camptothecin / therapeutic use
  • Cell Count
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology
  • DNA Mutational Analysis
  • Female
  • Fluorouracil / therapeutic use
  • Humans
  • Irinotecan / therapeutic use
  • Leucovorin / therapeutic use
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / genetics
  • Liver Neoplasms / mortality
  • Liver Neoplasms / secondary
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / mortality
  • Lung Neoplasms / secondary
  • Male
  • Microsatellite Instability
  • Middle Aged
  • Mutation
  • Neoplasm Staging
  • Neoplastic Cells, Circulating*
  • Organoplatinum Compounds / therapeutic use
  • Oxaliplatin / therapeutic use
  • Prognosis
  • Progression-Free Survival
  • Prospective Studies
  • Proto-Oncogene Proteins B-raf / genetics
  • Risk Assessment / methods
  • Young Adult
  • ras Proteins / genetics


  • Biomarkers, Tumor
  • Organoplatinum Compounds
  • folfirinox
  • Oxaliplatin
  • Bevacizumab
  • Irinotecan
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • ras Proteins
  • Leucovorin
  • Fluorouracil
  • Camptothecin

Supplementary concepts

  • Folfox protocol
  • IFL protocol

Associated data