Empowering Clinical Decision Making in Oligometastatic Colorectal Cancer: The Potential Role of Drug Screening of Patient-Derived Organoids

The definition of oligometastatic colorectal cancer (CRC) identifies a peculiar subpopulation of patients characterized by a limited metastatic spread of disease.1 Oligometastatic disease is defined as the involvement of up to two or occasionally three sites with five or sometimes more metastases that for their anatomic localization is amenable to local ablative therapies, thus rendering the patient free of disease.1-3 Thus, this subgroup is wide and has a significant cohort of patients with CRC. Among patients with oligometastatic CRC, those with liver-limited disease represent a more refined subset and should always be discussed in multidisciplinary teams since they appear to more likely benefit from multimodal approaches with curative intent.2,4-6 A perioperative systemic treatment integrated with surgical liver metastasectomy should be regarded as the best multimodal approach.2,7 However, the best drug regimen to be adopted for this subset of patients with CRC is still debatable and should be tailored case-by-case. Considering left-sided microsatellite stable, RAS and BRAF wild-type CRC, doublet cytotoxic regimens (FOLFIRI or FOLFOX) plus an anti-epidermal growth factor receptor (EGFR) drug can represent the best option on the basis of significant response rate (RR).8-10 However, triplet cytotoxic regimens FOLFOXIRI plus bevacizumab or anti-EGFR drug demonstrate an impressive RR up to 87%, which are increasingly regarded as potential novel neoadjuvant standard strategies.5,11 However, severe treatment-related toxicities have been reported in up to 80% of patients.11,12 Hence, both doublet or triplet combinations and anti-EGFR or antivascular endothelial growth factor are feasible options in this subset of patients. The generation of preclinical models such as patient-derived organoids (PDOs), recapitulating patient tumor histology and genetics, is emerging as a tool to predict treatment efficacy in oncology.13,14 Although genomics has already improved treatment choice in patients with CRC, especially for those carrying RAS/BRAF wild type, coclinical trials are becoming more and more important to directly test different treatment options in patient-derived tumors.15 Here, we present a proof-of-concept case report about the potential role of drug sensitivity testing in PDOs in the clinical decision making of oligometastatic CRC.