Comprehensive Review of Biomarkers for the Treatment of Locally Advanced Colon Cancer

Abstract

Despite the implementation of global screening programs, colorectal cancer (CRC) remains the second leading cause of cancer-related deaths worldwide. More than 10% of patients with colon cancer are diagnosed as having locally advanced disease with a relatively poor five-year survival rate. Locally advanced colon cancer (LACC) presents surgical challenges to R0 resection. The advantages and disadvantages of preoperative radiotherapy for LACC remain undetermined. Although several reliable novel biomarkers have been proposed for the prediction and prognosis of CRC, few studies have focused solely on the treatment of LACC. This comprehensive review highlights the role of predictive biomarkers for treatment and postoperative oncological outcomes for patients with LACC. Moreover, this review discusses emerging needs and approaches for the discovery of biomarkers that can facilitate the development of new therapeutic targets and surveillance of patients with LACC.

Keywords: biomarker; locally advanced colon cancer; predictive; prognostic.

Figure 1

The standard treatment of locally advanced colon cancer. Radical surgery with R0 resection followed by adjuvant chemotherapy adjuvant chemotherapy in the regimen of oxaliplatin and fluoropyrimidine (FOLFOX or CAPOX) remains the mainstay of standard treatment for LACC. Neoadjuvant chemotherapy with FOLFOX regimen can achieve adequate tumor downstaging with acceptable toxicity. Accumulated studies have explored the oncological benefits of neoadjuvant FOLFOX and anti-epidermal growth factor receptor (EGFR) therapy in LACC treatment. On the other hand, neoadjuvant immunotherapy showed promising downstaging effect in dMMR LACC at ESMO 2022.

Figure 2

Of all factors associated with LACC treatment outcome, the TNM staging system remains the foundation for LACC prognosis. For stage IIB/C, ≥12 retrieved LNs with adjuvant chemotherapy revealed favorable prognosis compared with those <12 retrieved LNs with or without adjuvant chemotherapy. The further analysis indicated that old age (≥70 year), incomplete resection margin, nodal positivity status are significantly associated with worse survival. Left side colon cancer is another independent favorable prognostic factor for LACC. MMR and MSI status played crucial predictive and prognostic roles in LACC patients receiving neoadjuvant or adjuvant FOLFOX or immunotherapy, and expression of ERCC1 is a significant predictive biomarker for colon cancer patients undergoing neoadjuvant or adjuvant oxaliplatin-based chemotherapy.