IHC-Based Consensus Molecular Subtypes as A Prognostic and Predictive Biomarker for Adjuvant Chemotherapy in Patients with Stage II Colorectal Cancer

Colorectal Cancer

Oncologist. 2020 Sep 14. doi: 10.1002/ONCO.13521. Online ahead of print.


BACKGROUND: For stage II colorectal cancer (CRC), the efficacy of adjuvant chemotherapy remains controversial. Consensus molecular subtype (CMS) have been validated to be a prognostic tool for CRCs. In this study, CMS status was investigated as prognostic biomarkers for the efficacy of adjuvant chemotherapy for stage II colorectal cancer.

MATERIALS AND METHODS: The tissue microarray (TMA) was retrospectively constructed of 165 non-consecutive, primary, and sporadic stage II CRCs. CMS status was determined by immunohistochemistry staining of CDX2, HTR2B, FRMD6, and ZEB1, combining with MSI testing. The prognostic for adjuvant chemotherapy efficacy of CMS status was calculated by Kaplan-Meier curves and Cox regression analysis. Subgroup analyses were conducted according to tumor location.

RESULTS: Kaplan-Meier curves indicated that CMS was associated with overall survival (OS) and disease-free survival (DFS) for stage II CRCs. Cox regression analysis showed that CMS was an independent risk factor for OS. Among high-risk clinicopathological factors, patients with CMS2/3 (HR: 0.445, 95%CI: 0.227-0.875), left-sided tumors (HR: 0.488, 95%CI:0.247-0.968) or less than 12 lymph nodes examined (HR: 0.307, 95%CI: 0.097-0.974) had survival benefit from adjuvant chemotherapy. Subgroup analysis showed that adjuvant chemotherapy only improved OS for patients with left-sided tumors of CMS2/3 subtype. Regardless of CMS, right-sided tumors had no benefit from adjuvant chemotherapy.

CONCLUSION: CMS is a better prognostic factor for adjuvant chemotherapy for stage II CRCs. Together with tumor location, CMS classification will aid in personalized treatment for stage II CRCs.

IMPLICATIONS FOR PRACTICE: For stage II colorectal cancer, the efficacy of adjuvant chemotherapy remains controversial, for that its minimal benefit (no more than 5% on average) is considered not worth the toxic effects of the drugs. There is still no effective prognostic and predictive biomarkers. Our study showed that Consensus Molecular Subtypes (CMS) status is a predictive marker for adjuvant chemotherapy efficacy. Patients with left-sided tumors of CMS2/3 subtype have survival benefit by receiving adjuvant chemotherapy, which will aid in personalized treatment for stage II CRCs. Moreover, this test of CMS based on IHC is cheap, not time consuming, and easily conducted in the laboratories of most hospitals.