Comparative effectiveness of immunotherapy and chemotherapy in patients with metastatic colorectal cancer stratified by microsatellite instability status

Chen-Gu Niu; Jing Zhang; Aniket-Vijay Rao; Utsav Joshi; Patrick Okolo

doi:10.5306/wjco.v15.i4.540

Comparative effectiveness of immunotherapy and chemotherapy in patients with metastatic colorectal cancer stratified by microsatellite instability status

World J Clin Oncol. 2024 Apr 24;15(4):540-547. doi: 10.5306/wjco.v15.i4.540.

Authors

Chen-Gu Niu¹, Jing Zhang², Aniket-Vijay Rao³, Utsav Joshi⁴, Patrick Okolo⁵

Affiliations

¹ Department of Internal Medicine, Rochester General Hospital, Rochester, NY 14621, United States. chenguniu@gmail.com.
² Department of Psychiatry, Rainier Springs, Vancouver, WA 98663, United States.
³ Department of Internal Medicine, Rochester General Hospital, Rochester, NY 14621, United States.
⁴ Department of Hematology and Medical Oncology, Moffitt Cancer Center, Tampa, FL 33606, United States.
⁵ Department of Gastroenterology, Rochester General Hospital, Rochester, NY 14621, United States.

Abstract

Background: Immunotherapy have demonstrated promising outcomes in patients with high microsatellite instability (MSI) (MSI-H) metastatic colorectal cancer. However, the comparative effectiveness of Immunotherapy and chemotherapy for patients with low MSI (MSI-L), and microsatellite stable (MSS) metastatic colorectal cancer remains unclear.

Aim: To investigate immunotherapy vs chemotherapy for treatment of MSI-L/MSS metastatic colorectal cancer, and to evaluate the success of immunotherapy against chemotherapy in managing MSI-H metastatic colorectal cancer during a follow-up of 50 months.

Methods: We conducted a retrospective cohort study using the National Cancer Database (NCDB) to evaluate the overall survival (OS) of patients with metastatic colorectal cancer treated with immunotherapy or chemotherapy. The study population was stratified by MSI status (MSI-H, MSI-L, and MSS). Multivariable Cox proportional hazard models were used to assess the association between treatment modality and OS, adjusting for potential confounders.

Results: A total of 21951 patients with metastatic colorectal cancer were included in the analysis, of which 2358 were MSI-H, and 19593 were MSI-L/MSS. In the MSI-H cohort, immunotherapy treatment (n = 142) was associated with a significantly improved median OS compared to chemotherapy (n = 860). After adjusting for potential confounders, immunotherapy treatment remained significantly associated with better OS in the MSI-H cohort [adjusted hazard ratio (aHR): 0.57, 95% confidence interval (95%CI): 0.43-0.77, P < 0.001]. In the MSS cohort, no significant difference in median OS was observed between immunotherapy treatment and chemotherapy (aHR: 0.94, 95%CI: 0.69-1.29, P = 0.715).

Conclusion: In this population-based study using the NCDB, immunotherapy treatment was associated with significantly improved OS compared to chemotherapy in patients with MSI-H metastatic colorectal cancer, but not in those with MSI-L/MSS metastatic colorectal cancer. Further studies are warranted to determine the optimal therapeutic approach for patients with MSI-L/MSS metastatic colorectal cancer.

Keywords: Chemotherapy; Immunotherapy; Metastatic colorectal cancer; Microsatellite instability; National cancer database.