Retrospective Cohort Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Oncol. Apr 24, 2024; 15(4): 540-547
Published online Apr 24, 2024. doi: 10.5306/wjco.v15.i4.540
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
Chen-Gu Niu, Aniket-Vijay Rao, Department of Internal Medicine, Rochester General Hospital, Rochester, NY 14621, United States
Jing Zhang, Department of Psychiatry, Rainier Springs, Vancouver, WA 98663, United States
Utsav Joshi, Department of Hematology and Medical Oncology, Moffitt Cancer Center, Tampa, FL 33606, United States
Patrick Okolo, Department of Gastroenterology, Rochester General Hospital, Rochester, NY 14621, United States
Author contributions: All authors jointly conceptualized the article. Okolo P critically revised the manuscript and provided substantial feedback; Okolo P and Zhang J were responsible for the statistical analysis; Niu CG, Zhang J, Rao AV and Joshi U conducted the literature review and drafted the manuscript. All authors approved the final version of the manuscript.
Institutional review board statement: The present study was a database analysis using de-identified data; therefore, institutional review board approval was not required for this type of study.
Conflict-of-interest statement: All the authors declare no conflicts of interest for this article.
Data sharing statement: The data that support the findings of this study are available from the corresponding author at chenguniu@gmail.com.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Chen-Gu Niu, MD, Assistant Professor, Department of Internal Medicine, Rochester General Hospital, 1425 Portland Avenue, Rochester, NY 14621, United States. chenguniu@gmail.com
Received: December 28, 2023
Peer-review started: December 28, 2023
First decision: January 19, 2024
Revised: March 19, 2024
Accepted: March 21, 2024
Article in press: March 21, 2024
Published online: April 24, 2024
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: Immunotherapy, Chemotherapy, Metastatic colorectal cancer, Microsatellite instability, National cancer database

Core Tip: Our population-based study demonstrates that immunotherapy treatment is associated with significantly improved overall survival in patients with high microsatellite instability (MSI-H) metastatic colorectal cancer. However, immunotherapy does not significantly benefit patients with microsatellite stable (MSS) metastatic colorectal cancer. The lower response rates to immunotherapy in MSS tumors can be attributed to the lower tumor mutational burden and reduced immunogenicity compared to MSI-H tumors. These findings indicate that while immunotherapy is a promising treatment for MSI-H colorectal cancer, its efficacy in MSS cases remains uncertain, warranting further investigation to develop targeted therapies for these patients.