Immunotherapy versus Chemotherapy as Adjuvant Therapy for Resected MSI-H/dMMR Colorectal Cancer: Real-World Evidence Informing Precision Strategies

Haifeng Sun¹Pin Lyu¹Shuaixi Yang¹Fuqi Wang¹Sifan Zhai¹Mengfei Zhao^2*Weitang Yuan^1*Quanbo Zhou^1*

• ¹The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
• ²Henan Cancer Hospital Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China

Abstract Background Immunotherapy has demonstrated unique advantages in MSI-H/dMMR colorectal cancer (CRC) for its later-line, first-line in metastatic status, and neoadjuvant therapy. However, evidence regarding its value in postoperative adjuvant therapy remains limited. Methods We retrospectively analyzed 261 stage II/III MSI-H/dMMR CRC patients who underwent radical resection with over 2 years of follow-up. Disease-free survival (DFS) curves were used to compare prognoses under different postoperative strategies, and factors associated with recurrence were investigated. Results The patients cohort (mean age 55.3, range 19-86 years and male for 56.3%) had a median follow-up of 30 (range 24-45) months. Recurrence occurred in 18 patients (6.9%), with an overall DFS rate of 93.1% during follow-up period. Overall, postoperative immunotherapy showed non-significant DFS advantage over watchful waiting (WW) (HR=0.19, 95%CI: 0.03-1.39, P=0.101), but it demonstrated statistically superior DFS compared to chemotherapy (HR=0.26, 95%CI: 0.08-0.89, P=0.033). Subgroup analyses revealed: 1) For patients achieving pathologic complete response after neoadjuvant therapy, postoperative WW and immunotherapy were equivalent (both DFS 100%); 2) For Stage II, WW and immunotherapy showed comparable DFS (HR=0.21, 95%CI: 0.003-13.04, P=0.463). 3) For Stage III, immunotherapy showed a trend toward superior DFS versus chemotherapy, though statistical significance was not reached (HR=0.28, 95%CI: 0.04-1.96, P=0.204), and both outperformed WW (HR=0.05, 95%CI: 0.004-0.54, P=0.014 and HR=0.34, 95%CI: 0.05-2.17, P=0.113, respectively). Factors significantly associated with recurrence included Lynch-negative (P=0.02) and perineural invasion (P=0.014). Conclusions MSI-H/dMMR CRC exhibits excellent prognosis after radical surgery. Postoperative WW remains the preferred strategy for Stage II patients, While patients with stage III requires intensive adjuvant therapy, and immunotherapy may surpass conventional chemotherapy recommended by the current guidelines.