Safety and Efficacy of Serplulimab Combined with Neoadjuvant Chemoradiotherapy in High-Risk Locally Advanced Rectal Cancer: A Retrospective Study.

Background: Neoadjuvant chemoradiotherapy (nCRT) followed by total mesorectal excision (TME) is the standard treatment regimen for locally advanced rectal cancer (LARC). However, pathologic complete response (pCR) rates remain suboptimal, and distant metastasis remains a significant cause of treatment failure. While immune checkpoint inhibitors (ICIs) has demonstrated promising efficacy and safety in microsatellite instability-high (MSI-H) rectal cancer patients, less than 5% of rectal cancers exhibit MSI-H characteristics. The majority are microsatellite stable (MSS) types, which are generally unresponsive to immunotherapy alone. Recent studies have indicated that the addition of radiotherapy can convert immune checkpoint-insensitive "cold" tumors into more responsive "hot" tumors. Therefore, combining immunotherapy with nCRT may enhance the pCR rate and improve prognosis in LARC patients. Objective: The study aimed to evaluate the safety and efficacy of serplulimab in combination with conventional nCRT for treating LARC, particularly in patients with high-risk factors. Methods: A retrospective analysis was conducted using data from patients with LARC treated at the First Affiliated Hospital with Nanjing Medical University between November 2023 and July 2024. All enrolled patients received conventional radiotherapy combined with CapeOX or capecitabine monotherapy, along with serplulimab, followed by TME 8-12 weeks post-nCRT. The primary endpoint was the pCR rate, while secondary endpoints included the incidence of adverse events. Results: A total of 29 patients were enrolled, with a median age of 60 years. About 79.3% patients had tumors located within 10 cm from the anal margin. Pre-treatment stages were uniformly categorized as IIIB or IIIC, with 51.7% classified as cT4 and 86.2% as cN2. Additionally, 65.5% exhibited tumor invasion of the mesorectal fascia. All 29 patients underwent R0 resection. Postoperative pathology revealed that 31.0% (9/29) patients achieved tumor regression grade (TRG) 0, 31.0% (9/29) patients achieved TRG 1. The most common adverse events included lymphocytopenia, fatigue, neutropenia, and anal pain. Grade 3 toxicity was observed in 48.3% of patients, with no grade 4 or 5 adverse reactions noted. Conclusion: The combination of serplulimab with nCRT demonstrated safety and efficacy in patients with high-risk pMMR LARC. However, further verification through longer follow-up periods and large-scale prospective studies is warranted.