Long-Term Outcomes of dMMR/MSI-H Rectal Cancer Treated With Anti–PD-1–Based Immunotherapy as Curative-Intent Treatment

Authors:
Jie-Hai Yu State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China

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Le-En Liao State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China

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Bin-Yi Xiao State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China

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Xuan Zhang Department of Colorectal Surgery, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Kunming, China

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Ai-Wen Wu Department of Gastrointestinal Surgery, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Gastrointestinal Cancer Center, Peking University Cancer Hospital and Institute, Beijing, China

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Yong Cheng Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China

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Jing-Hua Tang State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China

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Wu Jiang State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China

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Ling-Heng Kong State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China

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Kai Han State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China

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Wei-Jian Mei State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China

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Zhi-Gang Hong State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China

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Wan-Jun Yang State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China

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Dan-Dan Li State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
Department of Biotherapy, Sun Yat-sen University Cancer Center, Guangzhou, China

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Zhi-Zhong Pan State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China

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Yun-Feng Li Department of Colorectal Surgery, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Kunming, China

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Xiao-Shi Zhang State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
Department of Biotherapy, Sun Yat-sen University Cancer Center, Guangzhou, China

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Pei-Rong Ding State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China

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Background: Neoadjuvant anti–PD-1 therapy has shown encouraging efficacy in patients with deficient DNA mismatch repair (dMMR)/microsatellite instability-high (MSI-H) locally advanced rectal cancer (LARC), which suggests its potential as a curative-intent therapy and a promising treatment option for organ preservation. We aimed to investigate the long-term outcomes of patients with dMMR/MSI-H LARC who experienced clinical complete response (cCR) after anti–PD-1 therapy. Methods: We retrospectively analyzed patients with dMMR/MSI-H LARC who achieved cCR and received nonoperative management following neoadjuvant anti–PD-1–based treatment from 4 Chinese medical centers. Patients were followed up for at least 1 year after they achieved cCR, their clinical data were collected, and survival outcomes were analyzed using the Kaplan-Meier method. Results: A total of 24 patients who achieved cCR and received nonoperative management from March 2018 to May 2022 were included, with a median age of 51.0 years (range, 19.0–77.0 years). The median treatment course to reach cCR was 6.0 (range, 1.0–12.0). Fifteen patients (62.5%) continued their treatments after experiencing cCR, and the median treatment course was 17.0 (range, 3.0–36.0). No local regrowth or distant metastasis was observed in a median follow-up time of 29.1 months (range, 12.6–48.5 months) after cCR. The 3-year disease-free and overall survivals were both 100%. Conclusions: Patients with dMMR/MSI-H locally advanced or low-lying rectal cancer who achieved cCR following anti–PD-1–based therapy had promising long-term outcomes. A prospective clinical trial with a larger sample size is required to further validate these findings.

Submitted August 1, 2023; final revision received September 27, 2023; accepted for publication October 9, 2023. Published online March 18, 2024

Author contributions: Study concept and design: Yu, Liao, X. Zhang, Wu, Cheng, Pan, Y.F. Li, X.S. Zhang, Ding. Data acquisition: Yu, Liao, Xiao, X. Zhang, Wu, Cheng, Mei, Hong, Yang. Data analysis and interpretation: Yu, Liao, Xiao, X. Zhang. Funding acquisition: Jiang, Ding. Project administration: X. Zhang, Wu, Cheng, Pan, Y.F. Li, X.S. Zhang, Ding. Resources: Yu, Liao, Xiao, X. Zhang, Wu, Cheng, Tang, Jiang, Kong, Han, Mei, Hong, Yang, Y.F. Li. Supervision: Pan, X.S. Zhang, Ding. Manuscript preparation: All authors. Pei-Rong Ding had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Data availability statement: Due to patient privacy, patient-related data is not available for public access but can be obtained from Pei-Rong Ding at dingpr@sysucc.org.cn upon reasonable request. The key raw data have been uploaded to the Research Data Deposit public platform at www.researchdata.org.cn

Disclosures: The authors have disclosed that they have not received any financial considerations from any person or organization to support the preparation, analysis, results, or discussion of this article.

Funding: This study was supported by the National Natural Science Foundation of China under grant number 82073159 and Guangdong Basic and Applied Basic Research Foundation under grant number 2020A1515110544.

Correspondence: Pei-Rong Ding, MD, Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, No. 651, Dongfeng East Road, Guangzhou 510060, P. R. China. Email: dingpr@sysucc.org.cn;
Xiao-Shi Zhang, MD, Department of Biotherapy, Sun Yat-sen University Cancer Center, No. 651, Dongfeng East Road, Guangzhou 510060, P. R. China. Email: zhangxsh@sysucc.org.cn;
Yun-Feng Li, MD, Department of Colorectal Surgery, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, No. 519 Kunzhou Road, Kunming 650100, China, P. R. China. Email: liyunfeng@kmmu.edu.cn; and
Zhi-Zhong Pan, MD, Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, No. 651, Dongfeng East Road, Guangzhou 510060, P. R. China. Email: panzhzh@sysucc.org.cn
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