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Immunotherapy in rectal cancer patients—a propensity score matched analysis of the National Cancer Database

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International Journal of Colorectal Disease Aims and scope Submit manuscript

Abstract

Background

Rectal cancer patients with microsatellite instability (MSI-H) are candidates for immunotherapy. However, there is little evidence on its effect on overall survival (OS).

Methods

Retrospective analysis of stage II–IV rectal adenocarcinoma patients in the National Cancer Database (NCDB) between 2010 and 2019. Propensity score matching was adjusted for baseline and treatment confounders. The cohort was divided into patients who received immunotherapy and matched controls. The primary outcome was OS.

Results

5175/206,615 (2.5%) patients with rectal adenocarcinoma underwent immunotherapy. These patients were younger (58 vs 62 years; p < 0.001), more often male (64.4% vs 61.7%; p < 0.001), were more likely to have private insurance (50.8% vs 43.4%; p < 0.001), more metastatic disease at presentation (clinical TNM stage IV–80.8% vs 23.3%; p < 0.001), presented with larger tumors (median: 5 cm vs. 4.2 cm; p < 0.001) and less often underwent surgery (33.7% vs. 69.9%; p < 0.001), radiation therapy (21.5% vs 57.4%; p < 0.001), and standard chemotherapy (38.1% vs 61%; p < 0.001) than controls. After matching, 488 patients were in each group. OS was significantly shorter in the immunotherapy group (mean survival: 56.4 months (95% CI: –53.03–59.86)) compared to controls (mean survival: 70.5 months (95% CI: –66.15–74.92) (p = 0.004)). Cox regression analysis of factors associated with OS demonstrated that immunotherapy was associated with increased mortality (HR 2.16; 95% CI: 2.09–2.24; p < 0.001). After clinical staging stratification, immunotherapy was associated with improved OS in stage IV (HR 0.91, 95% CI: 0.88–0.95; p < 0.001) but lower survival in stage II (HR 2.38; 95% CI: 2.05–2.77; p < 0.001) and stage III (HR 2.43; 95% CI: 2.18–2.7; p < 0.001) patients.

Conclusion

Immunotherapy showed modest increase in OS in stage IV metastatic rectal cancer. OS was significantly lower in stage II–III disease treated with immunotherapy.

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Data availability

Data available upon reasonable request to first author.

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Authors and Affiliations

  1. Ellen Leifer Shulman and Steven Shulman Digestive Disease Center, Cleveland Clinic Florida, 2950, Cleveland Clinic Blvd, Weston, FL 33331, USA

    Nir Horesh, Sameh Hany Emile, Michael R. Freund, Zoe Garoufalia, Rachel Gefen & Steven D. Wexner

  2. Department of Surgery and Transplantations, Sheba Medical Center, Ramat Gan, Israel

    Nir Horesh

  3. Colorectal Surgery Unit, Faculty of Medicine, Mansoura University, Mansoura, Egypt

    Sameh Hany Emile

  4. Shaare Zedek Medical Center, Department of General Surgery, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel

    Michael R. Freund

  5. Department of General Surgery, Faculty of Medicine, Hadassah Medical Organization, Hebrew University of Jerusalem, Jerusalem, Israel

    Rachel Gefen

  6. Department of Hematology/Oncology, Cleveland Clinic Florida, Weston, FL, USA

    Arun Nagarajan

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Contributions

NH: conceptualization, methodology, validation, formal analysis, investigation, data curation, writing—original draft, and writing—review and editing; SHE: methodology, validation, formal analysis, data curation, and writing—review and editing; MF: methodology, validation, formal analysis, data curation, and writing—review and editing; ZG: methodology, validation, formal analysis, data curation, and writing—review and editing; RG: methodology, validation, formal analysis, data curation, and writing—review and editing; AN: conceptualization, validation, data curation, and writing—review and editing; SW: conceptualization, methodology, resources, writing—review and editing, supervision, and project administration.

Corresponding author

Correspondence to Steven D. Wexner.

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Competing interests

None of the authors report any relevant financial disclosures. Dr. Wexner reports receiving consulting fees from ARC/Corvus, Astellas, Baxter, Becton Dickinson, GI Supply, ICON Language Services, Intuitive Surgical, Leading BioSciences, Livsmed, Medtronic, Olympus Surgical, Stryker, Takeda and receiving royalties from Intuitive Surgical and Karl Storz Endoscopy America Inc.

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Presentation: Online presentation at the ASCO annual meeting, June 2–6, 2023, Chicago, IL, USA.

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Horesh, N., Emile, S.H., Freund, M.R. et al. Immunotherapy in rectal cancer patients—a propensity score matched analysis of the National Cancer Database. Int J Colorectal Dis 39, 8 (2024). https://doi.org/10.1007/s00384-023-04574-8

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