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Evaluation of smoking status as a prognostic factor under immune checkpoint inhibitor treatment: A single center analysis

  • Authors:
    • Christoph Schaefers
    • Annika Poch
    • Anika Forstreuter
    • Frederike Bokemeyer
    • Carsten Bokemeyer
    • Christoph Seidel
  • View Affiliations / Copyright

    Affiliations: Department of Oncology, Hematology and Bone Marrow Transplantation with Division of Pneumology, University Medical Center Hamburg‑Eppendorf, D‑20246 Hamburg, Germany, Department of Medical Psychology, University Medical Center Hamburg‑Eppendorf, D‑20246 Hamburg, Germany
    Copyright: © Schaefers et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 261
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    Published online on: April 24, 2026
       https://doi.org/10.3892/ol.2026.15616
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Abstract

Smoking may influence cancer treatment outcomes; however, there is conflicting evidence on the efficacy of immune checkpoint inhibitors (ICIs) in active smokers. It has been suggested that smokers receiving ICIs may achieve improved outcomes compared with non‑smokers. The present study aimed to challenge this assumption by investigating the prognostic impact of smoking status and other characteristics in patients with metastatic or advanced cancer undergoing ICI therapy. In the present study, patients with predetermined solid tumors who received ICIs either as a monotherapy or in combination regimens in a palliative treatment setting were retrospectively evaluated. Patients were included if they had received >1 dose of an ICI and had an available smoking status. Kaplan‑Meier estimates were used to analyze the associations between smoking status and overall survival (OS) and progression‑free survival (PFS). The patient baseline characteristics were assessed as potential prognostic markers using univariate and multivariate analyses. Of the 464 patients evaluated, 180 met the inclusion criteria. The cohort included patients with lung cancer (n=94), renal cell carcinoma (n=18), urothelial cancer (n=21), melanoma (n=3), and head and neck cancer (n=44). The median OS and PFS times for the whole cohort were 39.1 and 5.5 months, respectively. Patients were categorized as never‑smokers (n=45, 25%), former smokers (n=81, 45%) and active smokers (n=54, 30%). The median OS times for the never, former and active smokers were 66.4, 31.6 and 13.9 months, respectively. When comparing the active smokers with the former and never smokers, the median OS times were 13.9 vs. 41.1 months (P=0.069, trend). Multivariate analyses identified Eastern Cooperative Oncology Group (ECOG) performance status ≥3 [hazard ratio (HR), 5.85; P=0.002], neutrophil‑to‑lymphocyte ratio (NLR; HR, 1.11; P=0.017), lactate dehydrogenase (LDH; HR, 1.00; P<0.001) and C‑reactive protein (CRP) levels as continuous variables (HR, 1.01; P=0.002) as significant predictors of a poorer OS. For PFS, multivariate analysis identified sex (HR, 0.69; P=0.049), age (HR, 0.98; P=0.014) and ECOG performance status ≥3 (HR, 5.83; P<0.001) as independent predictors of a shorter PFS. In conclusion, contrary to prior hypotheses suggesting improved outcomes for smokers undergoing ICI therapy, the results of the present study demonstrated a trend towards impaired survival outcomes in active smokers compared with never and former smokers. The independent prognostic factors for a poorer OS included a poor ECOG performance status, CRP level, LDH level and NLR. 
View Figures

Figure 1

Study flow chart.

Figure 2

Active smoking reveals impaired
overall survival compared to non-active-smokers under ICI
treatment.
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Copy and paste a formatted citation
Spandidos Publications style
Schaefers C, Poch A, Forstreuter A, Bokemeyer F, Bokemeyer C and Seidel C: Evaluation of smoking status as a prognostic factor under immune checkpoint inhibitor treatment: A single center analysis. Oncol Lett 31: 261, 2026.
APA
Schaefers, C., Poch, A., Forstreuter, A., Bokemeyer, F., Bokemeyer, C., & Seidel, C. (2026). Evaluation of smoking status as a prognostic factor under immune checkpoint inhibitor treatment: A single center analysis. Oncology Letters, 31, 261. https://doi.org/10.3892/ol.2026.15616
MLA
Schaefers, C., Poch, A., Forstreuter, A., Bokemeyer, F., Bokemeyer, C., Seidel, C."Evaluation of smoking status as a prognostic factor under immune checkpoint inhibitor treatment: A single center analysis". Oncology Letters 31.6 (2026): 261.
Chicago
Schaefers, C., Poch, A., Forstreuter, A., Bokemeyer, F., Bokemeyer, C., Seidel, C."Evaluation of smoking status as a prognostic factor under immune checkpoint inhibitor treatment: A single center analysis". Oncology Letters 31, no. 6 (2026): 261. https://doi.org/10.3892/ol.2026.15616
Copy and paste a formatted citation
x
Spandidos Publications style
Schaefers C, Poch A, Forstreuter A, Bokemeyer F, Bokemeyer C and Seidel C: Evaluation of smoking status as a prognostic factor under immune checkpoint inhibitor treatment: A single center analysis. Oncol Lett 31: 261, 2026.
APA
Schaefers, C., Poch, A., Forstreuter, A., Bokemeyer, F., Bokemeyer, C., & Seidel, C. (2026). Evaluation of smoking status as a prognostic factor under immune checkpoint inhibitor treatment: A single center analysis. Oncology Letters, 31, 261. https://doi.org/10.3892/ol.2026.15616
MLA
Schaefers, C., Poch, A., Forstreuter, A., Bokemeyer, F., Bokemeyer, C., Seidel, C."Evaluation of smoking status as a prognostic factor under immune checkpoint inhibitor treatment: A single center analysis". Oncology Letters 31.6 (2026): 261.
Chicago
Schaefers, C., Poch, A., Forstreuter, A., Bokemeyer, F., Bokemeyer, C., Seidel, C."Evaluation of smoking status as a prognostic factor under immune checkpoint inhibitor treatment: A single center analysis". Oncology Letters 31, no. 6 (2026): 261. https://doi.org/10.3892/ol.2026.15616
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