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Treatment selection bias for chemotherapy persists in colorectal cancer patient cohort studies even in comprehensive propensity score analyses

Authors Boakye D, Walter V, Martens UM, Chang-Claude J, Hoffmeister M, Jansen L, Brenner H

Received 16 May 2019

Accepted for publication 9 July 2019

Published 5 September 2019 Volume 2019:11 Pages 821—832


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Professor Irene Petersen

Daniel Boakye1,2, Viola Walter1, Uwe M Martens3, Jenny Chang-Claude4, Michael Hoffmeister1, Lina Jansen1,*, Hermann Brenner1,5,6,*

1Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany; 2Medical Faculty Heidelberg, Heidelberg University, Heidelberg, Germany; 3SLK-Clinics, Cancer Center Heilbronn-Franken, Heilbronn, Germany; 4Unit of Genetic Epidemiology, Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany; 5Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany; 6German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany

*These authors contributed equally to this work

Correspondence: Hermann Brenner
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, Heidelberg 69120, Germany
Tel +49 622 142 1300
Fax +49 622 142 1302

Introduction: Propensity score methods are increasingly used to address confounding related to treatment selection in observational studies. Studies estimating the effect of chemotherapy in colon cancer (CC) patients, however, often lacked information on pertinent comorbidities and functional status (FS). We assessed to what extent comorbidities and FS impact treatment decisions in colorectal cancer patients and explain the benefit of chemotherapy in stage III CC patients.
Methods: Stage II-III colorectal cancer patients diagnosed in 2003–2014 and recruited into a population-based study were included (N=1102). Associations of comorbidity and FS with treatment patterns were examined with multivariable logistic regression. The contribution of lower comorbidity and higher FS to the benefit of chemotherapy was estimated with propensity score weighted Cox models in 430 stage III CC patients who were followed over a median time of 4.7 years.
Results: In stage II (high-risk) and III CC patients, Charlson comorbidity scores 1, 2 and 3+ were associated with 57%, 66% and 70% lower odds of chemotherapy use, respectively. In combination with older age and poor FS, comorbidity was associated with 97% and 83% decreased odds of adjuvant chemotherapy use in CC and rectal cancer patients, respectively. In stage III CC patients, lower comorbidity and higher FS explained 38% and 24% of the overall and disease-specific survival benefits of chemotherapy, respectively. Selection bias was observed even in the comprehensive models, as chemotherapy was still associated with substantially higher non-disease-specific survival (hazard ratio (HR): 0.66; 95% confidence interval (CI): 0.46–0.92), especially in patients <75 years (HR: 0.33; 95% CI: 0.17–0.63).
Conclusion: Lower comorbidity and higher FS of recipients of chemotherapy explain approximately 40% of the benefits of chemotherapy in stage III CC patients. Regardless of how comprehensive propensity score analyses might be in observational studies, treatment selection bias might persist and affect estimates of treatment effects.

Keywords: comorbidity, functional status, treatment selection bias, chemotherapy, survival, colorectal neoplasm

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