Logical Imputation to Optimize Prognostic Risk Classification in Metastatic Renal Cell Cancer

Author:

Maurits Jake S.F.1,van der Zanden Loes F.M.1,Diekstra Meta H.M.23,Ambert Valentin4,Castellano Daniel5,Garcia-Donas Jesus6,Troyas Rosa Guarch7,Guchelaar Henk-Jan2,Jaehde Ulrich8,Junker Kerstin910,Martinez-Cardus Anna1112,Radu Marius T.413,Rodriguez-Antona Cristina14,Roessler Max15,Warren Anne16,Eisen Tim17,Oosterwijk Egbert1,Kiemeney Lambertus A.L.M.1,Vermeulen Sita H.1

Affiliation:

1. Radboud University Medical Center, Nijmegen, The Netherlands

2. Department of Clinical Pharmacy & Toxicology, Leiden University Medical Center, Leiden, The Netherlands

3. Department of Pharmacology, Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands

4. University of Medicine and Pharmacy Carol Davila, Bucharest, Romania

5. Medical Oncology Department, Hospital Universitario 12 de Octubre, + 12 Research Institute, (CiberOnc), Madrid, Spain

6. Medical Oncology, HM Hospitales-Centro Integral Oncológico HM Clara Campal, Madrid, Spain

7. Anatomía Patológica, Complejo Hospitalario de Navarra, Pamplona, Spain

8. Institute of Pharmacy, Department of Clinical Pharmacy, University of Bonn, Bonn, Germany

9. Clinic of Urology and Paediatric Urology, Saarland University, Homburg, Germany

10. Department of Urology, Jena University Hospital, Jena, Germany

11. Cancer Epigenetics and Biology Program, Bellvitge Biomedical Research Institute, Barcelona, Catalonia, Spain

12. Institut Catala d’Oncologia (ICO), Badalona Applied Research Group in Oncology (B-ARGO Group), Institut Investigació Germans Trias i Pujol (IGTP), Badalona, Spain

13. Spitalul Clinic de Nefrologie “Dr. Carol Davila”, Bucharest, Romania

14. Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre (CNIO) and Biomedical Network on Rare Diseases (CIBERER), Madrid, Spain

15. CESAR Central Office, CESAR Central European Society for Anticancer Drug Research-EWIV, Vienna, Austria

16. Department of Histopathology, Cambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Cambridge, UK

17. Department of Oncology, Cambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Cambridge, UK

Abstract

BACKGROUND: Application of the MSKCC and IMDC models is recommended for prognostication in metastatic renal cell cancer (mRCC). Patient classification in MSKCC and IMDC risk groups in real-world observational studies is often hampered by missing data on required pre-treatment characteristics. OBJECTIVE: To evaluate the effect of application of easy-to-use logical, or deductive, imputation on MSKCC and IMDC risk classification in an observational study setting. PATIENTS AND METHODS: We used data on 713 mRCC patients with first-line sunitinib treatment from our observational European multi-centre study EuroTARGET. Pre-treatment characteristics and follow-up were derived from medical files. Hospital-specific cut-off values for laboratory measurements were requested. The effect of logical imputation of missing data and consensus versus hospital-specific cut-off values on patient classification and the subsequent models’ predictive performance for progression-free and overall survival (OS) was evaluated. RESULTS: 45% of the patients had missing data for≥1 pre-treatment characteristic for either model. Still, 72% of all patients could be unambiguously classified using logical imputation. Use of consensus instead of hospital-specific cut-offs led to a shift in risk group for 12% and 7% of patients for the MSKCC and IMDC model, respectively. Using logical imputation or other cut-offs did not influence the models’ predictive performance. These were in line with previous reports (c-statistic ∼0.64 for OS) CONCLUSIONS: Logical imputation leads to a substantial increase in the proportion of patients that can be correctly classified into poor and intermediate MSKCC and IMDC risk groups in observational studies and its use in the field should be advocated.

Publisher

IOS Press

Subject

Nephrology,Oncology

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