Elsevier

The Lancet Oncology

Volume 14, Issue 2, February 2013, Pages 141-148
The Lancet Oncology

Articles
External validation and comparison with other models of the International Metastatic Renal-Cell Carcinoma Database Consortium prognostic model: a population-based study

https://doi.org/10.1016/S1470-2045(12)70559-4Get rights and content

Summary

Background

The International Metastatic Renal-Cell Carcinoma Database Consortium model offers prognostic information for patients with metastatic renal-cell carcinoma. We tested the accuracy of the model in an external population and compared it with other prognostic models.

Methods

We included patients with metastatic renal-cell carcinoma who were treated with first-line VEGF-targeted treatment at 13 international cancer centres and who were registered in the Consortium's database but had not contributed to the initial development of the Consortium Database model. The primary endpoint was overall survival. We compared the Database Consortium model with the Cleveland Clinic Foundation (CCF) model, the International Kidney Cancer Working Group (IKCWG) model, the French model, and the Memorial Sloan-Kettering Cancer Center (MSKCC) model by concordance indices and other measures of model fit.

Findings

Overall, 1028 patients were included in this study, of whom 849 had complete data to assess the Database Consortium model. Median overall survival was 18·8 months (95% 17·6–21·4). The predefined Database Consortium risk factors (anaemia, thrombocytosis, neutrophilia, hypercalcaemia, Karnofsky performance status <80%, and <1 year from diagnosis to treatment) were independent predictors of poor overall survival in the external validation set (hazard ratios ranged between 1·27 and 2·08, concordance index 0·71, 95% CI 0·68–0·73). When patients were segregated into three risk categories, median overall survival was 43·2 months (95% CI 31·4–50·1) in the favourable risk group (no risk factors; 157 patients), 22·5 months (18·7–25·1) in the intermediate risk group (one to two risk factors; 440 patients), and 7·8 months (6·5–9·7) in the poor risk group (three or more risk factors; 252 patients; p<0·0001; concordance index 0·664, 95% CI 0·639–0·689). 672 patients had complete data to test all five models. The concordance index of the CCF model was 0·662 (95% CI 0·636–0·687), of the French model 0·640 (0·614–0·665), of the IKCWG model 0·668 (0·645–0·692), and of the MSKCC model 0·657 (0·632–0·682). The reported versus predicted number of deaths at 2 years was most similar in the Database Consortium model compared with the other models.

Interpretation

The Database Consortium model is now externally validated and can be applied to stratify patients by risk in clinical trials and to counsel patients about prognosis.

Funding

None.

Introduction

Treatment of metastatic renal-cell carcinoma (RCC) has been revolutionised by targeted treatments such as those directed against VEGF. This class of agents—which includes sunitinib,1 sorafenib,2 bevacizumab,3, 4 pazopanib,5 and axitinib6—has been included in treatment for patients with this advanced disease. The new era of targeted treatment needs new prognostic models and updated survival data for accurate clinical trial design, patient counselling, and risk-specific treatment. Thus, the International Metastatic RCC Database Consortium7, 8 derived the first prognostic model since the development of targeted treatment from a large multicentre cohort. Six independent predictors of poor survival were identified: Karnofsky performance status of less than 80%, less than 1 year from diagnosis to treatment, anaemia (haemoglobin concentration <lower limit of normal), hypercalcaemia (corrected calcium concentration >upper limit of normal), neutrophilia (neutrophil count >upper limit of normal), and thrombocytosis (platelet count >upper limit of normal). According to the number of poor prognostic factors, patients were segregated into favourable (no factors), intermediate (one or two factors), and poor (more than three factors) risk groups.

Other prognostic models for metastatic RCC exist but are based on outcomes of patients treated with immunotherapy or on single-institution experiences (table 1). The most widely used system is the Memorial Sloan-Kettering Cancer Center (MSKCC) model,13 which contains many of the same factors as the Database Consortium model. Other models include the Cleveland Clinic Foundation (CCF) model,9 the updated French model adapted to the AVOREN trial,10, 11 and the International Kidney Cancer Working Group (IKCWG) model.12

An ideal prognostic model is easy to use, includes only the most relevant patient and disease characteristics, and is able to accurately distinguish between groups of patients with different outcomes. We tested the validity of the metastatic RCC Database Consortium model in a large international multicentre dataset and compared its accuracy with other prognostic models.

Section snippets

Participants

In this population-based analysis, we included consecutive patients from 13 international cancer centres (five in the USA, five in Canada, one in South Korea, one in Singapore, and one in Denmark). The 645 patients originally used7 to derive the Database Consortium model were not included in this analysis. We collected data between Aug 15, 2008, and Jan 14, 2011. Included patients had metastatic RCC treated between 2004 and 2010 with an anti-VEGF targeted treatment (sunitinib, sorafenib,

Results

1028 patients were eligible for this analysis. At the cutoff date, 851 patients (83%) had discontinued targeted treatment and 447 (43%) were alive. Median follow-up in those alive was 16·3 months (IQR 7·4–30·6) and the median overall survival of all patients was 18·8 months (95% CI 17·6–21·4). Table 2 shows baseline characteristics.

Because data were missing for some laboratory measurements, only 849 patients (83%) had complete data for the Database Consortium model and 672 (65%) had complete

Discussion

To our knowledge, this study is the largest external validation and comparison of prognostic models for metastatic RCC (panel). This study externally validates the International Metastatic RCC Database Consortium model. This study also provides clinicians with long-term overall survival data, which can be used for more accurate prognosis, patient counselling, and clinical trial design. A median overall survival of 43 months after the start of targeted treatment in the favourable risk group has

References (24)

  • TK Choueiri et al.

    Clinical factors associated with outcome in patients with metastatic clear-cell renal cell carcinoma treated with vascular endothelial growth factor-targeted therapy

    Cancer

    (2007)
  • BJ Escudier et al.

    Update on AVOREN trial in metastatic renal cell carcinoma (mRCC): efficacy and safety in subgroups of patients (pts) and pharmacokinetic (PK) analysis

    Proc Am Soc Clin Oncol

    (2008)
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