ArticlesExternal validation and comparison with other models of the International Metastatic Renal-Cell Carcinoma Database Consortium prognostic model: a population-based study
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)
- et al.
Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial
Lancet
(2007) - et al.
Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial
Lancet
(2011) - et al.
Prognostic factors of survival and rapid progression in 782 patients with metastatic renal carcinomas treated by cytokines: a report from the Groupe Francais d'Immunotherapie
Ann Oncol
(2002) - et al.
Clinical and molecular prognostic factors in renal cell carcinoma: what we know so far
Hematol Oncol Clin North Am
(2011) - et al.
Sunitinib versus interferon alfa in metastatic renal-cell carcinoma
N Engl J Med
(2007) - et al.
Sorafenib in advanced clear-cell renal-cell carcinoma
N Engl J Med
(2007) - et al.
Phase III trial of bevacizumab plus interferon alfa versus interferon alfa monotherapy in patients with metastatic renal cell carcinoma: final results of CALGB 90206
J Clin Oncol
(2010) - et al.
A randomized, double-blind phase III study of pazopanib in treatment-naive and cytokine-pretreated patients with advanced renal cell carcinoma (RCC)
Proc Am Soc Clin Oncol
(2009) - et al.
Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted agents: results from a large, multicenter study
J Clin Oncol
(2009) - et al.
A unified prognostic model for first- and second-line targeted therapy in metastatic renal cell carcinoma (mRCC): results from a large international study
Proc Am Soc Clin Oncol
(2010)
Clinical factors associated with outcome in patients with metastatic clear-cell renal cell carcinoma treated with vascular endothelial growth factor-targeted therapy
Cancer
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
Cited by (0)
- †
Joint first authors