Development and validation of a prognostic model in patients with metastatic renal cell carcinoma treated with sunitinib: a European collaboration

Abstract

Background:Accurate prediction of outcome for metastatic renal cell carcinoma (mRCC) patients receiving targeted therapy is essential. Most of the available models have been developed in patients treated with cytokines, while most of them are fairly complex, including at least five factors. We developed and externally validated a simple model for overall survival (OS) in mRCC. We also studied the recently validated International Database Consortium (IDC) model in our data sets.Methods:The development cohort included 170 mRCC patients treated with sunitinib. The final prognostic model was selected by uni- and multivariate Cox regression analyses. Risk groups were defined by the number of risk factors and by the 25th and 75th percentiles of the model's prognostic index distribution. The model was validated using an independent data set of 266 mRCC patients (validation cohort) treated with the same agent.Results:Eastern Co-operative Oncology Group (ECOG) performance status (PS), time from diagnosis of RCC and number of metastatic sites were included in the final model. Median OS of patients with 1, 2 and 3 risk factors were: 24.7, 12.8 and 5.9 months, respectively, whereas median OS was not reached for patients with 0 risk factors. Concordance (C) index for internal validation was 0.712, whereas C-index for external validation was 0.634, due to differences in survival especially in poor-risk populations between the two cohorts. Predictive performance of the model was improved after recalibration. Application of the mRCC International Database Consortium (IDC) model resulted in a C-index of 0.574 in the development and 0.576 in the validation cohorts (lower than those recently reported for this model). Predictive ability was also improved after recalibration in this analysis. Risk stratification according to IDC model showed more similar outcomes across the development and validation cohorts compared with our model.Conclusion:Our model provides a simple prognostic tool in mRCC patients treated with a targeted agent. It had similar performance with the IDC model, which, however, produced more consistent survival results across the development and validation cohorts. The predictive ability of both models was lower than that suggested by internal validation (our model) or recent published data (IDC model), due to differences between observed and predicted survival among intermediate and poor-risk patients. Our results highlight the importance of external validation and the need for further refinement of existing prognostic models.

Metastatic papillary renal cell carcinoma in the era of targeted therapy – a retrospective study from three European academic centres

“…The metastatic burden should be considered when predicting OS in mPRCC; we found a cutoff of three or more metastatic sites to be useful as prognosticator. A similar association has been demonstrated in clear cell mRCC [35]. In contrast, we found no clear survival impact of specific organ involvement when correcting for factors such as age, PS and number of metastatic sites in multivariable analysis, the exception being lymph node metastasis in patients treated with TA.…”

Prognosis of Japanese patients with previously untreated metastatic renal cell carcinoma in the era of molecular‐targeted therapy

“…Patients in both the VEGFR‐TKI and cytokines groups could be stratified into three groups using the JMRC prognostic classification, and the c‐indexes were 0.630 and 0.642, respectively. Several models have been proposed as prognostic models for OS . Heng et al .…”

“…Several models have been proposed as prognostic models for OS. (15,(19)(20)(21)(22) Heng et al (23) compared the IDC, Cleveland Clinic Foundation (CCF), French, International Kidney Cancer Working Group (IKCWG) and MSKCC models, and reported that their c-indexes were 0.664, 0.662, 0.640, 0.668 and 0.657, respectively; no marked differences were observed between these models. The c-index of the JMRC model in the present study was similar to these results.…”

Effects of local irradiation combined with sunitinib on early remodeling, mitochondria, and oxidative stress in the rat heart

“…By inhibiting tyrosine kinases, these agents target pathways involved in tumor angiogenesis, proliferation, and metastasis [7]. Several TKIs have been approved or are in clinical development for the treatment of thoracic cancers (e.g., breast, esophagus, and lung) [8–11] and metastatic cancers [12–15]. TKIs are commonly administered concurrently with (chemo)radiation therapy, and continuous dosing of the TKI follows for several months to years afterward.…”