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Abstract
Majority of patients with clear-cell renal cell carcinoma (ccRCC) at first line (1L) treatment are classified in the intermediate-risk (IR) subgroup according to International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) score. As these patients have different prognosis, the aim of this study is to better characterize IR patients in order to better tailor the treatment. Retrospective analysis was performed from IGReCC (Institut Gustave Roussy Renal Cell Carcinoma) database. Overall survival (OS) was defined from start of 1L therapy to death or last follow-up. A multivariable Cox model with backward selection procedure (α = 0.01) and a Classification and Regression Tree (CART) analysis were performed to identify which prognostic factors were associated to OS in IR patients.From 2005 to 2017, 777 patients with ccRCC were treated with an anti-VEGF 1L therapy. Among 571 evaluable patients for IMDC score, 290 (51%) were classified as IR. With median follow-up 5.8 years (min: 0, max: 12.4) 212 deaths (73%) were observed and median OS was 25 months. Only platelet count was significantly associated to OS (hazard ratio 1.88 [95% CI 1.27–2.88] p = 0.0017). Median OS for patients with PLT > UNL was 18 months [95% CI 12–23] versus 29 months [95% CI 21.4–35.7] for patients with normal PLT count. The selection of PLT count was confirmed on bootstrap samples and was also selected for the first split of the CART-tree analysis.Patients in the IR group have a heterogeneous prognosis. Elevated PLT count seems identifies a subgroup of patients with poor outcome in the IMDC intermediate-risk population with ccRCC.
Highlights
The risk stratification models for metastatic renal cell carcinoma patients were developed as clinical tool to guide counseling, to predict individual patient prognosis and to design clinical trial
578 patients were evaluable for International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) score: 199 (34%) patients were classified as good risk, 297 (51%) as intermediate risk and 82 (14%) as poor risk (Figure 1)
We further studied the correlations between the six prognostic factors used for IMDC score: DTT was associated to other prognostic factors: KPS, hemoglobin level, calcium level, platelet count and neutrophil count (p < 0.001)
Summary
The risk stratification models for metastatic renal cell carcinoma (mRCC) patients were developed as clinical tool to guide counseling, to predict individual patient prognosis and to design clinical trial. Consortium (IMDC) score is currently used as prognostic index to stratify patients with mRCC in three subgroups: good, intermediate and poor-risk groups [1, 2]. (< 1 year), corrected serum calcium (> upper normal level [UNL]), neutrophil count (> UNL) and platelet count (> UNL) Patients lacking these negative factors have a good prognosis and may reached a longer survival; patients presenting 1 or 2 factors have an intermediate risk of death with a median overall survival (OS) about 23 months; patients with 3 or more factors have an expected poor risk outcome with median survival about 8 months [2]. In the poor risk group the decisionmaking algorithm was different: these patients were not candidate for upfront cytoreductive nephrectomy and in selected cases could benefit of mTOR inhibitor temsirolimus in first-line setting [3]
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