Oncotarget: Identification intermediate-risk subgroups in metastatic clear-cell renal cell carcinoma


The cover for issue 49 of Oncotarget features Figure 4, "CART-Tree analysis for overall survival in IMDC intermediate risk group," by Guida, et al.recently published in "Identification of international metastatic renal cell carcinoma database consortium (IMDC) intermediate-risk subgroups in patients with metastatic clear-cell renal cell carcinoma" which reported that as these patients have different prognosis, the aim of this study is to better characterize IR patients in order to better tailor the treatment.

A multivariable Cox model with backward selection procedure and a Classification and Regression Tree analysis were performed to identify which prognostic factors were associated to OS in IR patients.

Median OS for patients with PLT > UNL was 18 months versus 29 months 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.

Elevated PLT count seems to identify a subgroup of patients with poor outcome in the IMDC intermediate-risk population with ccRCC.

"Elevated PLT count seems to identify a subgroup of patients with poor outcome in the IMDC intermediate-risk population with ccRCC"

Dr. Laurence Albiges from The Université Paris-Saclay said, "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 also to design clinical trial."

Patients lacking these negative factors have a good prognosis and may reach a longer survival; patients presenting 1 or 2 factors have an intermediate risk of death with a median overall survival about 23 months; patients with 3 or more factors have an expected poor risk outcome with median survival about 8 months.

Only in the poor risk group the decision-making 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.

In the phase III trial Checkmate-214 nivolumab plus ipilimumab immunotherapy combination significantly prolonged OS versus sunitinib in intermediate and poor-risk untreated patients with mRCC.

Figure 4: CART-Tree analysis for overall survival in IMDC intermediate risk group.

Figure 4: CART-Tree analysis for overall survival in IMDC intermediate risk group.

The Albiges Research Team concluded in their Oncotarget Research Paper that given the rapidly evolving field of systemic treatment in mRCC, one of the most important challenges in mRCC is how prognostic stratification will guide front-line treatment selection.

Additionally characterization of heterogeneous IMDC intermediate-risk groups of patients should be seeked for optimal clinical trials design and stratification.

High platelet count reflecting the cancer-related inflammatory status and seems to segregate patients with the worst prognosis in the intermediate-risk group.

Further analyses are ongoing to validate these findings in patients receiving first line CPI based combination in first line.

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DOI - https://doi.org/10.18632/oncotarget.27762

Full text - https://www.oncotarget.com/article/27762/text/

Correspondence to - Laurence Albiges - [email protected]

Keywords - metastatic clear-cell renal cell carcinoma, IDMC, intermediate-risk, heterogeneous prognostic, platelets

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