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Sources of Funding: none

Introduction

The International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model predicts prognosis in metastatic renal cell carcinoma (mRCC) patients, who are stratified into favorable-, intermediate-, and poor-risk groups (FG, IG, and PG, respectively), based on six clinical parameters, in which about half of mRCCs are classified as IG. We aimed to substratify IG as more favorable (fIG), poorer (pIG), and others (intermediate IG: iIG), as well as generate better risk model: [FG&fIG], iIG, and [PG&pIG] as modified IMDC model.

Methods

We analyzed the records of 213 consecutive mRCC patients who underwent molecular targeted therapy (MTT). Age, gender, histology (clear vs non-clear cell), type of initial MTT medications (tyrosine kinase inhibitors [TKIs] vs mammalian target of rapamycin inhibitors [mTORIs]), serum laboratory data (albumin [ALB], sodium, and C-reactive protein [CRP]), prior nephrectomy, immunotherapy, and metastatic sites (lung, liver, and bone) were used for IG sub-stratification. Overall survival (OS) was defined as the duration from the initial MTT. Modified and original models were compared using concordance correlation coefficient analysis.

Results

Median follow-up after the initial MTT was 17.8 months. According to the original criteria, total cohort were classified into FG (n=41 [19.2%], median OS=58.5 months), IG (n=109 [51.2%], median OS=33.5 months), and PG (n=63 [29.6%], median OS=17.1 months), respectively. Among IG cohort, multivariate analysis revealed that ALB <4 g/dL (hazard ratio [HR] =2.65), CRP ≥0.3 mg/dL (HR=2.86), and bone metastases (HR=2.73) were independent predictors of OS, although the remaining factors were not. IG was sub-stratified as fIG, pIG, and iIG, according to the number of predictors present: 0, 3, or other, respectively. Thus, the modified IMDC model was developed: FG&fIG (n=62 [29.1%], median OS=58.5 months) vs iIG (n=70 [32.9%], median OS=34.9 months) vs PG&pIG (n=81 [38.0%]; median OS=14.8 months). The concordance indices for the original and modified models were 0.68 and 0.73, respectively (p<0.001).

Conclusions

We successfully developed a modified IMDC model using a two-step process: original IMDC plus IG sub-stratification. Our preliminary data showed that PG&pIG group treated with mTORIs in second-line setting had significantly longer OS than with TKIs, based on modified model but not original model. In addition, we are seeking molecular markers for FG&fIG, iIG, and PG&pIG in the modified model, which may contribute to select of MTT as well as newly immunotherapy agents.

Funding

none