Introduction

Progression-free survival (PFS) of first-line targeted therapy (TT) greatly influences on the survival of patients with metastatic renal cell carcinoma (RCC). If we can predict disease progression early after an administration of first-line TT, we may be able to choose appropriate targeted agent (TA) for individual patients. In the present study, we evaluated whether post-treatment inflammatory marker and LDH levels had adoptive impacts on PFS prediction in addition to conventional prognostic factors.

Methods

In this multi-institutional study 325 patients with metastatic RCC were enrolled from 8 institutions. Of these patients 215 patients whose tumors were diagnosed as clear cell type and in whom first-line TAs could be continued for more than 1 month, were selected (median follow-up period: 20.6 mo). Pretreatment clinical factors, pathological factors, and laboratory data 1 month after TA administration including inflammatory markers [neutrophil count, neutrophil-to-lymphocyte rate (NLR) and C-reactive protein (CRP)] and lactate dehydrogenase (LDH), were reviewed. To identify predictors for PFS, univariate and multivariate analyses were done by cox proportional hazards model.

Results

Six TAs were used as first-line TT. Tyrosine kinase inhibitors were used for 205 patients and mTOR inhibitors for 10 patients. Nephrectomy was done for 184 patients and percutaneous needle biopsy was done for the diagnosis in 31 patients. MSKCC risk criteria was favorable in 62 patients, intermediate in 122, poor in 17, not determined in 14. The 1-year PFS rate was 47%. Univariate analysis showed that female patients, Karnofsky performance status (KPS) <80%, sarcomatoid differentiation, time from diagnosis to systemic treatment <12 months, anemia, thrombocytosis, pretreatment neutrophil count >upper limits of normal (ULN), pretreatment LDH >1.5 x ULN, LDH 1 month after TT (LDH-1M) >1.5 x ULN, pretreatment NLR >3.7, NLR 1 month after TT (NLR-1M) >3.0, pretreatment CRP >3.0 mg/dL, and CRP 1 month after TT (CRP-1M) >1.5 mg/dL, were significantly associated with PFS. In contrast, LDH decline 1M after TT, decline in neutrophil count 1M after TT, CRP decline 1M after TT, and NLR decline 1M after TT, were not significant factor even in univariate analyses. In multivariate analysis, female, KPS <80%, time from diagnosis to systemic treatment <12M, pretreatment CRP >3.0, and NLR-1M >3.0 were independent predictors for PFS. When all patients were stratified to 3 groups by these 5 factors (0 risk vs. 1 or 2 risks vs. 3 risks or more), there were significant differences in PFS rates between the groups (p<0.0001). The median time to progression was 27.6 months in 0 risk, 10.0 months in 1 or 2 risks, and 2.8 months in 3 or more risks. Furthermore, when we looked at overall survival (OS), there were also significant differences in OS rates between the groups (p<0.0001). The median OS was 58.5 months in 0 risk, 33.5 months in 1 or 2 risks, and 7.6 months in 3 or more risks.

Conclusions

Integration of NLR-1M >3.0 to pretreatment factors may lead to the establishment of effective predictive models for disease progression in patients with metastatic clear cell RCC who receive targeted argents. The absolute value of NLR appeared to be more important for PFS prediction compared to the NLR decline 1 month after targeted therapy.

Funding

None