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Background:There are no validated markers that predict response in metastatic renal cell cancer (RCC) patients treated with sunitinib. We aim to study the impact of single-nucleotide polymorphisms (SNPs) that have recently been proposed as predictors of outcome to anti-VEGF-targeted therapy in metastatic RCC in an independent cohort of patients.Methods:We genotyped 16 key SNPs in 10 genes involved in sunitinib pharmacokinetics, pharmacodynamics and VEGF-independent angiogenesis in patients with metastatic clear-cell RCC treated with sunitinib as the first-line targeted therapy. Association between SNPs, progression-free survival (PFS) and overall survival (OS) were studied by multivariate Cox regression using relevant clinical factors associated with PFS and OS as covariates.Results:In a series of 88 patients, both PFS and OS were associated significantly with SNP rs1128503 in ABCB1 (P=0.027 and P=0.025), rs4073054 in NR1/3 (P=0.025 and P=0.035) and rs307821 in VEGFR3 (P=0.032 and P=0.011). Progression-free survival alone was associated with rs2981582 in FGFR2 (P=0.031) and rs2276707 in NR1/2 (P=0.047), whereas OS alone was associated with rs2307424 in NR1/3 (P=0.048) and rs307826 in VEGFR3 (P=0.013).Conclusion:Our results confirm former communications regarding the association between SNPs in ABCB1, NR1/2, NR1/3 and VEGFR3 and sunitinib outcome in clear-cell RCC. Prospective validation of these SNPs is now required.

OBJECTIVETo develop a model to predict the outcome before surgery for non-metastatic renal cell carcinoma (RCC). PATIENTS AND METHODSThe records of 660 patients with nonmetastatic RCC, operated at three European medical institutes, were reviewed. Univariate and multivariate analyses were used to assess the clinical and pathological variables affecting disease-free survival. RESULTSThe median (range) follow-up was 42 (2-180) months; the disease recurred in 110 patients (16%). The 2-and 5-year overall survival was 87% and 54%, respectively. Five variables were significant in the univariate analysis, i.e. clinical presentation, clinical and pathological size, tumour grade and stage ( P < 0.05). The preoperative variables, e.g. clinical presentation and clinical tumour size, were retained from the multivariate model. A recurrence risk formula (RRF) was constructed from this model, as (1.28 ¥ presentation (asymptomatic = 0; symptomatic = 1) + (0.13 ¥ clinical size)). Using this equation, the 2-and 5-year disease-free survival was 96% and 93% for an RRF of £ 1.2 and 83% and 68% for an RRF of >1.2. CONCLUSIONA formula was developed which, independent of stage, can be used to predict the rate of treatment failure in patients who undergo nephrectomy for non-metastatic RCC. The RRF might be useful for more accurate subgrouping of good-prognosis patients, and for counselling patients before surgery, their personalized follow-up or adjuvant treatment once available.

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