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Genomic Renal Score for Assessing Risk of Recurrence in Renal Cancer: Subgroup Analyses from the Validation Study

2014; Elsevier BV; Volume: 25; Linguagem: Inglês

10.1093/annonc/mdu337.7

1569-8041

Bernard Escudier, Serge Koscielny, Margarita Lopatin, Cecilia Svedman, Virginie Verkarre, C. Radulescu, Y. Neuzillet, Marc‐Olivier Timsit, Isabelle Hemmerlé, T. Tsiatis, Michael Bonham, Dejan Knezevic, Thierry Lebrét, Audrey D. Goddard, Arnaud Méjean,

Cancer Genomics and Diagnostics

ABSTRACT Aim: New clinical tools are needed to improve risk assessment in ccRCC. The 16-gene (11 cancer related, 5 reference) Recurrence Score (RS) was developed in a cohort of 931 stage I-III ccRCC patients (pts) from Cleveland Clinic. A large prospectively-designed clinical validation study of the RS in stage I-III ccRCC pts diagnosed from 1995 to 2007 at the French consortium was recently reported. The present analysis assesses the performance of the score in clinically relevant subgroups. Methods: The genes, algorithm, endpoints, methods, and analysis plan were pre-specified prior to merging clinical and molecular data. RT-PCR in fixed paraffin-embedded primary ccRCC tissue was performed without knowledge of clinical data. Recurrence-free interval was analyzed using Cox regression stratified by stage with data censored at 5 years, and Kaplan-Meier methods. Results: RS was successfully generated in 626/645 pts (97%): 398 stage I, 54 stage II, 174 stage III. Most (71%) patients were male, 29% were 70 years or older, 36% with partial nephrectomy, 46% with tumors ≤4 cm, 65% with Fuhrman grade 3-4, and 27% with invasion. Median follow-up was 5.5 yrs. The continuous RS predicted recurrence risk (HR per 25 point increase in RS (HR/25) =3.9, 95% CI 2.6-5.8, p 7cm), Fuhrman grade, and presence/absence of invasion (all interaction p > 0.29). Conclusions: The 16-gene RS is validated as a predictor of clinical outcome in pts with stage I-III ccRCC and provides significant information beyond conventional pathologic measures. The performance of the score was similar across a wide range of clinically relevant covariates indicating potential broad utility. Disclosure: B. Escudier: has an interest in relation with Genomich Health for sponsored research; M. Lopatin: is an employee of Genomic Health; C. Svedman: I am an employee of Genomic Health; T. Tsiati, M. Bonham, D. Knezevic and A. Goddard: Employee of Genomic Health; T. Lebret: Part of research grant from Genomic Health to perform the study (with the IGR institution, not personally); A. Mejean: Part of research grant from Genomic Health to perform the study (with the IGR institution, not personally). All other authors have declared no conflicts of interest.