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16-Gene Assay Recurrence Score Predicts Recurrence After Surgery for Localized Renal Cell Carcinoma

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Key Points

  • The 16-gene assay recurrence score was significantly associated with risk of recurrence.
  • The recurrence score identified high-risk stage I patients and low-risk stage II to III patients. 

In a study reported in The Lancet Oncology, Rini et al developed a 16-gene assay and recurrence score that predicted postsurgery outcome in patients with stage I to III clear cell renal cell carcinoma.

Development Phase

In the development phase, examination of the association between expression of 732 genes measured by reverse­ transcription polymerase chain reaction and clinical outcome in 942 patients with stage I to III clear cell renal cell carcinoma who had undergone nephrectomy at the Cleveland Clinic yielded 516 genes that were associated with a recurrence-free interval. Of them, 11 were selected by additional statistical analyses and were combined with 5 reference genes, with a recurrence score (0–100) algorithm being developed. The genes included in the assay consisted of those involved in vascular processes (APOLD1, EDNRB, NOS3, PPAP2B), cell growth/division (EIF4EBP1, TUBB2A, LMNB1), immune response (CEACAM1, CX3CL1, CCL5), inflammation (IL6), and the reference genes (AAMP, ARF1, ATP5E, GPX1, RPLP1).

Validation Phase

In the validation phase, the recurrence score was investigated in a French cohort of 626 patients. On univariate analysis, continuous recurrence score (median = 37) was associated with recurrence-free interval, with a hazard ratio [HR] of 3.91 (P < .0001) for each 25-unit increase in score. In multivariate analysis, the recurrence score was associated with risk of recurrence, with a hazard ratio of 3.37 (P <.0001) for each 25-unit increase after stratification by stage and adjustment for tumor size, tumor grade, and Leibovich score.

The recurrence score identified high risk in patients with stage I disease and low risk in patients with stage II to III disease.  Recurrence score thresholds of 32 and 44 were identified post hoc as distinguishing risk levels, with scores < 32 indicating low risk, 32 to 44 indicating intermediate risk, and > 44 indicating high risk.

On this basis, 39% of stage I patients were at low risk, with a mean 5-year recurrence risk of 2%, and 15% were at high risk, with a mean 5-year recurrence risk of 23%. Among patients with stage II to III disease, 19% were at low risk, with a mean 5-year recurrence risk of 2%, and 44% were at high risk, with a mean 5-year recurrence risk of 39%. The recurrence score risk groupings distinguished 5-year overall survival and renal cancer–specific survival rates in patients with stage I disease and in those with stage II to III disease. 

The investigators concluded, “Our findings validate the recurrence score as a predictor of clinical outcome in patients with stage I–III clear cell renal cell carcinoma, providing a more accurate and individualized risk assessment beyond existing clinical and pathological parameters.”

Brian Rini, MD, of The Cleveland Clinic Taussig Cancer Institute, is the corresponding author of The Lancet Oncology article.

The study was funded by Genomic Health Inc and Pfizer Inc.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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