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Gene assay predicts recurrence following nephrectomy in renal cell carcinoma
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Recurrence scores based on a 16-gene assay accurately predicted clinical outcomes in patients with surgically treated clear cell renal cell carcinoma, according to study results.
Surgery or ablation represent curative options for patients with stage I to III clear cell renal cell carcinoma, but about 30% of patients with localized disease will relapse, according to study background. Clinicians frequently use clinical and pathological parameters to determine the probability of recurrence.
Brian Rini
“The current methods we use to assess recurrence can certainly be improved,” Brian Rini, MD, associate professor of medicine in the department of urology at the Cleveland Clinic and a HemOnc Today Editorial Board member, told HemOnc Today. “Researchers have utilized a similar testing method to predict breast cancer recurrence.”
Rini and colleagues conducted a developmental study to investigate the association between the clinical outcomes of 942 patients — who had stage I to III clear cell renal cell carcinoma and underwent nephrectomy at the Cleveland Clinic — and the expression of 732 genes. The cohort had a mean age of 62 years (range, 53-70) and was 63% male. Sixty-eight percent of patients had stage I disease.
Researchers identified 516 genes associated with recurrence-free intervals, from which they selected 11 genes for additional statistical analyses. The researchers added five reference genes to develop a 16-gene recurrence score algorithm.
Researchers then conducted a validation study using an independent cohort of 626 French patients. The median age of this cohort was 61 years (range, 53-71) and 71% were male. Sixty-four percent of patients had stage I disease.
Researchers sought to define an association between the recurrence score and the risk for recurrence and 5-year disease-specific survival, stratified by tumor stage (stage I vs. stage II vs. stage III) and adjusted by tumor size, grade or Leibovich score.
Median follow-up was 6.2 years (range, 5.1-8.4) in the developmental study and 5.5 years (range, 3.6-7.9) in the validation cohort.
Researchers observed a significant association between the continuous recurrence score (median = 37; interquartile range [IQR], 31-45) and recurrence-free interval (HR = 3.91; 95% CI, 2.63-5.79; based on a 25-unit increase in score). Analyses stratified by tumor stage indicated the continuous recurrence score was significantly associated with cancer-specific survival (HR = 5.55; 95% CI, 3.11-9.92), DFS (HR = 3.43; 95% CI, 2.45-4.7) and OS (HR = 3.55; 95% CI, 2.32-5.44).
Researchers conducted a multivariable analysis that demonstrated a significant link between recurrence score and the risk for recurrence (HR = 3.37; 95% CI, 2.23-5.08) when stratified by tumor stage.
In a model including Leibovich score and recurrence score, the recurrence score remained a significant predictor of recurrence (HR = 4.2; 95% CI, 2.76-6.4), whereas Leibovich score became insignificant.
Researchers also used the recurrence score to identify a clinically significant number of high-risk patients with stage I disease (n = 58) and low-risk patients with stage II or stage III disease (n = 43).
The researchers acknowledged several limitations of their study, including the use of different American Joint Committee on Cancer staging systems (2002 and 2010) for the developmental and validation cohorts. Further, follow-up could not be standardized.
“We have already seen genomic progress in other specialties,” Rini said. “One of our ultimate goals would be the ability to predict more overall outcomes using genetics.” – by Cameron Kelsall
For more information:
Brian Rini, MD, can be reached at the Cleveland Clinic Main Campus, Mail Code R35, 9500 Euclid Ave., Cleveland, OH 44195; e-mail: rinib2@ccf.org.
Disclosure: The study was funded by Genomic Health and Pfizer. Researchers report employment with Genomic Health and Pfizer. Rini reports research funding from Genomic Health for the development study.
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