He began by emphasizing that most trials to date, with the notable exception of S-TRAC, have failed to demonstrate a benefit to the use of adjuvant tyrosine kinase inhibitors following resection of renal cell carcinoma. Currently, the Leibovich score is the most widely used tool for risk stratification, to predict the risk of relapse, and for selection into adjuvant trials. However, outcomes within categories of the Leibovich score are heterogenous.
Previous work from the NIVOREN cohort presented at ESMO 2020 demonstrated that molecular subtypes ccrcc1 to ccrcc4 and the angiogenic gene signature are predictive of response to tyrosine kinase inhibitors among patients with metastatic clear cell renal cell carcinoma (ccRCC). In this presentation, Dr. Roussel presented data utilizing these molecular subtypes to identify risk of relapse and stratify patients for adjuvant therapy.
The authors included 75 patients with metachronous metastatic ccRCC, among whom 5 were low-risk, 24 were intermediate-risk, and 43 were high-risk based on Leibovich score. The authors tested the association between Leibovich score, molecular classification, and gene signatures (angiogenic and immunogenic) as well as the relationship with time to metastasis.
Notably, the unfavourable ccrcc1 and ccrcc4 subtypes were associated with higher Leibovich scores which the favourable ccrcc2 and ccrcc3 subtypes had higher angiogenic gene signatures.
While Leibovich score was not associated with the time to metastasis (hazard ratio 1.51, 95% confidence interval 0.90 to 2.52, p=0.12), molecular subtyping was with median time to metastasis of 41 months among those with favourable signatures and 14 months among those with unfavourable signatures (hazard ratio 1.70, 95% confidence interval 1.01 to 2.85). Similarly, the authors found that a high angiogenic gene signature was association with a longer time to metastasis (median difference in time to metastasis 24months; hazard ratio 2.41, 95% confidence interval 1.51 to 3.86). However, immunogenic gene signatures were neither associated with Leibovich score, not with time to metastasis.
The authors conclude that molecularly subtyping male allows for more precise prognostication among patients with resected ccRCC, particularly among patients with intermediate and high-risk of relapse based on Leibovich score. The authors propose that this approach may allow for the enrichment of patients with a high-risk of relapse in future trials of adjuvant therapy.
Presented by: Eduard Roussel, Resident in Urology, University Hospitals Leuven, Belgium
Written by: Christopher J.D. Wallis, Urologic Oncology Fellow, Vanderbilt University Medical Center Contact: @WallisCJD on Twitter at the 12th European Multidisciplinary Congress on Urological Cancers (EMUC) (#EMUC20 ), November 13th - 14th, 2020
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