EAU 2018: High Competing Risks Minimize Real-World Utility of Adjuvant Targeted Therapy in Renal Cell Carcinoma: A Population-Based Analysis

Copenhagen, Denmark (UroToday.com) Renal cell carcinoma (RCC) has traditionally been surgically managed. Extirpative surgery, either radical nephrectomy (RN) or partial nephrectomy (PNx), remains the standard of care for localized disease. Targeted therapies (TT), including tyrosine kinase inhibitors (TKIs) and mTOR inhibitors, have become a cornerstone of RCC therapy, specifically for metastatic RCC,  demonstrating extended progression-free survival. While the efficacy of targeted therapies is well established for metastatic RCC, its role as an adjuvant therapy is less clear. Two randomized controlled trials (RCTs) demonstrated conflicting cancer-specific survival outcomes with sunitinib and sorafenib in the adjuvant setting for high-risk localized RCC. In ASSURE, there was no significant difference in disease-free survival (DFS) between high-risk patients treated with sunitinib, sorafenib or placebo, while in S-TRAC, sunitinib-treated patients had a 1.2 year improved DFS. 

In this study, the authors utilized a population-based approach to address the role of adjuvant TT in the management of RCC. Specifically, they utilized the SEER database to identify all patients with RCC from 2006 to 2013; these patients were then stratified by the presence of metastatic disease at the time of diagnosis (cM0 / cM1). cM0 patients following surgical excision were stratified into low and high-risk based on a combination of ASSURE and S-TRAC criteria.

Based on above criteria, 79,926 patients were included - 71,682 cM0 and 8,244 cM1 patients. The median follow-up for the entire cohort was 40.1 months. Of 31,453 patients with histologic grade data, 18,328 and 13,125 were low- and high-risk cM0, respectively. 

Targeted Therapy

TT utilization in cM1 patients peaked at 50.6% and was associated with reduced CSM (HR 0.73, p<0.01). In contrast, TT utilization (which was presumed salvage therapy) never exceeded 2.2% in the entire cM0 cohort and 3.5% in the high-risk cM0 cohort. On competing risks analysis, TT receipt was associated with increased CSM in all cohorts, including subset analyses – though this probably represented selection bias for worse disease. 

Importantly, however, Kaplan-Meier survival analyses demonstrate that other-cause mortality exceeds cancer-specific mortality in the cM0 population.

Using this inferred analysis from population-level data, the authors conclude that, when compared to the cM1 patients, TT receipt in cM0 patients does not provide any cancer-specific survival benefit, even in the small percentage of patients that eventually progress to metastatic disease. Competing risks mortality (other-cause mortality) further limit any potential benefit in this population, as these patients are more likely to die of other causes than RCC. 

Presented by: Thenappan Chandrasekar, University Health Network, University of Toronto, Dept. of Surgical Oncology, Division of Urologic Oncology, Toronto, Canada

Written by: Thenappan Chandrasekar, MD Clinical Fellow, University of Toronto, twitter: @tchandra_uromd at the 2018 European Association of Urology Meeting EAU18, 16-20 March, 2018 Copenhagen, Denmark