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. 2018 Mar 30;9(24):16731-16743.
doi: 10.18632/oncotarget.24675.

High competing risks minimize real-world utility of adjuvant targeted therapy in renal cell carcinoma: a population-based analysis

Thenappan Chandrasekar  1 , Zachary Klaassen  1 , Hanan Goldberg  1 , Rashid K Sayyid  1 , Girish S Kulkarni  1 , Neil E Fleshner  1
Affiliations

High competing risks minimize real-world utility of adjuvant targeted therapy in renal cell carcinoma: a population-based analysis

Thenappan Chandrasekar et al. Oncotarget. .

Abstract

Objective: To utilize a population-based approach to address the role of adjuvant TT in the management of RCC.

Methods: Patients with RCC (2006-2013) in the SEER database were stratified by metastatic disease at the time of diagnosis (cM0/cM1). cM0 patients following surgical excision were stratified into low and high-risk (ASSURE and S-TRAC criteria). Multivariable analyses performed to identify predictors of TT receipt; Fine and Gray competing risks analyses used to identify predictors of cancer-specific mortality (CSM). Subset analyses included patients with clear cell histology and high-risk cM0. Survival analyses were used to evaluate overall survival (OS) and cancer-specific survival (CSS) for all cohorts, stratified on TT receipt.

Results: 79,926 patients included (71,682 cM0, 8,244 cM1); 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. 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 (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.

Conclusion: 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 further limit any potential benefit in this population. Based on current evidence, adjuvant TT cannot be recommended for RCC patients.

Keywords: carcinoma, renal cell; drug therapy; mortality; neoplasm metastasis; survival.

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Conflict of interest statement

CONFLICTS OF INTEREST All authors report no conflicts of interest.

Figures

Figure 1
Figure 1. Utilization of targeted therapy over time, stratified by cM status
Figure 2
Figure 2. Kaplan–Meier survival analyses
(A) Cancer-specific Survival and Overall Survival, cM1 patients (Entire cohort). (B) Cancer-specific Survival and Overall Survival, cM0 patients (Entire cohort). (C) Cancer-specific Survival and Overall Survival, High-risk cM0 patients.
See this image and copyright information in PMC

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