Abstract
// Thenappan Chandrasekar 1 , Zachary Klaassen 1 , Hanan Goldberg 1 , Rashid K. Sayyid 1 , Girish S. Kulkarni 1 and Neil E. Fleshner 1 1 Department of Surgical Oncology, Division of Urology, University Health Network, University of Toronto, Ontario, Canada Correspondence to: Thenappan Chandrasekar, email: thenappan.chandrasekar@gmail.com Keywords: carcinoma, renal cell; neoplasm metastasis; drug therapy; survival; mortality Received: August 29, 2017 Accepted: February 26, 2018 Published: March 30, 2018 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.
Highlights
Renal cell carcinoma (RCC) has traditionally been surgically managed
When compared to the cM1 patients, Targeted therapies (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
Summary
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 [1, 2]. Targeted therapies (TT), including tyrosine kinase inhibitors (TKIs) and mTOR inhibitors, were first introduced in 2006 [3–5] Since they have become a cornerstone of RCC therapy, for metastatic RCC [1]. Utilized in patients with de novo metastatic RCC or patients with metastatic progression following primary surgical management, they have been demonstrated to extend progression-free survival by 3-8 months in patients with clear-cell histology [1, 2, 6, 7]. Their introduction has even called into question the oncologic value of cytoreductive nephrectomy, which was first established in the cytokine era [8–11]
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