High competing risks minimize real-world utility of adjuvant targeted therapy in renal cell carcinoma

A population-based analysis

Thenappan Chandrasekar, Zachary W A Klaassen, Hanan Goldberg, Rashid K. Sayyid, Girish S. Kulkarni, Neil E. Fleshner

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)16731-16743
Number of pages13
JournalOncotarget
Volume9
Issue number24
DOIs
StatePublished - Mar 30 2018
Externally publishedYes

Fingerprint

Renal Cell Carcinoma
Population
Therapeutics
Mortality
Neoplasms
Survival
Salvage Therapy
Survival Analysis
Histology
Databases

Keywords

  • Carcinoma
  • Drug therapy
  • Mortality
  • Neoplasm metastasis
  • Renal cell
  • Survival

ASJC Scopus subject areas

  • Oncology

Cite this

High competing risks minimize real-world utility of adjuvant targeted therapy in renal cell carcinoma : A population-based analysis. / Chandrasekar, Thenappan; Klaassen, Zachary W A; Goldberg, Hanan; Sayyid, Rashid K.; Kulkarni, Girish S.; Fleshner, Neil E.

In: Oncotarget, Vol. 9, No. 24, 30.03.2018, p. 16731-16743.

Research output: Contribution to journalArticle

Chandrasekar, Thenappan ; Klaassen, Zachary W A ; Goldberg, Hanan ; Sayyid, Rashid K. ; Kulkarni, Girish S. ; Fleshner, Neil E. / High competing risks minimize real-world utility of adjuvant targeted therapy in renal cell carcinoma : A population-based analysis. In: Oncotarget. 2018 ; Vol. 9, No. 24. pp. 16731-16743.
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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.",
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T1 - High competing risks minimize real-world utility of adjuvant targeted therapy in renal cell carcinoma

T2 - A population-based analysis

AU - Chandrasekar, Thenappan

AU - Klaassen, Zachary W A

AU - Goldberg, Hanan

AU - Sayyid, Rashid K.

AU - Kulkarni, Girish S.

AU - Fleshner, Neil E.

PY - 2018/3/30

Y1 - 2018/3/30

N2 - 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.

AB - 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.

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KW - Drug therapy

KW - Mortality

KW - Neoplasm metastasis

KW - Renal cell

KW - Survival

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