The role of cytoreductive nephrectomy in elderly patients with metastatic renal cell carcinoma in an era of targeted therapy Dipesh Uprety, MD Amir Bista, MD Yazhini Vallatharasu, MD Angela Smith, MA David Marinier, MD GundersenHealth System
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The Oncologist February 1, 2011vol. 16 no. Supplement 2 1-3 Background
Background Cytoreductive nephrectomy (CN) occurs prior to systemic chemotherapy (sometimes debulking nephrectomy) CN followed by interferon therapy offered significant OS benefit for patients with mrcc in the interferon era 1 1. Flanigan et al. J Urol 171: 1071-1076, 2004.
Background 1. Flanigan et al. N Engl J Med. 2001 Dec6; 345 (23): 1655-9. 2. Mickisch et al. Lancet. 2001 Sep 22; 358 (9286): 966-70. OS: 13.6 months vs. 7.8 months Flanigan et al. J Urol 171: 1071-1076, 2004.
Background The role of CN is unclear since the approval of targeted therapeutic agents Rates of CN have declined in recent years and older age has been identified as an independent factor associated with decreased receipt of CN 1 1 Tsao et al. World J Urol. 2013 Dec; 31 (6): 1535-9.
Background Renal cell carcinoma occurs predominantly in the elderly population 1 Median age at diagnosis of RCC is 64 years 2 Its incidence increases with age and is most frequently diagnosed among patients between 65-74 years of age 3 1. Flanigan et al. J Urol 171: 1071-1076, 2004. 2. Thompson et al. J Urol. Pulte el al. Oncologist. 2011;16(11):1600-3 3. Tsao et al. World J Urol. 2013 Dec; 31 (6): 1535-9.
Objective To compare overall survival (OS) and cancer-specific survival (CSS) in elderly ( 65 years of age) patients with metastatic RCC between those who received cytoreductive nephrectomy and those who did not receive cytoreductive nephrectomy
Data source SEER (Surveillance, Epidemiology, and End Results Program) database of the National Cancer Institute A population-based database that assembles data related to incidence and survival on cancer patients in the United States It covers approximately 28% of the United States population
Case Selection Inclusion criteria Age 65 years Diagnosis of Stage IV RCC Histologically confirmed Actively followed Exclusion criteria Patients diagnosed from death certificate or at autopsy Patients who were alive but without survival data
Study Design Retrospective, population-based, case-control Treatment arm: Patients receiving cytoreductive nephrectomy (CN) Control arm: Patients not receiving CN
Measures of Survival Overall survival (OS) Cancer-specific survival (CSS)
Statistical Analysis Kaplan-Meier curve (3-year) and log rank test were used to compare overall survival (OS) and cancer-specific survival (CSS) between these two arms Cox proportional hazard model was used for multivariate analysis Statistical significance was defined for p-value 0.005
Results Parameters Total (n, %) No CN (n, %) CN (n, %) P value n= 3,365 n= 2,277 n=1,088 Sex 0.68 Male 1876 (55.8) 1275 (68) 601(32) Female 1489 (44.2) 1002 (67.3) 487 (32.7) Race <0.001 Caucasians 2820 (83.8) 1889 (67) 931 (33) African American 287 (8.5) 225 (78.4) 62 (21.6) Others 258 (7.7) 163 (63.2) 95 (36.8) Histology <0.001 Clear cell 1441 (42.8) 735 (51) 706 (49) Others 1924 (57.2) 1542 (80.1) 382 (19.9) Table 1: Baseline characteristics of study population n= sample size; CN= cytoreductive nephrectomy
Results:
Results Independent factors predicting better OS in patients who received CN: Younger age at diagnosis Race other than Caucasians and African Americans and Zero nodal (N0) stage
Conclusions There is a significant survival benefit associated with CN in elderly patients with metastatic renal cell carcinoma in the targeted therapy era
Elderly patients with low physiological reserve, multiple comorbidities and poor performance status are more likely to have worse operative outcomes. Underlying comorbidities and performance status should therefore be the guiding factors for selecting patients for cytoreductive nephrectomy and not just the chronological age.
Strengths SEER database is large and comprehensive and covers approximately 28% of the United States population It is comparable to the general United States population with regard to measures of poverty and education We got to know the real world impact of treatment
Limitations: Retrospective design: Allocation of patients to CN is not randomized, potentially leading to selection bias and hence overestimating the benefit of CN SEER database lacks individual patient information Prognostic factors Chemotherapy information Performance status
Summary Despite this limitation, our study showed that CN remains an independent predictor of OS It should therefore be a serious consideration even in elderly patients, particularly with excellent performance status
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