Population-based analysis of factors associated with survival in patients undergoing cytoreductive nephrectomy in the targeted therapy era

Abstract

Objectives

Despite level 1 evidence demonstrating a survival benefit of cytoreductive nephrectomy (CN) in well-selected patients with metastatic renal cell carcinoma (mRCC) in the cytokine era, its role in the contemporary period of targeted therapy remains understudied. To help facilitate improved patient selection for CN and clinical trial design in the targeted therapy era, this study sought to identify factors associated with RCC-specific survival in patients diagnosed with mRCC and undergoing CN between 2005 and 2010 using a large population-based cohort.

Materials and methods

Patients diagnosed with mRCC and undergoing CN between 2005 and 2010 were identified from the Surveillance Epidemiology and End Results cancer database. Kaplan-Meier methods were used to calculate disease-specific survival. Stepwise multivariable Cox proportional hazards regression analysis was used to identify factors independently associated with risk of RCC-specific death.

Results

A total of 2,478 patients were identified who were eligible for analysis with a median disease-specific survival of 21 months (95% CI: 19, 22). Factors independently associated with an increased risk of RCC-specific death included age at diagnosis≥60 years, African American race, higher American Joint Committee on Cancer T stage (≥T₃), high Fuhrman nuclear grade (3 or 4), primary tumor size≥7 cm, regional lymphadenopathy, both distant lymph node and visceral metastases, and sarcomatoid histology. A higher number of adverse factors correlated with an increased risk of RCC-specific death (P<0.001).

Conclusions

Factors associated with RCC-specific survival identified in this large population-based study can be used to better stratify patients suitable for CN and to help with future clinical trial design and interpretation.

Introduction

Up to 25% of patients continue to present with metastatic renal cell carcinoma (mRCC) at the time of diagnosis [1]. The introduction of targeted therapy (TT) in 2005 marked a major milestone in the treatment of mRCC. However, even with TT, the prognosis of patients with mRCC remains poor. The central role of cytoreductive nephrectomy (CN) before the advent of TT was based on level 1 evidence demonstrating a survival advantage when CN was performed before treatment with interferon alfa-2b (IFNα) compared with IFNα treatment alone [2], [3], [4]. Unfortunately, such evidence does not exist for CN in the context of TT [5]. Although 2 prospective randomized trials are currently underway to help define the benefit of CN in the present era of TT, the results may be limited based on their selection criteria and thereby not generalizable to all patients diagnosed with mRCC. Furthermore, the results of these trials are not likely to be available for years to come. Therefore, the purpose of this study was to use a large population-based database to identify factors associated with RCC-specific survival in patients diagnosed with mRCC and undergoing CN between 2005 and 2010, the period corresponding to the initial use of TT, to better stratify patients suitable for CN and to help with future clinical trial design and interpretation.