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Management of Locally Advanced Renal Cell Carcinoma

Abstract and Introduction

Abstract

Background: Renal cell carcinoma accounts for approximately 3% of adult malignancies and over 90% of primary renal tumors. Recurrence rates for patients with locally advanced renal cell carcinoma (LARCC) remain high.
Methods: The authors review literature regarding prognostic factors, potential biomarkers, surgical strategies, and adjuvant therapy trials for patients with LARCC.
Results: Molecular tumor markers may improve existing staging systems for predicting prognosis. Surgery is the best initial treatment for most patients with clinically localized renal tumors, although complete surgical resection can be challenging for patients with large tumors, bulky regional lymph node involvement, or inferior vena cava tumor thrombus. Significant recurrence rates for patients with LARCC undergoing nephrectomy indicate the presence of undetected micrometastases at the time of surgery. Adjuvant radiation, chemotherapy, and immunotherapy have been ineffective. Other trials of adjuvant therapy are ongoing.
Conclusions: Aggressive surgical resection alone for LARCC is not sufficient to prevent disease recurrence in a significant number of patients. Adjuvant therapies are needed to improve cancer-specific survival.

Introduction

Surgery is the most efficacious therapy for patients with nonmetastatic, localized renal cell carcinoma (RCC). Progression-free survival and overall survival following nephrectomy are dependent on factors such as pathologic T stage, tumor grade, lymph node status, and performance status.[1,2] Patients with low-stage, lowgrade, and often incidentally detected renal tumors have a favorable long-term prognosis.[1-3] For patients with metastatic disease at presentation, nephrectomy followed by systemic immunotherapy increases overall survival by 3 to 10 months compared with patients treated with immunotherapy alone.[4,5] Still, with multimodality therapy, the median survival for patients with metastatic disease is only 10 to 12 months, and just 2% of such patients survive long-term.[6] Centered between these two clinical extremes are many patients with locally advanced renal cell carcinoma (LARCC) at risk for progression and death from their renal tumors due to adverse clinical and pathologic variables determined at the time of presentation or following surgery. Given the almost uniformly fatal outcome for patients who develop metastatic disease, several factors are paramount to the successful treatment of these patients: a better understanding of the variables that influence disease recurrence and progression, an understanding of the surgical principals required to render a patient disease free, and the development of adjunctive therapies to extend recurrence and progression-free intervals of patients with locally advanced disease.

This article characterizes LARCC,reviews the markers associated with advanced disease, and examines the outcome for patients undergoing nephrectomy. Finally, different surgical options for managing LARCC are described, and the results of adjuvant therapy trials aimed at improving progression rates and survival are reviewed.