In 2008, an estimated 54,390 Americans were diagnosed with and 13,010 died of kidney cancer in the United States. The rate of renal cell carcinoma (RCC) has increased 2% per year for the past 65 years. Smoking and obesity are among the risk factors for RCC development, with tumor grade, local extent of the tumor, presence of regional nodal metastases, and evidence of metastatic disease at presentation the most important prognostic determinants of 5-year survival. These guidelines discuss evaluation, staging, treatment, and management after treatment. Important updates for 2009 include the addition of everolimus as second-line therapy after a tyrosine kinase inhibitor and the change to a category 1 recommendation for bevacizumab and interferon for first-line therapy for clear cell histologies.

Testicular Cancer

An estimated 8090 new cases of testicular cancer were diagnosed in the United States in 2008. Although relatively uncommon overall, germ cell tumors (GCTs) constitute the most common solid tumor in men between the ages of 15 and 34 years. The worldwide incidence of these tumors has more than doubled in the past 40 years. More than 90% of patients diagnosed with GCTs are cured, including 70% to 80% of patients with advanced tumors who are treated with chemotherapy. Standard therapy has been established at essentially all stages of management and must be closely followed to ensure the potential for cure. Updates to the 2009 NCCN Guidelines include the addition of doses for single-agent carboplatin for seminoma and changes to category 1 for recommendations on radiotherapy and surveillance.

Featured Articles

Optimal Management of Localized Renal Cell Carcinoma: Surgery, Ablation, or Active Surveillance
David Y.T. Chen, MD, and Robert G. Uzzo, MD

Renal cell carcinoma (RCC) accounts for approximately 3.5% of all malignancies and is the third most common cancer of the urinary tract. In 2008, an estimated 54,390 new cases were identified and 13,010 deaths resulted from RCC. Although historically patients presented with symptoms such as a palpable flank mass, hematuria, pain, or weight loss, most cases today are identified by chance. This shift is attributed to the increased frequency of cross-sectional diagnostic imaging; an asymptomatic incidental renal mass now accounts for at least 48% to 66% of RCC diagnoses. Over the past 3 decades, a steady increase has been seen in the incidence of RCC with downward stage migration, along with a matching increase in the rate of RCC interventions. An evolution in treatment options has accompanied this differing presentation of RCC. Surgery remains the mainstay of treatment for localized RCC, although open radical nephrectomy is arguably no longer the gold standard. Open radical nephrectomy has known procedure-related morbidity and can lead to renal insufficiency. Several alternatives have become available to reduce or avoid these inherent negative consequences. This article reviews different surgical and management approaches for localized RCC, and compares the data and role for each intervention.

New Treatments for Renal Cell Carcinoma: Targeted Therapies
Philip J. Saylor, MD, and M. Dror Michaelson, MD, PhD

Systemic treatment options for advanced renal cell carcinoma (RCC) have expanded considerably with the development of targeted therapies. Clear cell RCC commonly features mutation or inactivation of the von Hippel-Lindau gene and resultant overexpression of vascular endothelial growth factor (VEGF). The first drug to validate VEGF as a target in the treatment of clear cell RCC was the monoclonal antibody bevacizumab. Since then, anti-VEGF receptor therapy with multitargeted kinase inhibitors also has shown substantial efficacy. Sunitinib is now a standard first-line therapy for advanced disease and sorafenib is among the second-line treatment options. Other kinase inhibitors are in development. Mammalian target of rapamycin (mTOR) is a second validated therapeutic target. The mTOR inhibitor temsirolimus has been shown to prolong survival in first-line treatment of poor prognosis RCC of all histologies, and the oral mTOR inhibitor everolimus has been shown to prolong progression-free survival when used in second-line treatment. Non–clear cell and sarcomatoid RCC are both underrepresented in completed trials but are the subject of active research. Ongoing and planned studies will also evaluate the use of combinations of targeted agents, a strategy that is not advisable outside of clinical trials. Finally, postnephrectomy adjuvant treatment with targeted agents is not yet standard but is under investigation in phase III trials. This article describes recent advances in the use of targeted therapies for advanced RCC and focuses on agents that have been evaluated in published phase III and randomized phase II trials.

Non�Clear Cell Renal Cancer: Features and Medical Management
Daniel Y.C. Heng, MD, and Toni K. Choueiri, MD

The treatment of metastatic renal cell carcinoma (RCC) has changed dramatically with the introduction of targeted therapies against vascular endothelial growth factor and the mammalian target of rapamycin. Because patients with clear cell histology account for more than 80% of patients with RCC, little evidence is available on treating patients with non–clear cell histologies. Most clinical trials have excluded them from enrolment, except for a randomized study investigating temsirolimus. Many retrospective studies on the use of all 3 of these targeted therapies in patients with non–clear cell histology have shown response rates ranging from 3.7% to 16%. Prospective studies in non–clear cell histologies are ongoing. Although response rates may not be as high as those in patients with clear cell histologies, targeted therapy may provide a clinically meaningful response. New investigational therapies are on the horizon for papillary RCC—the most-common non–clear cell RCC histology—targeting pathways specific to this histology, such as the c-MET pathway. This article outlines emerging data on the treatment of non–clear cell RCCs.

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