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 as the mTOR inhibitor temsirolimus has been shown to prolong survival in first-line treatment of poor prognosis RCC of all histologies. Everolimus is an oral mTOR inhibitor and 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.
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Philip J. Saylor and M. Dror Michaelson
Presenters: Chad A. LaGrange, M. Dror Michaelson, and Colleen H. Tetzlaff
A number of therapeutic options are available for the treatment of advanced kidney cancer, including targeted therapy, immunotherapy, and nephrectomy. Choice of therapy for advanced kidney cancer is guided by risk stratification. Immunotherapy combinations are generally superior to vascular endothelial growth factor -based monotherapy, and overall survival rates continue to increase substantially. With new systemic therapy options, additional improvements have been noted in durable responses to treatment and in quality of life. Nephrectomy remains an important consideration in selected patients, particularly those with minimal burden of metastatic disease. Managing the adverse events of treatment of advanced kidney cancer requires close attention and multidisciplinary collaboration.
Gary R. Hudes, Michael A. Carducci, Toni K. Choueiri, Peg Esper, Eric Jonasch, Rashmi Kumar, Kim A. Margolin, M. Dror Michaelson, Robert J. Motzer, Roberto Pili, Susan Roethke, and Sandy Srinivas
The outcome of patients with metastatic renal cell carcinoma has been substantially improved with administration of the currently available molecularly targeted therapies. However, proper selection of therapy and management of toxicities remain challenging. NCCN convened a multidisciplinary task force panel to address the clinical issues associated with these therapies in attempt to help practicing oncologists optimize patient outcomes. This report summarizes the background data presented at the task force meeting and the ensuing discussion.
Ayal A. Aizer, Jonathan J. Paly, Anthony L. Zietman, Paul L. Nguyen, Clair J. Beard, Sandhya K. Rao, Irving D. Kaplan, Andrzej Niemierko, Michelle S. Hirsch, Chin-Lee Wu, Aria F. Olumi, M. Dror Michaelson, Anthony V. D’Amico, and Jason A. Efstathiou
NCCN Guidelines recommend active surveillance as the primary management option for patients with very-low-risk prostate cancer and an expected survival of less than 20 years, reflecting the favorable prognosis of these men and the lack of perceived benefit of immediate, definitive treatment. The authors hypothesized that care at a multidisciplinary clinic, where multiple physicians have an opportunity to simultaneously review and discuss each case, is associated with increased rates of active surveillance in men with very-low-risk prostate cancer, including those with limited life expectancy. Of 630 patients with low-risk prostate cancer managed at 1 of 3 tertiary care centers in Boston, Massachusetts in 2009, 274 (43.5%) had very-low-risk classification. Patients were either seen by 1 or more individual practitioners in sequential settings or at a multidisciplinary clinic, in which concurrent consultation with 2 or more of the following specialties was obtained: urology, radiation oncology, and medical oncology. Patients seen at a multidisciplinary prostate cancer clinic were more likely to select active surveillance than those seen by individual practitioners (64% vs 30%; P<.001), an association that remained significant on multivariable logistic regression (odds ratio [OR], 4.16; P<.001). When the analysis was limited to patients with an expected survival of less than 20 years, this association remained highly significant (72% vs 34%, P<.001; OR, 5.19; P<.001, respectively). Multidisciplinary care is strongly associated with selection of active surveillance, adherence to NCCN Guidelines and minimization of overtreatment in patients with very-low-risk prostate cancer.
NCCN Guidelines Insights: Kidney Cancer, Version 2.2020
Featured Updates to the NCCN Guidelines
Robert J. Motzer, Eric Jonasch, M. Dror Michaelson, Lakshminarayanan Nandagopal, John L. Gore, Saby George, Ajjai Alva, Naomi Haas, Michael R. Harrison, Elizabeth R. Plimack, Jeffrey Sosman, Neeraj Agarwal, Sam Bhayani, Toni K. Choueiri, Brian A. Costello, Ithaar H. Derweesh, Thomas H. Gallagher, Steven L. Hancock, Christos Kyriakopoulos, Chad LaGrange, Elaine T. Lam, Clayton Lau, Bryan Lewis, Brandon Manley, Brittany McCreery, Andrew McDonald, Amir Mortazavi, Phillip M. Pierorazio, Lee Ponsky, Bruce G. Redman, Bradley Somer, Geoffrey Wile, Mary A. Dwyer, CGC, Lydia J. Hammond, and Griselda Zuccarino-Catania
The NCCN Guidelines for Kidney Cancer provide multidisciplinary recommendations for the clinical management of patients with clear cell and non–clear cell renal cell carcinoma, and are intended to assist with clinical decision-making. These NCCN Guidelines Insights summarize the NCCN Kidney Cancer Panel discussions for the 2020 update to the guidelines regarding initial management and first-line systemic therapy options for patients with advanced clear cell renal cell carcinoma.