uRoloGIC onColoGy - University of Michigan Health System

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The CurrenT STaTe of urologiC onCology | iSSue 1 | winTer 2012 continued from p. 1 laparoscopic and robotic techniques for partial nephrectomy. Despite the early detection of many renal cell cancers, there is a stable population of patients who present with very large renal masses that have vascular extension into the vena cava and occasionally into the heart. the management of these patients is quite challenging; at the University of michigan we have developed a coordinated team of urologists, vascular surgeons, cardiovascular surgeons, and support staff to manage these complex patients. With this team concept, we have significantly improved the outcomes of these patients with lethal cancers and have been able to offer sophisticated adjuvant clinical trials using newly available biological agents. Because of our clinical and research growth, within these pages we also highlight and introduce the members of the Division of Urologic oncology with brief descriptions of their clinical and research focuses. if you have any patient care questions or concerns or have any patient with a urologic malignancy that you would like to refer to the University of michigan, please do hesitate to contact us: University of michigan cancer center Hotline : 734-647-8903 or contact me personally at: 734-936-0054. Best Wishes Jim montie, mD Interim Head, Division of Urologic Oncology Valassis Professor of Urologic Oncology 2 A tailored Approach to the management of small renal masses Alon Weizer, MD, MS Assistant Professor of Urology Surgery renal cell carcinoma affects more than 50,000 people each year and roughly 14,000 die of the disease annually. However, most people diagnosed with kidney cancer have small tumors (< 4 cm) that are picked up when they undergo radiographic evaluation because of other symptoms. on cursory review, it would seem like this would lead to more people getting treated earlier and fewer people dying from kidney cancer. there are several problems with this logic. first, it is still the people diagnosed with large tumors that die from kidney cancer, while a much smaller number of people with small renal masses die from their disease despite receiving aggressive surgical treatment. second, many of the small renal masses identified incidentally on imaging are non-cancerous, so treating these patients not only does not impact survival but also exposes them to the risk of surgery. finally, many patients continue to undergo radical nephrectomy (removal of the entire kidney) despite the fact that partial nephrectomy (removal of just the tumor) might be equally affective as might be ablative therapy, which destroys the tumor in place. the chief benefit of removing the tumor while preserving the kidney over total kidney removal is that preservation of kidney function protects patients from the risk of chronic kidney disease over a long period of time without compromising cancer control. over the last several years, we have worked to improve the treatment of patients with small renal masses. for instance, we now have a team of urologists dedicated to individualizing treatment for each patient who is seen at U-m’s Department of Urology. this means that we first try to determine whether a person with a newly diagnosed kidney tumor needs treatment at all. most of our patients with a tumor < 4 cm are evaluated with a renal mass biopsy, which our radiology colleagues perform as an outpatient procedure in patients under sedation. this well-tolerated biopsy allows us to identify the almost 30 percent of patients with non-cancerous tumors who do not require any further treatment. A biopsy positive for kidney cancer provides us with information about the type of cancer and its aggressiveness, allowing us to counsel patients regarding the best treatment option for them. treatment options include close surveillance of patients with non-aggressive kidney cancers, kidney preserving surgeries (ablation, partial nephrectomy through an open incision or a laparoscopic/robotic approach), and complete kidney removal when the biopsy findings identify a very aggressive cancer that would benefit from this approach. in conclusion, we’re working hard at U-m to find the most effective treatment regimen for each individual patient with a small renal mass. However, our personalized care program for patients with small renal masses and early kidney cancer is at an early stage. through cuttingedge translational research, we hope to further refine our ability to determine who can avoid treatment for their renal mass, who would benefit from nephron sparing procedures, and who requires multidisciplinary care by our excellent team of doctors at U-m.
ecent Developments in Kidney cancer treatment Bruce Redman, DO Professor of Internal Medicine in the past five years, the fDA has approved six new agents for the treatment of metastatic kidney cancer. though the common target of these agents is angiogenesis, they can be grouped into three distinct classes based on their mechanisms of action. 1. tyrosine kinase inhibition (tKi): represented by sunitinib, pazopanib, and sorafenib 2. monoclonal antibody: represented by bevacizumab 3. mammalian target of rapamycin (mtor) inhibition: represented by everolimus and temsirolimus the fDA approved all of these agents because they demonstrated clinical benefits in randomized trials. specifically, these compounds delayed metastatic disease progression; temsirolimus was the only agent, however, to show an overall survival advantage (albeit compared to the inactive interferon alfa). yet none of these agents are curative for metastatic clear cell carcinoma of the kidney, the only curative therapy for metastatic kidney cancer remains high-dose interleukin-2, and it only works in highly selected patients. Patients with metastatic clear cell carcinoma should be referred to a cancer center that has experience in, and expertise at, utilizing high-dose il-2 to discuss this potentially curative treatment option. for a more detailed discussion of the agents and how they fit in the treatment paradigm of advanced kidney cancer, visit the national comprehensive cancer network treatment Guidelines webpage (www.nccn.org). As in the case of all clinical research, advances lead to additional questions. the following represent several of the more prominent research questions that have arisen in regard to the care of patients with kidney cancer. 1. What role does cytoreductive nephrectomy play in the treatment of stage iV kidney cancer in the current era of targeted therapies? 2. What are the mechanisms of resistance to targeted therapies? a. in primary failure (no response to initial therapy) b. in acquired resistance (initial response followed by disease progression) 3. What is the role, if any, for the adjuvant treatment of high-risk patients after definitive surgery? 4. When and how do we evaluate novel investigational therapies in the treatment of stage iV kidney cancer? Cytoreductive Nephrectomy there is currently no clinical trial data defining what role cytoreductive nephrectomy, in conjunction with the use of targeted therapies, plays in the outcome of patients with kidney cancer. Previous clinical trial results supported the use of cytoreductive nephrectomy plus interferon in selected patients with metastatic kidney cancer, but these results are difficult to translate to other targeted agents. interferon is now considered an inactive therapy for kidney cancer. the current front line tyrosine kinase inhibitors (tKis) have much greater clinical activity than interferon and thus may abrogate any benefit from cytoreductive nephrectomy. the question of whether cytoreductive nephrectomy, followed by the use of a tKi, is most effective is being addressed in ongoing national and international trials. Mechanisms of Resistance At the present time, we have no definitive answer to the question: What are the mechanisms of resistance to targeted therapies? We are, however, testing multiple hypotheses in our active clinical research. Adjuvant Treatment there is currently no validated adjuvant therapy for the treatment of high-risk resected kidney cancer. However, at U-m, we are participating in a national cooperative group trial, led by the southwest oncology Group, of a randomized double blind placebo controlled trial of everolimus as adjuvant therapy. Investigational Therapy there are no curative treatment options for patients who have not responded to il-2 or who are not candidates for il-2. While current targeted therapies can meaningfully improve progression free survival, resistance ultimately develops in all patients. At U-m, we are performing clinical trials to evaluate new novel therapies for patients with metastatic kidney cancer; these are either part of our ongoing Phase ii trial of anti-PD-1 immunomodulating trial or they are part of our Phase i program. 3
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uRoloGIC onColoGy - University of Michigan Health System

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