Renal Cell Carcinoma

A Reappraisal

Chintan Patel, MD; Asma Ahmed, CUNP; Pamela Ellsworth, MD


Urol Nurs. 2012;32(4):182-190. 

In This Article

Treatment Options for Stage IV Disease

The value of nephrectomy in metastatic RCC has long been debated. For Stage IV disease, surgery may be considered in carefully selected patients. Cytoreductive nephrectomy can be considered for palliation of local symptoms before initiating systemic immunotherapy. Two welldesigned randomized-controlled trials comparing immuno therapy alone versus immuno therapy and radical nephrectomy showed increased survival in the combined group (Flanigan et al., 2001; Mickisch, Garin, von Poppel, de Prijck, & Sylvester, 2001). Reports have documented regression of metastatic RCC after removal of the primary tumor; however, this is extremely uncommon (Marcus et al., 1993).

Removal of a solitary metastasis is indicated in select patients with good overall performance status. A retrospective analysis from a single institution revealed improved cancer-specific survival advantage, even with removal of more than one metastatic lesion. The authors also reported increased risk of death due to RCC in patients who did not undergo surgical resection of metastasis (Alt et al., 2011). This area is still under great debate, and more studies are needed.

Paraneoplastic syndromes in RCC include hypercalcemia, polycythemia, galactorrhea, anemia, nonmetastatic hepatic dysfunction (Stauffer's syndrome), hypertension, Cushing's syndrome, altered glucose metabolism, amyloidosis, neuromyopathies, vasculopathies, nephropathies, and prostaglandin elevation (Palapattu, Kristo, & Rajfer, 2002). Palliative nephrectomy can be considered in patients with metastatic disease for alleviation of symptoms, such as pain, hemorrhage, malaise, hypercalcemia, erythrocytosis, or hypertension, but many clinicians believe most symptoms can be treated medically without surgical intervention.

Biological therapies include interferons, interleukins, colonystimulating factors, monoclonal antibodies, vaccine gene therapy, and non-specific immunomodulators. Interferons are natural glycoproteins with antiviral, antiproliferative, and immunomodulatory properties. Interleukin-2 (IL-2) is a T-cell growth factor and activator of T cells, as well as a natural killer cell. IL-2 affects tumor growth by activating lymphoid cells in vivo without directly affecting tumor proliferation. Interferons and interleukins are cytokines with low response rates (5% to 20%); a median overall survival is approximately 12 months (Fisher, Rosenberg, & Fyfe, 2000; Janzen, Kim, Figlin, & Belldegrun, 2003; McDermott et al., 2005).

Immunomodulators, such as lenalidomide, a derivative of thalidomide, inhibits vascular endo thelial growth factor (VEGF), stimulates T and natural killer cells and inhibits inflammatory cytokines. Currently in phase 2 trials, this drug showed an antitumor effect in selective cases (Choueiri et al., 2006; Patel et al., 2008). Vaccine trials are still being developed, and autologous vaccine therapy is now being tried in combination with cytokine therapy. Rahma et al. (2010) carried out a pilot clinical trial testing mutant von Hippel-Lindau peptide as a novel immune therapy in metastatic RCC.

More recent developments have focused on targeted cancer therapies (see Table 6). Targeted cancer therapies are drugs or other substances that block the growth and spread of cancer by interfering with specific molecules involved in tumor growth and progression (everolimus, sorafenib tosylate, sunitinib maleate, temsirolimus). Pazopanib (Votrient®) is an oral medication that interferes with angiogenesis. It is a kinase inhibitor indicated for treatment of patients with advanced RCC (Kidney Cancer Assoication, 2012). Several targeted therapies have been approved for the treatment of metastatic RCC. One newer form of therapy under investigation is low intensity stem cell transplantation with multiple lymphocyte infusions to treat advanced RCC (NCI, 2012).

Although these therapies are more commonly administered by oncologists, an awareness of these agents by nursing staff and urologists is helpful. Patients with advanced disease are often followed by both urologists and oncologists, and an understanding of the indications and contraindications for use, as well as method of administration and potential adverse effects, may allow urologists and nurses to alleviate some anxieties of patients with metastatic and/or unresectable disease. Urologists and their nursing staff can also provide these patients with basic information that will better prepare the patient for his or her meeting with the oncologist. Finaly, since management of advanced RCC involves a multidisciplinary approach, questions pertinent to therapy may arise in the urologist's office, and thus, an awareness of these agents may allow the urologist and/or urology nurse to address some of the patient's questions.


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