Managing the Complex Journey of Renal Cell Carcinoma

Volume 1, Number 1
Release date: December, 2007 - Expiration date: December 2008
Estimated time to complete activity: 1.0 hours
Educational credits: 1.0 contact hours

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Overview of Renal Cell Carcinoma and Treatment Modalities
Laura S.Wood RN, MSN, OCN®
Cleveland Clinic Taussig Cancer Center, Ohio

The American Cancer Society estimates that 51,190 new cases of kidney cancer and 12,890 related deaths occur annually (Jemal et al., 2007; National Comprehensive Cancer Network, 2007). Renal cell carcinoma (RCC), which accounts for approximately 85% of kidney cancers, has presented treatment challenges due to its resistance to chemotherapy and radiation therapy (Cohen & McGovern, 2005). Approximately 20% to 40% of patients diagnosed with localized kidney cancer who undergo surgical resection will eventually develop metastatic disease and require additional therapy (Bukowski & Wood, 2007). Collaboration between the urologic surgeon and the medical oncologist regarding treatment planning can improve coordination of care. Advances in surgical techniques, including minimally invasive approaches and partial nephrectomy, radiation therapy, and targeted systemic therapies have enhanced the clinical outcomes of patients with RCC. Many institutions have multidisciplinary clinics which foster real-time collaboration between disciplines when determining the optimal management strategy for an individual patient.

Kidney cancer is a heterogeneous disease consisting of different histologic types. Differences between the subtypes of renal cancer are related to molecular events leading to oncogenesis and distinct morphologic and immunophenotypic patterns (Uzzo et al., 2003). The most common histology of RCC is clear cell (also known as conventional carcinoma), which accounts for approximately 75% of renal cancers. Papillary renal cancers include type 1, which are autosomal dominant inherited cancers associated with multifocal and often bilateral tumors, and type 2, which are typically sporadic tumors not associated with c-Met mutations. Figure 1 describes the various histologies associated with RCC (Linehan, Walthan, & Zbar, 2003).

The von Hippel-Lindau (VHL) gene functions as a tumor suppressor. It is responsible for targeting the hypoxia-inducible factor (HIF)-1a for ubiquitination and proteasome degradation (Cohen & McGovern, 2005). Individuals with VHL disease acquire a germline mutation in an autosomal dominant manner where one somatic hit silences the second copy of the gene, which then results in unregulated cell growth (Uzzo et al., 2003). In 50% to 80% of sporadic renal cancers, both VHL alleles are inactivated by acquired mutations or epigenetic dysregulation, resulting in loss of VHL function (Pantuck et al., 2003). Under conditions where normal VHL function is lost, the VHL protein does not bind to HIF-1a. This leads to an accumulation of HIF-1a and the activation of hypoxia-inducible genes (Figure 2). These genes include vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), transforming growth factor (TGF)-a, and erythropoietin. Loss of VHL gene function results in increased secretion of VEGF, PDGF, TGF-a, and erythropoietin, leading to increased renal tumor vascularization (Kim & Kaelin, 2004; Cohen & McGovern, 2005; Rini & Small, 2005). In addition, loss of VHL gene function leads to increased activation of the Ras-Raf and mTOR pathways. The mTOR pathway enables growth factors to promote cellular proliferation and angiogenesis; therefore, primary and metastatic renal masses are highly vascular and occasionally may require preoperative tumor embolization to reduce blood loss during surgery (Pantuck, Zeng, Belldegrun, & Figlin, 2003).

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