Management of Renal Cell Carcinoma

Introduction

Renal cell carcinoma has been characterized as the “internist’s tumor” based on the diversity of presenting symptoms. These range from microscopic hematuria to abdominal pain to an abdominal or flank mass. An estimated 30,000 new cases of renal cell carcinoma will occur in the United States in the year 2000, and approximately 12,000 people will die from this disease. The majority (75% to 85%) of tumors are of clear cell histologic type, with papillary, chromophobic, oncocytic, and collecting-duct tumors comprising the remainder.

Although the incidence of kidney cancer has increased by 43% since 1973 in the United States, the 5-year survival rate improved by approximately 9% between 1974 and 1994. This increase in survival may be attributable to a stage migration resulting from earlier diagnosis. The more frequent use of sensitive abdominal imaging modalities in recent years may have contributed to the greater number of tumors detected at an early stage; this includes incidental renal masses detected during evaluation for other medical conditions.

The major etiologic factors implicated in the development of renal cell carcinoma are cigarette smoking, obesity (especially in females), and hypertension. Recently, mutations of the von Hippel-Lindau (VHL) gene have been identified in large numbers of patients with both sporadic and familial forms of renal cell carcinoma. Evolving evidence suggests that the VHL gene acts as a tumor suppressor and that restoration of the wild-type gene product can inhibit growth of renal cell carcinoma cell lines. The altered form of this protein can also enhance expression of vascular endothelial growth factor, which may contribute to the progression of kidney cancer by promoting vascularization.

Surgery

Approximately 45% of patients present with disease localized to the kidney and undergo surgical resection. Radical nephrectomy, entailing resection of the affected kidney, perirenal fat, and ipsilateral adrenal gland, has been the benchmark procedure for managing localized kidney cancer. Recent investigations have questioned the need for adrenalectomy and lymph node dissections in patients without an obvious abnormality of the adrenal gland on computed tomography (CT).

More conservative surgical approaches, such as a partial nephrectomy (nephron-sparing surgery), are reserved for those with an absent, abnormal, or at-risk contralateral kidney. Patients with a normal contralateral kidney and small (£ 4 cm), polar primary lesions may also be candidates for nephron-sparing surgery.

More aggressive surgical treatment is considered for patients presenting with a tumor that has invaded the renal vein and inferior vena cava. When a careful radiologic evaluation does not detect metastatic disease, these patients should be referred to a center staffed by surgeons who are experienced in performing resections of tumors extending into these venous structures.

The likelihood that localized kidney cancer will be cured by surgical removal of the tumor depends on several prognostic factors. The most important of these is pathologic stage on presentation. Patients who have a small tumor that is confined within the renal capsule have a more favorable prognosis than do those whose tumor extends beyond the capsule, invades the renal vein, or involves the local lymph nodes.

There is no established role for adjuvant systemic therapy following resection in patients with localized kidney cancer. Several trials of adjuvant radiotherapy or immunotherapy with interferon-alfa (Intron A, Roferon-A) or experimental autologous vaccines have failed to show a significant advantage for these approaches in preventing recurrence. Ongoing trials of interleukin-2 (IL-2 [Proleukin]) and new vaccine trials are evidence of the continued interest in identifying effective adjuvant therapy for patients at high risk of relapse.