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Management of Renal Cell Carcinoma

Management of Renal Cell Carcinoma

ABSTRACT: Surgical resection remains the cornerstone of management for localized renal cell carcinoma. No effective postsurgical adjuvant therapy has been established for patients with locally advanced disease who are at high risk for recurrence. The effective treatment of metastatic kidney cancer remains a challenge. Immunologic therapy with cytokines, such as interferon-alfa (Intron A, Roferon-A) and interleukin-2 (IL-2 [Proleukin]), benefit relatively small numbers of patients. Preclinical research and clinical investigations aimed at identifying new agents and treatment programs with improved antitumor activity against metastases remain the highest priorities in this refractory disease. New immunologic approaches to the treatment of both advanced and high-risk postsurgical disease are focusing on novel vaccine therapies to target both renal epithelial and vascular antigens.[ONCOLOGY 14(1):29-35, 2000]

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.

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