Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)

Stage IV renal cell cancer is defined by the following stage groupings:

• T4, N0, M0
• T4, N1, M0
• Any T, N2, M0
• Any T, any N, M1

The prognosis for any treated renal cell cancer patient with progressing, recurring, or relapsing disease is poor, regardless of cell type or stage. Almost all patients with stage IV renal cell cancer are incurable. The question and selection of further treatment depends on many factors, including prior treatment and site of recurrence as well as individual patient considerations. Carefully selected patients may benefit from surgical resection of localized metastatic disease, particularly if they have had a prolonged, disease-free interval since their primary therapy. Because of early reports of success, progestational agents have been administered to patients with metastatic renal cell cancer, but the response rates have been disappointingly low; therefore, no rationale currently exists for their use as anticancer therapy. Progestational agents may, however, offer subjective palliation.

Local Therapy

Tumor embolization, external-beam radiation therapy, and nephrectomy can aid in the palliation of symptoms caused by the primary tumor or related ectopic hormone production. Minimal evidence suggests that nephrectomy induces regression of distant metastases; therefore, a nephrectomy performed with the hope that it will be followed by spontaneous regression of metastases is not advised. Spontaneous regressions occasionally occur. A prospective surveillance series of 73 patients with advanced renal cell cancer demonstrated apparent temporary objective regression in five patients (7%) without nephrectomy or any therapy.[1] Selected patients with solitary or a limited number of distant metastases can achieve prolonged survival with nephrectomy and surgical resection of the metastases. Even patients with brain metastases had similar results.[2] The likelihood of achieving therapeutic benefit with this approach appears enhanced in patients with a long disease-free interval between the initial nephrectomy and the development of metastatic disease. Cytoreductive nephrectomy in selected patients who will receive postoperative interferon-a may convey a modest impact on survival. (See the Cytokine therapy section below.)

Cytokine Therapy

Cytokine therapy has been shown to induce objective responses and have a modest impact on survival in selected patients. Interferon-alpha has approximately a 15% objective response rate in appropriately selected individuals.[3] In general, these patients have nonbulky pulmonary and/or soft tissue metastases with excellent performance status (PS) ratings of zero or one, according to the Eastern Cooperative Oncology Group rating scale, and the patients show no weight loss. The interferon-alpha doses used in studies reporting good response rates have been in an intermediate range (6-20 million units 3 times weekly). A Cochrane analysis of six randomized trials, with a total of 963 patients, indicated a hazard rate (HR) for survival of 0.78 (confidence interval [CI], 0.67-0.90) or a weighted average improvement in survival of 2.6 months.[3][Level of evidence: 1iiA]