Should radical nephrectomy be performed in the face of surgically incurable disease

Abstract The role of cytoreductive nephrectomy in the management of metastatic renal cancer remains controversial. Recent trials, like SWOG 8949 have suggested the usefulness of this approach at least in selected patients with good performance status and other favorable indicators. The timing of cytoreductive nephrectomy has also been controversial and remains so to this time. Commentary An estimated 30,000 new cases of renal cell carcinoma (RCC) are detected annually in the U.S. In approximately one-third of these cases, metastatic disease is diagnosed at presentation. Multi-modality treatment combines biologic response modifier (BRM) therapy with surgery in an attempt to improve survival with either form of treatment alone. The optimal timing of surgery relative to BRM therapy continues to be debated. Prior to the advent of multi-modality therapy, there were relatively few indications for nephrectomy in patients with metastatic RCC. The incidence of spontaneous regression of metastatic RCC following removal of the primary tumor is only 1–4% and, therefore, nephrectomy on this basis is not justified. There is a palliative role for nephrectomy in selected patients with metastatic RCC who are experiencing severe disability from associated local symptoms; however, some patients in this category can be managed with percutaneous renal angioinfarction. A small subset of patients with a solitary metastasis may benefit from nephrectomy and resection of the metastatic lesion based on reported 5-year survival rates of up to 30–35%. There has been controversy concerning the appropriate timing of adjuvant or cytoreductive nephrectomy in the multi-modality approach to treatment of metastatic RCC. Many protocols have involved preliminary removal of the primary tumor before the administration of BRM therapy. The rationale for this has been to enhance response rates to BRM therapy by reducing tumor volume and, in some cases, to provide immunoreactive cells for treatment. A drawback of this approach was that many patients underwent nephrectomy without subsequently receiving BRM therapy due to postoperative morbidity/mortality or rapid tumor progression. This prompted interest in an alternative approach of delayed adjuvant nephrectomy wherein BRM therapy was administered initially and nephrectomy was subsequently performed only in those patients who demonstrated a response to systemic therapy. The relative merits of initial versus delayed adjuvant nephrectomy in conjunction with BRM therapy for metastatic RCC have recently been clarified through two phase III prospective multicenter clinical trials conducted in Europe (EORTC) and the United States (SWOG). The results of both of these carefully done studies have indicated improved survival with initial nephrectomy followed by BRM therapy. The latter comprised interferon monotherapy in both studies, which opens the studies to criticism, however the essential observation of extended survival with preliminary nephrectomy appears to be valid. On this basis, there is now objective evidence to suggest that initial cytoreductive nephrectomy is the preferred approach in patients with metastatic RCC who are candidates for multi-modality therapy. The most appropriate candidates for such therapy remain patients with good performance status and low-volume (preferably pulmonary) metastatic disease. The ability to perform cytoreductive nephrectomy laparoscopically in some of these patients, with reduced morbidity, is a further development that has strengthened the argument in favor of initial nephrectomy. Andrew C. Novick, M.D.