Metastatic Renal Cell Carcinoma: An Invincible Enemy?

Abstract

Renal cell carcinoma (RCC) remains an important cause of cancer death, with a worldwide annual increase of 1.5–5.9% and an estimated 58 240 new cases and approximately 13 040 deaths in 2010 [1]. Despite the widespread application of cross-sectional imaging, approximately 30% of patients with RCC continue to present with metastases [2], whereas several studies report that between 14% and 29% of patients who are treated for clinically localized RCC subsequently develop recurrence of the disease [3,4]. Patients with untreated metastatic disease have a poor prognosis, with a 5-yr survival rate of 2 yr (26.4 mo) [5]. From this perspective, the role of surgery and metastasectomy represents an important treatment for mRCC. Fiveyear survival rates of 30–45% have been reported in patients with mRCC after metastasectomy; in fact, the complete resection of all metastases has been associated with a twofold decrease in the risk of death [2]. An interval from RCC diagnosis to occurrence of metastases >1 yr, a unique metastatic site, and age <60 yr have been identified as favorable survival predictive factors following RCC metastases resection. In cases of pulmonary resection, delay from RCC diagnosis to metastases occurrence, complete resection, number of nodules to remove, and metastatic nodule size appear to be major prognostic factors. The 5-yr survival rate seems to be superior in cases of pulmonary resection (54%) than in cases of brain resection (18%). Pancreatic metastases are likely to occur late in the natural history of the metastatic disease and seem to have a good prognosis when surgical resection is feasible [7]. Nevertheless, if the efficacy of resection for RCC metastases has been demonstrated in the presence of solitary metastasis and/or disease in the lungs only [2], the utility of metastasectomy in patients with multiple metastases has been less well defined. Recently, Alt et al. [8] investigated the survival of patients with multiple metastases from RCC who underwent complete surgical metastasectomy. The authors considered the importance of metastatic features, including disease site, timing and number of disease sites, and the impact of patient performance status, on outcomes after resection. Of 887 patients, 125 (14%) underwent complete surgical resection of all metastases. Complete metastasectomy was associated with a significant prolongation of median cancer-specific survival (CSS) (4.8 yr vs 1.3 yr; p < 0.001). Patients who had lung-only metastases had a 5-yr CSS rate of 73.6% with complete resection versus 19% without complete resection. A survival advantage for complete metastasectomy also was observed among patients with multiple, non–lung-only metastases, who had a 5-yr CSS rate of 32.5% with complete resection versus 12.4% without complete resection (p < 0.001). Complete resection remained predictive of improved CSS for patients who had three or more metastatic lesions and for patients who had synchronous and asynchronous