Renal Cell Carcinoma With Tumor Thrombus Extension: Biology, Role of Nephrectomy and Response to Immunotherapy

PURPOSE: We outline the biology, prognosis and role of immunotherapy for renal cell carcinoma with gross venous tumor thrombus. MATERIALS AND METHODS: A total of 207 patients with unilateral renal cell carcinoma and tumor thrombus into the renal vein (107) and inferior vena cava (100) who underwent nephrectomy and thrombectomy were compared with 607 without tumor thrombus. RESULTS: At diagnosis 77 patients (37%) had N0M0 disease and 130 (63%) had lymph node (N+) or distant (M1) metastases. Compared with nontumor thrombus cases tumor thrombus was associated with more advanced stage, N+ (26% versus 12%), M1 (54% versus 31%) disease, higher grade and Eastern Cooperative Oncology Group performance status. In N0M0 cases with inferior vena caval tumor thrombus capsular penetration, collecting system invasion and extension into the hepatic vein were more important prognostic variables then the level of inferior vena caval thrombus. In patients with confined N0M0 tumors mean 2 and 5-year survival +/- SD was 83% +/- 8.8% and 72% +/- 10.7% in those with inferior vena caval tumor thrombus, and 90% +/- 9.4% and 68% +/- 16.1% in those with renal vein tumor thrombus, similar to the 93.4% +/- 1.7% and 81 +/- 3.1% rates, respectively, in those without thrombus who had no recurrence within 6 months after nephrectomy. Of patients with M1 disease in whom cytoreductive surgery was done those with and without thrombus showed a similar response to immunotherapy. When there was inferior vena caval and renal vein thrombus, mean 2-year survival was higher after nephrectomy and immunotherapy than after nephrectomy alone (41% +/- 9% and 52% +/- 7% versus 32% +/- 13% and 45% +/- 7%), immunotherapy alone (0% and 13% +/- 12%, respectively) and no treatment (0%). CONCLUSIONS: Renal cell carcinoma with tumor thrombus is associated with worse characteristics. Local tumor extension has greater prognostic importance than the level of inferior vena caval tumor thrombus. Survival is fair in patients with truly confined N0M0 disease and thrombus. The combination of surgery and immunotherapy has a role in thrombus cases. Our data provide the rationale for a prospective study of adjuvant immunotherapy after surgery in N0M0 cases with extensive tumor thrombus.