High-risk patients with metastatic renal-cell carcinoma (RCC) and venous tumor thrombus derived no benefit from cytoreductive nephrectomy and should be evaluated for clinical trials of systemic therapy, suggested a retrospective multicenter review.
Patients with thrombus above the diaphragm had a median overall survival of 6.8 months after surgery, which is approximately 33% of the median survival for patients with thrombus in the renal veins only or in the inferior vena cava (IVC) below the hepatic veins. In addition, patients classified as unfavorable according to M.D. Anderson criteria had a 9-month mortality rate of 63%, according to E. Jason Abel, MD, Assistant Professor of Urology, University of Wisconsin, Madison, at the 2016 Genitourinary Cancers Symposium.
“Poor overall survival following cytoreductive nephrectomy in metastatic renal-cell carcinoma patients with tumor thrombus can be predicted,” said Dr Abel. “Patients who have level 3/4 thrombus and are poor risk by prognostic criteria are high-risk patients and should be considered for upfront systemic therapy in clinical trials.”
Patients with IVC thrombus below the hepatic veins “probably should undergo surgery and be treated similarly to other patients undergoing cytoreductive nephrectomy,” he said.
Approximately 10% of patients with RCC have tumors that produce thrombus in the venous system. The presence of thrombus increases the complexity of and risk for surgery, but few studies have systemically evaluated the outcomes of cytoreductive nephrectomy in patients with thrombus, said Dr Abel.
One multi-institutional review of nephrectomy and thrombectomy in patients with RCC showed a 90-day mortality rate of 5%. The trial included patients with metastatic and nonmetastatic disease and tumor thrombus at all levels (Abel EJ, et al. J Urol. 2013;190:452-457).
A recent review of 162 patients with RCC and IVC thrombus above the hepatic veins showed a 90-day mortality rate of 10% and a 34% rate of major complications. The study included patients with metastatic and nonmetastatic disease, and the surgery included cardiac bypass or intervention for hepatic ischemia in some cases (Abel EJ, et al. Eur Urol. 2014;66:584-592).
“The rationale for complex surgery in nonmetastatic renal-cell carcinoma is simple—50% of the patients are cured,” said Dr Abel. “In patients with metastatic disease, are the risks of surgery justified for patients who have limited life expectancies?”
Whether surgery in patients with RCC and tumor thrombus improves survival remains unclear, Dr Abel noted. However, surgery can provide local disease control and can prevent thrombus extension, leading to hepatic or cardiac failure. Moreover, systemic alternatives have limited impact on the tumor and on disease progression. Identifying patients with metastatic RCC and venous thrombus who have poor overall survival could help patients avoid unnecessary risks for complications and morbidity while more efficiently using resources.
To address the issues, Dr Abel and colleagues reviewed the data on patients with metastatic RCC and tumor thrombus who were treated at 4 different centers from 2000 to 2014. They sought to determine whether thrombus location or level and risk models could predict poor survival.
The risk models evaluated were from Memorial Sloan Kettering Cancer Center (MSKCC), M.D. Anderson, and the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC). The MSKCC and IMDC criteria were developed to stratify patients according to overall survival from systemic treatment to death. The M.D. Anderson criteria were developed specifically to determine whether patients might benefit from cytoreductive nephrectomy.
Of the 293 patients investigators identified, 29 (10%) had thrombus above the diaphragm (level IV) and 45 (15%) had thrombus between the hepatic veins and the diaphragm; the remainder had thrombus below the hepatic veins, including 39% that were primarily limited to the renal veins.
Overall, the study population had a 30-day mortality rate of 6.1%; however, 35.5% of the patients died within the first year after surgery, suggesting that many patients did not benefit from surgery and leading Dr Abel to conclude that maybe patients can be selected better.
Comparing thrombus location and mortality, the investigators found that patients with thrombus in the renal veins or below the hepatic veins had similar survival of approximately 19 months, but those with thrombus above the hepatic veins (level 3/4) fared significantly worse (14.5 months for thrombus between hepatic veins and diaphragm vs 6.8 months for thrombus above the diaphragm; P = .0048).
An evaluation of the risk models showed that the MSKCC and IMDC criteria showed a separation in survival curves for patients with favorable, intermediate, and poor risks (P = .0027 and P = .0053, respectively).
The M.D. Anderson criteria were derived from a comparison of 566 patients who underwent cytoreductive nephrectomy and 110 patients who had medical therapy only. The model is based on preoperative variables that influenced survival after surgery: serum albumin below the lower limit of normal; serum lactate dehydrogenase above the upper limit of normal; liver metastasis; metastasis-associated symptoms; retroperitoneal lymph node involvement; supradiaphragmatic nodal involvement; and clinical stage T3/4.
The model demonstrated that patients with ≤3 risk factors had better survival with cytoreductive nephrectomy than medically or surgically treated patients with ≥4 risk factors (Culp SH, et al. Cancer. 2010;116:3378-3388).
Applying risk criteria, thrombus location, and mortality, Dr Abel and colleagues found that patients with unfavorable M.D. Anderson risk criteria had a 25% mortality rate at 3 months and a 63% mortality rate at 9 months, and with level 4 thrombus, a 35% mortality rate at 3 months and 56% at 9 months. Using the IMDC criteria, for patients who were classified as poor risk, the 3-month and 9-month mortality rates were 17% and 50%, respectively. Using MSKCC risk grouping, poor-risk patients had 3-month and 9-month mortality rates of 18% and 49%, respectively, and for patients with level 3 thrombus, the rates were 21% and 41%, respectively.
