March 2016, Vol. 5, No. 2
No Benefit from Nephrectomy in High-Risk RCC with ThrombusGenitourinary Cancers Symposium
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, a retrospective multicenter review suggested.
Patients with thrombus above the diaphragm had a median overall survival of 6.8 months after surgery, about a third of the median survival for patients with thrombus in the renal veins only or inferior vena cava (IVC) below the hepatic veins. Additionally, patients with unfavorable risk by MD Anderson criteria had a 9-month mortality of 63%, according to a presentation at the Genitourinary Cancers Symposium.
“Poor overall survival following cytoreductive nephrectomy in metastatic renal cell carcinoma patients with tumor thrombus can be predicted,” said E. Jason Abel, MD, an assistant professor of urology at the University of Wisconsin in Madison. “Patients who have level 3/4 thrombus and are poor risk by prognostic criteria are high-risk patients and should be considered for up-front 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.
About 10% of patients with RCC have tumors that produce thrombus in the venous system. The presence of thrombus increases the complexity and risk of surgery, but few studies have systemically evaluated outcomes of cytoreductive nephrectomy in patients with thrombus, said Abel.
One multi-institutional review of nephrectomy and thrombectomy in patients with RCC showed a 5% 90-day mortality. The trial included patients with metastatic and nonmetastatic disease and tumor thrombus at all levels (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 of 10% and major complications in 34%. The study included patients with both metastatic and nonmetastatic disease, and the surgery included cardiac bypass or intervention for hepatic ischemia in some cases (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 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, he continued. However, the surgery can provide local control and prevent thrombus extension leading to hepatic or cardiac failure. Moreover, systemic alternatives have limited impact on the tumor or disease progression. Identifying patients with metastatic RCC and venous thrombus who have a poor overall survival could help avoid unnecessary risk and morbidity and at the same time make more efficient use of resources.
To address the issues, Abel and colleagues reviewed data on patients with metastatic RCC and tumor thrombus 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, MD Anderson, and the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC). The Sloan Kettering and IMDC criteria were developed to stratify patients according to overall survival from systemic treatment to death. The MD Anderson criteria were developed specifically to determine whether patients might benefit from cytoreductive nephrectomy.
Investigators identified 293 patients, 29 (10%) of whom had thrombus above the diaphragm (level IV), 45 (15%) of whom had thrombus between the hepatic veins and the diaphragm, and the remainder below the hepatic veins, including 39% primarily limited to the renal veins.
Overall, the study population had a 30-day mortality of 6.1%. However, 35.5% of the patients died within the first year after surgery, “suggesting that a lot of these patients, especially those who were farther out, didn’t benefit from surgery, and maybe we can select these patients better,” said Abel.
Comparing thrombus location and mortality, investigators found that patients with thrombus in the renal veins or below the hepatic veins had similar survival (about 19 months), but those with thrombus above the hepatic veins (level III-IV) fared significantly worse (14.5 months for thrombus between hepatic veins and diaphragm and 6.8 months for thrombus above the diaphragm; P = .0048).
Evaluation of the risk models showed that the Sloan Kettering and IMDC criteria showed a separation in survival curves for patients with favorable, intermediate, and poor risk (P = .0027, P = .0053, respectively).
The MD 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 influence 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 T≥3.
The model demonstrated that patients with 3 or fewer risk factors had better survival with cytoreductive nephrectomy than either the medically treated patients or surgically treated patients with 4 or more risk factors (Cancer. 2010;116:3378-3388).
Applying risk criteria, thrombus location, and mortality, Abel and colleagues found that patients with unfavorable MD Anderson risk criteria had a 25% mortality at 3 months and 63% at 9 months; level IV thrombus, 35% mortality at 3 months and 56% at 9 months; IMDC poor risk, 17% and 50%; Sloan Kettering poor risk, 18% and 49%; and level III thrombus, 21% and 41%, respectively.
In the United States, the standard of care for locally advanced bladder cancer after radical cystectomy is to “consider” adjuvant chemotherapy and adjuvant radiation. In a 3-arm randomized trial, adjuvant radiation therapy alone or combined with chemotherapy (ie, chemoradiotherapy) did not significantly improve disease-free survival (DFS) compared with adjuvant chemotherapy [ Read More ]
Personalizing Oncology Care and the Quest for Companion Diagnostics: A Researcher’s Perspective
An Interview with Suso J. Platero, PhD, of Janssen Pharmaceuticals
Today we interview Dr Suso J. Platero, whose research is probing the frontiers of next-generation sequencing, transcriptional profiling, and proteomics in the validation of biomarkers for lung cancers. In his 2009 book, Molecular Pathology in Drug Discovery and Development, Dr Platero makes the case for clinicians and researchers working together [ Read More ]